100 Cases in Pulmonary Medicine

00 Cases in
Pulmonary
Medicine
Rajendra Prasad
Nikhil Gupta luroi
Co-authors Foreword
Harsh Saxena SurinderKJindal
100 Cases in
Pulmonary Medicine
100 Cases in
Pulmonary Medicine
Authors
Rajendra Prasad
MD DTCD FAMS FCCP (USA) FRCP (Glasgow) FNCCP FICS FCAI FIAB
FIMSA FCCS DSc (Honoris Causa)
Director, Medical Education Professor and Head
Department of Pulmonary Medicine
Era’s Lucknow Medical College and Hospital
Era University
Lucknow, Uttar Pradesh, India
Formerly
Director, Vallabhbhai Patel Chest Institute
University of Delhi
New Delhi, India
Professor and Head, Department of Pulmonary Medicine
King George’s Medical University
Director, UP Rural Institute of Medical Sciences and Research
Saifai, Etawah, Uttar Pradesh, India
Nikhil Gupta MBBS MD (Medicine)

Assistant Professor
Department of General Medicine
Dr Ram Manohar Lohia Institute of Medical Sciences
Co-author
Harsh Saxena MBBS
Junior Resident
Department of Pulmonary Medicine
Era’s Lucknow Medical College and Hospital
Foreword
Surinder K Jindal
JAYPEE BROTHERS MEDICAL PUBLISHERS

The Health Sciences Publisher
New Delhi | London
Jaypee Brothers Medical Publishers (P) Ltd
Headquarters
Jaypee Brothers Medical Publishers (P) Ltd
4838/24, Ansari Road, Daryaganj
New Delhi 110 002, India
Phone: +91-11-43574357
Fax: +91-11-43574314
Email: [email protected]
Overseas Office
J.P. Medical Ltd
83 Victoria Street, London
SW1H 0HW (UK)
Phone: +44 20 3170 8910
Fax: +44 (0)20 3008 6180
Website: www.jaypeebrothers.com
Website: www.jaypeedigital.com
© 2020, Jaypee Brothers Medical Publishers
The views and opinions expressed in this book are solely those of the original contributor(s)/author(s)
and do not necessarily represent those of editor(s) of the book.
All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form
or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior
permission in writing of the publishers.
All brand names and product names used in this book are trade names, service marks, trademarks or
registered trademarks of their respective owners. The publisher is not associated with any product or
vendor mentioned in this book.
Medical knowledge and practice change constantly. This book is designed to provide accurate,
authoritative information about the subject matter in question. However, readers are advised to
check the most current information available on procedures included and check information from the
manufacturer of each product to be administered, to verify the recommended dose, formula, method
and duration of administration, adverse effects and contraindications. It is the responsibility of the
practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s)
assume any liability for any injury and/or damage to persons or property arising from or related to use
of material in this book.
This book is sold on the understanding that the publisher is not engaged in providing professional
medical services. If such advice or services are required, the services of a competent medical
professional should be sought.
Every effort has been made where necessary to contact holders of copyright to obtain permission to
reproduce copyright material. If any have been inadvertently overlooked, the publisher will be
pleased to make the necessary arrangements at the irst opportunity.
Inquiries for bulk sales may be solicited at: [email protected]
100 Cases in Pulmonary Medicine / Rajendra Prasad, Nikhil Gupta
First Edition: 2020

ISBN: 978-93-90020-09-6
Dedicated to
My teachers for their guidance, wisdom and inspiration, and
My parents, wife and children for their love and patience
FOREWORD
Diagnostic problems faced by a clinician remain the most exciting challenges in

medical practice, more so in the field of pulmonary medicine. The physician makes
the diagnosis essentially required to treat patients, effectively with the help of history
and physical examination, supported by a variety of radiological images, physiological
measurements, microbiological, histological and other relevant laboratory tests. In the
context, the publication of this book on 100 cases in Pulmonary Medicine is a timely and
useful addition in the existing literature on clinical practice. In this book, Dr Rajendra
Prasad has presented diagnostic approach to 100 interesting and challenging cases
in Pulmonary Medicine. He has also discussed the salient features of pathophysiology
and clinical presentation. Various other aspects of diagnosis and treatment in light of
current evidence based knowledge have been also deliberated upon. There are a large
number of radiological images of interesting cases in this book which make its reading
extremely interesting for clinicians treating pulmonary diseases.
Professor Rajendra Prasad is a nationally acclaimed chest physician and tuberculosis
expert. He possesses more than four decades of illustrious experience with proven
excellence in teaching, research and administrative activities. He is also a very popular
medical teacher in pulmonary medicine. He is currently the Director, Medical Education,
Professor and Head, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar
Pradesh, India. He has earlier served as Director of Vallabhbhai Patel Chest Institute,
Delhi, India; Professor and Head, Department of Pulmonary Medicine King George’s
Medical University, Lucknow; and Director, UP Rural Institute of Medical Sciences and
Research, Saifai, Etawah, Uttar Pradesh, India.
Dr Prasad has devoted his energy throughout his life in promoting medical
education, patient care and research. His contribution in the field of Pulmonary
Medicine, tuberculosis and multidrug-resistant tuberculosis (MDR-TB) are well
recognized. His dynamic leadership in academic, patient care and administrative
areas has earned him large number of awards from various international and national
scientific societies including the prestigious Dr BC Roy National Award.
This comprehensive, well-referenced book contains plethora of knowledge and will
remain a valuable educational source for undergraduate and postgraduate medical
students, clinicians, healthcare workers caring for patients of chest diseases. I am
quite hopeful that this book will help in better understanding of pulmonary diseases
including tuberculosis. This handbook deserves a place in the library of every medical
college and healthcare institutions.
Surinder K Jindal MD FCCP FAMS FNCCP

JINDAL CLINICS
Medical Director, Jindal Clinics, SCO 21, Sector 20 D, Chandigarh, India, 160020
Emeritus-Professor, Postgraduate Institute Medical Education and Research, Chandigarh, India
Websites: www.jindalchest.com, www.ivfchandigarh.com
Blogspot: medicalviganettes.blogspot.in
PREFACE
It occurred to me that presentation of interesting cases in a concise format would

provide valuable information that is difficult to find and not readily available in
standard textbook for practicing physicians and PG students interested in diagnosis
and management of pulmonary diseases. As a senior author of this book, I have
come across many interesting cases in my more than 4 decades of clinical practice
in Pulmonary Medicine. Of all those cases, I have compiled 100 Cases which are
challenging and educative for general physician and consultants in medicine,
pulmonary medicine and allied branches. These cases are collection of interesting
case studies in day-to-day clinical practice of pulmonary medicine in Indian scenario.
Each case follows a step-by-step approach which includes good history points, salient
findings in physical examination and relevant investigations for diagnosis. There are a
large number of radiological images of interesting cases which will make the reading
extremely interesting. Treatment of cases is also discussed. Each case report is also
followed by discussion of the salient features of pathophysiology, clinical presentation,
diagnosis and treatment in light of current evidence-based knowledge. These
interesting cases included various diffuse Parenchymal lung diseases, Tuberculosis
including MDR and extensively drug-resistant tuberculosis (XDR-TB), Pleural diseases,
Lung infection, Allergic bronchopulmonary aspergillosis and Thoracic malignancies.
Cases with rare presentation such as Alveolar microlithiasis, Pulmonary sequestration,
Chilaiditi syndrome, Endobronchial polyp, Carcinoid syndrome and Lympho tracheal
fistula which are generally difficult to diagnose are also included. This book will be
useful for both undergraduate and postgraduate medical students, general physicians,
consultants in pulmonary medicine and allied branches interested in diagnosis and
treatment of pulmonary diseases.
Rajendra Prasad
ACKNOWLEDGMENTS
As a senior author of this book, I wish to acknowledge my indebtedness to a number

of people who significantly contributed to the publication of this book. The individual
to whom I would like to acknowledge first is Late Professor BK Khanna who as a
Head of Department of Tuberculosis at the King George’s Medical College, Lucknow,
Uttar Pradesh, India, while I was postgraduate student in that department, markedly
stimulated my interest in tuberculosis and other chest diseases. Professor BK Khanna’s
own tremendous knowledge and wisdom in the field of tuberculosis set an example
of thoughtfulness and meticulousness which I have always tried to emulate. I am
also indebted to Professor PK Mukherjee, Late Dr MS Agnihotri, Late Dr Jafar Jameel
and Late Dr J Nath, for their great inspiration as teachers during my postgraduate
days. I am greatly indebted to many postgraduate students who have been trained
with me in the department at King George’s Medical College, Lucknow; Vallabhbhai
Patel Chest Institute, Delhi, India, and Era’s Lucknow Medical College and Hospital,
Lucknow, especially Dr Sanjay Verma, Dr Kiran Vishnu Narayan, Dr Suneesh C Anand,
Dr Giridhar BH, Dr Abhijeet, Dr Abhishek Agrawal, Dr Saurabh Karmakar, Dr Mandeep
Singh, Dr Pawan Gupta, Dr Visweswaran Balasubramanian, Dr Faizan Ahmad, Dr Amitabh
Banka, Dr Sakshi Batra, Dr Ronal Naorem, and Dr Asna Khan, Dr Harsh Saxena, Dr Rishabh
Kacker, Dr Huda Shamim, Dr Syed Ahmed Hussain Kazmi, Dr Mohammad Tanzeem and
Dr Tanmay Bhargava. The efforts of these postgraduate students in part is responsible
for generating much of the data that can be incorporated in making the chapters in
book more evidence based.
I also wish to express my appreciation to Dr Nikhil Gupta, for helping me in preparing
and correcting the manuscript. I also wish to express my special appreciation Dr Harsh
Saxena my PG Student, Era’s Lucknow Medical College and Hospital for providing
tremendous help in preparing the cases. I also wish to express my thanks Miss Seema
Shukla, Mr Gyan Prakash and Mr Mithun, for their invaluable help in the preparation and
typing of manuscript. I am also thankful to all my patients, who gave me experience in
the field of Pulmonary Medicine.
I am very grateful to the whole team of M/s Jaypee Brothers Medical Publishers
(P) Ltd, who helped and guided me, Shri Jitendar P Vij, Mr Ankit Vij, Dr Richa Saxena,
Ms Pooja Bhandari, Ms Sunita Katla and team members for all their support to work
in this project and make it a success. Without their co-operation, I could not have
completed this project.
CONTENTS
1. Spontaneous Pneumothorax: An Unusual Complication of Pregnancy 1
2. Pulmonary Mucormycosis Presenting as Reversed Halo Sign 4
3. Pulmonary Mucormycosis Mimicking as Pulmonary Tuberculosis 7
4. Pulmonary and Nodal Multiple Myeloma with a

Pleural Effusion Mimicking Bronchogenic Carcinoma 10
5. Bronchiectasis as a Cause of Unexplained Breathlessness in

HIV-infected Patient 14
6. Progressive Increase in Cavitation with the Evolution of

Fungus Ball: A Clue to the Diagnosis of Chronic Necrotizing
Pulmonary Aspergillosis 18
7. Pericardial Effusion as a Paradoxical Response to Therapy for

Mediastinal Lymph Node Tuberculosis 22
8. Occupational Emphysema Following Long-term Exposure to Metal 26
9. Isoniazid-induced Gynecomastia 30
10. Isolated Left Upper Lobe Aplasia and Lower Lobe Hypoplasia with
Bronchial Asthma 34
11. Ischemic Cavitation in Conglomerate Silicosis 38
12. Intralobar Sequestration of Lung 41
13. Herniation of Lung Following Lung Abscess in a Child: A Case Report 44
14. Hemorrhagic Pleural Effusion Secondary to Sarcoidosis 47
15. Exfoliative Dermatitis Secondary to Ethambutol and Pyrazinamide 51
16. Bilateral Chylothorax in a Young Female Secondary to Tuberculosis 54
17. Concomitant Pulmonary Tuberculosis and Borderline Leprosy with

Type-II Lepra Reaction in Single Patient 60
18. Community-Acquired Miliary Pneumonia Mimicking as

Miliary Tuberculosis 67
19. Coexistence of Bronchiectasis and Chronic Obstructive

Pulmonary Disease as Separate Entity 70
20. Bilateral Hemorrhagic Pleural Effusion due to Kerosene Aspiration 73
21. Bilateral Chylothorax in a Child after Mild Trauma 77

xiv 100 Cases in Pulmonary Medicine
22. An Unusual Case of Actinomycosis Presenting as a Pulmonary Mass 81
23. A Rare Case of Congenital Anomaly Presenting as Hemoptysis 85
24. Allergic Bronchopulmonary Aspergillosis with Aspergilloma

Developing in a Cane Sugar Mill Worker 88
25. A Rare Coexistence of Pulmonary Nocardiosis and Aspergillosis in

Patient of Chronic Obstructive Pulmonary Disease 93
26. Necrotizing Mediastinal Lymph Nodes in Sarcoidosis 99
27. New Case of Pulmonary Tuberculosis with Radiological Clearing

after Stoppage of Antitubercular Treatment 103
28. Case of Retreatment Pulmonary Tuberculosis Presented as Mass Lesion 110
29. Left-sided Infrapulmonary Effusion 115
30. Right-sided Infrapulmonary Pleural Effusion 117
31. Multidrug-resistant Tuberculosis Treated with Injection

Kanamycin PAS, Ethionamide and Cycloserine 119
32. Primary Multidrug-resistant Tuberculosis Treated with

Injection Kanamycin PAS, Ethionamide and Cycloserine 121
33. Multidrug-resistant Tuberculosis Treated on Emperical Grounds 123
34. Multidrug-resistant Tuberculosis Treated with

CAT IV Regimen with Good Response 125
35. Multidrug-resistant Tuberculosis under Treatment with

Residual Lesion and Adverse Drug Reaction 127
36. Multidrug-resistant Tuberculosis Treatement with

CAT IV Regimen Including Ofloxacin 129
37. Multidrug-resistant Tuberculosis under Treatment with

CAT IV Regimen Containing Ofloxacin with Residual Lesion 131
38. Multidrug-resistant Tuberculosis Treated with

CAT IV Regimen for 26 Months 133
39. Extensively Drug-resistant Tuberculosis Treated with

Modified CAT IV Regimen 136
40. Multidrug-resistant Tuberculosis (Pre XDR-TB) Treated

with CAT IV Regimen 142
41. Multidrug-resistant Tuberculosis Treated with CAT IV Regimen 146
42. Extensive Drug-resistant Tuberculosis Treated as

Multidrug-resistant Tuberculosis 151
43. Multidrug-resistant Tuberculosis Following Adverse Drug Intolerance

due to Severe Adverse Drug Reaction 155
Contents xv
44. Extensively Drug-resistant Tuberculosis Treated as

MDR-TB Ignoring Drug Susceptibility Report 159
45. Achalasia Cardia Presenting as Uncontrolled Asthma 167
46. Walking Pneumonia Diagnosed as Allergic

Bronchopulmonary Aspergillosis 171
47. A Case of Allergic Bronchopulmonary Aspergillosis

Presenting as Collapse Right Upper Lobe 176

Mimicking Tuberculosis 180
49. A Case of Allergic Bronchopulmonary Aspergillosis Presenting as

Bilateral Homogenous Shadows 182

Mimicking Multidrug-resistant Tuberculosis 185
51. A Case of Allergic Bronchopulmonary Aspergillosis with

High-density Mucus Impaction Mimicking Mass Lesion 187
52. Allergic Bronchopulmonary Aspergillosis Presenting as

a Pulmonary Mass 190
53. Treatment of Tuberculosis in Pregnancy and

Lactation: Case-based Approach 195
54. Treatment of Tuberculosis in Renal Insufficiency: Case-based Approach 198
55. Treatment of Tuberculosis in Liver Diseases: Case-based Approach 204
56. Pulmonary Aspergilloma Presenting as a Moving Ball 208
57. Allergic Bronchopulmonary Aspergillosis and Allergic Aspergillus Sinusitis 211
58. Multiple Encysted Effusion Presenting as Mass Lesion 216
59. A Case of Pulmonary Alveolar Microlithiasis 219
60. Hydropneumothorax in Tropical Pulmonary Eosinophilia 222
61. Eventration of Diaphragm 225
62. Eventration of Diaphragm in a 7-year-old Male 228
63. A Case of Chilaiditi Syndrome Mimicking Pleural Effusion 233
64. Multiple Myeloma with Lung Plasmacytoma 237
65. Endobronchial Tuberculosis in a 30-year-old Female 242
66. Endobronchial Tuberculosis in a 26-year-old female 245
67. Endobronchial Tuberculosis in a 44-year-old Female

Presenting as Hemoptysis 247
xvi 100 Cases in Pulmonary Medicine
68. Endobronchial Tuberculosis in a 44-year-old Male

Presenting as Recurrent Hemoptysis 249
69. A Rare Case of Tuberculous Endobronchial Sinus 251
70. Endobronchial Polyp Presenting with Recurrent Hemoptysis 256
71. Carcinoid Tumor Presenting with Recurrent Hemoptysis 260
72. Bronchial Carcinoid Presenting as Recurrent Massive Hemotysis 262
73. Tuberculous Lympho Tracheal Fistula 266
74. Ruptured Hydatid Cyst Presenting as Recurrent Hemoptysis 271
75. A Case of Squamous Cell Carcinoma Presenting with Cavitation 277
76. Squamous Cell Carcinoma Presenting with Cavitating Mass in

a Patient of Chronic Obstructive Pulmonary Disease 279
77. Squamous Cell Carcinoma Presenting as Lung Abscess 282
78. Squamous Cell Carcinoma Presenting as

Superior Vena Cava Syndrome 286
79. Squamous Cell Carcinoma Presenting as Parahilar Mass 289
80. Squamous Cell Carcinoma in Chronic Obstructive

Pulmonary Disease Patient 291
81. A Case of Squamous Cell Carcinoma Presenting as

Pleural Effusion 293
82. Squamous Cell Carcinoma Presenting as Pleural Effusion in

a Patient of Chronic Obstructive Pulmonary Disease 295
83. Squamous Cell Carcinoma with Osteolytic Secondaries in Spine 299
84. Squamous Cell Carcinoma Presenting with Recurrent Hemoptysis 301
85. Squamous Cell Carcinoma in a Patient of Chronic Obstructive

Pulmonary Disease Presenting as Recurrent Hemoptysis 303
86. Adenocarcinoma Presenting as a Recurrent Pleural Effusion 308
87. Adenocarcinoma in a 65-year-old Nonsmoker Female 312
88. A Case of Adenosquamous Cell Carcinoma in a 40-year-old Male 314
89. Small-cell Carcinoma Presenting as Pleural Effusion in a Patient of COPD 318
90. Small-cell Carcinoma with Secondaries in Brain 322
91. Small-cell Carcinoma in a Patient of Chronic Obstructive

Pulmonary Disease 324
92. Large Cell Carcinoma Presenting as Parahilar Mass in

a Patient of COPD 328
Contents xvii
93. Large-cell Carcinoma Presenting with Massive Pleural Effusion 330
94. Pulmonary Langerhans Cell Histiocytosis in

a 15-year-old Nonsmoker Male 334
95. A Case of Chronic Hypersensitivity Pneumonitis in a 30-year-old Male 338
96. A Case of Cryptogenic Organizing Pneumonia in a 60-year-old Female 341
97. A Case of Drug-induced Interstitial Lung Disease in a 63-year-old Female 345
98. A Case of Idiopathic Pulmonary Fibrosis Misdiagnosed as Bronchial Asthma 349
99. A Case of Rheumatoid Arthritis-associated Interstitial Lung Disease 353
100. A Case of Combined Pulmonary Fibrosis and Emphysema 357
Index 361
CASE 1
Spontaneous Pneumothorax: An Unusual

Complication of Pregnancy
CASE REPORT
A 30-year-old woman (gravida 3 para 2) at 28 weeks gestation was admitted to the emer
gency department with complaint of chest pain (right side) followed by breathlessness.
Breathlessness was sudden in onset and progressively worsened over 5 days. Chest pain
was pleuritic in nature. She was also having history of exposure to household smoke. She
was in mild respiratory distress but her vital signs were stable while breathing room air. Her
breath sounds were decreased with hyper resonance over her right chest. A chest radio
graph with abdominal shield confirmed right-sided pneumothorax (Fig. 1). Results of other
prenatal laboratory tests were normal. The patient was treated with oxygen and observed.
After 10 days of conservative treatment, she recovered spontaneously. With supportive
care, her condition improved and lung re-expansion was achieved without chest tube
placement. A subsequent chest radiograph showed no evidence of residual pneumothorax,
bullae, or any pulmonary pathology. Ultrasound assessment revealed a singleton fetus in
FIG. 1: A chest radiograph showing right-sided

pneumothorax.
2 100 Cases in Pulmonary Medicine
cephalic presentation, with fetal parameters corresponding to a gestational age of 28 weeks.

The fetus was active and liquor was normal. She experienced no further chest pain and
the remainder of her pregnancy was uncomplicated. At 39 weeks gestation, the patient
underwent a spontaneous vaginal delivery of a viable female infant of weight 2.2 kg with
good Apgar scores.
DISCUSSION
Primary spontaneous pneumothorax is defined as air in the pleural space, i.e., between
the lung and the chest wall in otherwise healthy people without any lung disease.
Spontaneous pneumothorax in pregnancy is extremely rare, with only 55 cases reported
till now. Review of 56 cases showed that the patients were young (average age, 26.4 years),
which is similar to the age group (20–30 years) of nonpregnant female in whom pneumo
thorax commonly occurs. Risk factors most commonly associated in these patients were
asthma, cocaine use, hyperemesis gravidarum, history of previous pneumothorax (44%),
and underlying infection (30%); whereas pulmonary tuberculosis is the most common
cause in nonpregnant females. Pneumothorax occurred during the first or second
trimester in 51% and during the perinatal period in 49% of patients. Initial treatment was
observation in 29.6%, tube thoracostomy in 66.6%, and thoracotomy in 3.8% of patients.
Of the total group of patients, 52% ultimately required thoracotomy for recurrence or
persistent pneumothorax. The obstetric outcome was good, with 80.8% of patients
having vaginal delivery, 17.3% having cesarean delivery, and one being fetal loss (1.9%).
Typical pneumothorax symptoms such as chest pain and dyspnea are often attributed to
paroxysmal tachycardia, neuralgia, or asthma exacerbation, thus contributing to under-
reporting of spontaneous pneumothorax. Diagnosis of pneumothorax can be confirmed
by chest radiograph and it is safe to proceed with the standard chest radiography with
abdominal shield without placing the fetus at substantial risk from ionizing radiation.
Shielded computed tomography (CT) is also a useful imaging technique that can help in
defining the underlying anatomic abnormality and in planning an operative approach
when surgical treatment is indicated. Treatment of acute pneumothorax in pregnancy
or labor is identical to that of nonobstetric patients. Admission and close observation
of the patients was usually done with small pneumothorax (<20% of hemithorax). Large
pneumothorax (>20% of hemithorax) should be treated with tube thoracostomy. Recurrent,
persistent, or bilateral pneumothorax necessitates thoracotomy or thoracoscopy. In order
to avoid increased air leak secondary to valsalva maneuvers, delivery should be expedited
and positive pressure anesthesia avoided. Cesarean section is not absolutely indicated
and should be performed for obstetric reason only. Although surgery may be indicated for
recurrent pneumothorax episodes, specific criteria for operative intervention are lacking.
Thoracotomy or video-assisted thoracoscopic surgery (VATS) have been increasingly
successful in the management of recurrent pneumothorax and no adverse outcome or
mortality has been reported. Nevertheless, preventive measures should include smoking
cessation and avoidance of rapid or drastic change in ambient pressure such as high
altitudes, scuba diving, or flying in unpressurized aircraft. Pneumothorax warrants
consideration in any pregnant patient with acute chest pain, dyspnea, or history of prior
pneumothorax and must be confirmed radiographically. Neither pneumothorax nor its
treatment causes serious adverse effects on the course of pregnancy or delivery, but prompt
recognition and treatment of pneumothorax is essential for preventing complications.
Spontaneous Pneumothorax: An Unusual Complication of Pregnancy 3
FURTHER READING
1. Garg R, Sanjay, Das V, Usman K, Rungta S, Prasad R. Spontaneous pneumothorax: An unusual
complication of pregnancy—A case report and review of literature. Annals of Thoracic Med.
2008;3:104-5.
2. Wong MK, Leung WC, Wang JK, Lao TT, Ip MS, Lam WK, et al. Recurrent pneumothorax in pregnancy:
What should we do after placing an intercostals drain. Hong Kong Med J. 2006;12:375-80.
3. Van Winter JT, Nichols FC 3rd, Pairolero PC, Ney JA, Ogburn PL Jr. Management of spontaneous
pneumothorax during pregnancy: Case report and review of the literature. Mayo Clin Proc.
1996;71:249-52.
4. Reid CJ, Burgin GA. Video-assisted thoracoscopic surgical pleurodesis for persistent spontaneous
pneumothorax in late pregnancy. Anaesth Intensive Care. 2000;28:208-10.
5. Wright JD, Powell MA, Horowitz NS, Huettner PC, White F, Herzog TJ. Placental site trophoblastic
tumor presenting with a pneumothorax during pregnancy. Obstet Gynecol. 2002;100:1141-4.
6. Yoshioka H, Fukui T, Mori S, Usami N, Nagasaka T, Yokoi K. Catamenial pneumothorax in a pregnant
patient. Jpn J Thorac Cardiovasc Surg. 2005;53:280-2.
7. Toyoda K, Matsumoto K, Inoue H, Komori M, Fujita M, Hashimoto S, et al. A pregnant woman with
complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura. Intern
Med. 2006;45:1097-100.
8. Sills ES, Meinecke HM, Dixson GR, Johnson AM. Management approach for recurrent spontaneous
pneumothorax in consecutive pregnancies based on clinical and radiographic findings. J
Cardiothorac Surg. 2006;1:35.
9. Lal A, Anderson G, Cowen M, Lindow S, Arnold AG. Pneumothorax and pregnancy. Chest.
2007;132:1044-8.
10. Nakamura H, Konishiike J, Sugamura A, Takeno Y. Epidemiology of spontaneous pneumothorax in
women. Chest. 1986;89:378-82.
11. Terndrup TE, Bosco SF, McLean ER. Spontaneous pneumothorax complicating pregnancy: Case
report and review of literature. J Emerg Med. 1989;7:245-8.
12. Gueirn JM, Barbotin-Larrieu F, Meyer P, Habib Y. Pneumothorax in pregnancy: Apropos of 3 cases.
Rev Pneumol Clin. 1988;44:297-9.
CASE 2
Pulmonary Mucormycosis Presenting as

Reversed Halo Sign
CASE REPORT
A 45-year-old human immunodeficiency virus male, current smoker, presented with com
plaints of acute onset cough associated with 20–30 mL of black-brownish-colored sputum for
the past 15 days. Subsequently he developed exertional dyspnea [grade 1 mMRC (modified
Medical Research Council)] accompanied with right-sided pleuritic chest pain for the last
10 days. At the onset, he also had low grade, intermittent fever without chills and rigors which
lasted for 5 days. There was no history suggestive of sinusitis, hemoptysis, and loss of weight
or appetite. Laboratory investigations showed a high random blood sugar and a high
glycosylated hemoglobin (12.3%) and he was diagnosed to have diabetes mellitus. Complete
blood count, electrocardiogram, hepatic, and renal function testing were within normal
limits. Chest radiograph (Fig. 1) showed multiple cavitary lesions on the right side and a
FIG. 1: Chest radiograph (posteroanterior view)

showing multiple cavitary lesions on the right side
and a consolidation with irregular margins in the left
parahilar region.
Pulmonary Mucormycosis Presenting as Reversed Halo Sign 5
consolidation with irregular margins in the left parahilar region. Contrast-enhanced computed
tomography (CECT) of the chest (Figs. 2A and B) revealed bilateral multiple cavitary opacities.
These opacities were defined as focal round area of ground-glass attenuation surrounded by
a crescent or ring of consolidation [reversed halo sign (RHS)]. Sputum examination yielded
negative results for acid-fast bacilli, pyogenic organisms, and malignant cells. Sputum for
fungus on direct microscopy showed broad, aseptate, branching hyphae with focal bulbous
dilatations. The culture growth confirmed Rhizopus oryzae from three consecutively collected
sputum samples. Fiberoptic bronchoscopy showed hyperemic endobronchial mucosa. Culture
of bronchoalveolar lavage (BAL) fluid, postbronchoscopy sputum, and the endobronchial
biopsy also yielded R. oryzae. Overall, six consecutive samples confirmed the growth of
R. oryzae. The patient was started on treatment with parenteral amphotericin B. However, on
day 4 of treatment, the patient had an episode of massive hemoptysis and died. Patient was
diagnosed as a case of pulmonary mucormycosis with poorly controlled diabetes mellitus.
A B
FIGS. 2A AND B: Contrast enhanced computed tomography (CECT) chest: (A) axial view and
(B) coronal view showing bilateral multiple cavitary opacities with focal round area of ground-
glass attenuation surrounded by a crescent or ring of consolidation.
DISCUSSION
The timely diagnosis of invasive fungal pneumonias relies profoundly on identification
of radiographic pattern in chest computed tomography (CT). The CT finding of RHS
has been described as a focal round area of ground-glass attenuation surrounded by
a ring of consolidation. The RHS is also known as “fairy ring sign” and “atoll sign”. In a
retrospective analysis, RHS was identified as an early sign, present in about 4% of
patients diagnosed with pulmonary mold infections, usually zygomycosis. Histopatho
logy of RHS in invasive fungal pneumonia reveals infarcted lung with a greater amount
of hemorrhage in the peripheral solid ring than in the center ground-glass region. The
RHS has been described most commonly for cryptogenic organizing pneumonia (COP),
though not specific to it. The other conditions where RHS has been described include
pulmonary paracoccidioidomycosis, invasive pulmonary aspergillosis, lymphomatoid
granulomatosis, Wegener’s granulomatosis, pulmonary tuberculosis, lipoid pneumonia,
pulmonary sarcoidosis, drug-induced interstitial pneumonitis, cellular [nonspecific
interstitial pneumonia (NSIP)], and pulmonary infarction. In the present case, clinical
and radiographic findings were suggestive and fungal culture confirmed the diagnosis of
pulmonary mucormycosis. It is imperative to diagnose mucormycosis early, given that

delayed treatment increases the mortality rate.
FURTHER READING
1. Gupta N, Kumar R, Prasad R. Reverse halo sign. Indian J Chest Dis Allied Sci. 2014;56;247-8.
2. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, et al. Defining opportunistic invasive
fungal infections in immunocompromised patients with cancer and hematopoietic stem cell
transplants: an international consensus. Clin Infect Dis. 2002;34:7-14.
3. Voloudaki AE, Bouros DE, Froudarakis ME, Datseris GE, Apostolaki EG, Gourtsoyiannis NC. Crescentic
and ring-shaped opacities: CT features in two cases of bronchiolitis obliterans organizing pneumonia
(BOOP). Acta Radiol. 1996;37:889-92.
4. Walker CM, Mohammed TL, Chung JH. Reversed halo sign. J Thorac Imaging. 2011;26:W80.
5. Wahba H, Truong MT, Lei X, Kontoyiannis DP, Marom EW. Reversed halo sign in invasive pulmonary
fungal infections. Clin Infect Dis. 2008;46:1733-7.
6. Kim SJ, Lee KS, Ryu YH, Yoon YC, Choe KO, Kim TS, et al. Reversed halo sign on high-resolution CT of
cryptogenic organizing pneumonia: diagnostic implications. Am J Roentgenol. 2003;180:1251-4.
7. Gasparetto EL, Escuissato DL, Davaus T, de Cerqueira EM, Souza AS Jr, Marchiori E, et al. Reversed
halo sign in pulmonary paracoccidioidomycosis. Am J Roentgenol. 2005;184:1932-4.
8. Marchiori E, Grando RD, Simoes Dos Santos CE, Maffazzioli Santos Balzan L, Zanetti G, Mano CM, et
al. Pulmonary tuberculosis associated with the reversed halo sign on high-resolution CT. Br J Radiol.
2010;83:e58-60.
9. Marchiori E, Zanetti G, Mano CM, Hochhegger B, Irion KL. The reversed halo sign: another atypical
manifestation of sarcoidosis. Korean J Radiol. 2010;11:251-2.
10. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical
manifestations of mucormycosis. Clin Infect Dis. 2012;54:S23-34.
CASE 3
Pulmonary Mucormycosis Mimicking as

Pulmonary Tuberculosis
CASE REPORT
A 70 year-old male, smoker for 50 years, presented with history of fever, cough, chest pain,
mucopurulent expectoration, and recurrent hemoptysis for last 25 days. He was given
symptomatic treatment for hemoptysis. Patient was also taking antitubercular treatment
(rifampicin, isoniazid, ethambutol, pyrazinamide) for last 10 days after which he developed
drug-induced hepatitis. So, he was referred to us. On general examination, patient was
emaciated. His pulse rate was 94 beats/min, blood pressure 120/70 mm Hg, and respiratory
rate was 28 breaths/min. Examination of the respiratory system revealed bronchial breath
sound over left mammary area. Chest radiograph revealed presence of air space consolidation
in mid zone of the left lung. Computed tomography (CT) revealed large thick-walled cavity on
left side in left upper lobe abutting chest wall and encroaching toward arch of aorta (Fig. 1).
Serial investigations showed uncontrolled blood sugar in the range of 232–
360 mg/dL. A complete blood count showed hemoglobin of 11.4 g/dL, total leukocyte
count of 7,500 cells/mm3, and differential count of 70% neutrophils, 29% lymphocytes, and
FIG. 1: Computed tomography revealed large thick-walled cavity on left side

in left upper lobe abutting chest wall and encroaching toward arch of aorta.
1% eosinophils. Sputum examination did not reveal acid-fast bacilli (AFB) on Ziehl–Neelsen
staining and sputum culture for pyogenic organisms was also sterile after 48 hours of
incubation. Mantoux test (10 tuberculin units) showed indurations of 6 mm at 72 hours.
He was put on antibiotics (co-amoxiclav and clindamycin) for 2 weeks without any
clinical and radiological response. Patient refused for bronchoscopy. Transthoracic needle
aspiration from left cavitary lesion was done and sent for AFB smear, malignant cells,
and fungal smear examination. Aspirate was negative for AFB and malignant cells. Direct
potassium hydroxide (KOH) mount and Gomori methenamine silver (GMS) staining of
the aspirate showed a few broad aseptate thin-walled fungal hyphae with right angle
branching, characteristic of zygomycetes (Fig. 2). Fungal culture of the aspirate inoculated
on to Sabouraud dextrose agar (SDA) media yielded white cottony colonies with no reverse
pigmentation in 7 days. Lacto phenol cotton blue mount from the culture showed broad
hyaline, thin-walled aseptate fungal hyphae with right angle branching, typical of zygomycetes
fungi. He was started on multiple subcutaneous insulin regimens for glycemic control and
intravenous amphotericin-B (50 mg/day) after which he showed improvement, clinically as
well as radiologically. He is on regular follow-up with no further complaints.
FIG. 2: Gomori methenamine silver (GMS) staining from fine needle aspiration sample
showing broad randomly branched and aseptate hyphae of mucormycosis. (For color
version, see Plate 1)
DISCUSSION
Pulmonary mucormycosis is less common opportunistic fungal disease, localized in the
lungs or the mediastinum. Its estimated incidence was 1.7 cases per million people per
year in the United States. In India, few cases have been reported but exact prevalence
is not known. Mucormycosis is found in patients of wide age range but with a male
predominance. It presents with fever, dyspnea, cough, and chest pain. Invasion of blood
vessel by fungal hyphae results in necrosis of tissue parenchyma, which may ultimately
lead to cavitation and/or hemoptysis.
Most common predisposing conditions for mucormycosis are uncontrolled diabetes
mellitus, malignancy, chronic illnesses, and transplants. Radiographically, a variety
of findings may be present. In descending order of frequency, these may include lobar
consolidation, isolated masses, nodular disease, and cavitation. High-resolution chest CT
scan is the most sensitive method of determining the extent of pulmonary mucormycosis.
An important finding is expansion of the mass or consolidation across tissue planes, in
Pulmonary Mucormycosis Mimicking as Pulmonary Tuberculosis 9
particular, toward the great vessels in the mediastinum as is evident in this case. The most
common method used for diagnosis is microscopic examination of specimens obtained
via flexible fiberoptic bronchoscopy. Due to refusal of the patient for bronchoscopy, we
opted for transthoracic route for collecting samples to reach the diagnosis in the present
case. Though, usefulness of fine-needle aspiration cytology (FNAC) in lung lesions is well
documented but for the diagnosis of pulmonary mucormycosis it is sparingly reported.
Bronchoalveolar lavage (BAL), a relatively safe diagnostic tool, may also allow the diagnosis
of mucormycosis in cases where lung biopsy is contraindicated.
Treatment of pulmonary mucormycosis is based on rapidity of diagnosis, reversal
of the underlying predisposing factors (if possible) along with prompt institution of
antifungal therapy and extensive surgical debridement. Pulmonary mucormycosis is
relatively uncommon disease but with an increasing prevalence of diabetes in India,
it is likely to be seen more commonly than before. A high level of clinical suspicion is
important in any patient, in the presence of appropriate clinical setting, and a non
resolving pulmonary opacity despite antibiotic therapy. The diagnosis is generally
missed in patients with diabetes mellitus where tuberculosis is more common than
any other cause of nonresolving pneumonia. A high index of clinical suspicion should
be maintained for pulmonary mucormycosis while investigating such patients for
nonresolving pneumonia.
In conclusion, pulmonary mucormycosis should be suspected in high-risk patients
for fungal pulmonary infections, particularly when they present with cavitation on
chest radiograph with negative sputum smear for AFB in a country like India where
prevalence of tuberculosis is very high. The diagnosis of fungal pneumonia requires the
demonstration of fungi within the pulmonary parenchyma on lung biopsy; however, BAL,
a relatively safe diagnostic tool, may also allow the diagnosis of mucormycosis in cases
where lung biopsy is contraindicated.
FURTHER READING
1. Garg R, Marak RSK, Verma SK, Singh J, Sanjay, Prasad R. Pulmonary Mucormycosis mimicking as
Pulmonary TB: A Case Report. Lung India. 2008;25:129-31.
2. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000;13:236-
301.
3. Spellberg B, Edwards J, Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology,
presentation, and management. Clin Microbiol Rev. 2005;18:556-69.
4. Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years. Arch Intern Med.
1999;159:1301-9.
5. Rees JR, Pinner RW, Hajjeh RA, Brandt ME, AL Reingold. The epidemiological features of invasive
mycotic infections in the San Francisco Bay area, 1992–1993: results of population-based laboratory
active surveillance. Clin Infect Dis. 1998;27:1138-47.
6. Tedder M, JA Spratt, MP Anstadt, SS Hegde, SD Tedder, JE Lowe. Pulmonary mucormycosis: results of
medical and surgical therapy. Ann Thorac Surg. 1994;57:1044-50.
7. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in
hematopoietic stem cell transplant. Clin Infect Dis. 2002;34:909-17.
8. Latif. Pulmonary mucormycosis in persons on chelation therapy. Am J. Kidney Dis. 1997;29:461-4.
9. McAdams HP, Rosado de Christenson M, Strollo DC, Patz EF Jr. Pulmonary mucormycosis: radiologic
findings in 32 cases. Am J Roentgenol. 1997;168:1541-8.
10. Reid VJ, Solnik DL, Daskalakis T, Sheka KP. Management of bronchovascular mucormycosis in a
diabetic: a surgical success. Ann Thorac Surg. 2004;78:1449-51.
11. Bakshi NA, Volk EE. Pulmonary mucormycosis diagnosed by fine needle aspiration cytology. A case
report. Acta Cytol. 2001;45:411-4.
12. Glazer M, Nusair S, Breuer R, Lafair J, Sherman Y, Berkman N. The role of BAL in the diagnosis of
pulmonary mucormycosis. Chest. 2000;117:279-82.
CASE 4
Pulmonary and Nodal Multiple Myeloma

with a Pleural Effusion Mimicking
Bronchogenic Carcinoma
CASE REPORT
A 60-year-old male, bidi smoker (pack year 18) was admitted to our department with
complaints of left-sided chest pain for 2-month duration; dry cough, and breathlessness
for 1 month duration; and about 6 kg weight loss over 4 weeks. The pain was moderate in
intensity, constant, and localized primarily to the upper part of the chest wall both anteriorly
and posteriorly. The pain increased to some extent on movement. Since the last 2 years,
he was diabetic and was on oral hypoglycemic drugs. Physical examination revealed mild
pallor. His chest radiograph revealed opacity in the left lung with a widened mediastinum
and obliteration of the left costophrenic angle and erosion of the left second and third
rib (Fig. 1). A computed tomographic scan of the thorax (CT thorax) revealed mass in the
FIG. 1: Chest radiograph revealed opacity in the left

lung with mediastinal widening and obliteration of
the left costophrenic angle.
Pulmonary and Nodal Multiple Myeloma with a Pleural Effusion... 11
anterior segment of the left upper lobe with irregular margins measuring 4 × 5 × 3 cm in
size and a pleural effusion on the left side. The lesion was infiltrating the pleura. There was
also present a large mass with irregular margins in the prevascular region of the anterior
mediastinum infiltrating the mediastinal pleura. Multiple mediastinal lymph nodes were
present and fewer of them conglomerated suggestive of extracapsular spread of the disease.
There was an osteolytic lesion in the body of D10 vertebra (Fig. 2). Biopsy of the lung mass
revealed atypical plasma cells arranged in sheets along with pulmonary parenchymal cells
suggestive of malignant myeloma. Fine-needle aspiration cytology (FNAC) of the osteolytic
lesion of the body of D10 vertebra revealed plasma cell infiltration. The patient had also
complained of backache and hence we carried out an magnetic resonance imaging (MRI)
of the spine which revealed a diffuse and patchy altered signal intensity with the collapse
of sixth cervical and first lumbar vertebra, with the picture suggestive of diffuse marrow
infiltration indicative of multiple myeloma (MM) (Figs. 3A and B). His skull X-ray revealed
multiple lytic lesions. Serum protein electrophoresis was done which revealed raised
total proteins (11 g/dL) (normal 6.5–8.5 g/dL) with normal albumin, α1, α2, ad β globulin
but markedly raised g globulin (5 g/dL) (normal 0.75–1.8 g/dL), and the electrophoresis
showed an M-spike. Serum immunoglobulin determination revealed markedly raised IgG
immunoglobulin (3,000 g/dL) (normal 1,700 g/dL). Beta-2 microglobulin was 3,815 ng/mL
(normal 1,010–1,730 ng/mL). Urinary examination for Bence Jones proteins was negative.
Bone marrow biopsy revealed a hypocellular marrow with >25% plasma cells. Thus, diagnosis
of MM with extramedullary dissemination into the lung was made on the basis of plasma
cell infiltration of the bone marrow, the lytic bone lesions, the presence of monoclonal
immunoglobulins in the serum, and the myeloma plasma cells in the lung mass. The patient
was planned to be referred to the oncology department for chemotherapy but was not willing
to undergo any form of definitive treatment; he ultimately expired.
FIG. 2: Computed tomography (CT) thorax revealed a mass in the anterior segment of the left
upper lobe with irregular margins measuring 4 × 5 × 3 cm in size with a large mass with irregular
margins in the prevascular region of the anterior mediastinum with multiple lymph nodes seen
in the mediastinum. A moderate-size pleural effusion was noted on the left side and an osteolytic
lesion was present in the body of the D10 vertebral body.
A B
FIGS. 3A AND B: Magnetic resonance imaging (MRI) of the spine revealed a diffuse and patchy
altered signal intensity with the collapse of sixth cervical and first lumbar vertebra; the picture is
suggestive of diffuse marrow infiltration indicative of multiple myeloma.
DISCUSSION
Multiple myeloma may manifest as a diffuse bony disease (myelomatosis), as a solitary
plasmacytoma of bone, or as extramedullary (extraosseous) plasmacytoma. Myeloma
cells found at the extramedullary site may thus either be due to extramedullary
plasmacytoma or due to extramedullary dissemination of MM. Extramedullary
plasmacytoma is a variant of MM. It usually involves submucosal lymphoid tissues
of nasopharynx or paranasal sinuses without bone marrow involvement. It is highly
responsive to local irradiation and has excellent prognosis. Extramedullary dissemination
of MM occurs in advanced disease but is a rare phenomenon. The sites of extramedullary
dissemination reported in the literature are spleen, liver, lymph nodes, kidneys, thyroid
gland, adrenal gland, ovary, testes, lung, pleura, pericardium, intestinal tract, and skin.
Lung involvement is extremely rare. In fact, it is so rare that in one large case series of
869 cases, there was no mention of lung involvement. Shin et al. had described two cases
of extramedullary plasmacytoma involving the lung parenchyma. The first case had
a mass lesion in the right infrahilar region while the second case had reticulonodular
opacities in the lower zones of both lungs. The first case did not have generalized
myelomatosis but he developed it 5 years after treatment, namely, local radiotherapy,
while the second case had generalized myelomatosis. Because it is a disorder of the aged
population, with its severe clinical course and heterogeneous symptoms, the diagnosis
is difficult. This disorder presents primarily in the elderly with organ dysfunctions and
symptoms such as bone pains, renal dysfunction, anemia, susceptibility to infections,
hypercalcemia, hyperviscosity, and neurological manifestations. The most frequent
thoracic involvement by MM is pulmonary infiltrate secondary to an infectious process.
In our patient, after encountering atypical plasma cells in lung parenchyma, we first
investigated in order to find out whether he was having extramedullary plasmacytoma
or MM with extramedullary dissemination since the treatment and prognosis of
these two conditions are vastly different. For the diagnosis of MM, at least two of the
following three criteria should be present: Marrow plasmacytosis, lytic bone lesions,
and M component, i.e., monoclonal immunoglobulin in blood and/or urine. In our
Pulmonary and Nodal Multiple Myeloma with a Pleural Effusion... 13
patient, all the three were present. In a recent study to investigate the causes, and the
frequency and the effects of prognosis of the pulmonary involvement, it was found that
the cases with pulmonary involvement were associated with progressive diseases, which
included mainly renal failure and pathological bone fractures. Despite advances in the
management of MM in the past few decades, it remains an incurable disease. The disease
follows a relapsing course in majority of patients, regardless of the treatment regimen
or initial response to treatment. Traditionally, newly diagnosed myeloma patients have
been classified as either transplant or nontransplant candidates. This classification
is based on a number of factors including age, performance status, comorbid medical
conditions, and patient performance. Transplant candidates were typically treated
with nonalkylating agents to prevent marrow damage. Nontransplant candidates often
received alkylating agent-based therapy (most oncologists prefer cyclophosphamide or
melphalan as an alkylating agent with prednisolone). However, cyclophosphamide is
preferred more because it is less toxic to the bone marrow. These agents are administered
over 4 days every 4 weeks till the disease reaches a plateau phase which is defined as
the phase when patient’s hemoglobin, paraprotein, and beta-2 microglobulin levels have
become stable, and the patient is asymptomatic or minimally symptomatic over a period
of at least 3 months. Lately, a high-dose alkylating agent with hematopoietic support has
been used. It has improved the remission rate from <10–50%. However, such therapy is
suitable for younger patients only. Recently, the management of patients with MM has
been transformed by introduction of three novel agents: Thalidomide, lenalidomide, and
bortezomib. We have reported the above case in order to demonstrate variability in the
presentation of MM.
FURTHER READING
1. Kushwaha RA, Mehra S, Verma SK, Prasad R. Pulmonary and nodal multiple myeloma with plural
effusion mimicking Bronchogenic carcinoma. J Cancer Res Ther. 2009;5:297-9.
2. Pinto RG, Mandreker S, Vernekar JA. Multiple myeloma presenting as a subcutaneous nodule on the
chest wall: Diagnosis by fine needle aspiration. Acta Cytol. 1997;41:1233-4.
3. Longo DL. Plasma cell disorders. In: Fauci A, Braunwald E, Isselbacher K, Wilson J, Martin J, Kasper
D, Hauser S, Longo D (Eds.). Harrison’s Principles of Internal Medicine, 14th edition. New York:
McGrawHill; 1998. pp. 713-7.
4. Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. 1975;50:29-40.
5. Shin MS, Carcelen MF, Ho KJ. Diverse roentgenographic manifestations of the rare pulmonary
involvement in myeloma. Chest. 1992;102:946-8.
6. Mackie MJ, Ludlam CA. Diseases of blood. In: Davidson’s Principles and Practice of Medicine, 17th
edition. Edinburgh: Churchill Livingstone; 1995. pp. 821-3.
CASE 5
Bronchiectasis as a Cause of Unexplained

Breathlessness in HIV-infected Patient
CASE REPORT
A 32-year-old male, teacher by occupation was admitted to Department of Pulmonary
Medicine, King George's Medical University, Lucknow with chief complaints of cough with
minimal expectoration and progressive breathlessness for 1 year. There was no history of
fever, loss of appetite, and hemoptysis. There was no family history of pulmonary disease
or a personal history of severe chest illness in childhood. Patient was a known case of HIV
seropositive for last 2 years. His CD4 count was 209/μL at that time. He was on antiretroviral
therapy (lamivudine, stavudine, nevirapine) along with cotrimoxazole as prophylaxis for
Pneumocystis carinii infection. He also had a course of adequate antitubercular treatment
3 months back. Patient was a chronic smoker (10 pack years) and chronic alcoholic. He
was also a known intravenous drug abuser and had stopped 3 years before when he was
diagnosed to be a case of HIV seropositive. On admission, he was ill looking, afebrile with
a blood pressure of 110/68 mm Hg; pulse rate of 92 beats/min and respiratory rate of
30 breaths/min. The oxygen saturation by pulse oximetry was 86% on room air. There
was clubbing of his fingers and toes of grade 2. Examination of respiratory system and
other systems was unremarkable. His hematological and biochemical investigations were
within normal limits. His PPD test showed 12 mm indurations after 72 hours. On admission,
his CD4 count was 497/μL. His chest radiograph was normal (Fig. 1). Distribution of
bronchiectasis was bilateral with predominance for both lower lobe and right middle lobe.
The patient underwent fiberoptic bronchoscopy that did not reveal any endobronchial
growth. Bronchoalveolar lavage smears revealed no bacteria, acid-fast bacilli, fungal element,
and P. carinii.
Bronchiectasis as a Cause of Unexplained Breathlessness in HIV-infected Patient 15
FIG. 1: Normal looking chest radiograph.
DISCUSSION
Pulmonary complications have been an important source of morbidity and mortality in
the HIV-infected patients. Both infectious and noninfectious complications have been
well described. However, evidence exists that HIV-infected individuals may acquire
unexplained alterations in pulmonary function and high resolution chest computed
tomography (CT) independent of or prior to overt pulmonary complications (as in our
case also) (Fig. 2). No classical causes of genetic or acquired bronchiectasis such as
pertussis or measles pneumonia, foreign body inhalation, mycobacterial infection,
cystic fibrosis hypogammaglobulinemia, and rheumatoid arthritis, were identified
in the present patient. Although our patient was smoker, the clinical course was not
compatible with smoke-related bronchial disease alone because of short time over which
the patient develops bronchiectasis. Our patient was a known intravenous drug abuser.
However, he had not used intravenous drug for >4 years when he developed dyspnea.
Airway function analysis, chest radiography, and chest CT scan depicted differing
pathologies from the panlobular emphysema or foreign particle embolization commonly
associated with intravenous drug abusers. Our patient did not have a past history of
overdose or aspiration pneumonia, both of which are classical causes of bronchiectasis in
intravenous drug abusers. Other lung diseases related to intravenous drug abuse such as
noncardiogenic pulmonary edema, bronchospasm, and eosinophilic pneumonia, clearly
differ from the manifestations observed in the present patient. Obstructive disorders
due to opportunistic pneumonia or Kaposi's sarcoma have been reported previously in
HIV-infected patients. No evidence of mycobacterial, parasitic or mycotic agents was
isolated from sputum and bronchoalveolar sample in this patient. Radiological and
endobronchial evidence of Kaposi's sarcoma was also absent. The obstructive disease
observed in this patient was different from emphysema like syndrome, described in
patients with prolonged HIV infection. This emphysema like syndrome is characterized
by hyperinflation with an increase in residual volume but only minimal airway
obstruction. The radiological aspect differs from cases of bronchiolitis obliterans with
FIG. 2: High-resolution computed tomography

of the chest showing bilateral bronchiectasis with
predominant distribution in both lower lobe and
right middle lobe.
organizing pneumonia previously reported in HIV-infected patients and characterized

by pulmonary consolidation. Airway obstruction was associated with bronchiectasis in
this patient. Diffuse bronchiectasis has been reported previously on chest CT scan studies
in HIV-infected patients. In a previous study, it was documented that acquired immune
deficiency syndrome (AIDS) patient have an accelerated form of bronchiectasis which
can develop within 4 weeks. This accelerated form of bronchiectasis can develop in the
absence of mycobacterial infection or a history of prior recurrent pyogenic infection as it
was seen in our patient also. In conclusion, accelerated airway obstruction associated with
bronchiectasis should be added to the wide spectrum of respiratory complications of HIV
infection which is one of the causes of unexplained dyspnea in these patients. The practice
of pulmonary function tests in HIV-infected patients complaining of exertional dyspnea
permits a better characterization of this bronchial disease in future.
FURTHER READING
1. Prasad R, Garg R, Sanjay. Bronchiectasis as a cause of unexplained breathlessness in HIV infected
patient. The Internet journal of Medicine. 2007;8:2.
2. Bard M, Couderc LJ, Saimot AG, Scherrer A, Frachon I, Seigneur F. Accelerated obstructive pulmonary
disease in HIV infected patients with bronchiectasis. Eur Respir J.1998;11:771-5.
3. McGuinness G, Naidich DP, Garay S, Leitman BS, McCauley DI. AIDS associated bronchiectasis: CT
features. J Comput Assisted Tomogr. 1993;17:260-6.
4. Moskovic E, Miller R, Pearson M. High resolution computed tomography of pneumocystis carinii
pneumonia in AIDS. Clin Radiol. 1990;42:239-43.
5. Holmes AH, Trotman-Dickenson B, Edwards A, Peto T, Luzzi GA. Bronchiectasis in HIV disease. Q J
Med. 1992;85:875-82.
6. Verghese A, AI-samman M, Nabhan D, Naylor AD, Rivera M. Bacterial bronchitis and bronchiectasis
in human immunodeficiency virus infection. Arch Intern Med. 1994;154:2086-91.
7. Holmes AH, Pelton S, Steinbach S, et al. HIV-related bronchiectasis (letter). Thorax. 1995;50:1227-8.
8. Hopewell PC, Luce JM. Pulmonary involvement in the acquired immunodeficiency syndrome. Chest.
1985;87:104-12.
Bronchiectasis as a Cause of Unexplained Breathlessness in HIV-infected Patient 17
9. Stover DE, White DA, Romano PA, Gellene RA, Robeson WA. Spectrum of pulmonary diseases
associated with the acquired immune deficiency syndrome. Am J Med. 1985;78:429-37.
10. Murray JF, Mills J. Pulmonary infectious complications of human immunodeficiency virus infection:
Part II. Am Rev Respir Dis. 1990;141:1356-72.
11. Rosen JJ, Lou Y, Kvale PA, Rao AV, Jordan MC, Miller A, et al. Pulmonary function tests in HIV-infected
patients without AIDS. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care
Med. 1995;152:738-45.
12. King MA, Neal DE, St. John R, Tsai J, Diaz PT. Bronchial dilatation in patients with HIV infection: CT
assessment and correlation with pulmonary function tests and findings at bronchoalveolar lavage.
AJR Am J Roentgenol. 1997;168:1535-40.
13. Schimdt RA, Glenny RW, Godwin JD, Hampson ND, Cantino ME, Reichenbach DD. Panlobular
emphysema in young intravenous Ritalin abusers. Am Rev Respir Dis.1991;143:649-56.
14. Benson MK, Bentley AM. Lung disease induced by drug addiction. Thorax. 1995;50:1125-27.
15. Mitchell DM, Fleming J, Pinching AJ, Harris JR, Moss FM, Veale D, et al. Pulmonary function in human
immunodeficiency virus infection. Am Rev Respir Dis. 1992;146:745-51.
16. Diaz PT, Clanton TL, Pacht ER. Emphysema like pulmonary disease associated with human
immunodeficiency virus infection. Ann Intern Med. 1992;116:124-8.
17. Sanito NJ, Morley TF, Condoluci DV. Bronchiolitis obliterans organizing pneumonia in an AIDS
patient. Eur Respir J. 1995;8:1021-4.
CASE 6
Progressive Increase in Cavitation with
the Evolution of Fungus Ball: A Clue to
the Diagnosis of Chronic Necrotizing
Pulmonary Aspergillosis
CASE REPORT
A 40-year-old male who was known to have type I (insulin-dependent) diabetes mellitus
(T1DM), presented with complaints of productive cough, breathlessness, fever, weight
loss, and hemoptysis for 3 years. His previous chest radiograph revealed left upper lobe
cavitary infiltrate (Fig. 1). His routine investigation revealed uncontrolled blood sugar and
negative sputum smear for acid-fast bacilli (AFB) at that time. Patient had received 2 years of
antitubercular treatment along with insulin from a private practitioner, though his sputum
did not show any AFB. Despite adequate antitubercular treatment, he deteriorated clinically
as well radiologically.
On admission, general examination revealed grade 3 clubbing of fingers and toes. Exami
nation of respiratory system revealed bronchial breath sound over left mammary area and
coarse crepts in bilateral suprascapular region. Review of his serial chest radiograph revealed
progressive increase in cavitation with the evolution of fungus ball and progression of disease
on right side (Fig. 2). His hematological and biochemical investigations were within normal
FIG. 1: Chest radiograph showing left upper

lobe cavitary infiltrate.
Progressive Increase in Cavitation with the Evolution of Fungus
Progressive
Ball: A Clue to
Increase
the Diagnosis
in Cavitation
of Chronicwith
Necrotizing
the Evolution
Pulmonary
of Fungus
Aspergillosis
Ball... 19
limits except uncontrolled blood sugar (fasting blood sugar: 202 mg/dL and post prandial:
368 mg/dL). Enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency
virus was negative. Multiple sputum smears revealed no bacteria and AFB. The culture by
BACTEC did not show any mycobacteria. The sputum on fungal culture grew Aspergillus
fumigatus. A computed tomography (CT) scan of the chest revealed a crescent-shaped
lucency (air crescent sign) within the area of consolidation in the left upper lobe and right
middle lobe (Figs. 3 and 4). Fiberoptic bronchoscopy showed purulent secretions coming
from both upper lobe bronchi and left lower lobe bronchi. Bronchoalveolar lavage (BAL)
smears did not reveal any bacteria or AFB but the growth of Aspergillus fumigatus. Thus, he
was diagnosed as a case of chronic necrotizing pulmonary aspergillosis (CNPA) with diabetes
mellitus. He was given insulin for glycemic control and oral itraconazole 200 mg twice daily.
After 1 month of itraconazole therapy, the patient started showing clinical improvement,
became afebrile, gained weight, and the volume and the purulence of sputum also reduced
considerably.
FIG. 2: Chest radiograph after 2 years of antitubercular

treatment showing increased cavitation along with
fungus ball and progression of disease to right side.
FIG. 3: Computed tomography scan of the chest showing

a crescent-shaped lucency (air-crescent sign) within the
area of consolidation right middle lobe.
FIG. 4: Computed tomography scan of the chest

showing a crescent-shaped lucency (air crescent sign)
within the area of consolidation left upper lobe.
DISCUSSION
Chronic necrotizing pulmonary aspergillosis (CNPA), also termed semi-invasive
pul
monary aspergillosis (SIPA), is an uncommon, indolent pulmonary infection
commonly seen in patients with altered local defense due to pre-existing lung disease
such as chronic obstructive pulmonary disease, bronchiectasis, pneumoconiosis,
and mildly compromised systemic defense due to diabetes mellitus, alcoholism, poor
nutrition or low-dose corticosteroid therapy. Our patient was also a known case of
diabetes mellitus. This usually occur in middle-aged to older individuals who present
with fever, productive cough, and weight loss that occurs over a period of months,
thereby mimicking tuberculosis and often resulting in a delay in the diagnosis (as
happened in our case also). In contrast to the patients with simple mycetomas, CNPA
nearly always presents with pulmonary or systemic symptoms. In addition, hemoptysis,
the most common symptom in patients with mycetoma, is reported in only 10% of
patients with CNPA and is rarely an isolated symptom. Aspergilloma, a noninvasive
form of aspergillosis, may develop in a healthy host in which the organism colonizes
a pre-existing cavity whereas, CNPA instead of developing in a pre-existing cavity, it
may create its own cavity in immunocompromised host and then grow as a relatively
noninvasive organism. Radiographic manifestation usually consists initially of an area
of consolidation in the upper lobe, which develops progressive cavitation over several
weeks or months. The cavitation may be associated with intracavitary soft tissue opacity
which can be recognized radiographically with the appearance of an air crescent sign.
The air crescent sign may be visualized on chest CT well before it is seen on the chest
radiograph. The diagnosis is suggested by the clinical course and the isolation of the
fungus from pulmonary secretions, negative cultures for other pathogens, and failure
to respond to antibacterial or antimycobacterial therapy. Diagnostic confirmation
requires histologic evidence of local lung tissue invasion by septate hyphae, consistent
with Aspergillus species; however, this is often difficult to obtain. Both transbronchial
and percutaneous biopsy have low diagnostic yields for locally invasive aspergillosis
when compared with autopsy findings. Sputum is also unavailable for culture in
Progressive Increase in Cavitation with the Evolution of Fungus
Progressive
Ball: A Clue to
Increase
the Diagnosis
in Cavitation
of Chronicwith
Necrotizing
the Evolution
Pulmonary
of Fungus
Aspergillosis
Ball... 21
many cases; even when present, the sensitivity of such culture is probably in the order
of 50–60%. Similar values have been found for culture of respiratory tract secretions
sampled by bronchoalveolar lavage (BAL) or bronchial washing or brushing. A positive
sputum culture may also reflect simple colonization. However, in the appropriate clinical
setting, repeated positive sputum or BAL fluid cultures have been found to be a reliable
method of diagnosis. Unlike Aspergillus fungal ball, in which medical therapy has very
little proven benefit, successful treatment of CNPA has been reported. A treatment
protocol utilizing itraconazole, followed if necessary, by intravenous amphotericin B or
surgical excision or intracavitary amphotericin has been proposed. The dose and duration
of therapy should be based on clinical response. Maintenance therapy with itraconazole
can be considered in patients with residual parenchymal scarring. Voriconazole and
Micafungin are useful in refractory cases. In this disorder, diagnosis is usually delayed,
patients are poor operative candidates, and postoperative complications are common.
Treatment outcome is likely to be influenced by the severity of comorbid conditions, the
extent of the underlying disease, delays in diagnosis, and initiation of effective therapy.
In a country like India, cavity in upper zone of chest radiograph is considered a case of
pulmonary tuberculosis even in the absence of acid-fast bacilli (AFB). Diagnosis of
chronic necrotizing pulmonary aspergillosis must be considered in those patient in
which disease progress along with evolution of fungus ball after a trial of antitubercular
treatment.
FURTHER READING
1. Prasad R, Garg SR. Progressive increase in cavitation with the evolution of fungus ball: A clue to the
diagnosis of chronic necrotizing pulmonary aspergillosis. Lung India. 2009;26:95-7.
2. Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. “Semi-invasive” pulmonary aspergillosis: A
new look at the spectrum of Aspergillus infections of the lung. Radiology. 1981;140:313-21.
3. Parakh UK, Sinha R, Bhatnagar AK, Singh P. Chronic necrotizing pulmonary aspergillosis: A rare
complication in a case of silicosis. Indian J Chest Dis Allied Sci. 2005;47:199-203.
4. Saraceno J, Phelps D, Ferro T, Futerfas R, Schwartz D. Chronic necrotizing pulmonary aspergillosis:
Approach to management. Chest. 1997;112:541-8.
5. Gefter WB. The spectrum of pulmonary aspergillosis. J Thorac Imaging.1992;7:56-74.
6. Binder RE, Falling LJ, Pugatch RD, Mahasaen C, Snider GL. Chronic necrotizing pulmonary aspergil
losis: A discrete clinical entity. Medicine.1982;61:109-24.
7. Vogeser M, Haas A, Aust D, Ruckdeschel G. Postmortem analysis of invasive aspergillosis in a tertiary
care hospital. Eur J Clin Microbiol Infect Dis. 1997;16:1-6.
8. Horvath JA, Dummer S. The use of respiratory-tract cultures in the diagnosis of invasive pulmonary
aspergillosis. Am J Med. 1996;100:171-8.
9. Jewkes J, Kay PH, Paneth M, Citron KM. Pulmonary aspergilloma: Analysis of prognosis in relation to
hemoptysis and survey of treatment. Thorax. 1983;38:572-8.
10. Ouchi H, Fujita M, Ikegame S, Inoshima I, Harada E, Nakanishi Y. Successful treatment of
refractory chronic necrotizing pulmonary aspergillosis with micafungin. J Infect Chemother.
2007;13:258-62.
CASE 7
Pericardial Effusion as a Paradoxical

Response to Therapy for Mediastinal
Lymph Node Tuberculosis
CASE REPORT
A 19-year-old female was admitted with chief complaints of progressively increasing
breathlessness since the last 1 month followed by orthopnea and low-grade fever since the
last 15 days . On initial examination, her respiratory rate was 24 breaths/min, pulse rate was
92 beats/min, and BP was 90/60 mm Hg.
Her oxygen saturation was 92%. Jugular venous pressure (JVP) was elevated and a positive
hepatojugular reflux was elicited. Auscultation revealed diminished heart sounds and
pericardial friction rub.
Laboratory investigations revealed Hb of 11 g/dL; RBC count of 4.72 million/mm3, white
blood cell (WBC) count of 9,600/mm3 with polymorphs 61%, lymphocytes 35%, eosinophils
3% and monocytes 1%, platelet count of 2.15 lac/mm3 and an erythrocyte sedimentation
rate (ESR) of 45 mm. She was seronegative for human immunodeficiency viruses (HIV) and
nondiabetic. Her immunology profile (ANA, RF factor, ANCA) and s. ACE were within normal
limits. Chest X-ray (CXR) posteroanterior (PA) view revealed cardiomegaly. Contrast enhanced
computerized tomography (CECT) thorax revealed pericardial effusion and normal cardiac
chambers.
Echocardiogram revealed 15 mm thick effusion and no evidence of cardiac tamponade
or constrictive pericarditis. An Echo-guided pigtail catheter insertion was done and a total
of 800 mL of straw-color pericardial fluid was drained. Pericardial fluid was sent for bio
chemical and microbiological investigation. Pericardial fluid investigation was reported as:
TLC 1,100 cells/mm3, DLC-lymphocyte 80%, neutrophil 20%, protein 5.4 g/dL, sugar 80 g/dL,
and adenosine deaminase (ADA) 72 IU/mL.
Pericardial fluid was negative on ZN and Gram-staining and aerobic cultures were sterile.
Her sputum was Acid-fast bacilli (AFB) negative on smear. Her past history and treatment
history revealed that the patient had developed low-grade fever and loss of appetite/
weight for 3 months, 4 months back and had undergone a full work-up at previous center.
CECT thorax had revealed mediastinal and hilar lymphadenopathy with 17 mm induration
on purified protein derivative (PPD) administration. She was subsequently started on
antitubercular therapy (ATT) regimen comprising of rifampicin 450 mg, isoniazid 300 mg,
ethambutol 800 mg, and pyrazinamide 1,000 mg by physician at the previous center to which
she had responded clinically and radiologically on serial CXR (Figs. 1 and 2).
Pericardial Effusion as a Paradoxical Response to Therapy... 23
FIG. 1: Computed tomography thorax before

antitubercular therapy (ATT) showing mediastinal
lymphadenopathy.
FIG. 2: Computed tomography thorax showing

pericardial effusion and resolution of lymph nodes
while on antitubercular therapy (ATT).
Pyrazinamide and ethambutol were stopped after 3 months by the treating physician.
After 4 months of treatment, she started developing above-mentioned symptoms, which
increased over 15 days and she was referred to our center. She had no intolerance or
interruption during her period of ATT. The patient responded well to pericardial fluid
drainage with the subsidence of breathlessness and chest pain. We continued rifampicin
450 mg and isoniazid 300 mg and started her on tablet prednisolone 40 mg in a dosage of
1 mg/kg body weight. Fever subsided over 2 weeks and she was discharged subsequently,
with prednisolone tapered over next 2 weeks and stopped. The patient responded to
the treatment, with no recurrence of symptoms or any signs of deterioration when last
followed up 1 month after discharge. Her CXR PA view 1 month after discharge showed
resolution of pericardial effusion and no new lesions. Subsequently, we stopped her ATT after
total duration of therapy of 9 months (Fig. 3).
FIG. 3: Chest X-ray posteroanterior (PA) after adding steroid to anti

tubercular therapy (ATT) showing resolution of pericardial effusion.
DISCUSSION
Paradoxical response in tuberculosis (TB) is defined as transient worsening of disease
at a pre-existing site, or the development of new lesions in a patient who initially
improved during successful antitubercular therapy (ATT). Another term often used is
immune reconstitution inflammatory syndrome (IRIS). However, the term IRIS should
be reserved for paradoxical responses in human immunodeficiency viruses (HIV)
seropositive patients due to antiretroviral therapy, while the term paradoxical response
is used in both HIV-seropositive and -seronegative patients in whom ATT has been
initiated. Although this phenomenon is more common and severe in HIV co-infected
individuals, 2–15% of HIV-negative patients infected with TB will experience paradoxical
worsening during treatment. It is seen more frequently in patients with extra-pulmonary
TB, and among those with low baseline lymphocyte counts. Paradoxical responses develop
between 4 weeks and 18 months after the initiation of ATT.
The mechanism for this phenomenon remains unclear and it remains a diagnostic
dilemma. Rapid killing of bacilli by effective ATT can cause the release of large amounts
of tuberculoproteins and other cell wall products. Hypersensitivity to tuberculoproteins
released from the dying mycobacteria and enhanced focal immune responses
(immunological rebound) will recruit lymphocytes and macrophages at the site of
previously inactive tuberculous foci which enlarge and then become evident.
This immunological explanation is supported by a relatively low mycobacterial
culture rate from the paradoxically expanded lesions and significant resolution of
the par adoxical response after use of steroids. The overall inflammatory response
to Mycobacterium tuberculosis would reflect the number and function of immune
cells and the amount of antigen that they encounter. The severity and frequency of
paradoxical response would therefore be higher if disseminated or extensive single organ
disease was present.
Paradoxical response is a diagnosis of exclusion, made after noncompliance, drug
resistance, drug fever, alternative diagnoses or progression of original disease have
been ruled out. The patient experienced an initial clinicoradiological improvement with
ATT so the phenomenon known as the paradoxical response was suspected. On taking
the patient's treatment history meticulously, she revealed that the she was regular in
Pericardial Effusion as a Paradoxical Response to Therapy... 25
her ATT intake and a perusal of prescriptions revealed that ATT was according to weight
and of reputed brand. Her mediastinal lymphadenopathy had responded to the ATT
without any modification of regimen, ruling out drug resistance, treatment failure or
progressive disease. During paradoxical response, she defervesced even while ATT was
continued, ruling out drug fever. She was not positive for markers of any other disease
and had a successful treatment outcome with ATT; ruling out any alternative diagnosis.
We propose that in our patient, successful ATT for mediastinal lymph node tuberculosis
led to enhanced focal immune response causing accumulation of inflammatory exudates
at previously invisible microscopic tuberculous foci in her pericardium, appearing as
pericardial effusion. The diagnosis of paradoxical response in our patient was based on
temporal correlation of occurrence of symptoms with continuation of ATT, absence of any
other etiology on exhaustive investigations, and rapid resolution of pericardial effusion
on adding steroid to ATT.
She had taken ATT for a longer than recommended duration from previous
center but paradoxical response requires continuation of ATT till the crisis is over.
Mild-to-moderate paradoxical response can be treated symptomatically with con
tinuation of ATT. For severe responses, corticosteroids are added (prednisone
1 mg/kg/day for 1–2 weeks followed by a taper). Pericardial effusion is a rare
manifestation of paradoxical response in non-HIV patients. Extensive search of world
literature revealed only one case of pericardial effusion occurring as paradoxical
response to ATT in a non-HIV person till date. Our case report emphasizes the
importance of recognizing the phenomenon of paradoxical response and diligently
differentiating it from treatment failure in order to avoid unnecessary modification of the
drug regimen.
FURTHER READING
1. Prasad R, Nath A, Karmakar S, Karmakar S. Pericardial effusion as a paradoxical response to therapy
for mediastinal lymph node tuberculosis-case report. J Biosci Tech. 2011;2:335-9.
2. Colebunders R, John L, Huyst V, Kambugu A, Scano F, Lynen L. Tuberculosis immune reconstitution
inflammatory syndrome in countries with limited resources. Int J Tuberc Lung Dis. 2006;10:946-53.
3. Cheng VC, Yam WC, Woo PC, Lau SK, Hung IF, Wong SP, et al. Risk factors for development of paradoxical
response during antituberculosis therapy in HIV-negative patients. Eur J Clin Microbiol. 2003;22:597-602.
4. Breen RA, Smith CJ, Bettinson H, Dart S, Bannister B, Johnson MA, et al. Paradoxical reactions during
tuberculosis treatment in patients with and without HIV coinfection. Thorax. 2004;59:704-7.
5. Bukharie H. Paradoxical response to antituberculosis drugs: Resolution with corticosteroid therapy.
Scand J Infect Dis. 2000;32:96-7.
6. Cheng VCC, Ho PL, Lee RA, Chan KS, Chan KK, Woo PCY, et al. Clinical spectrum of paradoxical
deterioration during antituberculosis therapy in non-HIV-infected patients. Eur J Clin Microbiol
Infect Dis. 2002;21:803-9.
7. Janmeja AK, Das SK. Cervico mediastinal lympadenopathy as a paradoxical response to chemo
therapy in pulmonary tuberculosis: A Case Report. Respiration. 2003;70:219-20.
8. Park JM, Shin YH, Chon GR, Shin HJ. A case of newly developed pulmonary lesion during the anti
tubercular agents in tuberculous pleurisy: A paradoxical response. Korean J Pediatr. 2009;52:717-20.
9. Park IS, Son D, Lee C, Park JE, Lee JS, Cheong MH, Kim YM. Severe paradoxical reaction requiring
tracheostomy in a human immunodeficiency virus (HIV)-negative patient with cervical lymph node
tuberculosis. Yonsei Med J. 2008;49:853-6.
10. Treatment of tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society of
America. MMWR Morb Mortal Wkly Rep. 2003; 52:51-5.
11. Bloch S, Wickremasinghe M, Wright A, Rice A, Thompson M, Kon OM. Paradoxical reactions in non-
HIV tuberculosis presenting as endobronchial obstruction. Eur Respir Rev. 2009;18:295-9.
12. Ohkouchi M, Inase N, Yasui M, Miura H. Case of pubic tuberculous osteomyelitis and pericarditis
during anti-tuberculosis chemotherapy. Kekkaku. 2004;79:531-5.
CASE 8
Occupational Emphysema Following

Long-term Exposure to Metal
CASE REPORT
An 80-year-old male patient, a lifetime nonsmoker, presented with persistent cough
with scanty sputum, and progressively worsening dyspnea on exertion that had become
prominent for the past 3 years causing severe limitation of activities, currently grade
4 of the modified Medical Research Council scale. There was no history of wheezing, fever,
hemoptysis, and joint pains. There was no previous history of any significant respiratory or
other systemic disease nor was there any significant family history of a similar disorder. He
had worked in an electroplating industry where he was exposed to metals fumes emanating
from the use of nickel and aluminium for 30 years. He started developing symptoms while
still in the job but quit a few months later and had now been symptomatic for 3 years.
Detailed questioning did not reveal significant exposure to environmental tobacco smoke or
any other noxious substance at home or at work. He had received oral bronchodilators with
corticosteroids from time to time. Examination revealed evidence of a barrel-shaped chest
with signs of hyperinflation, scattered end-inspiratory crackles and prolonged expiration with
wheeze. There was no cyanosis, clubbing or edema. Pulse oximetry showed oxygen saturation
(SpO2) of 90%.
Chest radiograph showed hyperinflated lung fields with a long tubular heart (Fig. 1).
Laboratory investigations, namely, blood counts, glucose, and serum biochemistry including
hepatic and renal function were in the normal range. The lung function data are shown in
the Table 1. Spirometry revealed a mild obstructive ventilatory impairment with lack of
any significant response to inhaled salbutamol. The functional residual capacity (FRC) was
increased suggesting hyperinflation. The single breath diffusion capacity for carbon monoxide
(DLCOSB) was severely reduced, even after correction for alveolar volume (VA).
High-resolution computed tomography (HRCT) of the chest (Fig. 2) revealed bilateral
extensive centrilobular emphysema, more in the upper lobes and a sabre-sheath trachea
with a sagittal: coronal diameter >2:1 (not shown). There was no evidence of mediastinal
lymphadenopathy (Fig. 2). Electrocardiogram showed low voltage complexes and poor
progression of R waves. Arterial blood gas analysis revealed pH of 7.44, arterial carbon
dioxide tension 49.5 mm Hg, arterial oxygen tension 69.6 mm Hg and bicarbonate
32.9 mmol/L, suggestive of mild hypoxemia with metabolic alkalosis.
Occupational Emphysema Following Long-term Exposure to Metal 27
FIG. 1: Plain chest radiograph (posteroanterior view)

showing hyperinflated lung fields with a long tubular heart,
prominent hila and peripheral pruning of vasculature.
TABLE 1: Lung function data.

Pleural fluid Prebronchodilator Postbronchodilator
FVC (L) 2.79 (104%) 2.75 (103%)
FEV1 (L) 1.23 (72%) 1.29 (75%)
FEV1/FVC 44 47
TLC (L) 4.67 (103%)
FRC (L) 3.51 (119%)
RV (L) 1.86 (82%)
DLCOSB (mL/min/mm-1Hg) 10.03 (33%)
DLCO/VA 2.11 (50%)
(DLCOSB: diffusion capacity for carbon monoxide; FEV1: forced expiratory volume in 1 second; FRC:
functional residual capacity; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity;
VA: alveolar volume)
Based on the history of occupational exposure to heavy metal fumes, absence of any
other exposures, clinical features, and characteristic lung function and HRCT findings, a
diagnosis of occupational emphysema was established. He was advised inhaled long-acting
bronchodilators that provided some relief in symptoms.
FIG. 2: High-resolution computed tomography (HRCT) chest

showing bilateral centrilobular emphysema in affecting all lobes.
DISCUSSION
Unlike occupational and work-associated asthma, the role of occupational factors as the
main or contributory cause in the development of emphysema has received remarkably
little attention. The true population attributable risk due to occupational exposure is
unclear as occupational chronic obstructive pulmonary disease (COPD) is rarely clinically
diagnosed. Establishing a true cause-effect relationship is difficult as it takes years of
exposure to the offending agent. Off-work amelioration of symptoms and recurrence
on re-exposure as well objective lung function monitoring on and off work that are the
standard tools to diagnose occupational asthma are not applicable to occupational
COPD. Further, smoking often confounds the estimation of the risk of developing COPD.
The association of dusts, fumes, and chemicals of industrial origin with the develop
ment of COPD has been documented in some studies. A systematic epidemiological
review by the American Thoracic Society showed that about 15% of COPD cases might
be attributable to workplace exposure. Findings of seven population-based studies on
occupational COPD revealed that a population-attributable risk for occupational COPD
to be 15%. The population-attributable fraction for COPD associated with occupational
exposure has been estimated between 9 and 31%.
Industrial exposures to metal fumes have also been associated with airways obs
truction. A high prevalence of COPD has been reported in iron steel and ferrochrome
industry workers. Metal smelting activities have also been related to worsening annual
decline of forced expiratory volume in 1 second (FEV1), suggesting that it may result in
an increased risk of COPD. The main observations in these studies have been a higher
prevalence of chronic productive cough and lower FEV1 in the exposed workers after
taking into account the confounding effect of smoking. In contrast, the development of
emphysema following prolonged industrial exposure is less well established. It has been
suggested that heavy exposure to cadmium may lead to emphysema. In vivo diagnosis
of emphysema requires high-resolution computed tomography (HRCT) of the chest
or measurement of diffusion capacity. Both are usually not feasible in the settings in
which occupational COPD has been studied. Hence, the true prevalence of occupational
emphysema and specific occupation associated with it has never been established.
Occupational Emphysema Following Long-term Exposure to Metal 29
Electroplating is a process that uses electrical current to reduce dissolved metal

cations so that these form a coherent metal coating on an electrode. Metals used for
plating include nickel, cadmium, platinum, gold, silver, chromium, etc. Throughout the
electroplating process, operators are exposed to hazardous chemical vapor, fume, and
mist. In addition, metal dust is generated. Chromium, nickel, and cadmium are all on the
International Agency for Research on Cancer’s (IARC) list of known human carcinogens.
Some studies have shown the risk of development of asthma upon exposure to nickel dust
but none has shown an association with COPD.
A limitation in proving cause-effect relationship in occupational emphysema is the
prolonged exposure required to produce the characteristic features. Amelioration and re
currence of symptoms on avoidance and re-exposure or objective lung function monitoring
on and off work are of little help in diagnosing occupational COPD. Diagnosis remains
circumstantial. In this case report, we illustrate the association of emphysema with nickel
exposure. The patient worked in an electroplating industry for 30 years with exposure of
nickel fumes in the working place. We based our diagnosis on the history of occupational
exposure to nickel fumes and absence of any other exposures, clinical features, and
characteristic lung function and HRCT findings.
FURTHER READING
1. Mittal R, Gupta P, Dash JP, Prasad R, Chhabra SK. Occupational emphysema following long-term
exposure to metal fumes during electroplating in a non-smoker. Indian J Chest Dis Allied Sci.
2016;58:123-5.
2. Blanc P, Toren K. Occupation in chronic obstructive pulmonary disease and chronic bronchitis: an
update. Int J Tuberc Lung Dis. 2007;11:251-7.
3. Rodríguez E, Ferrer J, Zock JP, Serra I, Antó JM, de Batlle J, et al. Lifetime occupational exposure to
dusts, gases and fumes is associated with bronchitis symptoms and higher diffusion capacity in
COPD patients. PLoS One. 2014;9:e88426.
4. Kjuus H, Istad H, Langård S. Emphysema and occupational exposure to industrial pollutants. Scand J
Work Environ Health. 1981;7:290-7.
5. Davison AG, Fayers PM, Taylor AJ, Venables KM, Darbyshire J, Pickering CA, et al. Cadmium fume
inhalation and emphysema. Lancet. 1988;1:663-7.
6. Hnizdo E, Vallyathan V. Chronic obstructive pulmonary disease due to occupational exposure to silica
dust: a review of epidemiological and pathological evidence. Occup Environ Med. 2003;60:237-43.
7. Kuempel ED, Vallyathan V, Green FHY. Emphysema and pulmonary impairment in coal miners:
quantitative relationship with dust exposure and cigarette smoking. J Phys Conf Ser. 2009;151:012024.
8. Schilling RSF, Hughes JPW, Dingwall-Fordyce I. Disagreement between observers in an epidemio
logical study of respiratory disease. Br Med J. 1955;1:65-8.
9. Decramer M, Sibille Y. European conference on chronic respiratory disease. Lancet. 2011;377:104-6.
10. Balmes J, Becklake M, Blanc P, Henneberger P, Kreiss K, Mapp C, et al. American Thoracic Society
Statement: Occupational contribution to the burden of airway disease. Am J Respir Crit Care Med.
2003;167:787-97.
11. Blanc PD. Occupation and COPD: a brief review. J Asthma. 2012;49:2-4.
12. Blanc PD, Iribarren C, Trupin L, Earnest G, Katz PP, Balmes J, et al. Occupational exposures and the risk
of COPD: dusty trades revisited. Thorax. 2009;64:6-12.
13. Bala S, Tabaku A. Chronic obstructive pulmonary disease in iron-steel and ferrochrome industry
workers. Cent Eur J Public Health. 2010;18:93-8.
14. Becklake MR, Irwig L, Kielkowski D, Webster I, de Beer M, Landau S. The predictors of emphysema in
South African GOLD miners. Am Rev Respir Dis. 1987;135:1234-41.
15. McConnell LH, Fink JN, Schlueter DP, Schmidt MG. Asthma caused by nickel sensitivity. Ann Intern
Med. 1973;78:888-90.
16. Malo JL, Cartier A, Doepner M, Nieboer E, Evans S, Dolovich J. Occupational asthma caused by nickel
sulfate. J Allergy Clin Immunol. 1982;69:55-9.
CASE 9
Isoniazid-induced Gynecomastia
CASE REPORT
SN, a 60-year-old male smoker, nonalcoholic patient presented to Department of
Pulmonary Medicine, King George’s Medical University, Lucknow with complaints of
cough, expectoration, low-grade fever, decreased appetite, and streaking. On further
evaluation, he was diagnosed as a case of sputum positive pulmonary tuberculosis. Patient
was put on isoniazid 300 mg, rifampicin 450 mg, ethambutol 800 mg, and pyrazinamide
1,000 mg once daily. Pyrazinamide was stopped after 2 months. Patient responded
well to the treatment and gained 5 kg weight during the initial intensive phase of treat
ment. Under treatment follow-up at 5th month while continuing with rifampicin, isoniazid,
and ethambutol patient complained of pain and swelling in both breasts. On examination,
patient had bilateral tender mobile breast lump (Figs. 1 and 2), about 5 × 6 cm in diameter.
Suspecting it to be drug-induced gynecomastia, isoniazid which appeared to be most
FIG. 1: Frontal view of the patient showing gyne

co
mastia developed during isoniazid-based anti
tubercular treatment (ATT).
Isoniazid-induced Gynecomastia 31
obvious cause of it was withdrawn immediately from the treatment and rest were continued
with further investigation of the patient to know the cause of gynecomastia. On examination,
secondary sexual characters and external genitalia were found normal, his mammogram
showed features suggestive of bilateral benign mammary tissue hyperplasia (Fig. 3). His
ultrasonogram showed it to be glandular tissue hyperplasia. Patient’s thyroid stimulating
hormone level was 0.77 µIU/mL (0.3–6.0), luteinizing hormone was 6 mIU/mL (0.7–7.4),
follicle-stimulating hormone 6.8 mIU/mL (1.0–14.0), prolactin 11.0 ng/mL (1.8–17 ng/mL),
testosterone 4.0 ng/mL (3–20 ng/mL), and estradiol was 54.9 pg/ mL (21–79 pg/mL). His
hepatic and renal functions were within normal limits. Ultrasonogram of external genitalia
revealed no abnormality. He recuperated well after stopping isoniazid, pain from the breast
subsided within a month. Follow-up at 6 months after the prescribed 9 months of treatment
revealed an asymptomatic patient with nontender slightly enlarged breast.
FIG. 2: Lateral view of the patient showing gyneco-

mastia.
FIG. 3: Mammogram of the patient showing glandu-

lar hypertrophy indicating true gynecomastia.
DISCUSSION
Gynecomastia is one of the most common breast problems in men and was first
described by Paulus Aegineta (ad 625–690), who thought it was due to formation of
fat. It can occur due to numerous causes which include developmental gynecomastia,
congenital causes like Klinefelter syndrome, hermaphroditism, enzyme defects of
testosterone production, acquired causes such as trauma, infection, torsion (twisted
testicles), radiation, mumps, chemotherapy, malignancies such as bronchogenic
carcinoma, alcoholism, systemic causes such as congenital adrenal hyperplasia,
cirrhosis, renal failure, thyrotoxicosis, and drugs. Drugs are a very common cause
of gynecomastia and should always be entertained as the possible causal agent of
such a condition. Most of the drugs causing gynecomastia have been reported by
means of case reports, which document temporal association of the offending drug.
Clinically significant gynecomastia caused by drugs may be due to an impaired
balance in the serum estrogen to androgen ratio or a rise in prolactin level. In case
of isoniazid-induced gynecomastia, it has been hypothesized that disturbance in
vitamin B complex activation in liver leads to altered estrogen-androgen metabolism.
It has also been postulated that isoniazid probably acts by phenomenon called
“Refeeding gynecomastia,” which is supposed to be caused by restoration of weight,
gonadotrophin secretion, and gonadal functions. Among antitubercular drugs,
isoniazid, thioacetazone, and ethionamide have been implicated as causes of
gynecomastia. First report of isoniazid-induced gynecomastia came in 1953 from
France, a year after its introduction in 1952, then from Italy in 1957, and another
French report came in 1976. The only Indian report was published in 2003. French
report described painless, bilateral gynecomastia in 52-year old man who was receiving
600 mg of isoniazid daily for 4 months along with rifampicin and ethambutol. On
investigation, he was slow acetylator. Strikingly similar to the only other Indian case
report, ours was also receiving isoniazid 300 mg daily and also had bilateral painful
enlargement of breast in contrast to other foreign reports which had reported it with
higher dose of isoniazid and painless enlargement of the breast. The acetylator status
was not carried out in this case and the same is also not available in other Indian report.
In contrast to other Indian report we stopped isoniazid only, rather than all the anti
tubercular treatment (ATT) after initiation of symptoms and were able to achieve good
symptomatic relief. There appears to be temporal association with this offending drug
as in all the reports it has occurred in later part (continuation phase) of the therapy.
It is difficult to distinguish true breast enlargement from increased adipose tissue
(lipomastia). True glandular tissue is often palpable, especially around the areola, as it
is firmer and contains cord like features distinct from the texture of adipose tissue. In
difficult cases, true gynecomastia can be identified by ultrasound, which is recommended
as the first-line imaging investigation although mammography may be added to confirm
the diagnosis. In this case both were done to confirm the true gynecomastia which was
not done in any of the previous reported cases. Most patients with gynecomastia require
no treatment other than the removal of any inciting cause. Specific treatment of enlarged
breast tissue is indicated if it is causing sufficient pain, embarrassment, or emotional
discomfort to interfere with patient’s daily life. The other antituberculosis drugs which are
implicated in the list of drugs causing gynecomastia are thioacetazone and ethionamide
only. As of now, there are no reports implicating rifampicin and ethambutol causing
gynecomastia which prompted us to attribute isoniazid as the inciting etiology. Our
case appears to be the first well worked up case after the similar case report in English
Isoniazid-induced Gynecomastia 33
literature and highlights the fact that isoniazid therapy can lead to development of painful
gynecomastia which may be very embarrassing to the patient, especially if the patient is
elderly.
FURTHER READING
1. Garg R, Vaibhav, Mehra S, Prasad R. Isoniazid induced gynaecomastia: a case report. Indian J Tuberc.
2009;56:51-4.
2. Girling DJ. Adverse effects of antituberculosis drugs. Drugs. 1982;23:56-74.
3. Park AJ, Lamberty BGH. Gynaecomastia: Have Webster’s Lesson Been Ignored? J R Coll Surg
Edinb.1998;43:89-92.
4. Braunstein GD. Gynaecomastia. Gynecomastia. N Engl Med. 1993;328: 490-5.
5. Khanna P, Panjabi C, Maurya V, Shah A. Isoniazid associated, painful, bilateral gynaecomastia. Indian
J Chest Dis Allied Sci. 2003;45:277-9.
6. Guinet P, Garin JP, Morpex A. Uncas de gynecomastie chez un tuberculeuxpulmonaire grave en
coursdetraitment par I’hydrazide de I’acide isonicotinique. (A case of gynecomastia in pulmonary
tuberculosis during the course treatment with isonicotinic acid hydrazide). Lyon Med. 1953;85:
281-4.
7. Bergogne-Berezin E. Nouhouayi A. Letonturier P, Tourneur R. Gynaecomastia caused by isoniazid:
Value of determination of inactivation of phenotype. NouvPresse Med. 1976;5:213-4.
8. Borsella C, Merelli B. Appearance of gynaecomastia in pulmonary tuberculosis patients during
isoniazid therapy. G Clin Med. 1957;38:1744-58.
9. Garcia Rodriguez LA, Jick H. Risk of gynaecomastia associated with cimetidine, omeprazole, and
antiulcer drugs. BMJ. 1994;308:503-6.
10. Hugues FC, Gourlot C, Le Jeunne C. Drug induced gynecomastia. Ann Med Interne [Paris].
2000;151:10-7.
11. Thompson DF, Carter JR. Drug induced gynecomastia. Phrmacotherapy.1993;13:37-45.
12. Wilson JD. Endocrine disorders of the breast. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo
DL, Jameson JL. Harrison’s principles of internal medicine, 15th edition. New York: McGraw-HillCo.;
2001. pp. 2170-1.
13. Bembo SA, Carlson HE. Gynaecomastia: Its Feature, and when and how to treat it. Cleve Clin J Med.
2004;7:6.
14. Chunhaswasdikul B. Gynaecomastia in association with administration of thiacetazone in the
treatment of tuberculosis. J Med Assoc Thai. 1974;57:323-7.
CASE 10
Isolated Left Upper Lobe Aplasia and Lower

Lobe Hypoplasia with Bronchial Asthma
CASE REPORT
A 36-year-old nonsmoker man was admitted to our department with complaints of cough
with expectoration and episodic breathlessness since early childhood. Previously he
had received two adequate courses of primary line antituberculosis drugs without any
clinicoradiological improvement. His resting pulse rate was 92 beats/min, blood pressure was
128/74 mm Hg, and respiratory rate was 24 breaths/min. Respiratory system examination
revealed flattened left side chest with ipsilateral mediastinal shift and also there were reduced
chest movements on the left side. Percussion note was dull on the left side. Breath sounds
were normal vesicular in character on the right side with random polyphonic rhonchi but the
intensity of breath sounds on the left side was grossly reduced. Heart sounds were normal.
Chest X-ray showed complete opacification of left hemithorax with hyperinflation of right
lung and herniation with shifting of mediastinum to left lung (Fig. 1). Sputum for acid-fast
bacilli (AFB) smear on three consecutive days was negative. His hemoglobin was 12 g%, total
leukocyte count 8,100/mm3, neutrophils 72%, lymphocytes 25%, and eosinophils 3%. His
FIG. 1: Chest X-ray revealed complete opacification of left hemithorax with hyperinflation
of the right lung and herniation with shifting of the mediastinum to the left lung.
Isolated Left Upper Lobe Aplasia and Lower Lobe Hypoplasia... 35
blood urea was 28 mg/dL, serum creatinine 0.5 mg/dL. His serum bilirubin was 0.6 mg/dL,
SGPT 28 U/L, SGOT 19 U/L, and SAP 193 U/L. Spirometry showed forced expiratory volume
in 1 second (FEV1%) of 48 and FEV1of 770 mL (24% of predicted). There was a significant
reversibility of 230 mL in FEV1 after inhaled salbutamol. Thus, diagnosis of bronchial asthma
was made. Subsequently his computed tomography (CT) was done that revealed small left
main bronchus with very small left lower lobe bronchus (Fig. 2). Left upper and lingular
lobe bronchi were absent with no lung tissue of upper and lingular lobes of the left lung.
The right lung was overinflated with compensatory emphysematous changes. On contrast
administration, the left pulmonary artery was normal in caliber; however, branching to
upper and lingular lobes was not seen. His fiberoptic bronchoscopy revealed a short left
main bronchus with absent left upper lobe bronchus. The left lower lobe bronchus was very
narrow and the scope could not be passed forward. On the right side the tracheobronchial
tree was normal. His MRI thoracic angiography was done that did not reveal any vascular
anomaly (Fig. 3). His Ultrasonography (USG) abdomen was normal. Thus, diagnosis of left
upper lobe aplasia with left lower lobe hypoplasia with bronchial asthma was made. The
patient's symptoms of breathlessness relieved were abolished after initiation of inhaled
bronchodilator and corticosteroids with oral mast cell stabilizer.
FIG. 2: Computed tomography (CT) thorax revealed left upper

lobe aplasia and very small left lower lobe (hypoplasia).
FIG. 3: Reveal magnetic resonance imaging (MRI) thoracic angiography.

DISCUSSION
Agenesis of the lung is an extremely rare congenital anomaly representing failure
of development of the primitive lung bud. This condition was first described by De
Pozze, who discovered it accidently at the autopsy of an adult female in 1673. Munch
Meyer first diagnosed unilateral agenesis of the lung clinically in 1885. From India,
the first case was reported by Muhamed in 1923, of a left-sided pulmonary agenesis.
Pulmonary agenesis is classified into three categories depending upon the stage of
development of the primitive lung bud: (1) Agenesis: Complete absence of lung and
bronchus and no vascular supply to the affected side, (2) Aplasia: Rudimentary bronchus
with complete absence of pulmonary parenchyma (left upper lobe aplasia in present
case), and (3) Hypoplasia: Presence of variable amounts of bronchial tree, pulmonary
parenchyma, and supporting vasculature (left lower lobe hypoplasia in present case).
The causes of pulmonary hypoplasia may be primary [deficient thyroid transcription
factor-1 (TTF-1), GATA factors, hepatocyte nuclear factor HNF310, epidermal growth
factor and its receptor, estimated glomerular filtration rate (EGFR); mitogen-activated
protein (MAP) kinase] but it is usually secondary (small fetal thoracic volume, prolonged
oligohydramnios, early rupture of membranes at 15–28 weeks' gestation, longer
latent period before delivery, decreased fetal breathing, congenital heart diseases,
and trisomies 18, 13, 21). The true incidence is unknown. No sex predilection has
been noted. Congenital lung defects with bronchial asthma is very rare. Till now only
three cases are reported. The onset of symptoms in pulmonary agenesis is remarkably
variable. In many cases, presence of this anomaly usually comes to light during
infancy because of recurrent chest infections, cardiopulmonary insufficiency or due to
associated congenital anomalies. Nearly 50% cases of pulmonary hypoplasia or aplasia
have associated congenital defects, which usually involve cardiovascular, skeletal,
gastrointestinal, and genitourinary system. Chest radiograph usually reveals homogenous
density on the involved side. Other findings are mediastinal shift, compensatory
herniation of the contralateral lung across the mediastinum, bell-shaped chest, and rib
deformities. Computed tomography (CT) thorax is now emerged as diagnostic modality
of choice. It helps to delineate pulmonary parenchyma, pulmonary vasculature and the
bronchus, while CT angiography and echocardiography detail the pulmonary vasculature.
With the advent of these techniques, the exact diagnosis can be established without
opting for invasive procedures such as bronchography and pulmonary angiography. In
roentgenographic differential diagnosis of hypoplasia or aplasia are collapse, thickened
pleura, destroyed lung, and pneumonectomy. Surgery is seldom required for agenesis
or aplasia, which can be managed on conservative lines. The prognosis of such cases
depends upon the functional integrity of the remaining lung as well as upon the presence
of associated anomalies. Our report highlights the fact that a high index of suspicion is
required to diagnose congenital lung anomalies and that asthma can occur in such
patients. Appropriate antiasthma therapy can alleviate symptoms and reduce morbidity.
FURTHER READING
1. Kushwaha R, Verma S, Mahajan V, Singh R, Prasad R. Isolated left upper lobe aplasia and lower lobe
hypoplasia with bronchial asthma. Internet J Pulm Med. 2006;9:1-4.
2. Sbokos CB, McMillan IRK. Agenesis of the lung. Brit J Dis Chest. 1977;3:183-97.
3. Rathkopf MM, Napoli D, Walls JG. Allergic rhinitis and asthma in a patient with unilateral pulmonary
agenesis. Ann Allergy Asthma Immunol. 2004;92:403-8.
4. Pozze D, Brescia MA, Amermon EE, Sharma KK. Agenesis of the left lung. Arch Paediatric.1960;77:485-90.
Isolated Left Upper Lobe Aplasia and Lower Lobe Hypoplasia... 37
5. Ferguson FF, Meuhauser EBD. Congenital absence of lung and other anomalies of tracheobronchial
tree. Am J Reontgen. 1944;52:459-71.
6. Muhamed KSN. Absence of left lung. Ind Med Gaz.1923;58:262-64.
7. Boyden EA. Developmental anomalies of lung. Am J Surg. 1955;89:79-88.
8. Yoshimura S, Masuzaki H, Miura K, Muta K, Gotoh H, Ishimaru T. Diagnosis of fetal pulmonary
hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler
ultrasonography. Am J Obstet Gynecol. 1999;180:441-6.
9. Warburton D, Olver BE. Coordination of genetic, epigenetic, and environmental factors in lung
development, injury, and repair. Chest. 1997;111:119S-122S.
10. Khanna P, Panjabi C, Shah A. Klippel-Feil syndrome with associated agenesis of lung and gall bladder
presenting with asthma and allergic rhinitis. Saudi Med J.2005;26:862-5.
11. Sahay S, Mathur RK, Shah A. Isolated left lung aplasia with bronchial asthma. Indian Pediatr.
2006;43:817-20.
12. Oymada A, Gasul BM, Holinger PM. Agenesis of the fung. Am J Dis Child. 1953;85:182-7.
13. Mendelson DS, Hahn P, Cohen BA, Pedill MJ. Hypoplasia of lung. CT Appearance. Mount Sinai J
Med.1986;53:297-8.
14. Bhagat R, Panchal N, Shah A. Pulmonary aplasia: a CT appearance. Indian Pediatr. 1992;29:1410-2.
15. Rajshakher B, Gomber S, Krishna A. Pulmonary agenesis. Indian Pediatr. 1997;34:534-8.
CASE 11
Ischemic Cavitation in
Conglomerate Silicosis
CASE REPORT
The most common cause of cavitation in progressive massive fibrosis (PMF) in patients
with silicosis is infection with Mycobacterium tuberculosis. However, cavitation of PMF as a
result of ischemic necrosis has also been identified as a rare entity in silicosis. A 40-year-old
male, nonsmoker, working as a stone cutter for 30 years presented with 5 years history of
exertional breathlessness and 8 months of dry cough. He had no history of fever, hemoptysis,
chest pain, weight loss or loss of appetite. Physical examination was unremarkable. Routine
hematological and biochemical investigations were found to be normal. Chest radiograph
(posteroanterior view; Fig. 1) showed well-defined, multiple nodular opacities in both lung
fields along with massive fibrosis with cavitation in upper zones. Computed tomography
(CT) of the chest (Figs. 2A to C) revealed bilateral multiple randomly distributed nodules of
uniform size and attenuation involving all lobes with upper lobe predominance with massive
FIG. 1: Chest radiograph (posteroanterior view) showing

well-defined, multiple nodular opacities in both lung fields
along with massive fibrosis with cavitation in upper zones.
Ischemic Cavitation in Conglomerate Silicosis 39
A B
FIGS. 2A TO C: Computed tomography of

the chest showing bilateral multiple randomly
distributed nodules in upper, middle, and
lower lobes with progressive massive fibrosis
C with cavitation in both upper lobes (left > right).
fibrosis with cavitation in both upper lobes (left more than right). Two samples of sputum
for acid-fast bacilli (AFB) were negative. Mantoux test was negative. Pulmonary function test
showed mild impairment of lung functions.
Fiberoptic bronchoscopy was done and transbronchial lung biopsy revealed ill-defined
granulomatous inflammation surrounding anthracotic pigment. Bronchoalveolar lavage and
endobronchial brush were negative for atypical cells, gram’s stain, fungal stain, and AFB. A
diagnosis of silicosis with PMF was made on the basis of occupational history and radiological
imaging characteristic of silicosis.
DISCUSSION
Silicosis, also known as “potters rot,” is pneumoconiosis attributable to inhalation of
respirable particles of crystalline silica. Crystalline silica has been classified as a group
1 substance by the International Agency for Research on Cancer. A number of clinical
and pathologic varieties of silicosis have been identified including simple, or nodular,
silicosis, silicoproteinosis (acute silicosis), complicated silicosis (PMF), and interstitial
fibrosis. In the case presented, the patient had significant exposure to silica dust during
stone crushing and radiologically had complicated silicosis. Conglomerate silicosis or
complicated silicosis results from the coalescence and agglomeration of several smaller
nodules. In addition to the enlargement of nodules, profusion of nodular lesions results
in PMF.
Histopathologically, the condition is said to develop when the above described
pulmonary lesions coalesce forming pulmonary masses 2 cm or larger. However,
according to the Silicosis and Silicate Disease Committee, a PMF lesion is defined as a
lesion >2 cm in diameter in contrast to the 1 cm or larger radiographic size established
by the International Labour Office (ILO). PMF is often characterized by large fibrotic
masses in conjunction with a distortion of the lung architecture often involving an

upward displacement of the mediastinal and hilar structures attributable to volume
loss. In addition, lower areas of the lung may appear hyperinflated and emphysematous,
often in conjunction with multiple bullae. PMF lesions have a predilection to occur
in the upper lobes of the right lung. However, in advanced cases, lesions are bilateral
and the appearance being described sometimes as an “Angel’s Wing” appearance.
The conglomerate lesions appear against a background of smaller nodules and may
obliterate bronchi and vessels and cause marked distortion of lung structure and
function. Tuberculosis (TB) should be suspected when chest radiograph reveal the rapid
emergence of new opacities, together with pleural effusion and cavitation. Nevertheless,
cavitation is a relatively uncommon finding in silicosis. When it does occur, one should
consider TB as the likely cause. In this case, we excluded possibility of pulmonary
TB. The PMF lesions in accelerated silicosis may cause cavitation due to the resultant
ischemia and necrosis. In a series of 44 patients with silicosis and conglomerate masses
who underwent chest high-resolution CT, cavitations was noted in eight patients, and
of these, six had concomitant TB. Occasionally, cavitation due to ischemic necrosis may
occur in a conglomerate mass.
FURTHER READING
1. Prasad R, Goel N, Gupta P, Viswesvaran B, Singh A. Ischaemic cavitation in conglomerate silicosis.
Indian J Chest Dis Allied Sci. 2015;57:233-4.
2. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Silica, Some Silicates,
Coal Dust and Para-Aramid Fibrils. In: IARC Monographs on the Evaluation of Carcinogenic Risks to
Humans. Lyon: International Agency for Research on Cancer; 1997.
3. Greenberg MI, Waksman J, Curtis J. Silicosis: a review. Dis Mon. 2007;53:394-416.
4. Craighead JE, Kleinerman J, Abraham JL, Gibbs AR, Green FHY, Harley RA, et al. Diseases associated
with exposure to silica and non-fibrous silicate minerals. Arch Pathol Lab Med. 1998;112:673-720.
5. Castranova V, Vallyathan V. Silicosis and coal workers’ pneumoconiosis. Environ Health Perspect.
2000;108:675-84.
6. Yang JC, Liu KL. Coal workers’ pneumoconiosis with progressive massive fibrosis. CMAJ. 2012;184:
E878.
7. Bailey WC, Brown M, Buechner HA, Weill H, Ichinose H, Ziskind M. Silico-mycobaterial disease in
sandblasters. Am Rev Respir Dis. 1974;110:115-25.
8. Souza Filho AJ, Alice SH. Fibrose maciça pulmonar progressiva. J Pneumol. 1991;17:147-53.
9. Ferreira AS, Moreira VB, Ricardo HMV, Coutinho R, Gabetto JM, Marchiori E. Progressive massive
fibrosis in silica-exposed workers: high-resolution computed tomography findings. J Brasileiro de
Pneumologia. 2006;32:523-8.
10. Chong S, Lee KS, Chung MJ, Han J, Kwon OJ, Kim TS. Pneumoconiosis: comparison of imaging and
pathologic findings. Radiographics. 2006;26:59-77.
11. Kim KI, Kim CW, Lee MK. Imaging of occupational lung disease. Radiographics. 2001;21:1371-91.
CASE 12
Intralobar Sequestration of Lung
CASE REPORT
A 35-year-old man, a nonsmoker, was admitted to our department with complaints
of recurrent hemoptysis and cough with expectoration for 4 years. In the past, he had
received anti tubercular treatments without any clinicoradiological improvement. His
resting pulse rate was 102 beats/min, blood pressure 112/74 mm Hg, and respiratory rate
26 breaths/min. His general examination revealed no significant abnormality. His respiratory
system examination revealed coarse crepitations over the basal part of the left hemithorax.
His chest X-ray revealed double-contour of the left cardiac border and inhomogeneous
infiltrates on the left lower zone (Fig. 1). His blood examination showed normal hemogram.
The result of his tuberculin skin test was negative. His sputum was negative for acid-fast bacilli
(AFB) for three consecutive days. During hospital stay, the patient improved clinically after
appropriate course of antibiotics, but opacity in the left lower zone persisted. He was further
investigated and his computed tomography (CT) thorax was done. It revealed a cavity with
fluid level localized to left lower anterobasal and posteromediobasal segments. Hence, a
FIG. 1: Chest X-ray revealing double-contour of the left cardiac

border and inhomogeneous infiltrates on the left lower zone.
possibility of lung sequestration, along with other possibilities, was raised. His aortography
was done. It revealed that the anterobasal and posteromediobasal segments of left lower
lobe were perfused via a single feeding vessel originating from descending thoracic aorta
(Fig. 2). His selective angiography revealed an arterial supply from descending thoracic
aorta and venous drainage occurred via pulmonary veins. Hence, a diagnosis of intralobar
pulmonary sequestration was made. He was subjected to surgery with a right-sided double-
lumen endotracheal tube for selective ventilation to achieve left-sided thoracotomy. The
feeding vessel originating from descending thoracic aorta was ligated first and then the
sequestrated part of left lower lobe segment was resected. Postoperative period was
uneventful. Histopathology confirmed the diagnosis of intralobar sequestration (ILS).
FIG. 2: Aortography revealing anterobasal and posteromediobasal

segments of left lower lobe, perfused via a single feeding vessel
originating from descending thoracic aorta.
DISCUSSION
Pulmonary sequestration was first described by Rektorzik in 1861 as a malformation
comprising of dysplastic lung tissue with no normal communication with the
tracheobronchial tree and with an anomalous systemic arterial supply. There are two
types of pulmonary sequestrations: ILS, which is surrounded by normal lung tissue; and
extralobar sequestration (ELS), which has its own pleural investment. Intrapulmonary
sequestration is four times more common than the extralobar type. The origin of ILS
was described in the past as being congenital and was explained by the accessory lung
bud theory. But the current widely held theory is that ILS is acquired after one or more
episodes of necrotizing pneumonia resulting in obliterative bronchitis and obstruction
of a lower lobe bronchus. Most of the ILS’ are located in the medial and posterior basal
segments of the left lung. Overall, 98% occur in the lower lobes. Bilateral involvement
is uncommon. Associated congenital anomalies in ELS include diaphragmatic hernia,
congenital cystic adenoid malformation, bronchogenic cysts, cardiovascular malfor
mation, and pectus excavatum. These are rare in intrapulmonary sequestrations. In
ILS, the systemic arterial supply is via the descending thoracic aorta (72%), as seen in
the present case; abdominal aorta, celiac axis, or splenic artery (21%); intercostal artery
(3.7%); and rarely via the subclavian, internal thoracic, and pericardiophrenic arteries.
Most venous drainage (95%) is via the pulmonary veins. The clinical hallmarks of ILS
are recurrent cough with expectoration and hemoptysis. Chest radiographs can provide
a reasonable diagnostic clue to pulmonary sequestration. A mass in the posterobasal
segment of the lung in young patients with recurrent localized pulmonary infections
is suggestive of ILS (as in our case). In the past, aortography was frequently used for
Intralobar Sequestration of Lung 43
diagnosis. However, more recently, CT scan with contrast or magnetic resonance

angiography (MRA) has been found to be easier and more useful. The gold standard for
identifying pulmonary sequestration is angiography as it confirms the anatomy, identifies
the systemic supply, and shows the venous drainage. Management of an asymptomatic
pulmonary sequestration with no connection to the surrounding lung is controversial. At
present open surgery via posterolateral thoracotomy (PLT) remains the best established
approach for definitive resection of bronchopulmonary sequestration, as has been done
in the present case. The wide access by this approach facilitates the safe isolation and
division of any abnormal systemic feeding arteries. However, video-assisted thoracic
surgery (VATS) is now increasingly recognized as an equally effective, minimally invasive
approach for bronchopulmonary sequestration. In the current scenario of our country,
where a lot of misuse of antibiotics and other drugs is quite prevalent, correct and prompt
suspicion of nonresolving radiological lesions is needed to provide correct and early
diagnosis of bronchopulmonary sequestration.
FURTHER READING
1. Prasad R, Goel N, Gupta P, Viswesvaran B, Singh A. Ischaemic cavitation in conglomerate silicosis.
Indian J Chest Dis Allied Sci. 2015;57:233-34.
2. Felker RE, Tankin IL. Imaging of pulmonary sequestration. AJR Am J Roentgenol. 1990;154:241-9.
3. Nicolette LA, Kosloske AM, Bartow SA, Murphy S. Intralobar pulmonary sequestration: A clinical and
pathological spectrum. J Pediatr Surg. 1993;6:802-5.
4. Lin CH, Lin CT, Chen CY, Phen HC, Chen HC, Wong PY. Pulmonary sequestration. Chin Med J (Taipei).
1994;53:168-72.
5. Al-Bassam A, Al-Rabeeah A, Al-Nassar S, Al-Mobaireek K, Al-Rawaf A, Banjer H, et al. Congenital
cystic disease of the lung in infants and children (experience with 57 cases). Eur J Pediatr Surg.
1999;9:364‑8.
6. Bromley B, Parad R, Estroff JA, Benacerraf BR. Fetal lung masses: Prenatal course and outcome. J
Ultrasound Med. 1995;14:927-36.
7. Nicollette LA, Kosloske AM, Barlow SA, Murphy S. Intrapulmonary sequestration: A clinical and
pathological spectrum. J Pediatr Surg.1993;28:802-5.
8. Langstone C. New concepts in the pathology of congenital lungmal formations. Semin Pediatr Surg.
2003;12:17-37.
9. Carter R. Pulmonary sequestration (collective review). Ann Thoracic Surg. 1969;7:68-88.
10. Savic B, Birtel FJ, Tholen W, Funke HD, Knoche R. Lung sequestration: Report of seven cases and
review of 540 published cases. Thorax. 1979;34:96-101.
11. DeParedes CG, Pierce WS, Johnson DG. Pulmonary sequestration in infants and children: A 20 year
experience and review of the literature. J Pediatr Surg. 1970;5:136-47.
12. Stocker JT. Sequestration of the lung. Semin Diagn Pathol. 1986;3:106-21.
13. Laurin S, Aransons, Schuller H, Hennkson H. Spontaneous hemothorax from bronchopulmonary
sequestration, unusual angiographic and pathologic-anatomic finding. Paeditr Radiol. 1980;10:54.
14. Au VW, Chan JK, Chan FL. Pulmonary Sequestration diagnosed by contrast enhanced three-
dimensional MR anjiography. Br J Radiol. 1999;72:709-11.
15. Ettoree GC, Francioso G, Fracella MR, Strada A, Rizzo A. Pulmonary sequestration in the adult:
Diagnostic contribution of angiography. Radiol Med. 2000;99:41-5.
16. Hattori Y, Negi K, Takeda I, Iriyama T, Sugimura S, Watanabe K. Intrapulmonary sequestration with
arterial supply from the left internal thoracic artery: A case report. Ann Thorac Cardiovasc Surg.
2000;6:119-21.
17. Ikezoe J, Murayama S, Godwin JD, Done SL, Verschakelen JA. Bronchopulmonary sequestration CT
assessment. Radiology. 1990;176:375-9.
18. Kouchik K, Yoshida M, Matsunga T, Ohtsuka Y, Kuroda H, Hishiki T, et al. Intralobar bronchopulmonary
sequestration evaluated by contrast enhanced three dimensional MR angiography. Paediatr Radiol.
2000;30:774-5.
CASE 13
Herniation of Lung Following

Lung Abscess in a Child: A Case Report
CASE REPORT
RK, a thin-built male child aged 6 years was admitted with complaints of moderate to high
grade fever, cough with minimal expectoration and left side chest pain for 1 month and
the appearance of a swelling, on left side chest-back, 10 days prior to admission. His parents
had noticed that the swelling got bigger on coughing and crying. There was no history of
trauma, nor family history of tuberculosis.
On physical examination, the patient was of thin built, anemic, pulse rate 120 beats/min,
respiratory rate 22 breaths/min, and 101°F body temperature. Chest examination revealed
an ill-defined, smooth, soft swelling in the left inter-scapular area, 10 × 6 cm size, crepitant,
tender baloomng out on coughing and going back when reduced manually. Left inter- and
infrascapular areas showed decreased respiratory movement, resonant note on percussion
and decreased entry with a few crepitations on auscultation.
His hemoglobin was 8.5 g%, TLC 17,900/mm3, DLC p78L16E2M2 with normal blood sugar,
liver functions and urine analysis, Mantoux test showed an induration of 4 mm in transverse
diameter at 72 hours. Sputum for acid-fast bacilli was repeatedly negative. Staphylococcus
aureus grew on culture, sensitive to amoxicillin and gentamicin chest X-ray, PA view, revealed
a lung abscess in the left lower zone. Left lateral view clearly visualized the abscess with
herniation of lung posteriorly into the subcutaneous plane (Fig. 1). On fluoroscopy, the lung
tissue was protruding outside posteriorly. This protrusion increased on coughing and on
Valsalva maneuver. His computed tomography (CT) thorax showed lung abscess in left mid
and lower zones with irregular walls and a few septae and herniation of lung parenchyma
posteriorly and subcutaneously with compression of surrounding subcutaneous tissue
(Fig. 2).
The patient was managed with amoxicillin and gentamicin with supportive treatment
such as bed rest, analgesics, antipyretics, cough suppressants, and hematinics. The patient
responded within a week: fever came down, the blood counts became normal, and cough
disappeared. After 2 weeks, the superficial swelling was reduced in size and radiologically
the abscess cavity was much smaller. The patient was discharged after 1 month but got lost to
follow-up.
Herniation of Lung Following Lung Abscess in a Child: A Case Report 45
FIG. 1: Chest X-ray left lateral view showing lung abscess

with herniation of lung posteriorly.
FIG. 2: Computed tomography (CT) thorax showing

lung abscess with herniation of lung posteriorly.
DISCUSSION
A majority of lung hernias (82%) are acquired; as many as 52% of them are secondary
to penetrating or nonpenetrating trauma to chest and just 1% are the pathological type.
About 65% of the lung hernias are located in the thoracic region and 35% in the cervical
region. The pathological variety of the reported lung hernias were mainly following tuber
culosis. The present case is of special interest as it developed following lung abscess. The
child was thin-built and had weak muscle mass in the chest. Probably, the inflammatory
process of lung abscess extended to the inter costal muscles leading to further weakness
precipitating lung hernia due to persistent coughing.
The diagnosis of lung hernia is usually made by the clinical presentation of a soft
swelling which becomes prominent on coughing, sneezing, and straining and can be
reduced manually. Roentgenograms and fluoroscopy during Valsalva maneuver show a
radiolucent area protruding outside the confines of thoracic cage. CT scan of thorax is a
useful diagnostic procedure.
Usually, conservative treatment is sufficient. Surgical repair is indicated only when
there is constant pain, recurrent infection, respiratory distress, progressive increase
in size of hernia, cosmetic concern or when there are chances of excessive increase
in intrathoracic pressure and impending lung rupture due to heavy physical activity.
Surgical repair of the defect is done by means of peritoneal flaps pulled from the
adjacent ribs. Marlex mesh or teflon bands have also been used for repair.
FURTHER READING
1. Prasad R, Kant S. Herniation of lung following lung abscess in a child: A case report. Ind J Tub.
2000;47:47.
2. Adkins PC. The chest wall. In: Blades B (Ed). Surgical Diseases of Chest. St. Louis: CV Mosby Company;
1961. p. 87.
3. Bidstrup P, Noidentoft M, Peterson B. Hernia of the lung brief survey and report of two cases. Acta
Radial. 1966;4:490.
4. Hiscol B, Digman J. Types and incidence of lung hernias. J Thor Surg. 1955;30:335.
5. Donate AT, Hipona FA, Navani S. Spontaneous lung hernia. Chest. 1973;64:254.
6. Prasad R, Mukerji PK, Gupta H. Herniation of the lung. Indian J Chest Dis Allied Sci. 1990;32:129.
7. Bagga AS, Kakodkar U, Lawande D, Chatterji R. Herniation of the lung: A case report. Ind J Tub.
1995;42:47.
8. Ghanchi FD, Patel KR. Herniation of lung. Ind J Chest Dis Allied Sci. 1996;38:49.
9. Sadler MA, Shapiro RS, Wagieich J, Halton K, Hecht A. CT diagnosis of acquired intercostal lung
herniation. Clin Imaging. 1997;21:104.
10. Goodmann HL. Herniation of lung. J Thorac Surg. 1933;2:368.
11. Giunwald RP, Knox WG. Chest wall lung hernia method of repair using marlex mesh. Am J
Surg.1964;108:730.
12. Munnell ER. Herniation of lung. Ann Thorac Surg. 1968;5:204.
CASE 14
Hemorrhagic Pleural Effusion

Secondary to Sarcoidosis
CASE REPORT
A 53-year-old female bidi smoker (pack year: 14) was admitted to our department with
complaints of loss of appetite and left-sided chest pain for 5 months. On examination,
the patient was alert and well oriented. She was not in obvious distress. Her vital signs
were stable. The only significant finding on examination of the chest was reduced breath
sound at the left lower axillary area with bi basilar crept in the infrascapular area. Her chest
radiograph revealed bilateral hilar prominence with left-sided pleural effusion (Fig. 1). A
left thoracentesis revealed thin, grossly hemorrhagic pleural fluid that did not clot and did
not clear on sequential samples and had no obvious odor. Thus, considering the age of
the patient (53 years) and her smoking habits and hemorrhagic pleural fluid, a malignant
process was considered in the differential diagnosis. The pleural fluid was exudates with
cytology showed 2,200 cells/mm3 with 88% lymphocytes and 12% neutrophils, red blood
cell (RBC) count of 2,200,000/mm3, and pleural fluid hematocrit was 26%. Biochemical
analysis revealed sugar 44 mg/dL, proteins 5.4 g/dL, and adenosine deaminase 32 U/L
(normal limit being <40 U/L). Pleural fluid cultures were negative for both pyogens and
Mycobacterium tuberculosis. Pleural fluid was negative for malignant cells on five consecutive
FIG. 1: Chest X-ray revealed bilateral hilar

prominence with left-sided pleural effusion.
occasions. Her pleural biopsy was performed by Abraham’s needle, which was negative.
Her purified protein derivative (PPD) skin test was negative. A computerized tomographic
scan of her chest revealed bilateral hilar lymphadenopathy with parenchymal opacity
and left-sided pleural effusion (Figs. 2A and B). Further, ultrasonography of the neck and
abdomen, mammography, and gynecological evaluation were performed to rule out
any evidence of a malignant condition, but all were normal except for a deep cervical
lymphadenopathy. An excisional biopsy of the upper deep cervical lymph node revealed
a noncaseating granuloma. Serum angiotensin-converting enzyme (ACE) was 168 IU/L.
Fiberoptic bronchoscopy revealed no endobronchial abnormality. Bronchial brushing and
bronchoalveolar lavage revealed predominance of lymphocytes and no malignant cells or
acid-fast bacilli (AFB). A repeat thoracoscopic-guided pleural biopsy revealed a noncaseating
granuloma. Thus, a diagnosis of sarcoidosis presenting as hemorrhagic pleural effusion
with bilateral hilar lymphadenopathy and deep cervical lymphadenopathy was made. She
was put on prednisolone 40 mg/day followed by in-tapered dosages. Her appetite was
improved and chest pain subsided gradually and without recurrence of symptoms of pleurisy
(Figs. 3A and B).
A B
FIGS. 2A AND B: Computed tomography revealed bilateral hilar lymphadenopathy with
parenchymal opacity and left-sided pleural effusion.
A B
FIGS. 3A AND B: Follow-up chest X-ray revealed resolution of pleural effusion as well as
parenchymal shadows.
Hemorrhagic Pleural Effusion Secondary to Sarcoidosis 49
DISCUSSION
In sarcoidosis, the involvement of the pleura may present as pleural effusion,
pneumothorax, pleural thickening, hydropneumothorax, trapped lung, and chylothorax.
Pleural sarcoidosis as pleural effusion is still a rare manifestation of sarcoidosis in all
published series and hemorrhagic effusion secondary to sarcoidosis is a very uncommon
clinical presentation. Apart from the present case, to the best of our knowledge, only
three cases of hemorrhagic pleural effusion secondary to sarcoidosis were published in
the literature. The most common causes of hemorrhagic pleural effusion include tumor
(both primary Pleuroparenchymal as well as metastasis), trauma (both iatrogenic and
accidental), and tuberculosis. The causes of hemorrhagic pleural effusion are divided into
the following eight groups:
1. Pleuro pulmonary infections (M. tuberculosis, bacterial pneumonia, e.g., anthrax,
Brucella, Klebsiella pneumonia, and viral, e.g., dengue hemorrhagic fever).
2. Pleuropulmonary malignancy [bronchogenic carcinoma, leukemia (acute and
chronic), pleural tumor (myofibroblastoma, pleural hemangioma), lymphoma, e.g.,
Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, angiosarcoma of the chest wall,
tumors of the ribs, e.g., osteosarcoma, metastasis to pleura and mediastinal nodes,
e.g., breast carcinoma, choriocarcinoma, malignant melanoma, hypernephroma
retroperitoneal chondrosarcoma, and bony tumor, e.g., ewing sarcoma.
3. Connective tissue diseases, e.g., systemic lupus erythematosus (SLE).
4. Asbestos associated, both in benign as well as in malignant mesothelioma.
5. Abdominal diseases [(acute pancreatitis, chronic pancreatitis), ovarian tumors:
Benign (Meig’s syndrome as well as malignant tumor, mediastinal myelolipoma,
uremic pleuritis, and rarely, diaphragmatic hernia].
6. Cardiovascular (aneurysm rupture, pulmonary infarction, pulmonary thromboembo
lism, postcoronary artery bypass grafting).
7. Bleeding disorder (overdose of anticoagulant, thrombotic microangiopathies,
thalassemia intermediate, liver cirrhosis.
8. Miscellaneous causes (superior venal caval syndrome, Kawasaki disease, chronic renal
failure, and intralobar sequestration).
Sarcoidosis-related pleural effusions occur slightly more commonly in the right lung
(45%) than in the left lung (33%), but bilateral and massive effusions have been noted. The
reason for the right-sided predominance is unclear and is not related to organ involvement
(while in the present case pleural effusion was on the left side). The mechanism of pleural
fluid formation in patients with sarcoidosis is presumably similar to that of other infiltrative
diseases. Involvement of the pleura may lead to increased capillary permeability.
Superior vena cava obstruction, endobronchial sarcoidosis leading to bronchial stenosis
and lobar atelectasis, trapped lung and lymphatic disruption with the development of
chylothorax have been reported as a cause of sarcoid-related pleural fluid. The reasons
for the development of the bloody pleurisy might have been derived from vessels that
were involved and compressed by the granulomas. Sarcoid-related pleural effusion has
been described as both exudates and transudates (pleural effusion in the present case
was exudative in nature). The appearance of pleural fluid among most published case
series was serious, followed by serosanguinous and less commonly yellow whereas the
hemorrhagic effusion was observed very rarely. A hemorrhagic pleural effusion is a pleural
effusion that looks like it is blood. The RBC count is usually >100,000/mm3 (while in the
present case it was 220,000/mm3). The typical pleural fluid aspiration finding in sarcoid
pleural effusion reveals a paucicellular, lymphocyte predominant, with a pleural/serum
protein ratio more consistently in the exudative range (as seen in the present case). Sarcoid
pleural effusions may resolve spontaneously or require corticosteroids for resolution. The
time of spontaneous resolution is variable, but most resolve in 1–3 months. In the present
case, corticosteroid therapy resulted in marked improvement of the pleurisy as well as the
parenchymal infiltrates.
FURTHER READING
1. Kumar S, Verma SK, Singh R, Prasad R. Hemorrhagic pleural effusion secondary to sarcoidosis: A brief
review. Ann Thorac Med. 2009;4:27-31.
2. Soskel NT, Sharma OP. Pleural involvement in sarcoidosis. Curr Opin Pulm Med. 2000;6:455-68.
3. Aberg H, Bah M, Waters AW. Sarcoidosis complicated by chylothorax. Minn Med. 1966;49:1065-70.
4. Gordonson J, Trachtenberg S, Sargent EN. Superior vena cava obstruction due to sarcoidosis. Chest.
1973;63:292-3.
5. De Vuyst, P, DeTroyer A, Vernault JC. Bloody pleural effusion in a patient with sarcoidosis. Chest.
1979;76:607-9.
6. Takahashi N, Enomoto T, Hagiwara T, Horie T, Amagi S, Tanaka N, et al. A case of sarcoidosis presenting
with Heerfordt's syndrome, associated with hepatosplenomegaly, pleural effusion, and ascites.
Nihon Kyobu Shikkan Gakkai Zasshi. 1992;30:684-8.
7. Watarai M, Yazawa M, Yamanda K, Yamamoto H, Yamazaki Y. Pulmonary sarcoidosis with associated
bloody pleurisy. Intern Med. 2002;41:1021-3.
8. Chusid EL, Siltzbach LE. Sarcoidosis of the pleura. Ann InternMed. 1974;81:190-4.
9. Wilen SB, Rabinowitz JG, Ulreich S, Lyons HA. Pleural involvement is sarcoidosis. Am J Med.
1974;57:200-9.
10. Sharma OP, Gordonoson J. Pleural effusion in sarcoidosis: A report of six cases. Thorax. 1975;30:
95-101.
11. Selroos O. Exudative pleurisy and sarcoidosis. Br J Dis Chest. 1966;60:191-6.
12. Nicholls AJ, Friend JA, Legge JS. Sarcoid pleural effusion: Three cases and review of the literature.
Thorax. 1980;35:277-81.
13. Salazar A, Mana J, Corbella X, Vidaller A. Sarcoid pleural effusion: A report of two cases. Sarcoidosis.
1994;11:135-7.
14. Huggins JT, Doelken P, Sahn SA, King L, Judson MA. Pleural effusion in a series of 181 outpatients
with sarcoidosis. Chest. 2006;129:1599-604.
15. Beekman JF, Zimmet SM, Chun BK, Miranda AA, Katz S. Spectrum of pleural involvement in
sarcoidosis. Arch Intern Med. 1976;136:323-30.
16. Berte SJ, Pfotenhauer MA. Massive pleural effusion in sarcoidosis. Am Rev Respir Dis. 1962;86:261-4.
17. Kovant PJ, Donohoe RF. Sarcoidosis involving the pleura. Ann Intern Med. 1965;62:120-4.
18. Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: The diagnostic separation of
transudates and exudates. Ann Intern Med. 1972;77:507-13.
19. Durand DV, Dellinger A, Guerin C, Guerin JC, Levrat R. Pleural sarcoidosis: One case presenting with
an eosinophilic effusion. Thorax. 1984;39:468-9
CASE 15
Exfoliative Dermatitis Secondary to

Ethambutol and Pyrazinamide
CASE REPORT
An 18-year-old female was admitted to our department as a proven case of bilateral
pulmonary tuberculosis (TB) with complaints of severe generalized itching, erythema, and
scaling from last 10 days. It was also associated with facial and pedal edema. She was on
antitubercular therapy (rifampicin, isoniazid, ethambutol, and pyrazinamide) from last
2 months for pulmonary TB by some local practitioner. The initial one and half months of
the therapy was uneventful till 10 days back when she developed generalized itching and
erythema all over the body. Despite the erythema and pruritus, she continued her anti
tubercular chemotherapy which led to the progression of lesions to scaling and edematous
swelling of face and feet. Clinical examination revealed generalized erythema and edema
with scaling eruptions involving also the palms and soles (Figs. 1A and B). Skiagram
chest was suggestive of pulmonary TB. Laboratory investigations were not suggestive
of any systemic illness. Hb 10.4 g/dL, TLC 5,200/mm3, DLC P62L38, blood urea 26 mg/dL,
serum creatinine 0.4 mg/dL, and serum bilirubin 0.5 mg/dL. Sputum for acid-fast bacilli on
three consecutive days was negative. Bleeding profile was normal which was done to rule
out any antitubercular drugs-induced thrombocytopenic purpura. Skin biopsy showed
A B
FIG. 1A AND B: Revealed exfoliative dermatitis. (For color version, see Plate 1)
hyperkeratotic changes suggestive of exfoliative dermatitis. So, a provisional diagnosis of

antitubercular drugs-induced exfoliative dermatitis was made. Immediately antitubercular
drugs were stopped and she was started with steroids and antihistamines. After 7 days
of treatment, the symptoms subsided and there was regression of skin eruptions. Later
on, antitubercular drugs were restarted one by one in challenging dosages as per WHO
guidelines. She tolerated rifampicin and isoniazid very well without any recurrence of the
symptoms. When ethambutol was given on the 7th day of the challenge test, she developed
generalized pruritus, erythema, and facial puffiness within 6 hours. It proved ethambutol
to be the culprit which was never tested again. Similarly, she developed scaling eruptions
and edema with challenging dose of pyrazinamide. So, our diagnosis of ethambutol- and
pyrazinamide-induced exfoliative dermatitis was proved and patient was asymptomatic in
next 15 days on symptomatic treatment (Figs. 2A to C). She was discharged on rifampicin
and isoniazid and after completing the adequate 1 year of therapy, she is clinically and
radiologically normal.
A B
FIGS. 2A TO C: Image showing exfoliative

C dermatitis. (For color version, see Plate 2)
Exfoliative Dermatitis Secondary to Ethambutol and Pyrazinamide 53
DISCUSSION
Modern antitubercular chemotherapy regimens have been in use for over 30 years.
However, the frequency of severe complications is not known, probably due to lack of
notification and under-reporting. It is also difficult to measure the efficacy or toxicity
of a particular drug, since antitubercular drugs are usually administered in combination
regimens of several drugs. The main adverse effects of antitubercular drugs usually
occur during the first 2–3 weeks of treatment. Exfoliative dermatitis or erythroderma is
an erythematous, scaly dermatitis involving most, if not all of the skin. This generalized
scaling eruption of the skin is drug induced, idiopathic or secondary to underlying
cutaneous or systemic disease. Approximately 10% of the cases are the result of drug
reactions. Skin rashes and eruptions are very rare side effects of ethambutol and
pyrazinamide. Ethambutol-induced exfoliative dermatitis has been reported in a
patient of tubercular pleural effusion. Pyrazinamide-induced maculopapular rash has
been reported twice, one in a patient of skin TB and other in pulmonary TB. But even
after thorough search of the literature, no such case has been found in which a single
patient is having exfoliative dermatitis due to both ethambutol and pyrazinamide.
The individual should be questioned about exposure to other medications or skin
preparations, environmental contact, etc., that may be responsible. There should be
a careful examination to detect evidence of unrelated skin diseases (scabies, contact
dermatitis, childhood exanthem, acne, etc.). Unless an explanation is found for skin
reaction unrelated to anti-TB medications, all anti-TB medications should be discontinued
promptly and the individual examined each week until the skin reaction disappears. If
the rash is severe or if there is evidence of mucosal involvement, hypotension or severe
illness, corticosteroid treatment should be instituted. Cases of severe dermatologic
reactions, such as exfoliative dermatitis, and other cases of dermatitis associated with
severe systemic reactions should be referred for hospital admission for treatment, and
for establishing a new anti-TB regimen or for re-challenge according to WHO guidelines
under daily surveillance as an inpatient. In our patient the anti-TB drugs were stopped
immediately and steroids with antihistamines were given. It is appropriate to rechallenge
after the skin reaction clears or subsides. It may not be possible to identify the specific
causative agent by the characteristics of the skin reaction. Thus, it is appropriate to
restart the most important member or members of the regimen (isoniazid or rifampin)
immediately, before trying pyrazinamide and/or ethambutol. Treatment should be
continued with the original regimen modified by the deletion of the causative agent.
A longer period of treatment may be required if the offending agent was isoniazid or
rifampin, or pyrazinamide during the initial 2 months of treatment.
FURTHER READING
1. Garg R, Verma SK, Mahajan V, Prasad R. Exfoliative dermatitis secondary to ethambutol and
pyrazinamide. Internet J Pulm Med. 2007;9:1.
2. Bolognia JL, Braverman IM. Skin manifestations of internal disease. In: Braunwald E, Fauci AS, Kasper
DL, Hauser SL, Longo DL, Jameson JL (Eds). Harrison's Principles of Internal Medicine, 16th edition.
New York: McGraw-Hill; 2004. pp. 315-31.
3. Miranda MFM, Rege VL, Coelho VE. Exfoliative dermatitis due to ethambutol. Ind J Tub. 1996;43:103.
4. Perdu D, Lavaud F, Prevost A. Erythema multiforme due to pyrazinamide. Allergy. 1996;51:340-42.
5. Kishore P, Palaian S, Prabhu S, Prabhu M, Mishra P. Drug-induced maculopapular rash with the
commonly used first line antitubercular drug, Pyrazinamide. Int J Dermatol. 2007;5:42-4.
6. Pio A, Chaulet P. Tuberculosis handbook, 2nd edition. Geneva: World Health Organization; 2003.
CASE 16
Bilateral Chylothorax in a Young Female

Secondary to Tuberculosis
CASE REPORT
A 15-year-old female was admitted to our department with the complaints of breathlessness,
and off and on fever for 1 month. She came from a nonendemic zone of filariasis in Uttar
Pradesh. The resting pulse rate was 92 beats/min and blood pressure was 112/74 mm Hg.
There was no history of contact with a tuberculosis patient. Her physical examination revealed
hard, mobile lymph nodes of size 2 × 2 cm approximately, present bilaterally in the cervical
region, and pallor. On chest examination, there was stony dull note localized to the bilateral
infrascapular, lower axilla. Rest of the systems were within normal limits.
Her blood examination revealed anemia and hypoalbuminemia but normal total and
differential leukocyte counts. Her chest X-ray revealed bilateral pleural effusion (Fig. 1). The
pleural fluid was aspirated (about 2.0 litre from left side and 1.2 litre from right side) on both
FIG. 1: Chest X-ray revealed bilateral pleural effusion.

Bilateral Chylothorax in a Young Female Secondary to Tuberculosis 55
sides that revealed a milky white fluid. Then we thought about the chylothorax. Clearing of
the pleural fluid by adding ethyl-ether into it leads to the exclusion of pseudochylothorax.
The pleural fluid of both sides was sent for examination that revealed, for the right side,
protein 4.2 g%, sugar 44 mg%, and total leukocyte count 3,400 cells/mm3; differential
leukocyte count was neutrophils 20, lymphocytes 80, pleural fluid triglyceride 535 mg%,
and pleural fluid cholesterol 24.8 mg%; pleural fluid of the left side revealed protein 4.0 g%,
sugar 40 mg%, and total leukocyte count 3,280 cells/mm3; differential leukocyte count was
neutrophils 34, lymphocytes 66, pleural fluid triglyceride 188.0 mg%, and pleural fluid
cholesterol 24.0 mg% (Table 1). Serum triglyceride and serum cholesterol was 72.7 mg%
and 71.9 mg%, respectively. The Ziehl–Neelsen stain of the pleural fluid was negative but
Mycobacterium tuberculosis was isolated on the Lowenstein–Jensen culture. The pleural
fluid culture for pyogenic organisms was sterile in nature on both sides. PPD showed no
indurations. Her biopsy of the cervical lymph node revealed caseating granuloma, and
the Bactec culture for M. tuberculosis was also positive in the cervical lymph node biopsy
specimen. Her abdomen serum triglyceride 72.7 mg%, serum cholesterol 71.9 mg%,
Ziehl–Neelsen stain of the pleural fluid was negative but M. tuberculosis was isolated on
the Lowenstein–Jensen culture. Biopsy of the cervical lymph node revealed caseating
granuloma, and the Bactec culture for M. tuberculosis was also positive. Ultrasound also
revealed multiple retroperitoneal and para-aortic lymphadenopathy. Thus, a diagnosis
of bilateral chylothorax secondary to tuberculosis with cervical lymphadenopathy was
established.
To confirm the exact site of the thoracic duct tear, lymphangiography was planned but her
parents refuse for further investigations.
She was put on standard 6-month antitubercular treatment: A combination of isoniazid,
rifampicin, pyrazinamide, and ethambutol was started for 2 months followed by isoniazid and
rifampicin for a further 4 months. Following this, she showed clinical as well as radiological
improvement and chylothorax resolved after 2 months of treatment (Fig. 2), and on regular
follow-up she had no further symptoms.
TABLE 1: Characteristics of the pleural fluid on both sides of the cavity.

Pleural fluid Right pleural cavity Left pleural cavity
Protein 4.2 g% 4.0 g%
Sugar 44 mg% 40 mg%
TLC 3,400 cells/mm3 3,280 cells/mm3
DLC P20, L80 P34, L66
Pleural fluid 535 mg% 188 mg%
Pleural fluid cholesterol 24.8 mg% 24 mg%
Pleural fluid culture Sterile Sterile
(DLC: differential leukocyte count; TLC: total leukocyte count)
FIG. 2: Revealed radiological clearing of the

bilateral chylothorax after 2 months of antitubercular
treatment.
DISCUSSION
Chylothorax was recognized in the 17th century but it is still a rare enough entity to be
viewed by most physicians as a clinical curiosity. In a historical review by Johsman,
Bartolet is credited with the initial description of chylothorax in 1633, and Quincke
reported the first case in 1875. Sassion et al. divided the causes of chylothorax after
2 months of antitubercular treatment into four major categories: Trauma, tumor,
idiopathic, and miscellaneous. Trauma is the leading cause of chylothorax. This trauma is
usually a cardiovascular, pulmonary, or esophageal surgical procedure. Another leading
cause of chylothorax is malignancy. The most common malignancy to cause chylothorax
is a lymphoma, followed by bronchogenic carcinoma, and rarely leukemia. Very few cases
of chylothorax secondary to acute lymphoblastic leukemia (ALL) are reported. The third
category of chylothorax is idiopathic including most cases of congenital chylothorax.
Most cases of idiopathic chylothorax in adults are probably due to minor trauma such
as coughing or hiccupping after the ingestion of fatty meals. The fourth category of
chylothorax is the miscellaneous category and causes are thrombosis of superior vena cava
or subclavian vein, cirrhosis, lymphangioleiomyomatosis Gorham’s syndrome, Kaposi
sarcoma, Castleman disease, filirasis and familian lymphedema, sarcoidosis, radiation-
induced mediastinal fibrosis, and hypothyroidism.
Tuberculosis is described as a possible cause of chylous effusion, but only a single
case, described by Brandt in 1917, appears to have been recorded. Cakir et al. reported
the concurrence of chlothorax and endobronchial tuberculosis in a 4-month-old boy.
Grobbelaar et al. reported one case of bilateral and other case of unilateral chylous
effusions associated with extensive mediastinal and hilar lymphadenopathy secondary
to pulmonary tuberculosis, in children. Deniel et al. reported spontaneous bilateral
chylothorax secondary to disseminated tuberculosis complicated by massive pulmonary
embolism.
Tan et al. reported a patient with persistent chylothorax and generalized lymphade
nopathy who was subsequently diagnosed to have concurrent tuberculosis and malignant
lymphoma. Very few cases of bilateral chylothorax have being reported in the literature.
Chylothorax has no predilection for age and sex. Symptoms of chylothorax mostly depend
upon the amount of fluid in the pleural cavity.
The exact pathogenesis for the development of chylothorax secondary to tuberculosis
remains controversial. Fraser et al. and Yunis et al. reported that the enlarged lumber
and iliac group of lymph nodes produced obstruction of the cisterna chyli and thoracic
duct, as a result of which there was dilatation of the lumbar channels; this was followed
by the opening up of collateral anastomoses, many lymphaticovenous anastomosis
existing between the thoracic duct system and the azygos, intercostal, and lumbar veins.
The increased pressure in the system resulted in the transudation of chyle into the pleural
space. Grobbelaar et al. reported that the possible explanation for the development
of a chylothorax in our patients is the obstruction of the thoracic duct by tuberculous
lymphadenopathy with subsequent increase in pressure in the surrounding lymphatic
system and leaking of chyle into the pleural space.
Best way to establish the diagnosis of chylothorax is to determine the concentration
of triglycerides in the pleural fluid. The triglyceride concentration >110 mg/dL (in our
case it was 289.3 mg/dL), a ratio of pleural fluid to serum triglycerides of >1.0 (in our
case it was 3.77), and a ratio of pleural fluid to serum cholesterol of >1.0 (in our case
it was 0.344) usually confirm chylothorax. Chylothorax will be excluded if the pleural
fluid triglyceride concentration is >50 mg/dL. However, in the case of levels from
50 to 110 mg/dL, a lipoprotein analysis of the pleural fluid should be performed, and
the demonstration of chylomicrons in the fluid confirms the diagnosis of chylothorax
(Table 2).
Primary treatment in the case of chylothorax should be directed toward the
correction of malnutrition and compromised immunologic status which is due to
repeated pleural fluid aspirations of chyle with its high levels of protein, fat, electrolytes,
and lymphocytes. The defect in the thoracic duct often closes spontaneously in the case
of traumatic injury. In the case of severe dyspnea, the placement of the pleuroperitoneal
shunt or chest tube drainage is mandatory. If the chylothorax persists for >4 weeks,
consideration should be given to surgical exploration with ligation of the thoracic duct.
In our case, diagnosis of chylothorax was established on typical pleural fluid color,
high pleural fluid triglyceride level, high ratio of pleural fluid to serum triglyceride, and
low ratio of pleural fluid to serum cholesterol. She responded well to antituberculous
treatment.
TABLE 2: Differential points of chylothorax, pseudochylothorax, and empyema, and parental nutrition entering the pleural space via the
subclavian line.
Parameter Chylothorax Pseudochylothorax Empyema thoracis Parental nutrition entering
the pleural space via the
subclavian line
Definition Presence of chyle in the pleural Caused by high-lipid levels Pleural effusion due to Presence of high triglyceride
cavity; chyle contain chylomicrons, (cholesterol/lecithin–globulin bacterial pneumonia levels in the pleural cavity
triglycerides, and lymphocytes* complexes) in the pleural fluid
Color Milky white Milky white Milky white Milky white
Odor Odorless Odorless Foul smelling Odorless

Clinical onset Acute Chronic Acute Acute
Most common cause Bacterial pneumonia
On centrifugation Remain opalescent Remain opalescent Supernatant part clear Remain opalescent
Diagnostic criteria
• PF TG >110 mg/dL
• PF Cho/serum Cho ratio >110 mg/dL >1.0 Usually negative, even
• Pleural fluid culture <1.0 Usually negative in the case of frank
• PCR of the pleural fluid Usually negative pus in cavity
• Addition of 1–2 mL of ethyl Usually negative Usually negative
ether to the pleural fluid Remain opalescent Most specific to Remain opalescent
Ingestion of a fatty meal with Clears as cholesterol dissolved detect DNA of various The presence of
lipophilic dye (drug and cosmetic bacterial populations chylomicrons in the
green no. 6, a coal tar dye), lipoprotein electrophoresis
followed by thoracocentesis profile could be traced
30–60 min later and if color back to the lipofundin
changed to green fluid, then it also component of parental
confirms chylothorax nutrition
(PF TG: pleural fluid triglyceride; PF Cho/serum Cho ratio: pleural fluid cholesterol/serum cholesterol ratio)
*In the case of levels 50–110 mg/dL, a demonstration of chylomicrons in lipoprotein analysis confirms chylothorax. Levels below 50 mg/dL virtually exclude chylothorax.
FURTHER READING
1. Kant S, Verma SK, Anand SC, Prasad R, Verma RK. Development of bilateral chylothorax in a younger
female secondary to tuberculosis. Lung India. 2011;28:56-9.
2. Anton PA, Rubio J, Casan P, Franquet T. Chylothorax due to Mycobacterium tuberculosis. Thorax.
1995;50:1019.
3. Sassoon CS, Light RW. Chylothorax and pseudochylothorax. Clin Chest Med. 1985;6:163-71.
4. Valentine VG, Raffin TA. The management of chylothorax. Chest. 1992;102:586-91.
5. Menon BS, Juraida E, Mahfuzah M, Hishamshah I. Bilateral chylothorax in paediatric acute lympho
blastic leukaemia. Br J Haematol. 2006;132:253.
6. Kushwaha RAS, Prasad R, Verma SK, Mehra S. Bilateral chylothorax secondary to acute lymphoblastic
leukaemia(ALL). Indian J Med Paediatr Oncol. 2007;28:42-3.
7. Kushwaha RAS , Verma SK, Mahajan V, Prasad R. Bilateral chylothorax in a child after mild trauma-a
case report. Indian J Chest Dis Allied Sci. 2008;50:355-7.
8. Brandt M. Ein Beitrag zur Kasuistik der Ductus thoracicus-uberkulose und des Chylothorax. Inaug.
Diss. Heidelberg: Universitats-Buchdruckerei von J Horning; 1917.
9. Cakir E, Gocmen B, Uyan ZS, Oktem S, Kiyan G, Karakoc F, et al. An unusual case of chylothorax
complicating childhood tuberculosis. Pediatr Pulmonol. 2008;43:611-4.
10. Grobbelaar M, Andronikou S, Goussard P, Theron S, Mapukata A, George R. Chylothorax as a
complication of pulmonary tuberculosis in children. Pediatr Radiol. 2008;38:224-6.
11. Browse NL, Allen DR, Wilson NM. Management of chylothorax. Br J Surg. 1997;84:1711-6.
CASE 17
Concomitant Pulmonary Tuberculosis and

Borderline Leprosy with Type-II Lepra
Reaction in Single Patient
CASE REPORT
A 34-year-old, nonsmoker male was admitted, in September 2007, to the Department of
Pulmonary Medicine, as a follow through case of borderline lepromatous leprosy. He had
complaints of breathlessness, loss of appetite with cough with expectoration for last two
and half months and skin lesions over face, forearm, and dorsum of hands with exfoliative
skin lesions over forearm for last 2 months and recurrent hemoptysis for last 25 days. He was
on medication, tablet dapsone 100 mg daily, tablet clofazimine 500 mg daily and capsule
rifampicin 600 mg, once a month, for the last 9 months. He had also taken oral prednisolone
for >3 months duration about 6 months back for neurological complications. There was no
past history of tuberculosis as per information provided by the patient. Clinical examination
revealed multiple hypopigmented skin lesions varying in size from 2 to 4 cm over the
trunk with thickened left ulnar nerve and nodular lesions over face, forearm and dorsum
of hands (Figs. 1A and B) and exfoliative skin lesions over forearm (Fig. 1C). His resting
pulse rate was 102 beats/min and blood pressure was 112/74 mm Hg and his respiratory
rate was 26 breaths/min. His general examination revealed no significant abnormality. His
respiratory system examination revealed coarse crepts localized to left infraclavicular and
axillary areas. Initially he was put on symptomatic treatment for hemoptysis. Subsequently,
his chest X-ray showed a large cavity with a mass filled opacity confined to left upper zone
and fibrotic changes in right upper zone (Fig. 2). Computed tomography of thorax revealed
fibro-consolidation with cavitation in the anterior segment of left upper lobe, fibrotic nodule
in both anterior and posterior segments of right the upper lobe (Fig. 3). Thus, a possibility
of aspergilloma with other possibilities was raised. The clinical examination of the rest of
the system revealed no abnormality. His blood biochemistry revealed total leukocyte count:
10,200/mm3, differential leukocyte count: P 66%, L 34%. His purified protein derivative (PPD)
was 2,219 mm induration. His sputum for acid fast bacilli (AFB) on three consecutive days
was positive. Thus, a diagnosis of pulmonary tuberculosis was confirmed. For leprosy, patient
consulted the skin department, was diagnosed with borderline lepromatous leprosy (on the
basis of slit skin smear) with type-II lepra reaction (biopsy of nodular lesion revealed diffuse
sheets of foamy macrophages centered around adnexal structures with heavy infiltration of
lepra bacilli suggestive of erythema nodosum leprosum). He was advised to stop dapsone and
Concomitant Pulmonary Tuberculosis and Borderline Leprosy... 61
A B
FIGS. 1A TO C: (A and B) Revealed skin lesions

over face, forearm, and dorsum of hands due to
type-II lepra reaction. (C) Revealed exfoliative
skin lesions over forearm due to type-II lepra
C reaction. (For color version, see Plate 2)
FIG. 2: Chest X-ray reveals a large cavity with a mass

filled opacity confined to left upper zone and fibrotic
changes in right upper zone.
started oral prednisolone, thalidomide, and clofazimine. Thus, a final diagnosis of borderline
leprosy with type-II lepra reaction with concomitant pulmonary tuberculosis was made. The
patient was referred to DOTS clinic and started on Category I treatment. The oral prednisolone
was subsequently tapered and stopped while the other antileprotic drugs continued. The
patient’s general condition improved and was on regular follow-up.
FIG. 3: Computed tomography of thorax revealed

fibro-consolidation with cavitation in anterior
segment of left upper lobe with fibrotic nodule in
anterior and posterior segment of right upper lobe.
DISCUSSION
Leprosy and tuberculosis continue to be prevalent in our country. Prevalence of tuber
culosis is estimated to be 4.0 and 16.0/1,000 for bacteriologically and radiologically
active tuberculosis cases respectively, while the national prevalence rate of leprosy in
India is 0.88/10,000. The great attention about leprosy and tuberculosis coinfection was
carried out by Chaussinand in 1948, and concluded that the prevalence of leprosy was
inversely related with the prevalence of tuberculosis. In some leprosy communities,
however, tuberculosis appears to be quite common. This may be the result of a small
group of people unable to defend against either organism. Leprosy has failed to
return in areas where tuberculosis has been controlled, but this may be because
other conditions have changed (e.g., because of the introduction of Bacilli Calmette–
Guérin). The principal means of transmission of both leprosy and tuberculosis is
by aerosol spread. The incubation period in leprosy varies from 6 months to 40 years
or longer, while in case of tuberculosis it is only 4 weeks. Review of literature suggest
that the occurrence of leprosy and tuberculosis coinfection first time reported by
Concomitant Pulmonary Tuberculosis and Borderline Leprosy... 63
Relvich AL et al. in 1954 and strongly argued that association of tuberculoid form of
leprosy with tuberculosis was uncommon. Gajwani et al. in 1968 and Gupta et al. in
1971, reported the association of tuberculoid type of leprosy with tuberculosis. This
was further supported by Agnihotri MS et al. in 1974, who documented three cases
of tuberculoid leprosy with tuberculosis and Nigam P et al. (1979), who documented
two cases of tuberculoid leprosy in association with tuberculosis. On the other hand,
most of the cases of tuberculosis were associated with lepromatous leprosy followed
by borderline lepromatous leprosy, as observed in present case also. The duration of
gap between the development of leprosy and tuberculosis varied between two months
to 10–15 years, the study with largest data showed gap duration of about 10–15 years,
where duration of tuberculosis in most of the cases was within 6 months (while in
present case it was 11 months). Only two cases of tuberculosis were found to occur
earlier than leprosy whereas one study concluded that tuberculosis can occur during
full spectrum of leprosy. It is well known that tuberculosis infection can develop with
certain risk factors such as HIV infection, low socioeconomic status, silicosis, diabetes
mellitus, gastrectomy, renal failure, organ transplant; these have been incorporated in
the risk stratification in tuberculosis guideline (no such type of risk factor present in
present case). There are also other purporated risk factors such as smoking, rheumatic
disorders, and use of low dose immunosuppressive agents or glucocorticosteroids but
substantive epidemiological data about these risk factors of tuberculosis are scarce. In
case of leprosy, corticosteroids are used primarily in the treatment of type I (reversal)
reactions and type II reactions and silent neuropathy. Chandrashekhar et al. (2000)
reported development of pulmonary tuberculosis after corticosteroid intake in two cases
of leprosy. Agarwal et al. (2000), reported a case of leprosy and tuberculosis coinfection
in a patient of renal transplant recipient and who had taken prednisolone, azathioprine,
and cyclosporine for >9 years (while in the present case, he received corticosteroid for
>3 months). In leprosy, majority of the cases reported were pulmonary tuberculosis
while in two cases of extrapulmonary tuberculosis (tuberculosis of larynx and cutaneous
tuberculosis) were reported. Diagnosis of leprosy was established in majority by slit
skin smear but diagnosis by nasal smear and histopathological examination was also
reported (while in present case by slit skin smear and biopsy also). Most common
findings on chest radiographs were bilateral infiltrates (as in the present case). Sputum
smear for AFB was positive in majority of the cases with available data (as in present
case also). Available data among three cases of leprosy with tuberculosis had lepra
reaction including one of the author, in which one of them had type-II lepra reaction
(ENL) while one was type-I reversal reaction (while in present case it was type-II lepra
reaction). Management of tuberculosis in leprosy coinfection does not change; with the
same WHO treatment categorization, i.e., Cat I, Cat II or Cat III. The detailed features
of all the cases of tuberculosis and leprosy coinfection and their comparison with present
case are summarized in Tables 1 and 2.
TABLE 1: Comparative analysis of leprosy-tuberculosis coinfection reported by various authors.
Details Authors
Gupta MC Vinik LA Agnihotri MS Bhargava Nigam Ρ et al. (1979) Gatner Kumar Β et al. (1982)
(1971) (1971) et al. (1974) NC (1976) EM (1980)
No. of cases NA ΝΑ 3 ΝΑ 20 NA 9
Gap between development of ΝΑ ΝΑ ΝΑ ΝΑ 10–15 years duration of NA NA
leprosy and dev. of tuberculosis tuberculosis in most of them
was within 6 months
Types of leprosy Tuberculoid ΝΑ Tuberculoid ΝΑ 15 were of lepromatous. NA NA
leprosy leprosy 3 of dimorphous and 2 of

tuberculoid leprosy
Is tuberculosis developed first ΝΑ ΝΑ Only in one ΝΑ NO NA Tuberculosis was found
case to occur throughout
leprosy spectrum
Is leprosy developed first ΝΑ ΝΑ NA ΝΑ YES NA NA
Family history of tuberculosis ΝΑ ΝΑ NO ΝΑ NA NA NA
Any risk factors like use of ΝΑ ΝΑ NO ΝΑ NA NA NA
corticosteroids/diabetes mellitus/
smoking/HIV/others were present
TB: Pulmonary/extrapulmonary Pulmonary ΝΑ Pulmonary Pulmonary Pulmonary NA Radiological evidence
of tuberculosis found
Descriptions: Lesions of ΝΑ ΝΑ Bilateral ΝΑ Bilateral extensive pulmonary NA NA
tuberculosis on chest radiographs infiltrates lessons were seen in 14 cases
Sputum for AFB ΝΑ ΝΑ Positive in all ΝΑ Positive in 80% of cases NA NA
of cases
Diagnosis of leprosy ΝΑ ΝΑ NS ΝΑ NA NA NA
Lepra reaction ΝΑ ΝΑ NS ΝΑ NA NA NS
(NA: data not available; NS: not seen; TB: tuberculosis)
TABLE 2: Comparative analysis of leprosy-tuberculosis coinfection reported by various authors.
Details Authors
Flanagan PM Agarwal DK et al. Srilakshmi MA Lee HN et al. Chandrashekhar T Present author
et al. (1993) (2000) et al. (2003) (2003) et al. (2007)
No. of cases ΝΑ 1 1 1 2 1
Case-I Case-II
Gap between development of ΝΑ 2 months 10 year NA 3 months 2 year 11 months
leprosy and development of
tuberculosis
Types of leprosy LL LL LL BL BL LL BL
Is tuberculosis developed first ΝΑ YES NO NA NO NO NO
Is leprosy developed first ΝΑ NO YES NA YES YES YES
Family history of tuberculosis ΝΑ NO NO NA NA NA NA
Any risk factors like use of ΝΑ Renal transplant NO NA Corticosteroids Corticosteroids Corticosteroids
corticosteroids/diabetes recipient and had
mellitus/smoking/HIV/others taken prednisolone,
were present azathioprine, and
cyclosporin
TB: Pulmonary/extrapulmonary TB of larynx Pulmonary Pulmonary NA Pulmonary Pulmonary Pulmonary
Descriptions lesions of ΝΑ NA Bilateral NA Bilateral Bilateral Bilateral
tuberculosis on chest infiltrates infiltrates infiltrates infiltrates
radiographs
Sputum for AFB ΝΑ +ve and culture +ve +ve NA +ve +ve +ve
Diagnosis of leprosy NS Biopsy Slit skin smear Slit skin smear
Lepra reaction ΝΑ Seen NO Type-I NO Type-II Type-II
(NA: data not available; NS: not seen; TB: tuberculosis)
Concomitant Pulmonary Tuberculosis and Borderline Leprosy...
65
FURTHER READING
1. Prasad R, Verma SK, Singh R, Hosmane G. Concomitant pulmonary tuberculosis and borderline
leprosy with type-II lepra reaction in single patient. Lung India. 2010;27:19-23.
2. Chaussinand R. Tuberculose et lepre, maladies antagoniques. Int J Lepr. 1948;16:431-8.
3. Long ER. Antagonism among diseases. Int J Lepr. 1966;34:316-9.
4. WHO. Current Leprosy prevalence in India: Fact sheet, 2006.
5. Donoghue HD, Marcsik A, Matheson C, Vernon K, Nuorala E, Molto JE, et al. Coinfection of
Mycobacterium tuberculosis and Mycobacterium leprae in human archaeological samples: A possible
explanation for the historical decline of leprosy. Proc Biol Sci. 2005;272:389-94.
6. Relvich AL. The treatment of tuberculosis in leprosy patients. Lepr Rev. 1954;25:179-86.
7. Gupta MC, Prasad M. Associated infection of pulmonary tuberculosis and leprosy. Indian J Med Sci.
1971;25:183-5.
8. Gajwani BW, Verma BS, Marwaha RK, Pande RS. Leprosy and tuberculosis. J Ass Phy Ind. 1968;16:563.
9. Agnihotri MS, Rastogi S, Agarwal RC. Tuberculosis and leprosy. Ind J Tub. 1973;20:136-7.
10. Nigam P, Dubey AL, Dayal SG, Goyal BM, Saxena HN, Samuel KC. The association of leprosy and
pulmonary tuberculosis. Lepr India. 1979;51:65-73.
11. Agarwal DK, Mehta AR, Sharma AP, Sural S, Kumar A, Mehta B, et al. Coinfection with leprosy and
tuberculosis in a renal transplant recipient. Nephrol Dial Transplant. 2000;15:1720-1.
12. Kumar B, Kaur S, Kataria S, Roy SN. Concomitant occurrence of leprosy and tuberculosis-A clinical,
bacteriological and radiological evaluation. Lepr India. 1982;54:671-6.
13. Jick SS, Lieberman ES, Rahman MU, Choi HK. Glucocorticoid use, other associated factors, and the
risk of tuberculosis. Arthritis Rheum. 2006;55:19-26.
14. Targeted tuberculin testing and treatment of latent tuberculosis infection: Joint statement of the
American Thoracic Society and the Centers for Disease Control and Prevention. Am J Respir Crit Care
Med. 2000;161:S221-47.
15. Sreeramareddy CT, Menezes RG, Kishore PV. Concomitant age old infections of mankind–tuberculosis
and leprosy: A case report. J Med Case Rep. 2007;1:43.
16. Inamadar AC, Sampagavi VV. Concomitant occurrence of leprosy, cutaneous tuberculosis and
pulmonary tuberculosis--a case report. Lepr Rev. 1994;65:282-4.
17. Flanagan PM, McIlwain JC. Tuberculosis of the larynx in a lepromatous patient. J Laryngol Otol.
1993;107:845-7.
18. Srilakshmi MA, Amit H, Lal J, Raveendranath S, Pais N. Concomitant infection with pulmonary
tuberculosis and lepromatous leprosy. J Assoc Physicians India. 2003;51:528-9.
19. Lee HN, Embi CS, Vigeland KM, White CR Jr. Concomitant pulmonary tuberculosis and leprosy. J Am
Acad Dermatol. 2003;49:755-7.
20. Vinnik LA, Pogorelov VN, Loginov VK. Leprosy and tuberculosis. Probl Tuberk. 1971;49:39-44.
21. Bhargava NC, Mathur KC. Simultaneous occurrence of leprosy and pulmonary tuberculosis. Indian J
Chest Dis Allied Sci. 1976;18:101-4.
22. Gatner EM, Glatthaar E, Imkamp FM, Kok SH. Association of tuberculosis and leprosy in South Africa.
Lepr Rev. 1980;51:5-10.
CASE 18
Community-Acquired Miliary Pneumonia

Mimicking as Miliary Tuberculosis
CASE REPORT
A 14-year-old male, nonsmoker patient was admitted in emergency department with
the chief complaints of high-grade fever off and on and dry cough and breathlessness
for last 5 days. He had no history of chest pain, hemoptysis, and anorexia. On chest X-ray
posteroanterior (PA) view he was having bilateral miliary shadow. He was diagnosed as a
case of miliary tuberculosis by a local practitioner for which he was taking antitubercular
treatment (ATT) for last 2 days. He developed gastric intolerance for ATT after which he was
referred to us. He was having no history of contact to a tuberculosis patient. His medical
history was otherwise unremarkable. On general physical examination, he was conscious,
febrile (temperature 102°F) and well-nourished with a pulse rate of 116 beats/min, respiratory
rate of 32 breaths/min, and a right arm supine blood pressure of 102/60 mm Hg. Oxygen
saturation using pulse oximetry revealed hypoxemia (SaO2 84%). There was no cervical
lymphadenopathy, cyanosis or clubbing. There were no scars or sinuses in the neck. Chest
examination was unremarkable on inspection, palpation, and percussion. On auscultation,
bilateral coarse crepts were audible. Examination of other systems was unremarkable. Routine
investigation showed hemoglobin: 11 g%, total leukocyte count: 16,700/mm, differential
count: neutrophils 78%, lymphocyte 20%, eosinophil 2% (absolute eosinophil count was 334),
platelets count: 2.8 lacs|mm3, C-reactive protein: 72 mg/L, and erythrocyte sedimentation
rate: 17 mm/h. He was negative for human immunodeficiency virus. Rest of the biochemical
investigations were within normal limit. Mantoux test showed indurations of 3 mm at 72
hours. Repeat chest X-ray also revealed the miliary shadows (Fig. 1). Sputum examination
could not be done because of nonproductive cough. Bronchoalveolar lavage (BAL) obtained
via flexible fiberoptic bronchoscopy was sent for acid-fast bacilli (AFB) smear, Gram stain, and
culture sensitivity for pyogenic. BAL fluid was negative for AFB smear. Gram stain of BAL fluid
revealed gram-positive diplococci. Culture of BAL fluid was also positive for Streptococcus
pneumonia which was sensitive to amoxicillin. Blood culture was also positive for S. pneumonia.
Thus, he was diagnosed as a case of community-acquired miliary pneumonia. He was given a
course of coamoxiclav 1.2 g tds intravenous for 2 days followed by oral coamoxiclav 625 mg
tds for12 days. Patient improved clinically as well as radiologically after 14 days of treatment
(Fig. 2).
FIG. 1: Chest radiograph showing miliary FIG. 2: Chest radiograph showing the resolu-
shadow. tion of miliary shadows after 14 days of treat-
ment.
DISCUSSION
Community-acquired pneumonia (CAP) has been defined as symptoms and signs
consistent with an acute lower respiratory tract infection associated with new
radiographic shadowing for which there is no other explanation (e.g., pulmonary edema
or infarction). S. pneumonia is the leading cause of CAP. The usual clinical presentation
of acute pneumococcal pneumonia is abrupt, with fever, shaking chills, cough, slight
expectoration, and intense pleural pain. The temperature may be as high as 41°C. Cough
may be nonproductive at first but soon produces bloody, rusty or greenish material.
Typical findings on physical examination include decreased breath sounds, crackles, and
impaired percussion over the site of the pneumonia. Bronchial breathing, bronchophony,
and whispering pectoriloquy are audible on auscultation in a small number of patients.
The usual standard for the diagnosis of pneumonia is chest radiography. The characteristic
radiographic pattern of acute pneumococcal pneumonia consists of homogenous,
nonsegmental consolidation involving one lobe. In one study, 67% of patients with
pneumococcal pneumonia had the typical pattern, 20% had patchy areas of consolidation,
and 13% had mixed air-space and interstitial opacities. Our patient had the miliary
shadows on chest radiograph which has not been reported till now. A white cell count of
15,000/mm strongly suggests a bacterial (particularly pneumococcal) etiology, although
lower counts do not exclude a bacterial cause. Raised levels of C-reactive protein are a
relatively more sensitive marker of pneumonia than an increased temperature or raised
white cell count. One study found that all patients with CAP had levels above 50 mg/L and
75% of patients had level above 100 mg/L (in our case also CRP was 72 mg/L). Although
the diagnosis of acute pneumococcal pneumonia may be suspected from the clinical
picture and the radiographic pattern, isolation of the organism is necessary for a definitive
diagnosis. Presence of large numbers of gram-positive diplococci in purulent samples
from patients with CAP can indicate pneumococcal pneumonia. However, the sensitivity
of a good Gram-stain for the diagnosis of pneumococcal pneumonia is only in the order
Community-Acquired Miliary Pneumonia Mimicking as Miliary Tuberculosis 69
of 15% and sputum samples are often not obtained in a timely fashion. BAL obtained via
fiberoptic bronchoscopy is a useful and safe alternative for sampling cellular and humoral
materials from the lower respiratory tract. Our patient was also having the nonproductive
cough so we obtained the BAL fluid via flexible fiber-optic bronchoscopy. Reported
incidence of negative sputum culture in patients with pneumococcal pneumonia proved
by positive blood culture is as high as 45%. Radiographic changes of CAP resolve relatively
slowly and lag behind clinical recovery. Complete recovery of chest radiographic changes
occurred at 2 weeks after initial presentation in 51% of cases, by 4 weeks in 64% and at
6 weeks in 73%. In a developing country like India where the prevalence of tuberculosis
is high, miliary shadows are usually taken synonymous to miliary tuberculosis (as
happened in our case). Whereas in developed country, the continuing decline in
tuberculosis and the consequent decreasing experience and awareness of tuberculosis
has led to tuberculosis increasingly being diagnosed after rather than before death.
If the patient is having high-grade fever of abrupt onset without anorexia and weight
loss, with no history of contact to tubercular patient, other diagnosis must be taken into
consideration. If reasonable doubt exists, then the patient should be treated for both
conditions until a firm diagnosis can be reached. Nonmycobacterial pneumonia clears
much more rapidly than miliary tuberculosis.
FURTHER READING
1. Kushwaha R, Sanjay, Verma S, Prasad R. Community acquired miliary pneumonia mimicking as
miliary tuberculosis. Internet J Pulm Med. 2007;9.
2. British Thoracic Society. British Thoracic Society guidelines for the management of community-
acquired pneumonia in adults admitted to hospital. Br J Hosp Med.1993;49:346-50.
3. File TM Jr. Streptococcus pneumoniae and community acquired pneumonia: a cause for concern. Am
J Med. 2004;117:39s-50s.
4. Kulpati DDS, Khastgir T. Reappraisal of pneumonias. JAssoc Physicians India. 1988;36:660-64.
5. Metlay JP, Kapoor WN, Fine MJ. Does this patient have community-acquired pneumonia? Diagnosing
pneumonia by history and physical examination. JAMA. 1997;278:1440-5.
6. Levy M, Dromer F, Brion N, Leturdu F, Carbon C. Community-acquired pneumonia: Importance of
initial noninvasive bacteriologic and radiographic investigations. Chest. 1988;92:43-8.
7. Holmberg H, Bodin L, Jonsson I, Krook A. Rapid aetiological diagnosis of pneumonia based on
routine laboratory features. Scand J Infect Dis. 1990;22:537-45.
8. Smith RP, Lipworth BJ, Cree IA, Spiers EM, Winter JH. C-reactive protein. A clinical marker in
community-acquired pneumonia. Chest. 1995;108:1288-91.
9. Perlino CA. Laboratory diagnosis of pneumonia due to Streptococcus pneumonia. J Infect Dis.
1984;150:139.
10. Macfarlane J. An overview of community-acquired pneumonia with lessons learned from the British
Thoracic Society Study. Semin Respir Infect. 1994;9:153-65.
11. Barrett-Connor E. The nonvalue of sputum culture in the diagnosis of pneumococcal pneumonia.
Am Rev Resp Dis.1971;103:845-8.
12. Mittl RL, Schwab RJ, Duchin JS, Goin JE, Albeida SM, Miller WT. Radiographic resolution of
community-acquired pneumonia. Am J Respir Crit Care Med. 1994;149:630-5.
CASE 19
Coexistence of Bronchiectasis and

Chronic Obstructive Pulmonary Disease
as Separate Entity
CASE REPORT
A 56-year-old male, shopkeeper, ex-smoker presented with productive cough that had been
present for the last 20 years, exertional dyspnea for last 2 years and fever on and off for last
2 years. He had denied any history of chest pain, loss of weight, and appetite. Patient was
ex-smoker with smoking index of 25 pack years. Patient had history of acute exacerbation
2–3 times/year for last 2 years. He was being managed for the same through inhaled steroids
and bronchodilators. Clubbing was present in bilateral upper limbs on general examination.
Systemic examination revealed bilateral vesicular breath sounds with prolonged expiration
with coarse crepitations in the left infrascapular region.
Blood counts, serum biochemistry, and urine analysis were within normal limits. Human
immunodeficiency virus (HIV) was nonreactive and α-1 antitrypsin (AAT) levels were within
normal limit. The chest radiograph showed a right upper zone bulla with left lower zone
cystic shadows and signs of bilateral hyperinflation (Fig. 1). High-resolution computed
FIG. 1: X-ray of the patient showing a right upper zone bulla

and signs of hyperinflation with left lower zone cystic shadows.
Coexistence of Bronchiectasis and Chronic Obstructive Pulmonary Disease... 71
tomography (HRCT) thorax revealed right upper lobe bulla with emphysematous changes
and left lower lobe cystic bronchiectasis (Figs. 2A and B). Sputum examination was negative
for acid-fast bacilli (AFB) and fungus. Sputum for pyogenic culture showed a growth of
Pseudomonas aeruginosa. Pulmonary function test done showed severe irreversible airflow
obstruction and restriction and decreased diffusion capacity for carbon monoxide. Diagnosis
of left lower lobe bronchiectasis with chronic obstructive pulmonary disease (COPD) was
made.1
The patient was treated with combination of piperacillin-tazobactam and amikacin for
2 weeks based on culture sensitivity report and inhaled bronchodilators and steroids were
continued. Patient was discharged in a stable condition on inhaled corticosteroids and
long-acting bronchodilator agonist (LABA) along with advice for bronchial hygiene.
A B
FIG. 2A AND B: (A) High-resolution computed tomography (HRCT) of the patient showing a left
lower lobe cystic bronchiectasis. (B) The HRCT of the patient showing a right upper lobe bulla with
emphysematous changes.
DISCUSSION
Bronchiectasis, which was once considered to be an orphan disease in the developed
world in the late 20th century, is now being diagnosed with increasing frequency around
the globe. Bronchiectasis is an abnormal dilatation of bronchi and bronchioles due
to repeated cycles of airway infection and inflammation. Regardless of the underlying
cause, bronchiectasis results when inflammatory and infectious damage to the bronchial
and bronchiolar walls leads to a vicious cycle of airway injury. Establishing the cause
of bronchiectasis may be difficult. Even with clinical, laboratory, and pathologic testing,
up to 50–80% of cases of bronchiectasis may still be idiopathic. The HRCT is now accepted
as the imaging modality of choice for the evaluation of bronchiectasis and emphysema.
Due to increasing use of HRCT scanning in patients with pulmonary symptoms,
bronchiectasis is increasingly being recognized in patients with chronic cough and
dyspnea. Radiographic features may include cylindrical, varicose, and cystic/saccular
type of bronchiectasis. Overt bullous emphysema is seldom reported in bronchiectasis,
except in patients with AAT deficiency. Loubeyre et al. interpreted the CT finding of
widespread areas of decreased attenuation in bronchiectasis as indicative of emphysema.
In present case, CT findings of bullous emphysema could not be explained solely by
bronchiectasis. Eman et al. in one study showed that the prevalence of bronchiectasis
in patients with moderate-to-severe COPD was 47.8% and it was primarily of cylindrical
type and mainly localized in the lower lobes. In this study, bronchiectasis primarily
resulted from complication of COPD. Parr et al. in other study showed the higher
prevalence of bronchiectasis in the lobes most affected by emphysema. But in present
report bronchiectasis was primarily of cystic type and present in left lower lobes. The
relevant answer to CT findings in present report could be the presence of both diseases,
i.e., bronchiectasis and COPD. AAT deficiency can be associated with both emphysema
and bronchiectasis but AAT was normal in present report. Bronchiectasis can cause
airflow obstruction that produces clinical symptoms similar to COPD. Patients with
COPD and bronchiectasis have greater bronchial inflammation, chronic colonization
of bronchial mucosa by a pathogenic microorganism, and longer duration of acute
infectious exacerbations. P. aeruginosa is the most common pathogen in COPD patients
associated with bronchiectasis which was also the scenario in present report. The
goals of bronchiectasis treatment are to reduce the number of exacerbations and to
improve quality of life.
FURTHER READING
1. Goel N, Gupta P, Singh A, Prasad R. Co-existence of bronchiectasis and chronic obstructive pulmonary
disease. Indian J Chest Dis Allied Sci. 2015;57:125-7.
2. Barker AF, Bardana EJ. Bronchiectasis: update of an orphan disease. Am Rev Respir Dis. 1988;137:
969-78.
3. Reid LM. Reduction in bronchial subdivision in bronchiectasis. Thorax. 1950;5:233-47.
4. Morrissey BM. Pathogenesis of bronchiectasis. Clin Chest Med. 2007;28:289-96.
5. Shoemark A, Ozerovitch L, Wilson R. Aetiology in adult patients with bronchiectasis. Respir Med.
2007;101:1163-70.
6. Naidich DP, McCauley DI, Khouri NF, Stitik FP, Siegelman SS. Computed tomography of bronchiectasis.
J Comput Assist Tomogr. 1982;6:437-44.
7. Genevois PA, De Vuyst P, de Maertelaer V, Zanen J, Yernault JC. Comparison of computed density and
microscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1996;154:187-92.
8. Guest PJ, Hansell DM. High resolution computed tomography in emphysema associated with alpha-
1-antitrypsin deficiency. Clin Radiol. 1992;45:260-6.
9. Loubeyre P, Paret M, Revel D, Wiesendanger T, Brune J. Thin section CT detection of emphysema
associated with bronchiectasis and correlation with pulmonary function test. Chest. 1996;109:360-5.
10. Eman O, Mohamed M. Bronchiectasis in COPD patients. Egypt J Chest Dis Tuberc. 2012;61:307-12.
11. Parr DG, Guest PG, Reynolds JH, Dowson LJ, Stockley RA. Prevalence and impact of bronchiectasis in
alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2007;176:1215-21.
12. Cabello H, Torres A, Celis R, El-Ebiary M, Puig de la Bellacasa J, Xaubet A, et al. Bacterial colonization
of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study. Eur Respir J.
1997;10:1137-44.
13. Kim WJ, Hoffman E, Reilly J, Hersh C, Demeo D, Washko G, et al. Association of COPD candidate
genes with computed tomography emphysema and airway phenotypes in severe COPD. Eur Respir
J. 2011;37:39-43.
CASE 20
Bilateral Hemorrhagic Pleural Effusion

due to Kerosene Aspiration
CASE REPORT
A previously healthy 40-year-old male, presented to our emergency department, with the
chief complaints of progressively increasing breathlessness with chest pain of pleuritic
nature and high-grade fever for 3 days. On initial examination, his respiratory rate was
32 breaths/min and oxygen saturation was 88%. His BP was 112/80 mm Hg and pulse rate
was 98 beats/min. Rest of the general physical examination was within normal limits and
there was no cyanosis. Auscultation revealed diminished breath sounds bilaterally. Evaluation
of rest of the systems were within normal limits. The hemogram (hemoglobin level, red
blood cell (RBC) count, platelet count) except for total leukocyte count (TLC), coagulogram
[activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrin
degradation product level], and routine blood biochemistry (serum urea, creatinine, random
blood sugar) were within normal limits. His TLC at admission was 14,400/mm3. An arterial
blood gas analysis revealed arterial oxygen tension (pO2) 78 mm Hg, pCO2 40 mm Hg,
HCO3 25 mEq/L, and pH 7.38. Chest X-ray showed bilateral homogenous opacities with
bilateral pleural effusion (Fig. 1). The ultrasound thorax revealed 250 mL pleural fluid in the
right pleural cavity and 150 mL in the left pleural cavity. A contrast-enhanced computed
FIG. 1: The chest X-ray showing homogenous

opacities with bilateral pleural effusion.
tomography (CT) thorax at admission showed bilateral pleural effusion with consolidation in
the basal segment of both the lower lobes and nodular pleural thickening in the right lower
lobe (Fig. 2). Diagnostic USG-guided thoracocentesis of both the sides revealed hemorrhagic
effusion on gross appearance. Biochemical analysis revealed them to as exudative in nature
with adenosine deaminase (ADA) values of 9 IU/mL and 12 IU/mL of left and right side,
respectively. Microscopic examination of pleural fluid revealed plenty of RBCs and 100%
differential polymorph count in the left sided effusion and 80% differential polymorph
count in the right-sided effusion. They were also negative for acid-fast bacilli (AFB) or any
microorganism on smears. Fiberoptic bronchoscopy revealed generalized hyperemia of
the tracheobronchial tree with pus oozing out from the more distal airways bilaterally.
The Ziehl–Neelsen (ZN) staining of bronchoalveolar lavage (BAL) fluid was negative for
AFB. However, stained smear examination of BAL showed plenty of RBCs and neutrophils.
Pleural fluid and BAL samples were sterile on culture. The patient was treated with oxygen
supplementation, oral corticosteroids (prednisolone at 1 mg/kg body weight) and injection
ceftriaxone given 1 g thrice a day by intravenous route. The patient responded to the treatment
and became afebrile with improvement in breathlessness and pleuritic chest pain. His TLC
came down to 8,000/mm3 after 7 days of treatment. A repeat CT thorax done after 15 days
showed resolution in the areas of consolidation and effusion (Fig. 3). Antibiotics and steroids
after tapering were stopped after 3 weeks. The patient was discharged in a stable condition.
FIG. 2: Bilateral pleural effusion and nodular pleural

thickening in right lower lobe.
FIG. 3: A repeat computed tomography (CT) thorax shows the

effusion has resolved following conservative management.
Bilateral Hemorrhagic Pleural Effusion due to Kerosene Aspiration 75
DISCUSSION
Hydrocarbons are heterogeneous group of substances that are primarily composed of
carbon and hydrogen molecules. They are quite abundant in modern society. Some
of the most commonly used hydrocarbons include gasoline, lubricating oil, motor oil,
mineral spirits, lighter fluid/naphtha, lamp oil, and kerosene. Hydrocarbons can be
classified as being aliphatic (ethane and acetylene), aromatic (toluene and phenol), or
halogenated hydrocarbons which are a subgroup of aromatic hydrocarbons (chloroform
and carbon tetra chloride). Kerosene is a thin, clear liquid formed from a complex
mixture of hydrocarbons, with density of 0.78–0.81 g/cm3. It is obtained from the
fractional distillation of petroleum between 150 and 275°C, resulting in a mixture of
carbon chains that typically contain between 12 and 15 carbon atoms per molecule. In
India, kerosene is the main fuel used for cooking and lighting among the poor. The lethal
dose of kerosene for a 70 kg adult is 100 mL Hydrocarbon exposure can be divided into
the following four broad categories: Nonintentional nonoccupational (or accidental, as
occurred in our case), recreational, occupational, and intentional exposure. Kerosene
poisoning is rare among adults. It is a common practice in India for traders to buy kerosene
in drums in bulk and then sell them in small amounts to individuals who bring their own
jerry cans. To take out the kerosene from the drum, a vacuum is created in the hose by
siphoning out the air using one’s mouth. Our patient mistook the amount of negative
pressure required and ended up swallowing about 50 mL of kerosene of the vomitus.
Over the next 3 days, he had nausea but no vomiting. Nausea subsided after that. Signs
of oral kerosene poisoning include diarrhea, nausea, and vomiting. The most frequent
adverse effect of any hydrocarbon poisoning is aspiration, which can cause a chemical
pneumonitis from direct injury to the lung parenchyma. Pneumonia in the most cases of
aspiration of hydrocarbons like kerosene is interstitial and bilateral. This damage depends
on the viscosity [the resistance to flow, measured in Saybolt Seconds Universal (SSU)],
volatility (the propensity to vaporize), and the chemical side chains of the hydrocarbon.
Among them, viscosity is the single most important determinant of aspiration risk. Lower
viscosity, especially <60 SSU and higher volatility are associated with a greater chance of
aspiration with resultant pulmonary injury. The type II pneumocytes are the most affected
resulting in decreased surfactant production. This decrease in surfactant results in alveolar
collapse, ventilation−perfusion mismatch, and hypoxemia. Hemorrhagic alveolitis can
occur which peaks 3 days after ingestion. The end result of hydrocarbon aspiration is
interstitial inflammation, intra-alveolar hemorrhage and edema, hyperemia, bronchial
necrosis, and vascular necrosis. The hemorrhagic alveolitis and bronchial and vascular
necrosis can result in a hemorrhagic pleural effusion, which has been rarely reported. Rare
pulmonary complications include the development of a pneumothorax, pneumatocele, or
bronchopleural fistula. A rare complication of kerosene intoxication is cardiac arrhythmia
and ventricular fibrillation, attributed to increased myocardial sensitivity to endogenous
catecholamines. Gastrointestinal involvement, as observed in our patient, is manifested
by vomiting, abdominal pain, and diarrhea has been attributed to mucosal irritation.
Symptoms and radiological findings resolve rapidly after cessation of exposure and
corticosteroid therapy. To the best of our knowledge, our patient who developed bilateral
hemorrhagic pleural effusion following aspiration of kerosene while trying to siphon it out
is the first reported case in Indian literature. The patient recovered satisfactorily following
initial treatment consisting of oxygen inhalation, antibiotics, steroids, and supportive
measures without any residual pulmonary sequel.
FURTHER READING
1. Prasad R, Karmakar S, Sodhi R, Karmakar S. Bilateral hemorrhagic pleural effusion due to kerosene
aspiration. Lung India. 2011;28:130-2.
2. Bronstein AC, Spyker DA, Cantilena LR Jr, Green J, Rumack BH, Heard SE. Annual Report of the
American Association of Poison Control Centers’ National Poison Data System (NPDS). Clin Toxicol.
2007;45:815-917.
3. Ofusori DA, Ayoka AO, Adeeyo OA, Adewole SO. Mixture of kerosene and xylene: A contribution to
clearing agents. Int J Morphol. 2009;27:211-8.
4. Patel AL, Shaikh WA, Patel HL, Deshmukh D, Malaviya AP, Janawar P, et al. Kerosene poisoning--varied
systemic manifestations. J Assoc Physicians India. 2004;52:65-6.
5. Lall SB, Al-Wahaibi SS, Al-Riyami MM, Al-Kharusi K. Profile of acute poisoning cases presenting to
health centres and hospitals in Oman. East Mediterr Health J. 2003;9:944-54.
6. Wax PM, Beuhler MB. Hydrocarbons and volatile substances. In: Tintinalli JE, Kellen GD, Stapczynski
S, Ma OJ, Cline DM, (Eds). Emergency Medicine: A Comprehensive Study Guide, 6th edition. New
York: McGraw-Hill Medical Publishing Division; 2004. pp. 1124-30.
7. Lifshitz M, Sofer S, Gorodischer R. Hydrocarbon poisoning in children: A 5-year retrospective study.
Wilderness Environ Med. 2003;14:78-82.
8. Dyer KS. Hydrocarbons. In: Wolfson AB, Hendey GW, Ling LJ, Rosen CL, Schaider J, Sharieff GQ,
(Eds). Harwood-Nuss’ Clinical Practice of Emergency Medicine, 4th edition. Philadelphia: Lippincott
Williams and Wilkins; 2005. pp. 1590-3.
9. Domej W, Mitterhammer H, Stauber R, Kaufmann P, Smolle KH. Successful outcome after intravenous
gasoline injection. J Med Toxicol. 2007;3:173-7.
10. Bebarta V, DeWitt C. Miscellaneous hydrocarbon solvents. Clin Occup Environ Med. 2004;4:455-79.
11. Shotar AM. Kerosene poisoning in childhood: A 6-year prospective study at Princess Rahmat
Teaching Hospital. Neuro Endocrinol Lett. 2005;26:835-8.
CASE 21
Bilateral Chylothorax in a Child

after Mild Trauma
CASE REPORT
A 10-year-old male child was admitted to our department with the complaints of breath
lessness, off and on fever for 5 days. He came from a nonendemic zone of filariasis in
Uttar Pradesh. His medical history was otherwise unremarkable except for a minor injury
sustained after falling on his back, 10 days ago. The resting pulse rate was 102 beats/min,
blood pressure was 112/74 mm Hg, and his respiratory rate was 28 breaths/min. General
physical examination revealed pallor and bilateral pedal edema with no other abnormality.
Chest examination revealed stony dull note localized to bilateral infrascapular, lower axillary
areas. Rest of the systemic examination was unremarkable.
Laboratory examination showed anemia, hypoalbuminemia, and a normal total
and differential leukocyte counts. Chest radiograph revealed bilateral pleural effusion
(Fig. 1). Thoracentesis was done and 1.6 liter and 0.6 liter of milky white colored pleural
fluid aspirated from left and right sides respectively. Clearing of pleural fluid by adding
ethyl ether into it leads to the exclusion of pseudochylothorax. Pleural fluid examination
FIG. 1: Chest radiograph [posteroanterior

(PA) view] showing bilateral pleural effusion.
revealed protein 4.2 g/dL sugar 44 mg/dL, total leukocyte count 3,200 cells/mm, with a
differential leukocyte count of neutrophils 52%, lymphocytes 48%, triglycerides 289.3 mg/
dL, and cholesterol 24.8 mg/dL. Serum triglyceride and cholesterol levels were 72.7 mg/dL
and 71.9 mg/dL, respectively. The ratio of pleural fluid to serum levels of cholesterol were
3.77 and 0.344, respectively. Pleural fluid culture was sterile. Tuberculin skin test showed
no induration. Addition of ethyl ether resulted in the milky white pleural fluid turning
clear, there by ruling out pseudochylothorax. Thus, a diagnosis of bilateral chylothorax was
established.
Computed tomography (CT) of the thorax (Fig. 2) revealed bilateral pleural effusion (more
on the left side) without any significant lymphadenopathy. Anteroposterior and lateral
radiographs of the thoracic spine revealed no bony injury. To confirm the exact site of the
thoracic duct tear, lymphangiography was planned but could not be done as consent could
not be obtained.
Oral feeding was withheld for the initial 4 days. Initially 5% dextrose was intravenously
administered later on, high protein, high carbohydrate, low fat medium chain triglycerides
(MCT) containing diet was given. Along with these measures, pleural cavity was emptied daily
by thoracentesis. Blood infusion was also given after the age of 10 years.
FIG. 2: CT chest showing bilateral pleural effusion.
DISCUSSION
Chylothorax is described classically as having a white, milky, or opalescent appearance
associated with high pleural fluid triglyceride levels. It is formed when the thoracic duct is
disrupted and chyle enters into the pleural cavity. About 50% of the cases of chylothorax
are caused by tumors such as lymphoreticular malignancies and bronchogenic carcinoma
invading the thoracic duct. Trauma is the second leading cause in about 25% cases
with days of oral feeding with low fat MCT diet, chylothorax persisted. Oral feeding was
stopped and total parenteral nutrition consisting of 20% lipid, intravenous amino plasma,
and 10% dextrose solution was initiated. With these measures, the chylothorax resolved
after a period of 3 weeks (Fig. 3). chylothorax. Iatrogenic trauma during surgery accounted
Bilateral Chylothorax in a Child after Mild Trauma 79
FIG. 3: Chest radiograph [posteroanterior (PA) view]

after 3 weeks of conservative management showing
resolution of bilateral pleural effusion.
for the majority of these cases. Of the surgical procedures resulting in chylothorax,
esophagectomy and congenital heart surgery were the most common accounting for
more than half the cases due to surgery or trauma-related causes. Although chylothorax
is a relatively rare complication following thoracic and cardiovascular surgery, the
incidence of chylothorax has been higher after esophagectomy. Nonpenetrating injuries
like hyperextension of spine can also rarely lead to chylothorax. In about 25% cases with
chylothorax, no definite cause can be identified. They are presumed to be secondary to
minor trauma. Very few cases with bilateral chylothorax have been reported in literature.
Chylothorax has no predilection for age and sex. Symptoms of chylothorax mostly
depend upon amount of fluid in pleural cavity. Following trauma, the chylothorax usually
developed within 2–10 days; in our case, it developed after 5 days.
The best way to establish the diagnosis of chylothorax is to determine the concen
tration of triglycerides in the pleural fluid. The triglyceride concentrations >110 mg/dL
(in our case it was 289.3 mg/dL), a ratio of pleural fluid to serum triglyceride levels
>1.0 (in our case it was 3.77), and ratio of pleural fluid to serum cholesterol <1.0 confirms
the diagnosis of chylothorax. Pleural fluid triglyceride levels <50 mg/dL exclude the
diagnosis of chylothorax. However, in case the pleural fluid triglyceride levels are
between 50 to 110 mg/dL, a lipoprotein analysis of pleural fluid and demonstration
of chylomicrons in the pleural fluid confirms the diagnosis of chylothorax. Primary
treatment in patients with chylothorax should be directed toward correction of
malnutrition and compromised immunologic status. Nutritional management consists
of MCT diet initially followed by total parenteral nutrition if the chylothorax persists. With
these measures, the defect in the thoracic duct often closes spontaneously in case due
to traumatic injury. In case with severe dyspnea, placement of pleuroperitoneal shunt
or chest tube drainage is indicated. If chylothorax persists for >4 weeks of conservative
management, consideration should be given to surgical exploration and ligation of the
thoracic duct. Another case report from India also stresses on the usefulness of initial
conservative management of chylothorax.
FURTHER READING
1. Kushwaha RA, Verma SK, Sanjay, Mahajan V, Prasad R. Bilateral chylothorax in a child after mild
trauma. Indian J Chest Dis Allied Sci. 2008;50:355-7.
2. Valentine VG, Raffin TA. The management of chylothorax. Chest. 1992;102:586-91.
3. Doerr CH, Miller DL, Ryu JH. Chylothorax. Semin Report Crit Care Med. 2001;22:617-26.
4. Doerr CH, Allen MS, Nichols FC 3rd, Ryu JH. Etiology of chylothorax in 203 patients. Mayo Clin Proc.
2005;80:867-70.
5. Sassoon CS, Light RW. Chylothorax and pseudochylothorax. Clin Chest Med. 1985;6:163-71.
6. Chauvin O, Dore P, Meurice JC, Boita F, Patte F. Bilateral chylothorax after mild trauma: apropos of a
case. Rev Pneumol Clin. 1992;48:71-3.
7. Seriff NS, Cohen ML, Samuel P, Schulster PL. Chylothorax: diagnosis by lipoprotein electrophoresis of
serum and pleural fluid. Thorax. 1977;32:98-100.
8. Fogli L, Gorini P, Belcastro S. Conservative management of traumatic chylothorax: a case report.
Intensive Care Med. 1993;19:176-7.
9. Oak SN, Kulkarnin BK, Deshmukh H, Kamble M, Borwankar SS. Chylothorax: a conservative approach
(a case report). J Postgrad Med. 1991;37:222 B, 223-4.
10. Browse NL, Allen DR, Wilson NM. Management of chylothorax. Br J Surg. 1997;84:1711-6.
CASE 22
An Unusual Case of Actinomycosis

Presenting as a Pulmonary Mass
CASE REPORT
A 62-year-old male, retired coal-miner, ex-smoker presented with progressive exertional
dyspnea and productive cough that had been present for the last 8 years. He had been
diagnosed to have chronic obstructive pulmonary disease (COPD) and was receiving inhaled
steroids and bronchodilators. However, he had started noticing hemoptysis for the last
1 month. He denied any history of fever, chest pain or loss of weight and appetite. Also, he
was a diabetic since 5 years which was poorly-controlled despite regular treatment. Physical
examination was unremarkable except for a dull note on percussion in the right infra-
mammary region and prolonged expiration on auscultation.
Blood counts, kidney and liver function tests, and urine analysis were within normal limits.
Serological testing for human immunodeficiency virus was negative. The chest radiograph
demonstrated irregular, well-defined parahilar opacity in the right lower zone, silhouetting
the right heart border, and thus, raising the suspicion of a malignancy (Fig. 1A). A high-
resolution contrast-enhanced computed tomography of the thorax in the axial plane showed
A B
FIGS. 1 A AND B: (A) Chest radiograph [posteroanterior (PA) view] showing an irregular,
parahilar opacity in the right lower zone, silhouetting the right heart border. (B) High-resolution
computed tomography of chest of the same patient showing an irregular, spiculated mass in the
right middle lobe compressing the bronchus intermedius.
irregular, spiculated mass in the right middle lobe compressing the bronchus intermedius
(Fig. 1B). The diagnosis of a pulmonary neoplasm was strongly considered at this stage and
a bronchoscopic evaluation was planned. Bronchoscopy demonstrated the right middle
lobe bronchus to be partially obstructed by a white fungating mass with blood oozing from
it. Pseudomonas aeruginosa was cultured from the bronchial aspirate which was negative for
acid-fast bacilli, fungi, and malignant cells. Although atypical cells or granuloma were not seen,
the histopathological examination of the endobronchial biopsy from the mass surprisingly
showed numerous bacterial colonies within a neutrophilic background. Also a Gram stain of the
endobronchial biopsy (Fig. 2) revealed filamentous, branching Gram-positive organisms within
a neutrophilic inflammatory background. The diagnosis was now revised to be an infection
due to a filamentous organism. To differentiate between Actinomyces species and Nocardia
species, a modified Ziehl–Neelsen stain (1% H2SO4) was done which came out to be negative
that ruled-out nocardial infection. However, a culture of the same could not be performed.
The patient was diagnosed to have COPD with pulmonary actinomycosis and was treated
with an intravenous amoxicillin-clavulanate 1.2 g three times a day for 2 weeks followed by
oral therapy for 6 months. Follow-up radiograph at 3 months (Fig. 3) showed resolution of the
right lower parahilar opacity.
FIG. 2: Gram’s stain of the endobronchial biopsy specimen. Photo

micrograph showing thin, filamentous, branching gram-positive
organisms with a neutrophil-rich background (Gram's stain × 20).
(For color version, see Plate 3)
FIG. 3: Chest radiograph [posteroanterior (PA) view]

showing resolution of the right lower parahilar opacity.
An Unusual Case of Actinomycosis Presenting as a Pulmonary Mass 83
DISCUSSION
The Actinomyces species, are gram-positive anaerobic bacteria that normally colonize
human organs such as oropharynx, gastrointestinal tract, and female genitalia.
Actinomyces israelii is the most common agent that causes human diseases. Most cases of
pulmonary actinomycosis are related to poor oral hygiene, aspiration of gastrointestinal
fluid, and immunocompromised status. Established risk factors for pulmonary
actinomycosis include smoking in 61%, alcohol addiction in 14%, COPD in 20%, and
poor dental hygiene in 31% patients. Most cases of actinomycosis are associated with a
mixed flora comprising particularly of organisms like Pseudomonas species which was
also the scenario in our report. Actinomycosis is characterized by the ability to penetrate
tissue planes, resulting in fistula or abscess formation. Up to 25% of cases with thoracic
actinomycosis are initially misdiagnosed as malignancy or tuberculosis given the similar
radiological picture. The chest radiograph findings may range from small nodular lesion
to mass or consolidation. The radiological findings in the present case was consistent with
malignancy. The diagnosis of pulmonary actinomycosis is particularly challenging as
this organism, being an obligate anaerobe, needs to be carefully processed from clinical
specimens. In the present case, a culture could not be performed given the unavailability
of anaerobic methods of sample processing and culture. Although appearance of
radially arranged sulfur granules from discharging sinuses is the pathological hallmark
of this disease, the presence of these granules is neither sensitive nor specific. Invasive
investigations (e.g., bronchoscopy with transbronchial biopsy) are necessary to obtain
samples for histopathological and microbiological identification. The diagnosis in the
present report was established by endobronchial biopsy; Gram staining and modified
Ziehl–Neelsen staining was done to exclude nocardiosis.
Pulmonary actinomycosis has an excellent prognosis with adequate antibiotic
treatment. Antibiotic treatment duration should be individualized, and termination
of treatment can be considered 1 or 2 months after complete clinical and radiological
disease resolution in most patients. Diminution in the shadowing on a chest radiograph
is expected within 4 weeks. Many recent studies have reported that traditional long-term
regimen is not necessary and short-term treatment is successful. A high level of clinical
suspicion is required to differentiate pulmonary actinomycosis from malignancy.
FURTHER READING
1. Gupta P, Dogra V, Goel N, Chowdhary A, Prasad R, Gaur SN. An unusual cause of a pulmonary mass:
Actinomycosis. Indian J Chest Dis Allied Sci. 2015;57:177-9.
2. Mabeza GF, MacFarlane J. Pulmonary actinomycosis. Eur Respir J. 2003;21:545-51.
3. Mohan A, Chattopadhyay TK, Sharma SK, Dinda AK, Sharma R. Primary actinomycotic lung abscess.
Postgrad Med J. 1995;71:699-700.
4. Madhusudan KS, Gamanagatti S, Seith A, Hari S. Pulmonary infections mimicking cancer: report of
four cases. Singapore Med J. 2007;48:327-31.
5. Patel KB, Gupta G, Shah M, Patel P. Pulmonary actinomycosis in fine needle aspiration cytology. J
Cytol. 2009;26:94-6.
6. Smego RA, Foglia G. Actinomycosis. Clin Infect Dis. 1998;26:1255-61.
7. Weese WC, Smith IM. A study of 57 cases of actinomycosis over a 36-year period. Arch Intern Med.
1975;135:1562-8.
8. Heffner JE. Pleuropulmonary manifestations of actinomycosis and nocardiosis. Semin Respir Infect.
1988;3:352-61.
9. Yildiz O, Doganay M. Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med.
2006;12:228–34.
10. Holm P. Studies on the aetiology of human actinomycosis. The “other” microbes of actinomycosis
and their importance. Acta Pathol Microbiol Scand. 1950;27:736-51.
11. Flynn MW, Felson B. The roentgen manifestations of thoracic actinomycosis. AJR Am J Roentgenol.
1970;110:707-16.
12. Wong RH, Sihoe AD, Thung KH, Wan IY, Ip MB, Yim AP. Actinomycosis: an often forgotten diagnosis.
Asian Cardiovasc Thorac Ann. 2004;12:165-7.
13. Brown JR. Human actinomycosis: a study of 181 subjects. Hum Pathol. 1973;4:319-30.
14. Bassiri AG, Girgis RE, Theodore J. Actinomyces odontolyticus: two cases in lung and heart-lung
transplant recipients and a review of the literature. Chest. 1996;109:1109-11.
15. Kolditz M, Bickhardt J, Matthiessen W, Holotiuk O, Höffken G, Koschel D. Medical management of
pulmonary actinomycosis: data from 49 consecutive cases. J Antimicrob Chemother. 2009;63:839-41.
16. Song JU, Park HY, Jeon K, Um SW, Kwon OJ, Koh WJ. Treatment of thoracic actinomycosis: a
retrospective analysis of 40 patients. Ann Thorac Med. 2010;5:80-5.
CASE 23
A Rare Case of Congenital Anomaly

Presenting as Hemoptysis
CASE REPORT
A 42-year-old male was admitted with a history of hemoptysis of about 50 mL/per day of
4 days duration. There was no history of dyspnea, cough, orthopnea or chest pain or any
history of similar complaints in the past. He was a nonsmoker and a teetotaller. General
physical examination was unremarkable. Respiratory system examination revealed diminished
breath sounds intensity over the left infraclavicular and left mammary area. Examination of
other systems did not reveal any abnormality.
Investigations revealed a normal hemogram, erythrocyte sedimentation rate, liver and renal
biochemistry, bleeding and coagulation parameters. The chest radiograph (posteroanterior
view) showed a veiled opacity in the left hemithorax with a shift of the mediastinum to
the same side with both the diaphragms at the same level (Fig. 1A). Culture of the sputum
revealed no pathogen and two sputum direct smears were negative for acid-fast bacilli (AFB).
Contrast enhanced computed tomography (CECT) of thorax showed changes suggestive of
left lung hypoplasia (Fig. 1B). Fiberoptic bronchoscopy revealed hyperemic mucosa in the
entire right endobronchial tree. On the left side, the bronchial caliber was smaller than the
A B C
FIGS. 1A TO C: (A) Chest radiograph [posteroanterior (PA) view] showing veiled opacity in left
hemithorax with shift of the mediastinum to the same side and both the diaphragms at the same
level; (B) Axial CT thorax at tracheal bifurcation level showing hypoplastic lung parenchyma on the
left side; and (C) Bronchoscopy image showing the small caliber opening of the left main bronchus.
Source: Rajesh V, Prakasha SR, Giridhar BH, Prasad R. An adult with haemoptysis: A rare case of congenital
anomaly. Indian J Chest Dis Allied Sci. 2015;57(1):31-3.
right throughout the lung (Fig. 1C) and showed purulent secretion. The opening of lingular
and left lower lobar bronchi were inflamed. Bronchoalveolar lavage fluid was negative for
AFB while fluid culture grew extended spectrum ß-lactamase (ESBL) producing Escherichia
coli. Axial cuts of CECT of thorax showed absence of the left pulmonary artery (Fig. 2A) and
a right-sided aortic arch (RAA) with four branches arising from it (Fig. 2B). Both kidneys were
enlarged with multiple cysts and thinning of parenchyma (Fig. 2C).
A B C
FIGS. 2A TO C: Axial CT thorax showing: (A) Absence of left pulmonary artery (arrow shows right
pulmonary artery); (B) 3D-reconstruction image showing right-sided aortic arch and four branches
arising from it; and (C) Enlarged bilateral kidneys with multiple cysts and thinning of parenchyma.
DISCUSSION
Pulmonary hypoplasia is a rare entity that is seen in about 1–2 out of every 12,000
births. Warburton et al. described an interaction between blood vessels and airways
during the development of lung and also highlighted that development of the former
controlled airway growth, particularly the formation of alveoli. The possible mechanism
for recurrent pulmonary infections in pulmonary hypoplasia may be reduced blood
supply and defective ventilation of the lung parenchyma due to pulmonary artery defect,
altered venous pulmonary circulation and extrinsic compression of the large airways
by the great vessels. Hemoptysis may occur due to infection in the presence of above
predisposing factors or may be due to increased blood flow and pulmonary hyper
tension in the opposite lung due to unilateral absence of pulmonary artery (UAPA) and
consequent hypoplasia of the ipsilateral lung. The right-sided aortic arch (RAA) with
aberrant origin of great vessels is a rare, but well recognized cause of tracheobronchial/
esophageal compression. The RAA is described in 0.0–0.1% of radiology series. Edwards
described three main types of RAA: Type I (59%) with mirror image branching of the major
arteries; type II (39.5%) with an aberrant left subclavian artery; and type III (0.8%) with
isolated subclavian artery (where the subclavian artery is connected to the pulmonary
artery through the ductus arteriosus). About 85% of type 1 cases are associated with cardiac
anomalies, whereas in type 2 the association is much less common (<10%). A deletion in
chromosome 22q11 is known to be associated with a 24% incidence of isolated anomalies
of laterality of branching of the aortic arch. Though the condition can be asymptomatic,
this can present at any age with features of tracheobronchial or esophageal compression.
A Rare Case of Congenital Anomaly Presenting as Hemoptysis 87
A case of right lung hypoplasia with UAPA manifesting as hemoptysis was described in
an another case of pulmonary hypoplasia with RAA along with UAPA was reported in a
21-month-old child. A 5-month child with RAA, right descending aorta and agenesis of
the left pulmonary artery has been previously described in literature, presenting with lung
infection and progressive respiratory failure. In our case, the patient presented at the age
of 42 years with hemoptysis. On evaluation, he was found to have left lung hypoplasia
along with RAA. The diagnosis of hypoplasia of lung manifesting in adults is based on a
detailed history and physical examination, coupled with a reasonable index of suspicion.
The differential diagnosis should include collapse of a lobe or of one lung, chronic
tuberculous scarring, and complete obstruction of a main pulmonary artery secondary
to thromboembolism or neoplasm. Though this patient did not have a family history of
autosomal dominant polycystic kidney disease (ADPKD), he had multiple cysts in both
the kidneys which is a well-recognized genetic entity (chromosome 16p13 and 4q21) in
association with various extra-renal manifestations. To the best of our knowledge, this
is the first reported case with coexistence of RAA and probable ADPKD which are two
separate genetic entities, the former usually manifesting in childhood and the later in
adults.
FURTHER READING
1. Rajesh V, Prakasha SR, Giridhar BH, Prasad R. An adult with haemoptysis: A rare case of congenital
anomaly. Indian J Chest Dis Allied Sci. 2015;57:31-3.
2. Kuo PH, Wu HD, Lee LN. A patient with haemoptysis and a smaller right lung. Eur Respir J.
1996;9:847-9.
3. Bava G, Sacco O, Bava E, Borini I, Pesce F, Toma P, et al. Recurrent bronchopulmonary infections in the
left lung of a 21-month-old female. Eur Respir J. 2006;27:648-1.
4. Alison M, Garel L, Bigras JL, Déry J, Lapierre C. Unilateral absence of pulmonary artery in children:
bronchovascular anatomy, natural course and effect of treatment on lung growth. Pediatr Radiol.
2011;41:459-68.
5. Gülen F, Kar S, Midyat L, Demir E, Özyurt S, Özyürek AR, et al. A rare clinical presentation of pulmonary
hypoplasia. OJ Ped. 2011;1:75-8.
6. Warburton D, Schwarz M, Tefft D, Flores-Delgado G, Anderson KD, Cardoso WV. The molecular basis
of lung morphogenesis. Mech Devel. 2000;92:55-81.
7. Hislop AA. Airway and blood vessel interaction during lung development. J Anat. 2002;201:325-34.
8. Anand R, Dooley KJ, Williams WH, Vincent RN. Follow-up of surgical correction of vascular anomalies
causing tracheobronchial compression. Pediatr Cardiol. 1994;15:58-61.
9. Edwards JE. Anomalies of the derivatives of the aortic arch system. Med Clin North Am. 1948;
32:925-48.
10. McElhinney DB, Clark BJ, Weinberg PM, Kenton ML, McDonald-McGinn D, Driscoll DA, et al.
Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and
branching. J Am Coll Cardiol. 2001;37:2114-9.
11. Dodge-Khatami A, Backer CL, Dunham ME, Mavroudis C. Right aortic arch, right ligamentum, absent
left pulmonary artery: a rare vascular ring. Ann Thorac Surg. 1999;67:1472-4.
CASE 24
Allergic Bronchopulmonary Aspergillosis

with Aspergilloma Developing
in a Cane Sugar Mill Worker
CASE REPORT
A 37-year-old nonsmoker, male patient, sugar mill worker by occupation presented to us
with chief complaints of recurrent cough, breathlessness, and hemoptysis for 13 years. He
also gave history of recurrent low-grade febrile episodes associated with malaise without
any weight loss, and passage of mucus plugs with sputum. He had never smoked, consumed
alcohol, or chewed tobacco and had no history of diabetes mellitus or hypertension. There
was no family history of hypertension, diabetes mellitus, immunodeficiency disease or
neoplasm. Patient was having no history of contact to a tuberculosis patient. He had received
two courses of adequate antitubercular treatment without any bacteriological evidence
of Mycobacterium tuberculosis. On physical examination, the patient was afebrile with a
pulse rate of 96 beats/min, respiratory rate of 26 breaths/min and a right arm supine blood
pressure of 120/68 mm Hg. There was no pallor, cyanosis or clubbing. Chest examination
was unremarkable on inspection, palpation, and percussion. On auscultation, bilateral
rhonchi were audible. Examination of other systems was unremarkable. Routine investigation
showed: hemoglobin 11 g%, total leukocyte count 14,800/mm3, differential count: neutrophils
52%, lymphocyte 30%, eosinophil 18% (absolute eosinophils count was 2,664), platelets count:
2.9 lacs/mm3 and erythrocyte sedimentation rate: 18 mm/h. Enzyme linked immunosorbent
assay (ELISA) for human immunodeficiency virus was negative. Sputum smears for acid-fast
bacilli were repeatedly negative and the culture by BACTEC did not show any mycobacteria.
But the sputum on fungal culture grew Aspergillus fumigatus. Mantoux test (10 tuberculin units)
showed an induration of 4 mm at 72 hours. On further evaluation, his detailed history revealed
that he had episodes of running nose, sneezing, breathlessness and wheezes, since childhood,
especially with change of season in months of March and November for which he received
symptomatic medications. Family history of bronchial asthma was also present in his mother.
Review of his serial chest radiographs revealed evidence of cavity with “air crescent sign” in right
middle zone, gloved finger appearance in left upper zone and fleeting pulmonary infiltrates
(Figs. 1 to 6). High-resolution computed tomography (HRCT) of thorax revealed bilateral
central bronchiectasis with aspergilloma in anterior segment of right upper lobe (Fig. 7).
Thus, a possibility of allergic bronchopulmonary aspergillosis (ABPA) with aspergilloma was
suspected. Patient was investigated further for this. Skin prick test with Aspergillus fumigatus
antigen showed a positive reaction for type I and also late type III (Arthus) hypersensitivity
in comparison to positive control (histamine phosphate 1 mg/mL). Total IgE was 2,504 IU/mL
Allergic Bronchopulmonary Aspergillosis with Aspergilloma Developing... 89
FIG. 1: Chest X-ray showing rounded opacity in right

middle zone when patient received antitubercular drugs.
FIG. 2: Chest X-ray suggestive of fungal ball in right middle zone

with shadow in right parahilar and left upper and middle zone.
FIG. 3: Chest X-ray suggestive of fungal ball in right middle zone and
resolution of shadow in right parahilar and left upper and middle zone.
resolution of shadow in right parahilar and left upper and middle zone.
presence of nonhomogenous opacity in left upper and middle zone.
FIG. 6: Chest X-ray suggestive of fungal ball in right middle

zone and resolution of shadow in left upper and middle zone.
Allergic Bronchopulmonary Aspergillosis with Aspergilloma Developing... 91
FIG. 7: High-resolution computed tomography (HRCT) thorax

showing bilateral bronchiectasis and air crescent sign suggestive
of fungal ball in anterior segment of right upper lobe.
(reference range 0–100 IU/mL). Specific IgG and IgE against A. fumigatus by ELISA were 124.2 IU/L
and 24.24 KU/L. Thus, a diagnosis of ABPA with concomitant aspergilloma was established. Oral
corticosteroid being the mainstay of treatment, the patient was initiated on oral prednisolone
with a dose of 40 mg once daily along with inhaled budesonide 400 g with formoterol in two
divided doses and inhaled salbutamol as and when required. After 1 month of therapy, the
patient had improved clinically and radiographic pulmonary infiltrates got cleared, along with
fall in serum titers of IgE antibody.
DISCUSSION
Regarding coexistence of allergic bronchopulmonary aspergillosis (ABPA) and aspergil
loma, it is postulated that in genetically predisposed individuals aspergilloma may act
as nidus for antigenic exposure leading to development of ABPA. On the other hand, it
is also said that chronic lung damage induced by ABPA appears to provide a favorable
conditions for the formation of aspergilloma which might be accelerated by therapy with
corticosteroids. Although cavitations is uncommon in a case of ABPA, but it may occur
in 3% of cases, which can be colonized by Aspergillus to form aspergilloma. Occurrence
of ABPA in our patient, who is a sugar mill worker, is significant in the light of previous
literature on occurrence of this disease entity in sugar mill workers. Process of lung
destruction proceeds silently in ABPA as about one third of these cases are completely
asymptomatic. In present case, it appears that patient had already developed central
bronchiectasis and aspergilloma. It was this indolent course of disease which prevented
our patient from seeking timely medical advice on one hand and delayed the diagnosis
on the other hand. Frequently, symptoms like hemoptysis, cough, fever etc., caused by
ABPA/aspergilloma are attributed to active tuberculosis and managed incorrectly, as
happened in our case. Since it is not uncommon to detect evidence of hypersensitivity to
Aspergillus, in presence of aspergilloma, and aspergilloma can develop as a complication
of ABPA, it may almost be impossible to establish whether ABPA followed or preceded the
development of aspergilloma (as in our case). A wide variety of chest radiographic changes
are known to be associated with ABPA. These changes include normal chest radiography,
hyperinflation, various infiltrate patterns, consolidation, parallel lines and ring shadows,
nodules, avascular areas, “honey combing”, “tooth paste” shadows, “gloved finger”, band
shadows and tramline shadows, changes such as fibrosing alveolitis, lobar shrinkage,
and atelectasis as well as pseudo hilar adenopathy and pleural thickening. Although the
chest radiographic appearance is commonly abnormal in patients with ABPA, it is not
invariably so, nor does a normal appearance exclude the diagnosis of ABPA. CT of the
thorax can provide a sensitive method for the assessment of bronchial, parenchymal, and
pleural abnormalities in patients with ABPA and should constitute a part of the diagnostic
work-up of the disease along with plain chest radiographs. Oral corticosteroids, to date,
remain the cornerstone for the treatment of ABPA. The exact role of antifungal agents
is yet to be determined for both ABPA as well as aspergilloma. Specific therapy is not
required for patients with asymptomatic aspergilloma. Surgical treatment carries risk with
mortality ranging from 7 to 23%, due to which it should be considered in patients with
massive hemoptysis and adequate pulmonary reserve.
FURTHER READING
1. Prasad R, Garg R, Sanjay, Shukla A. Allergic bronchopulmonary aspergillosis with aspergilloma
developing in a cane sugar mill worker. Internet J Pulm Med. 2006;9.
2. Gefter WB. The spectrum of pulmonary aspergillosis. J Thorac Imaging. 1992;7:56-74.
3. Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic broncho pulmonary aspergillosis: staging
as an aid to management. Ann Intern Med. 1982;96:286-91.
4. Shah A, Khan ZU, Chaturvedi S, Ramchandran S, Randhawa HS, Jaggi OP. Allergic bronchopulmonary
aspergillosis with coexistent aspergilloma. A long-term follow up. J Asthma. 1989;26:109-15.
5. Kumar R. Allergic bronchopulmonary aspergillosis with aspergilloma mimicking pulmonary
tuberculosis. Indian J Tub. 2000;47:103-5.
6. Ein ME, Wallace RJ, Williams TW. Allergic bronchopulmonary aspergillosis-like syndrome consequent
to aspergilloma. Am Rev Respir Dis. 1979;199:811-20.
7. Phelan MS, Kerr IH. Allergic bronchopulmonary aspergillosis: The radiological appearances during
long term follow-up. Clin Radiol. 1984;35:385.
8. Metha SK, Sandhu RS. Immunological significance of A. fumigatus in cane sugar mills. Arch Environ
Health. 1983;38:41-6.
9. Safirstein BH, D'Souza MF, Simon G, Tai EHC, Pepy J. Five year follow up of allergic broncho
pulmonaryaspergillosis. Am Rev Respir Dis. 1973;108:450-9.
10. Israel RH, Poe RH, Bomba PA, Gross RA. The rapid development of an aspergilloma secondary to
allergic broncho pulmonary aspergillosis. Am J Med Sci. 1980;280:41-4.
11. Davies D, Sommer AR. Pulmonary aspergillomas treated with corticosteroids. Thorax. 1972;27:156-62.
12. Anderson CJ, Craig S, Bardana EJ Jr. Allergic bronchopulmonary aspergillosis and bilateral fungal
balls terminating in disseminated aspergillosis. J Allergy Clin Immunol. 1980;65:140-4.
13. Mintzer RA, Rogers LF, Kruglik GD, Rosenberg M, Neiman HL, Patterson R. The spectrum of radiologic
findings in allergic bronchopulmonary aspergillosis. Radiology. 1978;127:301-7.
14. Rosenberg M, Mintzer R, Aaronson DW, Patterson R. Allergic bronchopulmonary aspergillosis in
three patientswith normal chest X-ray films. Chest. 1977;72:597-600.
15. Cockrill BA, Hales CA. Allergic bronchopulmonary aspergillosis. Ann Rev Med. 1999;50:303-16.
CASE 25
A Rare Coexistence of Pulmonary

Nocardiosis and Aspergillosis in Patient of
CASE REPORT
A 62-year-old male patient, vegetable vendor by occupation, presented with a low grade
fever, breathlessness, and cough with mucoid expectoration for 4 days. He denied any
history of chest pain, loss of weight, and appetite. He was a previously diagnosed case
of grade D chronic obstructive pulmonary disease (COPD) taking inhaled long-acting
bronchodilators as well as steroids and was under regular follow-up since last 3 years.
The patient also had three exacerbations in the last 1 year despite adequate adherence
to treatment. He was an ex-smoker with 30 pack years of smoking, who had quit smoking
4 years back. He denied alcohol and illicit drug use, any history of hypertension or diabetes
in the past and history of exposure to organic or inorganic dust or other noxious substances.
Physical examination revealed tachycardia (120/min), tachypnea (28/min), and was in
respiratory distress with prominent accessory muscles of respiration. Arterial blood gas
analysis revealed type 1 respiratory failure. Systemic examination revealed vesicular breath
sounds with prolonged expiration and coarse crackles in bilateral infrascapular region on
auscultation. Blood counts showed leukocytosis (24,000/cm3). Other biochemical analysis
reports were within normal limits. The serology for human immunodeficiency virus (HIV)
was negative. The chest radiograph showed hyperlucent lung fields with bilateral middle
and lower zone air space consolidation (Fig. 1). Patient was initially admitted to ward and
treated for acute exacerbation with oxygen, injectable steroids, inhaled bronchodilators
as well as steroids and empirical course of piperacillin–tazobactam and amikacin. High-
resolution computed tomographic (HRCT) thorax revealed emphysematous changes with
bilateral lower lobe consolidation with cavitation (Figs. 2A and B). Despite the treatment,
patient’s clinical condition further deteriorated and so was shifted to intensive care unit after
24 hours. Serial chest radiograph revealed progression of bilateral air space consolidation
(Fig. 3). Patient landed into septic shock as fractional inspiratory oxygen (FiO2) requirement
increased and needed vasopressor support for hypotension. Blood and urine cultures were
sterile. Sputum for gram staining showed positive branching filaments suggestive of Nocardia
species together with hyaline septate branching filaments suggestive of Aspergillus species.
Further, lactophenol cotton blue mount of sputum under magnification 40× revealed acute
angle branching septate hyphae suggestive of Aspergillus species (Fig. 4). Ziehl–Neelsen
(Z–N) and Gomori Methenamine Silver (GMS) staining of sputum under magnification 400×
and 1,000× respectively revealed long delicate branched filaments that were weakly acid fast
FIG. 1: Chest skiagram at presentation

showing bilateral middle as well as lower
zone consolidation with cavitation on
left side.
A B
FIGS. 2A AND B: High-resolution computed tomographic scan of same patient (mediastinal
and lung window respectively) showing bilateral lower lobe consolidation with air bronchogram
with centriacinar emphysematous changes.
positive and beaded pattern suggestive of Nocardia species (Figs. 5A and B). These were later
confirmed in cultures as Nocardia asteroides sensitive to trimethoprim–sulfamethoxazole,
imipenem meropenem, amikacin, and gentamicin as well as Aspergillus fumigatus sensitive
to amphotericin B, voriconazole, and itraconazole. Antibiotics were upgraded to imipenem
500 mg every 6 hours and trimethoprim–sulfamethoxazole 80 mg every 8 hours to
provide adequate coverage for Nocardia and injectable voriconazole was administered
for Aspergillus at a dose of 4 mg/kg every 12 hours. Despite this, patient’s clinical condition
further deteriorated and patient developed septic shock with multiorgan failure. Patient
was electively intubated and put on mechanical ventilation in view of worsening clinical
status. Endotracheal aspirate sent for culture confirmed the presence of A. fumigatus and
A Rare Coexistence of Pulmonary Nocardiosis and Aspergillosis in Patient... 95
N. asteroides. Fiberoptic bronchoscopy revealed no tracheobronchial mucosal abnormality

and obvious endobronchial growth. However, same organisms were isolated on bronchial
lavage as sent for culture. Serum as well as lavage galactomannan levels were negative. After
3 days of mechanical ventilation, patient’s clinical condition further deteriorated requiring
high FiO2 requirement and vasopressor support. The patient eventually succumbed to death
despite of treatment. Postmortem biopsy of lung tissue was sent for culture and revealed the
growth of N. asteroids and A. fumigatus. Concurrent infection with both of these organisms was
established as consistently isolated in sputum, endotracheal aspirate, bronchoalveolar lavage,
and postmortem lung tissue.
FIG. 3: Serial chest skiagram after 3 days of

admission showing progression of bilateral
middle as well as lower zone consolidation
extending to upper zones.
FIG. 4: Lactophenol cotton blue mount of sputum

under magnification 40× showing acute angle branch
ing septate hyphae of Aspergillus species. (For color
A B
FIGS. 5A AND B: Ziehl–Neelsen (Z–N) staining and Gomori Methenamine Silver (GMS) mount
of sputum under magnification 400× and 1,000× respectively showing long delicate branched
filaments that are weakly acid fast and beaded pattern suggestive of Nocardia species. (For color
DISCUSSION
Nocardia species is an aerobic branching, filamentous gram positive, weakly acid-fast
bacteria that exists as soil saprophytes. N. asteroids are the most frequent cause of pul
monary infection in humans among various species with incidence of 85%. Aspergillus
species is a saprophytic, aerobic fungus that develops on dead or decaying organic matter,
produces airborne spores that can be inhaled by man and usually affects immunocom
promised patients but it can develop in immunocompetent as well. Concurrent infection
of Nocardia and Aspergillus though reported in literature is a rare occurrence. Clinically
pulmonary nocardiosis present with cough with sputum, dyspnea, fever, chest pain, and
less frequently hemoptysis. In general, the clinical course is chronic with the duration
of symptoms lasting for weeks to months often masquerading as lung cancer which was
similar to the clinical presentation of our patient. However, pulmonary aspergillosis has
varied manifestation depending on the host’s immune status or pulmonary structure.
The spectrum of pulmonary disease ranges from noninvasive disease, as colonization
of organism or the presence of a fungus ball (aspergilloma), or an allergic response
responsible for allergic bronchopulmonary aspergillosis (ABPA), to semi-invasive or
invasive infections such as chronic necrotizing pneumonia and invasive pulmonary
aspergillosis. Both Aspergillus and Nocardia infections are more likely to present in
patients who are immune compromised such as alcoholism, HIV, prolonged steroid
use, cancer chemotherapy, solid organ as well as bone marrow transplantation, have
structural lung diseases such as cystic fibrosis, bronchiectasis, old healed post tubercular
fibro-cavitary disease, COPD or a history of surgery or trauma. A patient with COPD may
have an increased susceptibility to fungal infection for several reasons, as a change in
bronchial architecture, use of steroids, frequent hospitalization or antibiotic treatments,
comorbidity factors (drug addiction and diabetes, etc.) and these reasons may be linked
to concurrent Aspergillus and Nocardia infections in our patient. The radiological presen
tation of pulmonary nocardiosis is nonspecific. The most common radiological findings
are consolidations and large irregular nodules. Nodules, cavitary masses, pleural effusion,
pneumothorax, ground-glass opacities, and interstitial patterns can occur as well.
Invasive aspergillosis radiologically presents as nodules surrounded by a halo of ground-
glass attenuation (“halo sign”) or pleura-based, wedge-shaped areas of consolidation.
A Rare Coexistence of Pulmonary Nocardiosis and Aspergillosis in Patient... 97
These findings correspond to hemorrhagic infarcts. In severely neutropenic patients,

the halo sign is highly suggestive of angio-invasive aspergillosis. In a similar case report
of concurrent Nocardia and Aspergillus in a patient with old tubercular cavity, contrast
enhanced computed tomography (CECT) thorax revealed a soft tissue density mass with
speculated margins and satellite nodular specks in the right lower lobe. Patient presented
with areas of ground glassing and consolidation with cavitation in present case. The
diagnosis should always be based on isolation of Nocardia species in respiratory secretions.
Previous study has found sputum cultures to be positive in 90% of the present patients, and
in 100% when bronchoalveolar lavage was performed. Nocardia species is a slowly growing
microorganism that requires a prolonged period of incubation. Cultures should be
maintained for at least 3 weeks before being discarded as negative. Sputum, endotracheal
samples for direct microscopy and culture showed the presence of gram positive branching
hyphae suggestive of Nocardia and hyaline septate branching hyphae suggestive of
Aspergillus. The sputum and endotracheal secretions for modified Z–N stain showed the
presence of weakly positive acid-fast bacilli further supporting the presence of Nocardia.
Treatment of nocardiosis usually involves a sulfonamide containing regimen such as
trimethoprim–sulfamethoxazole (TMP–SMX). Other alternatives are amikacin, imipenem,
third-generation cephalosporins, minocycline, netilmicin, and amoxicillin–clavulanic.
Experimental studies have shown in vitro synergy with imipenem–cefotaxime, cefotaxime–
amikacin, and imipenem–amikacin with good clinical results. Voriconazole is a potent
new antifungal compound that is efficacious in a significant proportion of patients with
aspergillosis. It is most efficacious as primary therapy for invasive aspergillosis. However,
in the present case, intravenous imipenem, voriconazole, and oral TMP–SMX were not
successful and patient succumbed to death and the reason could be rapid progression of
the disease. Pulmonary nocardiosis is associated with very high mortality, ranging from
14 to 40% increasing to 60–100% when dissemination to the central nervous system (CNS)
occurs. So a coexistent infection is expected to have a significant morbidity and mortality
and in this case despite timely diagnosis and appropriate intervention, patient died due
to sepsis-induced multiorgan dysfunction syndrome. Though occurrence of nocardiosis
and aspergillosis in immunocompromised subjects are well established, they should be
kept as a part of differential work up in immunocompetent patients with COPD as the
only risk factor. Both infections pose a diagnostic challenge to clinicians masquerading
as malignancy or pulmonary tuberculosis due to the indolent course of illness and
radiological presentation. The concurrent existence of Aspergillus and Nocardia deserves
special attention as both infections are associated with significant morbidity and mortality
requiring timely diagnosis and management.
FURTHER READING
1. Balasubramanium V, Singh A, Gupta P, Prasad R. A rare coexistence of pulmonary nocardiosis and
aspergillosis in patient of COPD. Egypt J Chest Dis Tuberc. 2016;65:405-9.
2. Rivière F, Billhot M, Soler C, Vaylet F, Margery J. Pulmonary nocardiosis in immunocompetent
patients: Can COPD be the only risk factor? Eur Respir Rev. 2011;121:210-2.
3. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: A clinical review. Eur Respir Rev. 2011;20:
156‑74.
4. He H, Jiang S, Zhang L, Sun B, Li F, Zhan Q, et al. Aspergillus tracheobronchitis in critically ill patients
with chronic obstructive pulmonary diseases. Mycoses. 2014;57:473-82.
5. Kontogiorgi M, Opsimoulis P, Kopterides P, Savva A, Kalodimou VE, Belesiotou E, et al. Pulmonary
nocardiosis in an immunocompetent patient with COPD: the role of defective innate response.
Heart Lung. 2013;42:247-50.
6. Beaman BL, Burnside J, Edwards B, Causey W. Nocardia infections in the United States, 1972–1974.
J Infect Dis. 1976;134:286-9.
7. Cabral FC, Marchiori E, Zanetti G, Takayassu TC, Mano CM. Semi-invasive pulmonary aspergillosis in
an immunosuppressed patient: a case report. Cases J. 2009;2:40.
8. Kearon MC, Power JT, Wood AE, Clancy LJ. Pleural aspergillosis in a 14 year old boy. Thorax.
1987;42:477-8.
9. Kaya S, Yavuz I, Cobanoglu U, Ural A, Yilmaz G, Koksal I. Fatal sino-orbital aspergillosis in an
immunocompetent case. Mikrobiyol Bul. 2011;45:546-52.
10. Kose S, Cavdar G, Senger SS, Akkoclu G. Central nervous system aspergillosis in an immunocompetent
patient. J Infect Dev Ctries. 2011;5:313-5.
11. Anderson M, Kuźniar TJ. Pulmonary nocardiosis in a patient with chronic obstructive pulmonary
disease—case report and literature review. Pneumonol Alergol Pol. 2012;6:565-9.
12. Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ. Clinical and laboratory features of the Nocardia
spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19:259-82.
13. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of
aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect
Dis. 2008;46:327-60.
14. Patterson TF, Kirkpatrick WR, White M, Hiemenz JW, Wingard JR, Dupont B, et al. Invasive aspergillosis.
Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group. Medicine
(Baltimore). 2000;79:250-60.
15. Feigin DS. Nocardiosis of the lung: chest radiographic findings in 21 cases. Radiology. 1986;159:
9-14.
16. Hwang JH, Koh WJ, Suh GY, Chung MP, Kim H, Kwon OJ, et al. Pulmonary nocardiosis with multiple
cavitary nodules in a HIV-negative immunocompromised patient. Intern Med. 2004;43:852-4.
17. Silva AC, Martins EM, Marchiori E, Neto GT. Nocardiose pulmonarempaciente com sı´ndrome da
imunodeficieˆncia adquirida: relato de caso. Radiol Bras. 2002;35:235-8.
18. Díez-García MJ, Andreu AL, Chiner E. Bronchopneumonia due to Nocardia asteroides in a man with
chronic obstructive pulmonary disease. Arch Bronconeumol. 2005;41:642-3.
19. Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia:
characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology.
1985;157:611-4.
20. Mohan A, Sharma SK, Arora VK, Sharma S, Prakash J. Concurrent pulmonary Aspergillosis and
Nocardiosis in an old tubercular cavity masquerading as malignancy in an immunocompetent
individual. Respir Med CME. 2008;1:231-4.
CASE 26
Necrotizing Mediastinal Lymph

Nodes in Sarcoidosis
CASE REPORT
A 27-year-old female presented with the complaints of dry cough, low-grade fever for 1 year,
and nodular skin lesions for 6 months. Her past history revealed that she was prescribed
moxifloxacin 400 mg, cycloserine 500 mg, ethionamide 500 mg, pyrazinamide 1,500 mg,
and combutol 800 mg with injection kanamycin. About 75 g daily for 6 months, for multidrug-
resistant tuberculosis on the basis of Gene Xpert report on bronchoalveolar lavage fluid which
showed Mycobacterium tuberculosis and rifampicin resistance. However, there was no response
even after 14 months of treatment, instead she developed adverse drug reactions like joint
pains and hypothyroidism in due course of time after starting antitubercular treatment.
Complete blood count, hepatic, and renal function tests were within normal limits. Her
serum uric acid was 15.9 mg/dL and thyroid-stimulating hormone was 15.9 µIU/mL. Her
contrast-enhanced computed tomography (CECT) of the chest (Fig. 1) 14 months back
FIG. 1: Contrast-enhanced computed tomography

(CECT) chest (mediastinal window) 14 months
back showing necrosis in the lymph nodes of aorto
pulmonary window.
showed necrosis in the lymph nodes of aorto pulmonary window. Follow-up CECT chest
after taking treatment for multidrug-resistant tuberculosis for 14 months showed multiple
large necrotic nodes in right paratracheal region measuring 15.5 mm, left paratracheal
region measuring 13 mm, aorticopulmonary (AP) window (14.5 mm) left hilar (16 m) right
hilar (12 mm), and sub carinal (14 mm) (Fig. 2). Her Mantoux test was negative. Her serum for
angiotensin-converting enzyme level was 62.8 U/L, total urinary calcium was 212.94 mg/24 h
and urinary calcium was 10.92 mg/dL. Histopathological examination of biopsy specimen
from the skin nodules revealed dermis with fair number of vaguely formed epithelioid
granuloma surrounded by mixed inflammatory infiltrate suggestive of sarcoidosis. Her
ophthalmic examination was normal and ultrasonography (USG) whole abdomen showed
no evidence of retroperitoneal lymphadenopathy and hepatospleenomegaly. She was put on
tablet prednisolone 40 mg daily on the basis of histopathological examination of the biopsy
specimen from the skin nodule. About 2 weeks after initiation of oral corticosteroids her skin
lesions subsided drastically with resolution of other chest symptoms. CECT chest (mediastinal
window) showed significant regression in the size of mediastinal lymph nodes after taking oral
corticosteroids (Fig. 3) for 2 months. On account of steroid-induced side effects (remarkable
weight gain), the dose of prednisolone was tapered rapidly and she was continued with 5 mg
prednisolone on alternate days till date.
FIG. 2: Follow-up contrast-enhanced computed

tomography (CECT) chest after taking treatment
for multidrug-resistant tuberculosis for 14 month
showing multiple large necrotic nodes in right para-
tracheal region, left paratracheal region measuring,
aorticopulmonary (AP) window, left hilar, right hilar,
and subcarinal.
Necrotizing Mediastinal Lymph Nodes in Sarcoidosis 101
FIG. 3: Follow-up contrast-enhanced computed

tomo graphy (CECT) chest (mediastinal window)
showing significant regression in the size of medias-
tinal lymph nodes after taking oral corticosteroids for
2 months.
DISCUSSION
Sarcoidosis is a multisystem disorder of unknown cause that is characterized by the
presence of noncaseating granulomas and the proliferation of epithelioid cells. The
lungs and mediastinal lymph nodes are involved in over 90% cases with thoracic
sarcoidosis, accounting for most morbidity and mortality. In general, sarcoidosis
affects young adults with a slightly higher prevalence in females. Hilar and mediastinal
lymphadenopathy are common manifestation of sarcoidosis and may be seen as notable
abnormality in conjunction with parenchymal disease. The lymphadenopathy is typically
symmetrical in distribution with involvement of hilar, paratracheal, aorto pulmonary
window, and subcarinal region, hilar involvement is most characteristic. Non-necrotizing
granulomas are characteristic histological finding of sarcoidosis but necrosis or cavitation
occurs in <1% of patients. Diagnosis is based on compatible clinical and radiological
findings and histological finding of noncaseating epithelioid cell granulomas and the
elimination of other granulomatous diseases. However, in our case significant necrosis was
visible in mediastinal lymph nodes in CT thorax. Rockoff et al. in a systematic review have
reported the relative incidence and classification of unusual thoracic manifestations of
sarcoidosis. V Karkhanis et al. reported a case of parotid swelling, provisionally diagnosed
as tuberculous inflammation in view of granuloma showing caseous necrosis on cytology,
later on it was diagnosed as sarcoidosis. The CT thorax of this patient had homogenously
enhancing mediastinal lymph nodes.
We report this case of sarcoidosis with significant necrosis in mediastinal lymph nodes
as this is a rare phenomenon and can mislead the treating physician to diagnose it as
tuberculosis.
FURTHER READING
1. Prasad R, Verma A, Batra S, Gupta N. Necrotising mediastinal lymph nodes in sarcoidosis. Indian J
Chest Dis Allied Sci. 2018;60:81-2.
2. Colby TV, Carrington CB. Infiltrative lung disease. In: Thurlbeck WM, (Ed). Pathology of the Lung.
Stuttgart: Thieme Medical. 1988. pp. 425-517.
3. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European
Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous
Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee,
February 1999. Am J Respir Crit Care Med. 1999;160:736‑55.
4. Hillerdal G, Nöu E, Osterman K, Schmekel B. Sarcoidosis: Epidemiology and prognosis. A 15‑year
European study. Am Rev Respir Dis. 1984;130:29‑32.
5. Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H Jr, Bresnitz EA, et al. Clinical
characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med.
2001;164:1885‑9.
6. Yeboah J, Afkhami M, Lee C, Sharma OP. Necrotizing sarcoid granulomatosis. Curr Opin Pulm Med.
2012;18:493‑8.
7. Rockoff SD, Rohatgi PK. Unusual manifestations of thoracic sarcoidosis. AJR Am J Roentgenol.
1985;144:513‑28.
8. Karkhanis V, Joshi JM. All that caseate is not T.B. Lung India. 2007;24:100-1.
CASE 27
New Case of Pulmonary Tuberculosis with

Radiological Clearing after Stoppage of
Antitubercular Treatment
CASE REPORT
A 45-year-old male chronic smoker (20 beedis per day for 25 years) came to us in 2004 in
a very low general condition with complaints of cough on and off for 3 months, fever for
3 months, decreased appetite for 3 months, and breathlessness for 2 months. On general
examination, respiratory rate was 26 breaths/min, and pulse was 96 beats/min. There was
no clubbing, cyanosis or lymphadenopathy. Respiratory system examination showed
bilateral crepts. Chest X-ray showed bilateral extensive disease (Fig. 1). Sputum for acid-
fast bacilli (AFB) was positive 3+. Patient was registered in RNTCP for Category I treatment
(isoniazid, rifampicin, pyrizinamide, and ethambutol) thrice weekly for 2 months followed by
4 months of isoniazid and rifampicin thrice weekly. After 2 months of treatment, he improved
bacteriologically (sputum for AFB was negative), radiologically as well as clinically. He gained
6 kg of weight in 2 month’s time. Patient improved radiologically further after completion of
treatment at the end of 6 months (Fig. 2). There were a lot of residual lesions present in chest
FIG. 1: Chest X-ray posteroanterior (PA) view

showing bilateral extensive disease.
X-ray even after completing 6 months of treatment but his treatment was stopped at the end
of 6 months as his sputum for AFB remained negative. Patient was followed up every 3 months
in the 1st year (Figs. 3 and 4) and then every 6 months for next 5 years (Fig. 5). It is very
interesting to note that he improved radiologically further without any treatment (Fig. 4). One
should always remember that radiological clearing lags behind the clinical and bacteriological
improvement and one should not unnecessarily overuse the antitubercular drugs. Patient
came in very low general condition because of the delay in the diagnosis.
FIG. 2: Chest X-ray posteroanterior (PA) view showing

lot of radiological clearing of lesions after 6 months of
treatment but lot of residual lesions were still present
when antituberculous drugs were stopped.
FIG. 3: Chest X-ray posteroanterior (PA) view after

3 months of completion of treatment showing further
clearing of lesions without any treatment.
New Case of Pulmonary Tuberculosis with Radiological Clearing... 105

15 months of completion of treatment showing
further clearing of lesions.

2 years of completion of treatment showing further
clearing of lesions.
DISCUSSION
Tuberculosis (TB) occurs worldwide and remains an important cause of morbidity
and mortality in many countries. Ideally, good treatment of TB should achieve sputum
conversion in almost all the patients provided correct regimens are prescribed and taken.
There will be hardly any relapse if duration of treatment has been sufficient and there will
be no emergence of drug resistance. In 2018, there were an estimated 10 million new cases
of TB causing death to 1.5 million people globally. There were an estimated 2.74 million
(27% of the total cases) new cases in India and 0.42 million people died in our country due
to TB in 2018.
Newer Changes in Definitions

The word TB suspect has been replaced with presumptive TB. Presumptive pulmonary
TB refers to a person with any of the symptoms or signs suggestive of TB: Cough
>2 weeks, fever >2 weeks, significant weight loss, hemoptysis, and any abnormalities
in chest radiography. Microbiologically confirmed TB case refers to a presumptive
TB patient with biological specimen positive for AFB, or positive for Mycobacterium
tuberculosis on culture, or positive for TB through quality assured rapid diagnostic
molecular test. Clinically diagnosed TB case refers to a presumptive TB patient who is not
microbiologically confirmed, but has been diagnosed with active TB by a clinician on the
basis of X‑ray abnormalities, histopathology or clinical signs with a decision to treat the
patient with a full course of anti‑TB treatment. “Ancillary diagnostic tests” refer to organ
system-specific tests such as pleural fluid adenosine deaminase activity (ADA) in pleural
TB, or cerebrospinal fluid (CSF) biochemistry and differential cell count in TB meningitis.
A presumptive case started on antitubercular therapy (ATT) empirically, without
microbiological testing, should also be considered a clinically diagnosed case. Relapse TB
case has been replaced with recurrent TB case which is defined as, TB patients previously
declared as successfully treated (cured/treatment completed) and who is subsequently
found to be microbiologically confirmed TB case is a recurrent TB case. Treatment after
loss to follow-up (previously treatment after default) are TB patients previously treated for
TB for 1 month or more and who was declared lost to follow-up in their most recent course
of treatment and subsequently found microbiologically confirmed TB cases. Presumptive
treatment failure, a patient who has no satisfactory clinical or imaging response to
treatment after completing 3–6 months ATT.
Newer Modalities in Diagnosis

Sputum smear microscopy and culture of M. tuberculosis and drug susceptibility (DST)
serves as the gold standard for diagnosis of TB. Many healthcare workers still rely on
a long-used reliable method called sputum smear microscopy to diagnose TB but
microscopy detects only half the number of TB cases and cannot detect drug-resistance.
Diagnosis of drug resistant TB is confirmed by DST from reliable and reputed laboratories
under constant quality control. However, one has to keep in mind the limitation of highly
specific DST because the technique is complex, difficult to perform accurately even when
skilled personnel are available and laboratory facilities are of high standard. Further one
should realize that laboratories vary in their reliability; errors do occur in laboratories,
different DST reports are obtained from the same patient from different laboratories.
Susceptibility result for isoniazid, rifampicin, flouroquinolones, and the injectables is
very reliable. For other drugs, it is less reliable and individualized treatments based on
DST for these drugs should be used with great caution. The effectiveness or ineffectiveness
of a drug cannot be predicted by DST with 100% certainty. Furthermore, the DST to
second-line drugs (SLDs) is very variable. Keeping above facts in mind it is pertinent that
DST should not be accepted uncritically and quality assured laboratories performing DST
is needed.
Treatment of Tuberculosis
Tuberculosis is a treatable and curable disease. Treatment of TB comprised of treatment of
drug sensitive and drug resistant TB.
Drug Susceptible Tuberculosis

Active, drug-susceptible TB disease is treated with a daily standard 6 month course
of anti TB drugs: 2 months of isoniazid (H), rifampicin (R), ethambutol (E), and
pyzinamide (Z) followed by 4 months of isoniazid (H) and rifampicin (R) or rifampicin
(R), isoniazid (H), and ethambutol (E) especially in countries where primary isoniazid
resistance is high. In India, rifampicin (R), isoniazid (H), and ethambutol (E) is given
for 4 months in continuation phase (Table 1 and Box 1 and 2). They are provided with
information, supervision, and support to the patient by a health worker or trained
volunteer. Without such support, treatment adherence can be difficult and the disease
can spread. TB patients returning after defaulting or relapsing from their first treatment
course may receive the retreatment regimen containing first-line drugs: 2 months of
isoniazid (H), rifampicin (R), ethambutol (E), pyzinamide (Z) and streptomycin (S)
followed by 1 month of isoniazid (H), rifampicin (R), ethambutol (E), and pyzinamide
(Z) followed by 5 months of isoniazid (H), rifampicin (R), and ethambutol (E); when
DST result becomes available regimen should be adjusted accordingly. As per WHO
2017 guidelines for treatment of drug-susceptible TB in patients who require TB
retreatment, the Category II regimen should no longer be prescribed and DST testing
should be conducted to inform the choice of treatment regimen. Patients eligible for
retreatment should be referred for a rapid molecular test or DST testing to determine at
least rifampicin resistance and preferably also isoniazid resistance status. On the basis
of the DST profile, a standard first-line treatment regimen (2HRZE/4HR or 2HRZE/4HRE
) can be repeated if no resistance is documented; and if rifampicin resistance is present,
an multidrug-resistant tuberculosis (MDR-TB) regimen should be prescribed according
to WHO’s recent drug-resistant TB treatment guidelines. In patients who have had
treatment interruption, the reason for the interruption such as medication stock-outs,
adverse effects from medicines or need for greater patient/provider education should
be addressed. The 4-month fluoroquinolone containing regimens should not be used
and the 6-month rifampicin-based regimen (2HRZE/4HR or 2HRZE/4HRE) remains the
recommended regimen. In all patients with drug-susceptible pulmonary TB, the use of
daily dosing is preferred over thrice-weekly dosing in both the intensive and continuation
phases of therapy. The use of fixed-dose combination (FDC) tablets is recommended
over separate drug formulations. Antiretroviral therapy (ART) should be started in all
Table 1: Dose of antitubercular drugs used in new patients of tuberculosis.

Drugs Daily Intermittent
Adult Children 3-weekly 2-weekly
H 5 10 10 15
(4–6) (10–15) (8–12) (13–17)
R 10 15 10 10
(8–12) (10–20) (8–12) (8–12)
Z 25 35 35 50
(20–30) (30–40) (30–40) (40–60)
E 15 20 30 45
(15–20) (15–25) (25–35) (40–50)
S 15 15 15 15
(12–18) (12–18) (12–18) (12–18)
(H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; S: streptomycin)
Box 1: Various standard chemotherapy for newly diagnosed patient.

Recommended standard 6-month regimen
• 2EHRZ/4HR
• 2EHRZ/4HRE
• 2SHRZ/4HR
• 2HRZ/4HR
Variants of standard 6-month regimen (supervised chemotherapy)
• 2HRZ/4H3R3
• 2HRZ/4H2R2
• 2E3H3Z3/4H3R3
• 2S3H3R3Z3/4H3R3
• 2E3H3R3Z3/4H3R3
Alternative less potent regimens of longer duration
• With a potent initial 4-drug phase
{{2SHRZ/6HT or 6HE
{{2SHRZ/6S H Z
2 2 2
• With a less potent or no initial phase
{{2SHR/7HR
{{2HER/7HR
{{9HR
{{2SHT/10HT
{{2SHE/10
{{2SHP/10HP
{{12HT or 12HE
{{12S H
2 2
(H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; S: streptomycin; T: thiacetazone)
Box 2: Duration of treatment in different regimens.

If Z is used during intensive phase: 6 months
• 2RHEZ/4RH
• 2RHZ/4RH
• 2SHRZ/4RH
If continuation phase is without R: 8 months
• 2RHEZ/6EH/TH
• 2RHZ/6EH/TH
• 2SHRZ/6EH/TH
If Z is not used in intensive phase: 9 months
• 2RHE/7RH
• 9RHE
If R and Z is not used: 1–2 years
• 2STH/10TH
• 2SHE/10HE
• 12TH
Such duration is enough for pulmonary tuberculosis as well as extrapulmonary tuberculosis
(H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; S: streptomycin; T: thiacetazone)
Note: In meningeal TB, ethambutol should be replaced by streptomycin. In tubercular meningitis (TBM), spinal TB
with neurological complications and other hematogenous tuberculosis continuation phase is prolonged for 3–6
more months.
TB patients living with HIV regardless of their CD4 cell count. TB treatment should be
initiated first, followed by ART as soon as possible within the first 8 weeks of treatment.
In patients with drug-susceptible pulmonary TB who are living with HIV and receiving
ART during TB treatment, a 6-month standard treatment regimen is preferred over an
extended treatment for 8 months or more. Treatment can be extended for 3–6 months in
tuberculous meningitis, spinal TB with neurological complications, etc. In patients with
tuberculous meningitis, an initial adjuvant corticosteroid therapy with dexamethasone
or prednisolone tapered over 6–8 weeks should be used. The vast majority of TB cases can
be cured when correct regimen are prescribed and they are taken properly by patients.
FURTHER READING
1. Prasad R, Srivastava DK. Multi drug and extensively drug-resistant TB (M/XDR-TB) management:
Current issues. Clinical epidemiology and global health. 2013;1:124-8.
2. Prasad R, Gupta N. Clinical Tuberculosis: Diagnosis and Treatment. New Delhi: Jaypee Brothers
Medical Publishers; 2015. pp. 367-73.
3. World Health Organization. Global Tuberculosis Report 2018. Geneva: World Health Organization.
2019.
4. World Health Organization. Treatment of Tuberculosis: Guidelines for National Programmes. Geneva:
World Health Organization. 2014.
5. Central TB Division. (2016). Technical and operational guidelines for TB control in India. [online]
Available from https://tbcindia.gov.in/index1.php?lang=1&level=2&sublinkid=4573&lid=3177. [Last
accessed February, 2020].
6. Prasad R, Nautiyal RG, Mukherji PK, Jain A, Singh K, Ahuja RC. Treatment of new pulmonary
tuberculosis patients: What do allopathic doctors do in India? Int J Tuberc Lung Dis. 2002;6:895-902.
7. Satyanarayana S, Subbaraman R, Shete P, Gore G, Das J, Cattamanchi A, et al. Quality of tuberculosis
care in India: a systematic review. Int J Tuberc Lung Dis. 2015;19:751-63.
8. World Health Organization. Guidelines for treatment of drug-susceptible tuberculosis and patient
care. [online] Available from https://www.who.int/tb/publications/2017/dstb_guidance_2017/en/.
[Last accessed February, 2020].
CASE 28
Case of Retreatment Pulmonary

Tuberculosis Presented as Mass Lesion
CASE REPORT
Sanyogita, 75-year-old female, having a history of diabetes mellitus and hypertension for
10 years presented to us with chief complaints of cough with expectoration, generalized
weakness, and off and on hemoptysis since last 2 months. She had earlier history of
pulmonary tuberculosis in 2009 for which she took complete course of antitubercular
drugs for a period of 6 months from DOTS (CAT I). General examination was within normal
limits. Sputum smear for acid-fast bacilli (AFB) was negative on both the occasions. Chest
X-ray showed a rounded shadow in right middle zone along with consolidation patch in
left lung. Computed tomography (CT) thorax revealed healed cavity with fungus ball in left
upper lobe and multiple cavitary lesions in right lung (Figs. 1 to 6). Fiberoptic bronchoscopy
showed stenosis of left lingular lobe and the right tracheobronchial tree was within normal
limits. Bronchial aspirate for AFB and malignant cytology were negative. However, bronchial
aspirate for culture detected growth of Mycobacterium tuberculosis. On the basis of clinical,
radiological, and microbiological assessment, patient was diagnosed as a case of relapse/
FIG. 1: Chest X-ray posteroanterior (PA) view at the

start of treatment.
Case of Retreatment Pulmonary Tuberculosis Presented as Mass Lesion 111
A B
FIGS. 2A AND B: Computed tomography (CT) thorax showing healed cavity with fungus ball in
left upper lobe and multiple cavitary lesions in right lung.

mass lesion with cavitation in right lung.

2 months of CAT II DOTS treatment.
A B
FIGS. 5A TO C: Computed tomography (CT)

C thorax after 2 months of treatment.
FIG. 6: Chest X-ray after completion of 8 months

of antitubercular treatment.
recurrent tuberculosis and was put on DOTS CAT II regimen comprising of 2 months of
isoniazid (H), rifampicin (R), ethambutol (E), pyzinamide (Z), and streptomycin (S) followed
by 1 month of isoniazid (H), rifampicin (R), ethambutol (E), and pyzinamide (Z) followed
by 5 months of isoniazid (H), rifampicin (R), and ethambutol (E). She improved clinically,
radiologically, and bacteriologically. On subsequent follow-up for 2 years, she remained
asymptomatic.
Case of Retreatment Pulmonary Tuberculosis Presented as Mass Lesion 113
DISCUSSION
Tuberculosis (TB) occurs worldwide and remains an important cause of morbidity
and mortality in many countries. Ideally, good treatment of TB should achieve sputum
conversion in almost all the patients provided correct regimens are prescribed and taken.
There will be hardly any relapse if duration of treatment has been sufficient and there will
be no emergence of drug resistance. In 2018, there were an estimated 10 million new cases
of TB causing death to 1.5 million people globally. There were an estimated 2.74 million
(27% of the total cases) new cases in India and 0.42 million people died in our country due
to TB in 2017.
Tuberculosis patients returning after defaulting or relapsing from their first treatment
course may receive the retreatment regimen containing first-line drugs: 2 months of
isoniazid (H), rifampicin (R), ethambutol (E), pyzinamide (Z), and streptomycin (S)
followed by 1 month of isoniazid (H), rifampicin (R), ethambutol (E), and pyzinamide
(Z) followed by 5 months of isoniazid (H), rifampicin (R), and ethambutol (E) when drug
susceptibility (DST) result become available regimen should be adjusted accordingly. As
per WHO 2017 guidelines for treatment of drug susceptible TB, in patients who require
TB retreatment, the Category II regimen should no longer be prescribed and DST testing
should be conducted to inform the choice of treatment regimen. Patients eligible for
retreatment should be referred for a rapid molecular test or DST testing to determine at
least rifampicin resistance and preferably also isoniazid resistance status. On the basis of
the DST profile, a standard first-line treatment regimen (2HRZE/4HR or 2HRZE/4HRE)
can be repeated if no resistance is documented; and if rifampicin resistance is present,
an multidrug-resistant tuberculosis (MDR-TB) regimen should be prescribed according
to WHO’s recent drug-resistant TB treatment guidelines. In patients who have had
treatment interruption, the reason for the interruption should be addressed. The 4-month
fluoroquinolone containing regimens should not be used and the 6-month rifampicin-
based regimen (2HRZE/4HR or 2HRZE/4HRE) remains the recommended regimen. In
all patients with drug-susceptible pulmonary TB, the use of daily dosing is preferred over
thrice-weekly dosing in both the intensive and continuation phases of therapy. The use of
fixed-dose combination (FDC) tablets is recommended over separate drug formulations.
Separate drug formulations can be used in case of adverse drug reactions.
FURTHER READING
1. Prasad R, Gupta N. Clinical Tuberculosis: Diagnosis and Treatment. New Delhi: Jaypee Brothers
Medical Publishers. 2015. pp. 367-73.
2. Treatment of tuberculosis: guidelines for national programmes-4th ed. WHO\HTM\TB\2009.420
3. World Health Organization. Global tuberculosis report 2019. Geneva: World Health Organization. 2019.
4. Central TB Division. (2016). Technical and Operational Guidelines for TB Control in India. 2016.
Available from https://tbcindia.gov.in/index1.php?lang=1&level=2&sublinkid=4573&lid=3177.
5. Prasad R, Nautiyal RG, Mukherji PK, Jain A, Singh K, Ahuja RC. Treatment of new pulmonary
tuberculosis patients: what do allopathic doctors do in India? Int J Tuberc Lung Dis. 2002;10:895-902.
6. Satyanarayana S, Subbaraman R, Shete P, Gore G, Das J, Cattamanchi A, et al. Quality of tuberculosis
care in India: a systematic review. Int J Tuberc Lung Dis. 2015;19:751-63.
7. World Health Organization. Guidelines for treatment of drug-susceptible tuberculosis and patient
care. [online] Available from https://www.who.int/tb/publications/2017/dstb_guidance_2017/en/.
8. World Health Organization. The use of molecular line probe assays for the detection of resistance
to second-line anti-tuberculosis drugs. [online] Available from https://apps.who.int/iris/
handle/10665/246131. [Last accessed February, 2020].
9. Nathavitharana RR, Cudahy PG, Schumacher SG, Steingart KR, Pai M, Denkinger CM, et al. Accuracy of
line probe assays for the diagnosis of pulmonary and multidrugresistant tuberculosis: a systematic
review and meta-analysis. Eur Respir J. 2017;49:1601075.
10. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis,
2011 Update. [online] Available from http://whqlibdoc.who.int/publications/2011/9789241501583_
eng.pdf. [Last accessed February, 2020].
11. World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis 2016 update.
[online] Available from https://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-
12. Nunn AJ, Phillips PPJ, Meredith SK, Chiang CY, Conradie F, Dalai D, et al. A trial of a shorter regimen
for rifampin-resistant tuberculosis. N Engl J Med. 2019;380:1201-13.
13. World Health Organization. Rapid Communication: Key changes to treatment of multidrug- and
rifampicin-resistant tuberculosis. [online] Available from who.int/tb/publications/2018/rapid_
communications_MDR/en/. [Last accessed February, 2020].
14. World Health Organization. WHO treatment guidelines for multidrug- and rifampicin-resistant
tuberculosis (2018 update). 2018. [online] Available from https://www.who.int/tb/areas-of-work/
drug-resistant-tb/guideline-update2018/en/. [Last accessed February, 2020].
CASE 29
Left-sided Infrapulmonary Effusion
CASE REPORT
A 25-year-old female came to us in March, 1982 with complaints of chest pain on left side
radiating to ipsilateral shoulder since 2 months with fever since 15 days. General physical
examination was within normal limits. Respiratory system examination revealed reduced
movement on the left infrascapular area. There was also stony dullness on percussion in
the same area. Chest X-ray posteroanterior (PA) view showed elevated left hemidiaphragm
and it also appeared thickened (Fig. 1). Ultrasonography showed pleural effusion on the
left side which was not encysted. Ultrasound-guided pleural aspiration was done and
pleural effusion was exudative in nature and was lymphocytic predominant. Pleural fluid
smear was negative for acid-fast bacteria (AFB) and culture of the pleural fluid was negative
for any pyogenic organism. She was diagnosed as tubercular infrapulmonary pleural effusion
on the left side. Patient was started with antitubercular drugs (injection streptomycin,
isoniazid, and ethambutol) along with prednisolone 40 mg daily. Pleural fluid disappeared and
left dome of diaphragm came back to normal position and shape in 2 months’ time (Fig. 2)
FIG. 1: Chest X-ray showing left-sided infrapulmonary

effusion.
when steroid and injection streptomycin was stopped and she continued with isoniazid and
ethambutol for next 10 months. Patient was completely asymptomatic and her chest X-ray
was normal after 1 year of follow-up.
FIG. 2: Chest X-ray showing resolution of infra

pulmonary effusion after treatment.
DISCUSSION
Please refer to Case 30 for discussion.
CASE 30
Right-sided Infrapulmonary
Pleural Effusion
CASE REPORT
A 30-year-old female came to us in May, 1999 with complaints of chest pain on right side
radiating to ipsilateral shoulder since 1 month with fever since 15 days and decreased
appetite since 15 days. General physical examination was within normal limits. Respiratory
system examination revealed reduced movement on the right infrascapular area. There
was also stony dullness on percussion in the same area. Chest X-ray posteroanterior (PA)
view showed elevated right hemidiaphragm (Fig. 1). Chest X-ray was also done in right
lateral decubitus position which showed displacement of fluid on the lateral chest wall
(Fig. 2). Ultrasonography showed pleural effusion on the right side which was not encysted.
Ultrasound-guided pleural aspiration was done and pleural effusion was exudative in
nature and was lymphocytic predominant. Pleural fluid smear was negative for acid-fast
bacteria (AFB) and culture of the pleural fluid was negative for any pyogenic organism. She
was diagnosed as tubercular infrapulmonary pleural effusion on the right side. Patient was
started on DOTS CAT I along with prednisolone 40 mg daily. Pleural fluid disappeared and
right dome of diaphragm came back to normal position and shape in 2 months’ time when

right-sided infrapulmonary effusion.
FIG. 2: Chest X-ray right lateral decubitus

showing displacement of fluid.
steroid was stopped. Rest of the medication was continued for next 4 months (rifampicin
and isoniazid thrice weekly). Patient was completely asymptomatic and her chest X-ray was
normal after 1 year of follow-up.
DISCUSSION
Subpulmonic pleural effusion is also called infrapulmonary effusion. Minimal to moderate
subpulmonic effusions can be missed unless chest X-rays are read carefully and kept in
mind. Many signs have been described to diagnose this condition on a plain chest X-ray
obtained in the upright position.
Raised dome of diaphragm, easier to diagnose when seen on left side, but a difference
of two intercostal spaces higher on right side also raises the suspicion of subpulmonic
effusion. In case of left-sided subpulmonic effusion, increased distance between left
diaphragmatic outline and the fundal gas bubble in the stomach is seen. Abrupt termi
nation of lung markings at the diaphragmatic interface attributable to fluid being denser
to the normal translucency of lung base. The pseudodiaphragm (visceral pleural interface)
appears flattened especially at medial margins, with blunting of the cardiophrenic angle.
The pseudodiaphragm shows a more lateral peak “lateralization of diaphragmatic apex.”
Crowding of lung markings at lower zones in cases of moderate to large subpulmonic
effusions. Lateral chest radiograph may show blunting of the posterior costophrenic
recess. Lateral decubitus view will confirm the diagnosis of subpulmonic effusion. In
larger subpulmonic effusions, there may be blunting of the lateral costophrenic angle on
chest X-ray posteroanterior (PA) view.
FURTHER READING
1. Federle MP, Mark AS, Guillaumin ES. CT of subpulmonic pleural effusions and atelectasis: criteria for
differentiation from subphrenic fluid. AJR Am J Roentgenol. 1986;146:685-9.
2. Kafura PJ, Barnhard HJ. Ascites simulating subpulmonary pleural effusion. Radiology. 1971;101:
525-6.
3. Schwarz MI, Marmorstein BL. A new radiologic sign of subpulmonic effusion. Chest. 1975;67:176-8.
4. Mueller PR. In evaluating fluid collections, how does one differentiate subpulmonic from subphrenic
collections? AJR Am J Roentgenol. 1994;163:739-40.
CASE 31
Multidrug-resistant Tuberculosis
Treated with Injection Kanamycin PAS,
Ethionamide and Cycloserine
CASE REPORT
TS, an 18-year-old female diagnosed as pulmonary tuberculosis in 1995, was prescribed
rifampicin, isoniazid, and ethambutol which she stopped herself after 4 months due to
improvement. After 5 months of asymptomatic period, she again developed symptoms and
prescribed rifampicin, isoniazid, and ethambutol which she stopped after 1 month due to
drug intolerance. Next time she received rifampicin, isoniazid, ethambutol, and pyrazinamide
in fix dose combination of controversial quality for next 3 months without any improvement.
Thereafter, treatment was changed to streptomycin, rifampicin, isoniazid, ethambutol,
and pyrazinamide for next 2 months, without any response. Then she received Category II
treatment under RNTCP for 9 months and still her sputum remained positive for acid-fast
bacilli (AFB). In June 1997, she was hospitalized and her sputum was sent for culture and
sensitivity for Mycobacterium tuberculosis (MTB) and was treated with daily streptomycin,
rifampicin, isoniazid, ethambutol, and pyrazinamide in adequate doses under supervision.
After 4 months of regular treatment, her sputum remained positive for AFB. Her sputum
culture and sensitivity report revealed resistance to rifampicin, isoniazid, and streptomycin.
Considering the past history of treatment, radiological, symptomatic deterioration, and
sensitivity report, she was diagnosed as multidrug-resistant tuberculosis (MDR-TB). She was
treated with injection kanamycin 0.75 g, para-aminosalicylic acid (PAS) 10 g (in two divided
doses), ethionamide 500 mg, and cycloserine 500 mg daily. About 300 mg of isoniazid was
also given. Her sputum smear was examined every month for AFB. Kanamycin was stopped
after 4 months when her sputum smear became negative for AFB. Rest of the treatment
was continued for a period of 18 months. At the end of the treatment, sputum smear, and
culture were negative for MTB. On subsequent follow-up for next 5 years, there was no relapse
(Figs. 1A to E).
A B C
D E
FIGS. 1A TO E: (A) Chest X-ray posteroanterior (PA) view at the start of multidrug-resistant (MDR)
treatment; (B) After 4 months of MDR treatment; (C) After 8 months; (D) After 2 years of treatment
when treatment was stopped; and (E) After 3 years follow-up after stopping MDR treatment.
DISCUSSION
CASE 32
Primary Multidrug-resistant Tuberculosis

Treated with Injection Kanamycin PAS,
Ethionamide and Cycloserine
CASE REPORT
SS, a 15-year-old female, weighing 35 kg was diagnosed as a sputum positive new case of
pulmonary tuberculosis in February, 1998, with bad family history of her brother, who died
of pulmonary tuberculosis after prolonged treatment for 4 years. She was prescribed four-
drug regimen comprising rifampicin, isoniazid, ethambutol, and pyrazinamide in adequate
doses, which she took regularly for 2 months, without any significant improvement clinically,
radiologically as well as bacteriologically. Then she sought advice from other physician who
added streptomycin and sparfloxacin to her previous regimen of four drugs. She took six-
drug regimen regularly for 6 months with negligible response clinically and radiologically.
Subsequently she consulted us, when her sputum was positive for AFB and was also sent
for culture and sensitivity for Mycobacterium tuberculosis. In light of her previous treatment
experiences and outcomes, she was suspected as a case of primary multidrug-resistant
tuberculosis (MDR-TB). Pending sensitivity report, she was started on kanamycin 0.75 g,
isoniazid 300 mg, para-aminosalicylic acid (PAS) 8 g (in two divided doses), ethionamide
500 mg, and cycloserine 500 mg daily in single dose, in September, 1998. With the passage
of time, she showed improvement clinically and radiologically, when her sputum became
negative after 4 months. At the same time, her sputum culture and sensitivity report from four
different laboratories (sent at beginning of treatment) showed lots of discrepancies, with two
of them labeling her as a case of MDR-TB while other labeling her as polydrug resistance other
than MDR. Regardless of conflicting sensitivity reports, we adhered to our regimen. Kanamycin
was stopped after she became sputum negative and rest of the treatment was continued for
another 20 months. At the end of 2 years of treatment, she was smear and culture negative
with dramatic clearing of chest radiograph and weight gain of about 7 kg. She was followed
for 5 years (till 2002), without any relapse (Figs. 1A to F).
A B C
D E F
FIGS. 1A TO F: (A) Chest X-ray posteroanterior (PA) view, showing lesions in left upper and mid
zone; (B) View after 6 weeks of primary line of antitubercular treatment (ATT); (C) Chest view, after
6 months of primary line of ATT pulmonary lesion in left lung progressed along with new lesions
in the right upper zone when multidrug-resistant (MDR) treatment was added; (D) Chest view after
4 months of MDR treatment showing improvement radiologically; (E) Chest view after 1 year of
MDR treatment; and (F) Chest view after 18 months of MDR treatment.
DISCUSSION
CASE 33
Treated on Emperical Grounds
CASE REPORT
MR, a 32-year-old male weighing 43 kg was diagnosed as a case of pulmonary tuberculosis
in 1992 and was treated with 2RHEZ/4RHE and declared cured. He has relapsed in 1994 and
was again treated by different doctors for 2 years with different inadequate regimens with
drug including streptomycin, rifampicin, isoniazid, ethambutol, and pyrazinamide without
any response. He consulted another physician and took kanamycin (2 months), ethionamide,
(2 months), isoniazid, and thiacetazone for 1 year without any response. He came to us in
September, 1997 with complains of cough, fever, loss of appetite, and weight. His serial chest
X-rays showed progressive deterioration and his sputum was positive for acid-fast bacilli
(AFB). Sputum was sent for culture and sensitivity for Mycobacterium tuberculosis (MTB).
Pending the culture and sensitivity report, he was prescribed streptomycin, rifampicin,
isoniazid, ethambutol, and pyrazinamide in adequate doses with intensive health education.
At the end of 3 months of regular treatment, he did not respond clinically and his sputum
remained positive for AFB. Sputum culture (sent at the time of starting five drugs) and
sensitivity showed resistance to streptomycin, pyrazinamide, para-aminosalicylic acid (PAS),
and ethionamide with susceptibility to rifampicin, isoniazid, ethambutol, thiacetazone, and
cycloserine. However, in view of past history of antitubercular treatment (ATT), his sensitivity
report was ignored and was assumed as a case of multidrug-resistant tuberculosis (MDR-TB)
and treatment was changed to injection kanamycin 0.75 g, PAS 10 g (in two divided doses),
ethionamide 500 mg, pyrazinamide 1,500 mg, and ofloxacin 600 mg daily in December,
1997, 300 mg of isoniazid was also given. His sputum smear was examined for AFB every
month. Patient developed gastric intolerance in the beginning of treatment, however, all
the drugs were continued. Injection kanamycin was stopped after 6 months in June, 1998
when his sputum became negative for AFB, and rest of the drugs were continued for another
18 months. Patient responded clinically, radiologically, and bacteriologically. Sputum smears
for AFB and cultures were negative for MTB at the end of the treatment. Till now, after 5 years
of regular follow-up, he has not relapsed (Figs. 1A to F).
A B C
D E F
FIGS. 1A TO F: (A) Chest X-ray posteroanterior (PA) view showing bilateral lesions getting
primary line of ATT (RSEZ/RSE); (B) Chest X-ray PA view after 3 months of primary line of
antitubercular treatment (ATT) without any response and put on multidrug-resistant (MDR)
treatment emperically; (C) Chest X-ray PA view after 6 months of primary line of ATT showing
good response; (D) Chest X-ray PA view after 10 months of MDR treatment showing further
response; (E) Chest view 18 months of MDR treatment; and (F) Chest view 2 years of follow-up
after stopping MDR treatment.
DISCUSSION
CASE 34
Multidrug-resistant Tuberculosis Treated

with CAT IV Regimen with Good Response
CASE REPORT
A 21-year-old male presented with chief complaints of fever for 1 month, loss of weight,
and loss of appetite. Patient was started on a regimen based on rifampicin, isoniazid,
pyrazinamide, and ethambutol by private practitioner which he took for 7 months but
patient continued to have fever and there was no resolution of chest infiltrates. Patient
was referred to our center in November, 2014. Gene Xpert in December, 2014 detected
rifampicin resistance. His culture sensitivity showed resistance to isoniazid, rifampicin,
pyrazinamide, ethambutol, streptomycin, ciprofloxacin, and was susceptible to kanamycin,
levofloxacin, amikacin, and capreomycin. Patient was put on a regimen for multidrug-
resistant tuberculosis (MDR-TB) in December, 2014 consisting of kanamycin, ethionamide,
cycloserine, levofloxacin, pyrazinamide, and ethambutol. Kanamycin was stopped at
9 months when sputum smear and culture for Mycobacterium tuberculosis (MTB) became
negative. Rest of the drugs including pyrazinamide were continued for 20 months. It is worth
to note that pyrazinamide were given throughout the treatment. Patient sputum smear
and culture remained negative for MTB. There was significant improvement clinically and
radiologically. Patient remained asymptomatic after 6 months of follow-up after stopping the
treatment (Fig. 1).
A B C
D E F
FIGS. 1A TO F: (A) Chest X-ray posteroanterior (PA) view showing infiltrates in the left upper
zone put on primary line of antitubercular treatment (ATT); (B) Chest X-ray PA view after 6 months
of primary line of ATT without any response and put on multidrug-resistant (MDR) treatment;
(C) Chest X-ray PA view after 56 months of MDR treatment; (D) Chest X-ray PA view after 9 months
of MDR treatment when Kanamycin was stopped; (E) Chest X-ray PA view after 2 years of MDR
treatment when treatment was stopped; and (F) Chest X-ray PA view after 6 months of follow*up
after stopping MDR treatment.
DISCUSSION
CASE 35
Multidrug-resistant Tuberculosis under

Treatment with Residual Lesion and
Adverse Drug Reaction
CASE REPORT
NR, a 35-year-male, weighing 40 kg, presented with bilateral pulmonary tuberculosis, with
previous history of antitubercular treatment, from different doctors in various inadequate
regimens, using streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. At
the time of presentation to us in January 2001, his sputum was positive for acid fast bacilli
(AFB), which was also sent for culture and sensitivity for Mycobacterium tuberculosis. Pending
sensitivity report, he was kept on regimen containing streptomycin 0.75 g, isoniazid 300
mg, rifampicin 450 mg, ethambutol 800 mg, and pyrazinamide 1,000 mg. Despite 4 months
of regular treatment, there was no response on clinical, radiological, and bacteriological
parameters. Sputum sensitivity sent at the beginning of treatment reported resistance to
streptomycin, isoniazid, ethambutol, and rifampicin. In light of this sensitivity report, previous
inadequate treatment and lack of response to 4 months treatment of five drugs, he was
diagnosed as a case of multidrug-resistant tuberculosis (MDR-TB), and kept on kanamycin
0.75 g, isoniazid 300 mg, PAS 8 g (in two divided doses), ethionamide 500 mg, and cycloserine
500 mg daily in single dose. After 1 month of this therapy, he developed psychosis with
suicidal tendency, which was managed by antipsychotic drugs and cycloserine was replaced
by ofloxacin 600 mg daily in single dose. His sputum became negative for AFB after 6 months
of treatment, when kanamycin was stopped, and rest of drugs continued for next 18 months
till April 2003, when he became smear and culture negative, and declared cured. While he was
on this regimen, chest radiographic picture deteriorated but sputum smear always remained
negative. Considering this radiological deterioration as intercurrent pyogenic infection, we
adhered to our antitubercular regimen with some appropriate antibiotics. He was followed
up for 2 years, without any relapse, although he experienced occasional bouts of streaking
of sputum during follow-up period, which used to improve with conservative treatment
(Figs. 1A to G).
A B C
D E F
FIGS. 1A TO G: (A) Chest X-ray posteroanterior (PA) view

showing bilateral lesion on CAT II treatment; (B) Chest X-ray PA
view after 4 months of CAT II treatment without response and put
on multidrug-resistant (MDR) treatment; (C) Chest X-ray PA view
after 6 months of MDR treatment when injection Kanamycin was
stopped; (D) Chest X-ray PA view after 2 years of MDR treatment;
(E) Chest X-ray PA view after 1 year follow-up after stopping MDR
treatment; (F) Chest X-ray PA view after 18 months of follow-up
after stopping the treatment and (G) Chest X-ray PA view after
G 2 years of follow-up after stopping the treatment.
DISCUSSION
CASE 36
Treatement with CAT IV
Regimen Including Ofloxacin
CASE REPORT
A 22-year-old female was diagnosed as a new case of sputum positive pulmonary
tuberculosis in 2006. She was started on a regimen based on rifampicin, isoniazid,
ethambutol, and pyrazinamide from private practitioner. She developed vomiting and gastritis
after which she stopped her antituberculosis drugs. She then consulted multiple private
practitioners taking the prescribed treatment consisting of primary line of antituberculosis
drugs for 1–2 months then stopping at her own with partial relief of symptoms each
time. In May, 2008 she presented to us, her sputum was found to be positive for acid fast
bacilli (AFB), sputum was sent for culture, and sensitivity for Mycobacterial tuberculosis and
she was started on a five drug regimen consisting of rifampicin, isoniazid, ethambutol,
pyrazinamide, and streptomycin. Her sputum culture sensitivity received in August, 2008
showed growth of M. tuberculosis which was resistant to rifampicin and isoniazid. She was
started on regimen for multidrug-resistant tuberculosis (MDR-TB) consisting of injection
kanamycin, pyrazinamide, ethambutol, ethionamide, cycloserine, and ofloxacin. Her clinical
condition improved, sputum for AFB and culture for Mycobacterium became negative 4 month
onward. Kanamycin and pyrazinamide were stopped after 6 months. Rest of the treatment was
continued for 18 months. Patient responded clinically, radiologically, and bacteriologically.
Sputum and culture were negative for M. tuberculosis at the end of treatment in 2010. On
subsequent follow-up for 1 year, she was asymptomatic (Figs. 1A to F).
A B C
D E F
FIGS. 1A TO F: (A) Chest X-ray posteroanterior (PA) view showing lesions on the right side with
CAT I treatment without response; (B) Chest X-ray PA view on treatment with CAT II regimen
without response; (C) Chest X-ray PA view showing increased lesion and multidrug-resistant (MDR)
treatment; (D) Chest X-ray PA view after 6 months of MDR treatment showing response when
injection Kanamycin was stopped; (E) Chest X-ray PA view after 2 years of MDR treatment with cure
and (F) Chest X-ray PA view after 1 year of follow-up after stopping MDR treatment.
DISCUSSION
CASE 37
Multidrug-resistant Tuberculosis under

Treatment with CAT IV Regimen Containing
Ofloxacin with Residual Lesion
CASE REPORT
NK, a 27-year-old male, weighing 40 kg presented with bilateral pulmonary tuberculosis with
previous antitubercular treatment. Different doctors treated him for 4 years for pulmonary
tuberculosis, with different regimens in various combinations with drugs including
streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. His sputum was positive for
acid fast bacilli (AFB), which was sent for culture and sensitivity for Mycobacterium tuberculosis.
Pending culture report, treatment was started with five drug regimen of streptomycin 0.75 g,
isoniazid 300 mg, rifampicin 450 mg, ethambutol 800 mg, and pyrazinamide 1,000 mg
daily in single dose, which he took regularly for 2 months without any clinical, radiological
or bacteriological response. Sputum culture and sensitivity sent earlier, revealed drug
resistance to streptomycin, isoniazid, and rifampicin. On basis of this report and previous
history of treatment, he was kept on kanamycin 0.75 g, ethionamide 500 mg, ofloxacin
600 mg, ethambutol 800 mg, and pyrazinamide 1,000 mg daily in single dose. Isoniazid in
single dose of 300 mg daily was also added. He responded clinically and bacteriologically,
but his chest radiograph revealed no change on left side (which was destroyed), with some
clearing of shadows in right lung. Sputum conversion occurred after 6 months of treatment,
when kanamycin was stopped and rest of drugs were continued for next 18 months. At the
end of treatment, his sputum was negative for AFB and he has gained weight of 6 kg, but
radiographical shadows persisted without much change, which in all likelihood will persist
throughout his life and may be source of infection and hemoptysis in future (Figs. 1A to D).
A B
C D
FIGS. 1A TO D: (A) Chest X-ray posteroanterior (PA) view with destroyed left lung
on CAT IV regimen; (B) Chest X-ray PA view after 6 months of multidrug-resistant
(MDR) treatment when injection kanamycin was stopped when sputum smear
became negative; (C) Chest X-ray PA view after 2 years of MDR treatment when
treatment was stopped though there is lot of residual lesion; and (D) Chest X-ray PA
view after 1 year follow-up after stopping MDR treatment with destroyed left lung
with sputum culture negative for MTB.
DISCUSSION
CASE 38
Treated with CAT IV Regimen for 26 Months
CASE REPORT
An 18-year-old male (weight 45 kg) presented with complaints of fever, cough with sputum,
and decreased appetite for 2 months. Sputum smear for acid-fast bacilli (AFB) was positive
and he was diagnosed as a new case of sputum positive pulmonary tuberculosis in January,
2009. He was started on a regimen based on rifampicin, isoniazid, ethambutol, pyrazinamide
from government hospital (CAT I) (Fig. 1). He developed hemoptysis in June, 2009. Sputum
smear for AFB was positive even after 5 months of treatment and his sputum was sent
for culture for Mycobacterium tuberculosis (Fig. 2). He was given CAT II treatment which
consisted of rifampicin, isoniazid, ethambutol, pyrazinamide, and injection streptomycin
in adequate doses. Sputum smear for AFB remained positive and the culture report came
out to be positive for Mycobacterium tuberculosis. Drug susceptibility (DST) report on
18th October, 2009 showed resistance to rifampicin, isoniazid, ethambutol, and streptomycin
(Fig. 3). Previous regimen was stopped with immediate effect and he was given multidrug-
resistant tuberculosis (MDR-TB) regimen (CAT IV) consisting of injection kanamycin 0.75 g,
ethionamide 500 mg, cycloserine 500 mg levofloxacin 750 mg, pyrazinamide 1,250 mg,
FIG. 1: Chest X-ray at the start of CAT I DOTS.

FIG. 2: Chest X-ray after 5 months of antitubercular

treatment (ATT) without any resolution of chest
infiltrates.
FIG. 3: Chest X-ray when drug susceptibility (DST)

report suggested multidrug-resistant tuberculosis
(MDR-TB) and patient was started treatment for
MDR-TB.
and ethambutol 800 mg. Sputum for AFB and culture for Mycobacterium became negative
4th month onward. Kanamycin and pyrazinamide were stopped after 6 months. Rest of the
treatment was continued for 18 months. Patient responded clinically, radiologically, and
bacteriologically. Sputum and culture were negative for Mycobacterium tuberculosis at the
end of treatment in 2011 (Fig. 4). On subsequent follow-up at regular intervals for 3 years
patient was asymptomatic.
Multidrug-resistant Tuberculosis Treated with CAT IV Regimen for 26 Months 135
FIG. 4: Chest X-ray on completion of multidrug-

resistant tuberculosis (MDR-TB) treatment showing
complete resolution of chest infiltrates.
DISCUSSION
CASE 39
Extensively Drug-resistant Tuberculosis

Treated with Modified CAT IV Regimen
CASE REPORT
A 17-year-old female presented with complaints of fever, loss of weight, and appetite for
1 month. Sputum for acid-fast bacilli (AFB) was positive (2+). Chest X-ray showed cavity in the
right upper zone. On detailed history of the treatment in the past it was found that she was
prescribed isoniazid, rifampicin, ethambutol, and pyrazinamide (HRZE) w.e.f. 22/7/2014 which
she took for 20 days and then discontinued by herself due to no perceived benefits. She was
again started on HRZE by other physician from 11/8/2014 which was subsequently modified
to HRE and was continued for next 10 months (Fig. 1). In spite of 12 months of antitubercular
treatment (ATT), the patient continued to have fever and there was no resolution of infiltrates
on chest X-ray. Patient was then given 5 drug regimen consisting of injection streptomycin,
isoniazid, rifampicin, pyrazinamide and ethambutol on (SHRZE) w.e.f. 4/12/2015 and
was referred to our center. Patient had sputum positive report on 26/12/2015. SHRZE was
continued. GeneXpert was done and rifampicin resistance was detected and sputum C/S was
positive for Mycobacterium tuberculosis complex and drug susceptibility test (DST) revealed
that bacteria was resistant to isoniazid, rifampicin, kanamycin, and ofloxacin and sensitive
to capreomycin and moxifloxacin (Fig. 2). Thus she was diagnosed a case of extensively
FIG. 1: Chest X-ray PA view when first-line antituber

cular treatment (ATT) was started.
Extensively Drug-resistant Tuberculosis Treated with Modified CAT IV Regimen 137
drug-resistant tuberculosis (XDR-TB) based on GeneXpert and culture sensitivity reports.

However, in view of past history of ATT where she has not taken any second-line injectables
and fluoroquinolones, DST report was ignored and she was given treatment for multidrug-
resistant tuberculosis (MDR-TB) in form of injection kanamycin 0.75 g, ethionamide 500 mg,
cycloserine 500 mg, moxifloxacin 600 mg, ethambutol 800 mg, and pyrazinamide 1,500 mg
daily w.e.f. 12/2/2016 (Fig. 3). Injection kanamycin was stopped after 6 months when she
became culture negative and rest of drugs were continued for next 18 months (Figs. 4 and 5).
Patient had responded well clinically, radiologically, and bacteriologically. Thus, treatment was
stopped in February, 2018 (Fig. 6). She was followed up for next 1 year at regular interval of
3 months and there was no relapse. In this case, it is to note that to make a proper regimen
four new drugs such as kanamycin, cycloserine, ethionamide, and moxifloxacin were added
other than pyrazinamide and ethambutol. Levofloxacin was replaced with moxifloxacin as
DST report showed sensitivity to moxifloxacin.
FIG. 2: Chest X-ray after 5 months of antitubercular

treatment (ATT) without any resolution of chest
infiltrates.
FIG. 3: Chest X-ray when multidrug-resistant tuber

culosis (MDR-TB) treatment was started.
FIG. 4: Resolution of chest infiltrates after

completing 6 months of treatment.
FIG. 5: Chest X-ray after 1 year of treatment

showing resolution of infiltrates.
FIG. 6: Chest X-ray on completion of treatment.

DISCUSSION
Diagnosis of MDR/RR-TB
A presumptive case of MDR/RR-TB is defined as a TB patient who fails new treatment
regimen and retreatment regimens with first-line anti-TB drugs who is sputum smear
positive at the end of the fourth month of treatment or later and close contacts of
drug-resistant TB cases. Diagnosis of MDR/RR-TB is based on clinical, radiological,
bacteriological, and molecular evidences.
Clinical Evidences
This comprises of the symptoms and signs suggestive of TB and past history of anti-
tubercular treatment. History of prior treatment with antitubercular drugs (ATD) is most
important. The main predictor of resistance to a particular drug is the demonstration of
its prior use in monotherapy for >1 month. To obtain evidence of possible inadvertent
or direct monotherapy, it is essential to be meticulous in obtaining the history of
antitubercular treatment in all patients suspected of MDR/RR-TB. There should be a
detailed evaluation into the drugs used, the drug dosages if previous drug prescriptions
are available, whether the drugs were fixed dose combinations or separate drugs, their
reliability in terms of bioavailability, whether the patients were compliant to these drugs,
supervised or unsupervised treatment and any drug intolerance that included partial
or complete drug defaulting. Any real masked monotherapy previously received by the
patient can be identified with reasonably good accuracy and one can accurately predict
resistance to specific drugs and prevent their inclusion in the retreatment plan. The other
important aspects of history include contacts with known case of resistant tuberculosis
and patient's place of residence which may have a high prevalence of drug resistance. It
must be remembered that clinical evidences are the least reliable for diagnosis of MDR/
RR-TB. However, clinical deterioration in the presence of sputum and culture positivity
and/or radiological worsening can be considered due to drug resistance.
Radiological Evidences
Radiological worsening is not a very reliable indicator for predicting drug resistance, it
serves to compliment the clinical and bacteriological evidence of the patient. Change in
size of cavities and increase in size of existing lesions and appearance of new lesions are
signs of disease progression and activity and suggest drug resistance. However, one should
realize that radiological worsening may be due to pneumonia, pulmonary embolism, and
supervening carcinoma.
Bacteriological Evidence
It serves as the gold standard in the detection of MDR/RR-TB. This is based on sputum
smear microscopy and culture of M. tuberculosis and DST. Sputum smear microscopy,
after starting standard chemotherapy can show a positive, negative or suboptimal
response. While positive response is characterized by sputum conversion at 2 to
3 months of chemotherapy, a negative response could mean persistent smear positivity
at the end of 3 months of adequate chemotherapy and a suboptimal response by an
initial fall in the sputum grade followed by a gradual rise - the so called ‘fall and rise’
phenomenon while the patient is on antitubercular therapy. The last two patterns
increase the probability of drug resistant tuberculosis. Diagnosis is confirmed by DST
from reliable and reputed laboratories under constant quality control. However, one
has to keep in mind the limitation of highly specific DST because the technique is
complex, difficult to perform accurately even when skilled personnel are available and
laboratory facilities are of high standard. Further one should realize that laboratories
vary in their reliability; errors do occur in labs, different DST reports are obtained from
the same patient from different labs. Susceptibility result for isoniazid, rifampicin,
fluoroquinolones and the injectables is very reliable. For other drugs, it is less reliable
and individualized treatments based on DST for these drugs should be used with great
caution. The effectiveness or ineffectiveness of a drug cannot be predicted by DST with
100% certainty. Furthermore, the DST to second line drugs (SLD’S) is very variable.
Keeping above facts in mind it is pertinent that DST should not be accepted uncritically
and quality assured labs performing DST is needed.
Molecular Evidences
It has been used for identification of resistance associated mutation. WHO with stop TB
partnership endorsed line probe Assays in low resource countries in 2008 which can
do rapid screening of patients with MDR/RR-TB risk within 2 days. First line LPA has a
sensitivity of 96.7% and specificity of 98.8% for the detection of rifampicin resistance and
a sensitivity of 90.2% and specificity of 99.2% for isoniazid resistance. InhA promoter
mutations, which are generally associated with low-level increase in MIC, are detected (and
in the absence of any katG mutation), increasing the isoniazid (maximum dose of 15 mg/
kg per day) dose may be effective. InhA promoter mutation also suggest cross resistance
to ethionamide/prothionamide. In the case of katG mutations, which are more commonly
associated with high-level increase in MIC, the use of isoniazid even at higher dose is
less likely to be effective. WHO recently recommended 2nd line probe assay (2nd LPA),
a rapid diagnostic test MTBDRsL that identifies genetic mutation in MDR strains that
detect resistance to fluoroquinolones and injectable second line anti-TB drugs. Second
line LPA has a sensitivity of 83.1% and specificity of 97.7% for fluoroquinolone resistance
and 76.9% sensitivity and 99.5% specificity for Second line injectables. Phenotypic
resistance to ofloxacin and levofloxacin is highly correlated with resistance conferring
mutations detected by SL-LPA. However, uncertainty remains about the susceptibility
to moxifloxacin and gatifloxacin for such strains with specific mutations in the gyrA and
gyrB genes. Mutations associated with the eis promoter region correlate with phenotypic
resistance to kanamycin only.
The Xpert MTB RIF assay endorsed by WHO in 2010 enables simultaneous detection
of M. tuberculosis and rifampicin resistance (reliable proxy for MDR/RR-TB) directly
from sputum and other extra pulmonary specimen except blood in <2 hours. The assay
is robust enough to be performed outside of conventional laboratories at district and
sub district level of health system but requires uninterrupted power supply. It provides
accurate results and can allow rapid initiation of MDR/RR-TB treatment pending results
from conventional culture and DST.
The limitation of existing molecular techniques is that only the most common
mutations are targeted. Thus novel mutations and mutations outside the drug resistance
determining region are missed. Whole-genome sequencing (WGS) can simultaneously
identify all known resistance associated loci with high concordance to conventional drug
susceptibility assays and characterize novel loci associated with drug resistance, with 96%
concordance reported between WGS and culture based DST methods. Next-generation
sequencing (NGS) has great potential as a method for rapidly diagnosing drug-resistant
tuberculosis in diverse clinical laboratory settings. However, uptake of these technologies
for DR-TB diagnosis has been hindered by consensus regarding costs, integration into
existing laboratories, technical training and skill requirement for utilization of technologies.
FURTHER READING
1. WHO. Global tuberculosis report 2018. Geneva: World Health Organization WHO/HTM/2018.13.
2018.
2. WHO. Companion Handbook to the WHO guidelines for the programmatic management of drug
resistant tuberculosis. 2014.
3. Caminero JA. Management of multidrug-resistant tuberculosis and patients in retreatment. Eur
Respir J. 2005;928-36.
4. Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J.
2005;564-9.
5. WHO. Treatment of tuberculosis: guidelines for national programmes. 4TH ed. 2009.
6. Ling DI, Zwerling AA, Pai M. GenoType MTBDR assays for the diagnosis of multidrug-resistant tuber
culosis: a meta-analysis. Eur Respir J. 2008;1165-74.
7. Nathavitharana RR, Cudahy PGT, Schumacher SG, Steingart KR, Pai M, Denkinger CM. Accuracy of
line probe assays for the diagnosis of pulmonary and multidrug-resistant tuberculosis: a systematic
review and meta-analysis. Eur Respir J. 2017;1601075.
8. WHO. The use of molecular line probe assays for the detection of resistance to second-line anti-
tuberculosis drugs. 2016.
9. Banada PP, Sivasubramani SK, Blakemore R, Boehme C, Perkins MD, Fennelly K, et al. Containment
of bioaerosol infection risk by the Xpert MTB/RIF assay and its applicability to point-of-care settings.
J Clin Microbiol. 2010;3551-7.
10. Small PM, Pai M. Tuberculosis diagnosis--time for a game change. The New England journal of
medicine. United States; 2010. p. 1070-1.
11. Walker TM, Kohl TA, Omar S V, Hedge J, Del Ojo Elias C, Bradley P, et al. Whole-genome sequencing for
prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort
study. Lancet Infect Dis. 2015;1193-202.
12. Shea J, Halse TA, Lapierre P, Shudt M, Kohlerschmidt D, Van Roey P, et al. Comprehensive Whole-
Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium
tuberculosis in New York State. J Clin Microbiol. 2017;1871-82.
13. McNerney R, Clark TG, Campino S, Rodrigues C, Dolinger D, Smith L, et al. Removing the bottleneck
in whole genome sequencing of Mycobacterium tuberculosis for rapid drug resistance analysis:
a call to action. Int J Infect Dis. 2017;130-5.
14. WHO. Technical guide on next-generation sequencing technologies for the detection of mutations
associated with drug resistance in Mycobacterium tuberculosis complex. WHO/CDS/TB/2018.19e.
2018.
CASE 40
(Pre XDR-TB) Treated with CAT IV Regimen
CASE REPORT
A patient aged 21 years, male (weight 55 kg) presented with complaints of fever, dry cough
for 3 weeks. Sputum for AFB was 2+. Chest X-ray showed infiltrates in left upper zone (Fig. 1).
Patient was started on isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) in adequate
doses w.e.f. 10/4/2014 for 2 months followed by isoniazid and rifampicin (HR) for 4 months.
At the end of the treatment, patient’s sputum smear was 3+ on 16/11/2014 and there was
radiological deterioration (Fig. 2). Patient developed severe gastritis, nausea, vomiting,
and loss of appetite. All the drugs were stopped. Patient was started with streptomycin
1 g, isoniazid 300 mg, ethambutol 1,000 mg, and moxifloxacin 400 mg. Later on when he
tolerated these medicines, rifampicin 600 mg and pyrazinamide 1,500 mg were added (Fig. 3).
GeneXpert on 18/11/2014 detected rifampicin resistance and sputum culture was positive for
Mycobacterium tuberculosis (Fig. 4) and was resistant to streptomycin, rifampicin, isoniazid,
ethambutol, pyrazinamide, ciprofloxacin, and sensitive to kanamycin, capreomycin, amikacin,
levofloxacin. Thus, he was diagnosed as a case of multidrug-resistant tuberculosis (MDR-TB)
with ciprofloxacin resistant (Pre XDR-TB) and was given injection kanamycin, ethionamide,
FIG. 1: Chest X-ray showing infiltrates in left upper

zone.
Multidrug-resistant Tuberculosis (Pre XDR-TB) Treated with CAT IV Regimen 143
FIG. 2: Chest X-ray showing deterioration and treat-

ment of multidrug-resistant tuberculosis (MDR-TB)
started.
FIG. 3: Chest X-ray after 3 months of multidrug-

resistant tuberculosis (MDR-TB) treatment.
cycloserine, levofloxacin, pyrazinamide, and ethambutol on 19/12/2014. Patient’s sputum

smear was positive at the end of 3 and 6 months. At the end of 8 months, sputum smear
for AFB became negative and culture also became negative for Mycobacterium tuberculosis
and he improved clinically and radiologically (Fig. 5). Injection kanamycin was stopped after
8 months and rest of the treatment was continued for 18 months (Figs. 6 and 7). Patient did
not experience any adverse drug reaction during treatment and he further improved clinically,
bacteriologically, and radiologically and treatment was stopped after completing 26 months
of treatment (Fig. 8). The last three sputum cultures remained negative for Mycobacterium
tuberculosis. After the completion of treatment, he was followed up after 2 years and remained
asymptomatic.

resistant tuberculosis (MDR-TB) treatment but
sputum remained positive.

resistant tuberculosis (MDR-TB) treatment sputum
smear and culture became negative and injection
kanamycin was stopped.
FIG. 6: Chest X-ray after 1 year of multidrug-

Multidrug-resistant Tuberculosis (Pre XDR-TB) Treated with CAT IV Regimen 145
FIG. 7: Chest X-ray after completion of 18 months of

multidrug-resistant tuberculosis (MDR-TB) treatment.
FIG. 8: Chest X-ray after completing 26 months of

multidrug-resistant tuberculosis (MDR-TB) treatment.
DISCUSSION
CASE 41
Treated with CAT IV Regimen
CASE REPORT
A 22-year-old female presented with chief complaints of fever cough, loss of weight, and loss
of appetite for 1 month. Sputum for acid-fast bacilli (AFB) was positive. Patient was started on a
regimen based on rifampicin, isoniazid, pyrazinamide, and ethambutol by private practitioner
in June, 2015 which she took for 6 months and was relieved symptomatically (Figs. 1 and 2).
Sputum smear for AFB was negative at the end of treatment. After 1 month, she developed
fever and other constitutional symptoms. Her sputum for AFB was positive in January, 2016.
Patient was started on Category II DOTS consisting of rifampicin, isoniazid, pyrazinamide,
ethambutol, and streptomycin. Even after 3 months of retreatment patient was not improving
symptomatically and there was no resolution in chest infiltrates (Figs. 3 and 4). Therefore,
GeneXpert was done which detected rifampicin resistance in April, 2016. Her culture sensitivity
showed resistance to isoniazid but was susceptible to kanamycin, ofloxacin, moxifloxacin, and
capreomycin. Thus, she was diagnosed as a case of multidrug-resistant tuberculosis (MDR‑TB)
FIG. 1: Chest X-ray at the start of first-line antitu

bercular treatment.
Multidrug-resistant Tuberculosis Treated with CAT IV Regimen 147
and was put on a regimen for MDR-TB in May, 2016 consisting of injection kanamycin,
ethionamide, cycloserine, moxifloxacin, ethambutol, and pyrazinamide. Isoniazid in dose
of 300 mg/day was also given (Figs. 5 to 11). Kanamycin was stopped after 8 months when
sputum smear and culture for Mycobacterium tuberculosis (MTB) became negative. Rest of the
drugs were continued for 16 months. Patient sputum smear and culture remained negative for
Mycobacterium tuberculosis. There was significant improvement clinically and radiologically.
After stopping the treatment, she was followed up every 3 months for 1 year and remained
asymptomatic.
FIG. 2: Chest X-ray on completion of first-line

antitubercular treatment.
FIG. 3: Chest X-ray on which patient was started

treatment for relapse of pulmonary tuberculosis.
FIG. 4: Chest X-ray after 3 months of retreatment

showing no signs of radiological improvement.
FIG. 5: Chest X-ray on which multidrug-resistant

tuberculosis (MDR-TB) treatment was started.
FIG. 6: High-resolution computed tomography (HRCT) thorax

showing bilateral infiltrates with multiple cavities in right side when
multidrug-resistant tuberculosis (MDR-TB) treatment was started.
Multidrug-resistant Tuberculosis Treated with CAT IV Regimen 149

(HRCT) thorax showing infiltrates in lower zone on
the right side.



resistant tuberculosis (MDR-TB) treatment when
smear and culture became negative and kanamycin
was stopped.
A B
FIGS. 11 A AND B: High-resolution computed tomography (HRCT) thorax after 1 year showing
resolution of infiltrates and cavity.
DISCUSSION
CASE 42
Extensive Drug-resistant
Tuberculosis Treated as
CASE REPORT
A 38-year-old male, known case of type 2 diabetes mellitus (T2DM), was diagnosed as a
case of tubercular meningitis (TBM) in 2008 for which he took antitubercular treatment for
9 months and improved symptomatically CXR at that time was normal (Fig. 1). He remained
asymptomatic for next 4 years when he developed fever, cough with sputum, and decreased
appetite for 1 month. Sputum smear for acid- fast bacilli (AFB) was positive and he was given
CAT II regime comprising of isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin
in adequate doses starting from March, 2013 for 18 months and improved symptomatically
clinically, methodologically, bacteriologically, and radiologically (Figs. 2 to 4). After completion
of CAT II DOTS in September, 2014, patient was asymptomatic for next 6 months when she
again developed constitutional symptoms. Sputum smear for AFB was positive in March
2015 and culture was positive for Mycobacterium tuberculosis. Pending drug susceptibility
testing report, patient was again put on five-drug regimen in March 2015 (SHREZ/RHEZ/RHE).
GeneXpert detected rifampicin resistance. Culture showed resistance to rifampicin, isoniazid,
kanamycin, and levofloxacin (R, H, Km, and Lfx) suggestive of extensively drug-resistant
tuberculosis (XDR‑TB). Since there was no history of administration of second-line injectables
FIG. 1: Chest X-ray in 2008 when he was diagnosed

with tubercular meningitis.
FIG. 2: Chest X-ray in March, 2013 when he was put

on CAT II regimen.
FIG. 3: Chest X-ray after 4 months of CAT II regimen.
FIG. 4: Chest X-ray after completion of CAT II regimen.

Extensive Drug-resistant Tuberculosis Treated as Multidrug-resistant Tuberculosis 153
and floroquinolone in the past, the drug susceptibility test (DST) report was ignored and
patient was treated as a case of multidrug-resistant tuberculosis (MDR-TB). Patient was put on a
regimen including injection kanamycin, ethionamide, cycloserine, moxifloxacin, pyrazinamide,
and ethambutol (Km, Eto, Cs, Mfx, Z, and E) in full doses from July, 2015 (Fig. 5). Sputum smear
for AFB became negative after 6 months but culture for Mycobacterium tuberculosis became
negative after 8 months of treatment when kanamycin was stopped. Rest all drugs were
continued for next 16 months. Patient improved clinically, bacteriologically, and radiologically
(Fig. 6). On subsequent follow-up at regular intervals for 3 years, patient remained asymptomatic
(Figs. 7 and 8).
FIG. 5: Chest X-ray at initiation of multidrug-resistant

tuberculosis (MDR-TB) regimen.
FIG. 6: Chest X-ray on completion of multidrug-

resistant tuberculosis (MDR-TB) regimen.
FIG. 7: Chest X-ray posteroanterior view showing

healed lesion after 3 years of follow-up after com
pletion of multidrug-resistant treatment.

(HRCT) thorax showing healed lesion after 3 years
of follow-up after completion of multidrug-resistant
treatment.
DISCUSSION
CASE 43
Multidrug-resistant Tuberculosis Following

Adverse Drug Intolerance due to Severe
Adverse Drug Reaction
CASE REPORT
A 20-year-old female complained of fever, cough with expectoration for 2 months. Sputum
smear for acid-fast bacilli (AFB) was positive. She was started on a regimen based on
rifampicin, isoniazid, ethambutol, and pyrazinamide (HRZE) w.e.f. 20th January, 2016 (Fig. 1).
After 1 month of treatment, she developed severe loss of appetite, nausea, and vomiting.
LFT was done which was within normal limits. Because of the severe gastric intolerance,
rifampicin, and pyrazinamide were stopped and she was taken on modified regimen
comprising of injection streptomycin, ethambutol and isoniazid along with levofloxacin (S, E,
H, and Lfx). Patient tolerated these drugs and after 10 days rifampicin and pyrazinamide was
introduced one by one which she could not tolerate again so she continued with modified
regimen. After 3 months, sputum smear for AFB remained positive. There was no improve
ment in patient’s conditions despite on modified ATT regimen for 3 months. GeneXpert
showed rifampicin resistance and culture was positive for Mycobacterium tuberculosis. Drug
susceptibility test (DST) report showed resistance to rifampicin and isoniazid and sensitivity
FIG. 1: Chest X-ray of the patient at the start of

treatment with first-line drugs.
to kanamycin, moxifloxacin, and levofloxacin. Previous regimen was stopped with immediate
effect and she was given MDR-TB regimen (CAT IV) on 5th May, 2016 (Fig. 2), consisting of
injection kanamycin, ethionamide, cycloserine, moxifloxacin, levofloxacin, pyrazinamide, and
ethambutol (Km, Eto, Cs, Mfx, and Z, E) (Fig. 2). Sputum culture became negative at the end of
7 months of treatment and kanamycin was stopped. Patient responded clinically, radiologically,
and bacteriologically (Figs. 3 to 5). She tolerated all the second-line antitubercular drugs.
Treatment was continued and sputum smear for AFB and culture was negative thereafter.
Treatment was stopped on 13th August, 2018 (Fig. 6). On subsequent follow-up for 1 year,
she was asymptomatic.


Multidrug-resistant Tuberculosis Following Adverse Drug Intolerance due to Severe Adverse Drug Reaction 157
FIG. 4: Chest X-ray after 5 months of multidrug-resistant

tuberculosis (MDR-TB) treatment.
FIG. 5: Chest X-ray after 7 months of multidrug-resistant

tuberculosis (MDR-TB) treatment when sputum smear and
culture became negative.
FIG. 6: Chest X-ray after completion of treatment.
DISCUSSION
CASE 44
Extensively Drug-resistant Tuberculosis

Treated as MDR-TB Ignoring Drug
Susceptibility Report
CASE REPORT
An 18-year-old female presented with complaints of fever and cough with expectoration and
loss of appetite for 3 months. Sputum smear for acid-fast bacilli (AFB) was positive. She was
started on a regimen based on HRZE (rifampicin, isoniazid, ethambutol, pyrazinamide) w.e.f.
January, 2015. She developed drug intolerance after 1 month and her liver function test (LFT)
was also deranged. Rifampicin and pyrazinamide was stopped and she was given injection
streptomycin, isoniazid, and ethambutol in full doses along with levofloxacin 750 mg daily from
February to April, 2015. She tolerated these drugs well and LFT became normal. Her sputum
remains positive and GeneXpert showed rifampicin resistance. First-line line probe assay
(LPA) showed rifampicin and isoniazid resistance. She was started with multidrug-resistant
tuberculosis (MDR-TB) regimen consisting of injection kanamycin, ethionamide, cycloserine,
moxifloxacin, pyrazinamide, and ethambutol (Km, Eto, Cs, Mfx, Z, E). Culture of sputum sent
earlier came out to be positive for Mycobacterium tuberculosis and drug susceptibility test
(DST) in June, 2016 to first-line and second-line drugs showed sensitive to all drugs. It was a
big surprise. Ignoring DST report, MDR-TB treatment was continued as she was showing signs
of clinical improvement and was tolerating these drugs. Patient developed hearing problem
after 4 months of kanamycin for which ENT consultation was sought. Kanamycin was stopped.
Cultures were positive till October, 2016. Another culture sensitivity was sent which showed
resistance to isoniazid, rifampicin, kanamycin, capreomycin, ofloxacin, ethionamide and
para-amino salicylic acid (R, H, Km, PAS, Eto, Cm, S, E, Z, Oflx) suggestive of extensively drug-
resistant (XDR-TB). Patient was continued MDR-TB treatment ignoring DST report as patient’s
condition improved clinically, bacteriologically and radiologically (Figs. 1 to 6). Sputum smear
for AFB and culture was negative for Mycobacterium tuberculosis after 9 months of treatment.
She was given treatment for total duration of 2 years. Treatment was stopped on 25/4/2018.
On subsequent follow-up for 1 year she was asymptomatic. Such types of different sensitivity
report from different laboratories are seen in day-to-day clinical practice and one should not
be dictated by these reports. This also suggests that culture and sensitivity reports should be
performed in quality-assured laboratories.

FIG. 2: Chest X-ray after completion of 8 months of

treatment when smear and culture became negative.
FIG. 3: Chest X-ray after 1 year of treatment.

Extensively Drug-resistant Tuberculosis Treated as MDR-TB... 161
FIG. 4: Chest X-ray at the time when drug suscep

tibility test (DST) report showing extensively drug-
resistant tuberculosis (XDR-TB) but same treatment
was continued since patient was improving.
FIG. 5: Chest X-ray after 18 months of treatment

showing resolution of infiltrates.
FIG. 6: Chest X-ray after 2 years of complete treatment.

DISCUSSION
For treatment of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-
TB), standardized, empirical, and individualized approaches have been laid down.
Individualized treatment based on individual DST and prior treatment history is costly
and needs skilled professionals and quality-assured bacteriological and molecular
diagnostic laboratories whereas standardized treatment is simple, less costly, and same
treatment is given to all patients. Treatment of MDR/RR-TB is very difficult in the hands
of many physicians with restricted knowledge who dare to treat these patients and create
worsening problems. Therefore, individualized treatment needs specialized physicians
experienced in dealing with such cases since these treatments represent the patient's last
chance of a cure.
There can be two types of treatment regimen: Conventional or shorter regimen
according to recent update from WHO in 2016 in which they have also reclassified anti-
tubercular drugs (ATD) for MDR/RR-TB. Drugs and doses according to new classification
are given in Table 1. In patients with MDR/RR-TB, a conventional regimen of least five
effective ATD during the intensive phase is recommended, including pyrazinamide and
four core second-line ATD: One chosen from group A (fluoroquinolones: levofloxacin,
moxifloxacin and gatifloxacin), one from group B (second-line injectable drugs:
Table 1: Drugs and doses recommended for the treatment of multidrug-resistant/rifampicin-

resistance tuberculosis (MDR/RR-TB).
Groups Drugs Average daily dose Daily dosage (mg)
Minimum Maximum
A. Fluoroquino Levofloxacin 7.5–10 mg/kg 750 1,000
lones Moxifloxacin 7.5–10 mg/kg 400 400
Gatifloxacin 7.5–10 mg/kg 400 400
B. Second-line Amikacin 15 mg/kg 500 1,000
injectable Kanamycin 15 mg/kg 500 1,000
agents
Capreomycin 15 mg/kg 500 1,000
Streptomycin 15 mg/kg 500 1,000
C. Other core Ethionamide/ 15–20 mg/kg 500 1,000
second-line Prothionamide
agent Cycloserine/Terizidone 10–20 mg/kg 500 1,000
Linezolid 600 mg 600 600
Clofazimine 4–5 mg/kg 100 300
D. A
dd on D1 Pyrazinamide 25 mg/kg 750 2,000
agents Ethambutol 15 mg/kg 600 1,200
High-dose isoniazid 16–20 mg/kg 600 1,500
D2 Bedaquiline 400 mg OD x 2 weeks and then 200 mg 3 times per week
Delamanid 100 mg twice daily (BD)
D3 PAS 200–300 mg/kg 10 g 12 g
Imipenem-cilastatin 1,000 mg – 1,000 mg BD
Meropenem 1,000 mg thrice daily (TID)
Amoxicillin-clavulanate 80 mg/kg/day 500/125 mg BD 1,000/250 mg BD
Thioacetazone 150 mg once daily (OD)
kanamycin, amikacin, capreomycin), and at least two from group C (other core second-line
drugs: Ethionamide/prothionamide, cycloserine/terizidone, linezolid, and clofazimine).
If the minimum of effective ATD cannot be composed as above, one drug from group D2
(Bedaquiline and Delamanid) and other drugs from D3 [para-aminosalicylic acid (PAS),
imipenem-cilastatin, meropenem, amoxicillin-clavulanate, and thioacetazone] may be
added to bring the total number of drugs to five. The regimen may be further strengthened
with rest of group D1 (high-dose isoniazid and/or ethambutol). While streptomycin is not
usually included with the second-line drugs it can be used as the injectable drug of the
core MDR/RR-TB regimen if none of the three other injectable drugs can be used and if
the strain can be reliably shown not to be resistant. Thioacetazone should not be used if
the patient is HIV seropositive. Intensive phase including injectables should be given for
at least 8 months for most patients which can be modified depending upon the response
of the patient. The total duration of treatment is at least 20 months which can be prolonged
up to 24 months depending upon the response of the patient. Pyrazinamide is usually
continued for the entire treatment especially if there is extensive disease. If the patient has
minimal disease, pyrazinamide can be stopped with injectables at end of intensive phase.
Bedaquiline or delamanid are used for 6 months in intensive phase and are presently not
recommended for whole treatment duration.
It is important that a single drug should never be added to a failing regimen and it is
ineffective to combine two drugs of the same group or to add a drug potentially ineffective
because of cross-resistance. No drug should be kept in reserve and the most powerful
drugs should be used initially and in maximum combination so as to ensure that first
battle is won and won permanently. All patients initiated on treatment and their family
members should be intensively counseled prior to treatment initiation and during all
follow-up visits. To reduce the risk of development of resistance to second-line ATD and
promote optimal treatment outcomes, all efforts should be made to administer treatment
under direct observation (DOT) over the entire course of treatment. If DOT is not possible,
attempts to ensure treatment adherence should be made by checking empty blister packs
during follow-up visits every month. All measures should be taken to persuade and
encourage patients not to stop treatment despite all its discomforts as it is the last resort
that stands between life and death.
The WHO has revised grouping of ATD in 2018 for use in MDR/RR-TB treatment
(Table 2). ATD were divided into three groups based on IPD of >13,000 patients depending
Table 2: WHO revised grouping of TB medicines 2018.

Group Medicine
Group A: Include all three medicines (unless • Levofloxacin or moxifloxacin
they cannot be used) • Bedaquiline
• Linezolid
Group B: Add both medicines (unless they • Clofazimine
cannot be used) • Cycloserine or terizidone
Group C: Add to complete the regimen and • Ethambutol
when medicines from Groups A and B cannot • Delamanid
be used • Pyrazinamide
• Imipenem-cilastatin or meropenem
• Amikacin (or streptomycin)
• Ethionamide or prothionamide
• Paraaminosalicylic acid
(TB: tuberculosis; WHO: World Health Organization)
on their individual efficacy, risk of relapse, treatment failure, and death. In 2018, WHO
updated that MDR/RR-TB patients on longer regimens should have all three group A
agents and at least one group B agent included to ensure that treatment starts with at
least four TB agents likely to be effective and that at least three agents are included for the
rest of treatment after bedaquiline is stopped. If only one or two group A agents are used,
both group B agents are to be included. If the regimen cannot be composed with agents
from groups A and B alone, group C agents are added to complete it. Kanamycin and
capreomycin are not to be included in the treatment of MDR/RR-TB patients on longer
regimens. WHO has advised for preferably oral regimens. Government of India is in the
process of adopting the changes based on the recent WHO guidelines.
Extrapulmonary MDR/RR-TB is treated with the same regimen and duration as
pulmonary MDR/RR-TB. If the patient has symptoms suggestive of central nervous
system involvement and is infected with MDR/RR-TB, the regimen should use drugs
that have adequate penetration into the central nervous system. Rifampicin, isoniazid,
pyrazinamide, prothionamide/ethionamide, and cycloserine have good penetration into
the cerebrospinal fluid (CSF); Kanamycin, amikacin and capreomycin do so only in the
presence of meningeal inflammation; PAS and ethambutol have poor or no penetration.
The fluoroquinolones have variable CSF penetration, with better penetration seen in
the later generations. Linezolid is believed to penetrate the central nervous system, and
has been used in meningitis treatment. Imipenem has good central nervous system
penetration, but children with meningitis treated with imipenem had high rates of seizures
and meropenem is preferred for meningitis cases and children. There is no data on central
nervous system penetration of clofazimine, clarithromycin, bedaquiline, and delamanid.
Surgical treatment should be considered as an adjunct to chemotherapy whenever
applicable and when results of chemotherapy are very unpredictable. Adjuvant use of
corticosteroids can be beneficial in conditions such as severe central nervous system or
pericardial involvement. Corticosteroids do not increase mortality when the patient is
on effective regimen and should be used with tapering of doses over several weeks. The
immunomodulators may have the potential to improve outcomes in all TB including
MDR/RR-TB as seen in evidence reviewed by expert group in 2007 but still evaluation of
efficacy and safety of such therapy is needed before any recommendation is made.
The MDR/RR-TB treatment should include nutritional assessment and counseling of
the all patients. Because of disease process, patient appetite is reduced and tends to be
malnourished, in addition, second-line anti-TB drugs can further reduce appetite. Patients
should be properly counseled for adequate food intake. One such step is to provide free
food which is thought to improve quality of life and may improve treatment adherence but
further research is necessary. Addition of vitamins probably does not improve weight gain
and also no studies have assessed their effect on quality of life but they may be added to
treat specific deficiencies such as vitamin A. Furthermore, vitamin B6 should be given if
treatment regimen consists of cycloserine, terizidone, high-dose isoniazid or linezolid to
prevent neurological side effects.
MONITORING OF TREATMENT
Monitoring of treatment should be done with bacteriological, radiological, and clinical
methods. Sputum specimens should be obtained for semi quantitative smear and culture
every month from third month onward during the intensive phase of therapy. Sputum
conversion is defined as two sets of consecutive negative smears and cultures, from
samples collected at least 30 days apart. Both bacteriological techniques (smear and
culture) should be used to monitor patients throughout therapy. After sputum conversion,
smear examination and culture are done once in 3 months until the end of therapy. If such
a large number of smears and cultures for follow-up are not possible, then at least five
smears and cultures must be done for follow-up (4, 6, 12, 18, and 24 months), X-rays should
be done every 6 months whereas clinical monitoring preferably should be done every
month. According to the latest WHO guidelines in 2018, MDR/RR-TB patients on longer
regimens, the performance of sputum culture in addition to sputum smear microscopy
is recommended to monitor treatment response. It is desirable for sputum culture to be
repeated at monthly intervals.
OUTCOME OF TREATMENT
The outcome of treatment of MDR/RR-TB is not very favorable and varied from 50–80% in
different studies.
FURTHER READING
1. World Health Organization. Companion handbook to the WHO guidelines for the programmatic
management of drug-resistant tuberculosis. [online] Available from https://apps.who.int/iris/
bitstream/handle/10665/130918/9789241548809_eng.pdf;jsessionid=9D497D4F2F4D1D8457C49
FB93B2BC624?sequence=1. [Last accessed February, 2020].
2. Caminero JA. Management of multidrug-resistant tuberculosis and patients in retreatment. Eur
Respir J. 2005;25:928-36.
3. Kim SJ. Drug susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J.
2005;25:564-9.
4. World Health Organization. Treatment of tuberculosis: guidelines-4th edition. [online] Available from
https://apps.who.int/iris/bitstream/handle/10665/44165/9789241547833_eng.pdf?sequence=1.
5. World Health Organization. Guidelines for programmatic management of drug resistant tuberculosis.
[online] Available from https://apps.who.int/iris/bitstream/handle/10665/44597/9789241501583_
eng.pdf?sequence=1. [Last accessed February, 2020].
6. Prasad R, Verma SK, Sahai S, Kumar S, Jain A. Efficacy and safety of kanamycin, ethionamide, PAS,
and cycloserine in multidrug resistant pulmonary tuberculosis patients. Indian J Chest Dis Allied Sci.
2006;48:18183-6.
7. Prasad R, Singh A, Srivastava R, Kushwaha RAS, Garg R , Verma SK, et al. Treatment outcome of multi
drug resistant tuberculosis patients in modified DOTS PLUS. ERJ. 2012;40:3321.
8. Lange C, Abubakar I, Alffenaar JW, Bothamley G, Caminero JA, Carvalho AC, et al. Management
of patients with multidrug resistant/extensively drug-resistant tuberculosis in Europe: a TBNET
consensus statement. Eur Respir J. 2014;44:23-63.
9. International Union against Tuberculosis and Lung Diseases. (2013). Guidelines for clinical and
operational management of drug-resistant tuberculosis. [online] Available from https://www.
theunion.org/what-we-do/publications/technical/english/mdr-tbguide_6-19-13_web.pdf. [Last
accessed February, 2020].
10. World Health Organization. WHO treatment guidelines for drug-resistent tuberculosis–2016 update.
11. Technical and operational guidelines for TB control in India 2016. [online] Available from https://
tbcindia.gov.in/index1.php?sublinkid=4573&level=2&lid=3177&lang=1. [Last accessed February,
2020].
12. World Health Organization. (2018). Rapid communication: Key changes to treatment of
multidrug- and rifampicin-resistant tuberculosis. [online] Available from https://www.who.int/tb/
publications/2019/WHO_RapidCommunicationMDRTB2019.pdf?ua=1. [Last accessed February,
2020].
13. Ahmad N, Ahuja SD, Akkerman OW, Alffenaar J-WC, Anderson LF, Baghaei P, et al. Treatment
correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual
patient data meta-analysis. Lancet. 2018;392:821-34.
14. World Health Organization. WHO treatment guidelines for multidrug- and rifampicin-resistant
tuberculosis: 2018 update. [online] Available from https://www.who.int/tb/areas-of-work/drug-
resistant-tb/guideline-update2018/en/. [Last accessed February, 2020].
15. Holdiness MR. Cerebrospinal fluid pharmacokinetics of antituberculosis drugs. Clin Pharmacokinet.
1985;10:532-4.
16. Tuberculosis drug information guide, 2nd edition. California: Curry International Tuberculosis Center
and California Department of Public Health; 2012.
17. Daley CL. Mycobacterium tuberculosis complex. In: Yu VL, Merigan TC Jr, Barriere SL, (Eds).
Antimicrobial therapy and vaccines. Philadelphia: Williams & Wilkins; 1999. pp. 531-6.
18. Partners In Health. (2003). PIH guide to medical management of multidrug-resistant tuberculosis.
Boston: Partners In Health. [online] Available from http://www.pih.org/publications/entry/pih-
guide-to-the-medical-management-of-multidrug-resistant tuberculosis/. [Last accessed February,
2020].
19. World Health Organization. (2007). Report of the expert consultation on immunotherapeutic
interventions for tuberculosis. [online] Available from https://apps.who.int/iris/bitstream/
handle/10665/43779/9789241595834_eng.pdf?sequence=1&isAllowed=y. [Last accessed February,
2020].
20. Sinclair D, Abba K, Grobler L, Sudarsanam TD. Nutritional supplements for people being treated for
active tuberculosis. Cochrane Database Syst Rev. 2011;CD006086.
21. Prasad R, Naorem R, Saxena H, Gupta N. Current treatment of multidrug resistant and rifampicin
resistant tuberculosis. Indian J Chest Dis Allied Sci. 2019;61:135-40.
CASE 45
Achalasia Cardia Presenting as

Uncontrolled Asthma
CASE REPORT
A 67-year-old male nonsmoker and a follow through case of bronchial asthma presented
with the complaints of difficulty in swallowing for 7 months, regurgitation of food for
7 months, dry cough for 5 months, low-grade fever for 5 months, and increased shortness
of breath for last 2 months. He was treated with antibiotics and optimal bronchodilatotors
without any satisfactory response. His mother was asthmatic. A chest radiograph (Fig. 1)
showed mediastinal widening with a paracardiac shadow. Mantoux test was nonreactive.
Hemoglobin was 10.8 g/dL, complete blood count, liver function test, and kidney function
tests were normal. Clinical examination revealed bilateral vesicular breath sounds with
scattered polyphonic rhonchi and few crepts in right infrascapular area. As dysphagia
was progressive, obstructive lesion in the gastrointestinal (GI) tract was suspected. An
esophagogram showed typical bird’s beak appearance as shown in Figure 2, confirming the
diagnosis of achalasia cardia. Contrast-enhanced computed tomography (CECT) of chest in
Figures 3 and 4 showed grossly dilated esophagus with fluid level and that confirmed the
FIG. 1: Chest radiograph (posteroanterior view)

showing dilated esophagus with fluid level.
FIG. 2: Esophagogram showing bird’s beak appearance.
FIG. 3: Contrast-enhanced computed tomography (CECT)

chest showing dilated esophagus with fluid level.
FIG. 4: Contrast-enhanced computed tomography (CECT)

chest showing dilated esophagus with fluid level.
Achalasia Cardia Presenting as Uncontrolled Asthma 169
diagnosis. Upper GI endoscopy revealed massively dilated esophagus with food particles and
secretions. He was referred for gastrosurgery consultation where modified Heller’s myotomy
was planned but he was lost to follow-up.
DISCUSSION
Primary achalasia is a disorder of the esophageal motility characterized by absent
primary peristalsis and incomplete relaxation of the lower esophageal sphincter
caused by loss of ganglion cells in the esophageal myenteric plexus whereas secondary
achalasia (pseudoachalasia) is caused by malignant tumor at the gastroesophageal
junction or rarely by Chagas disease. It has been associated with other diseases such
as Parkinson’s disease, progressive cerebellar ataxia, familial glucocorticoid deficiency,
and Down syndrome. The clinical symptoms and signs of patients with achalasia cardia
depend on the severity of the lesion and the associated complications. But the most
common presenting symptoms and signs include dysphagia, regurgitation, weight loss,
chest pain, and cough. The index case presented with difficulty in breathing, increased
cough, and dysphagia. However, the difficulty in breathing, swallowing, and cough may
be due to the dilated esophagus which is evident from the plain chest radiographs and
barium swallow. The radiological evaluation of a patient with achalasia includes plain
chest radiographs, barium esophagogram, and possibly transabdominal ultrasound.
Computed tomography (CT) and magnetic resonance imaging (MRI) have no useful
role in the diagnosis of primary achalasia. Plain chest X-ray may be normal or in most
cases show widened mediastinum with air fluid levels. Chest X-ray of the index case
showed widened mediastinum with fluid level. The fundal gas may be absent or partially
reduced; however, it was present in our case. Barium esophagogram in a patient with
achalasia will show a decrease or absent primary peristalsis, dilated thoracic esophagus
with a tapered distal part. But it must be stated that a normal finding on barium swallow
examination does not completely exclude achalasia cardia in its early stage. This
patient's barium study was able to demonstrate a grossly enlarged thoracic esophagus
with tapering at its distal end and absent peristaltic movement. Ultrasonography is not
recommended for the primary diagnosis of achalasia. Though, some workers are of the
opinion that this method may be useful as a screening test to differentiate achalasia
from pseudoachalasia. This patient had a transabdominal ultrasonography which was
normal. CT can be used in differentiating achalasia from pseudoachalasia in a patient
with esophageal dilatation. The wall thickness said to be uniform in achalasia as
against pseudoachalasia that is uneven. The wall of the esophagus appears uniformly
thickened (Figs. 2 and 4) as seen in achalasia cardia. It may show mass lesions in
esophagus. A diagnosis of achalasia supported by the results of radiological studies must
always be confirmed by performing upper gastrointestinal endoscopy and esophageal
manometry. These tests allow the direct evaluation and inspection of the esophageal
mucosa and objective measurement of esophageal contractility. Manometric study was
not done on this patient because of lack of facility in our center. Well-studied treatment
options include oral pharmacologic agents such as calcium channel blockers, chemical
denervation by endoscopic injection of botulinum toxin, pneumatic dilation, and
surgical myotomy. This patient was planned for Heller’s myotomy but he failed to come
for follow-up.
FURTHER READING
1. Park W, Vaezi MF. Etiology and pathogenesis of achalasia: the current understanding. Am J
Gastroenterol. 2005;100:1404-14.
2. Colombo JL, Hallberg TK. Recurrent aspiration in children: lipid-laden alveolar macrophage
quantitation. Pediatr Pulmonol. 1987,3:86-9.
3. Woodfeild CA, Levine MS, Rubesin SE, Langlotz CP, Laufer I. Diagnosis of primary versus secondary
achalasia, reassessment of clinical and radiographic criteria. AJR Am J Roentgenol. 2000;175:
727-31.
4. Kahrilas PJ, Kishk SM, Helm JF, Dodds WJ, Harig JM, Hogan WJ. Comparison of pseudoachalasia and
achalasia. Am J Med. 1987;82:439-46.
5. Nihoul-Fékété C, Bawab F, Lortat-Jacob S, Arhan P. Achalasia of the esophagus in childhood.
Surgical treatment in 35 cases, with special reference to familial cases and glucocorticoid deficiency
association. Hepatogastroenterology. 1991;38:510-13.
6. Myers NA, Jolley SG, Taylor R: Achalasia of the cardia in children: A worldwide survey. J Pediatr Surg.
1994;29:1375-79.
7. El-Takli I, O'Brien P, Paterson WG: clinical diagnosis of achalasia: How reliable is barium X-ray? Can J
Gastroenterol. 2006;20;335-42.
8. Eckardt VF, Scmitt T, Kanzler G. Transabdominal ultrasonography in achalasia. Scand J Gastroenterol.
2004;39:634-41.
9. Sezgin O, Ulkar A, Temucin G. Sonographic findings in achalasia. J Clin Ultrasound. 2001;29:31-40.
10. Carter M, Deckman RC, Smith RC, Burell MI. Differentiation of achalasia from pseudoachalasia by
computed tomography. AMJ Gastroenterol. 1997;72:627-56.
11. Chapman AHA. Achalasia. In: Davivd S (Ed). A textbook of radiology and imaging, 7th edition.
London: Churchill Livingstone; 2007. pp. 552-4.
12. Golanchanvit S, Fisher RS, Parkman HP. Diagnostic modalities for achalasia. Gastrointest Endosc Clin
N Am. 2001;11:293-310.
CASE 46
Walking Pneumonia Diagnosed as

CASE REPORT
A 20-year-old male presented in 1983 with complaints of breathlessness on and off since
12 years, fever for 2 months, cough for 2 months, and hemoptysis for 15 days. Multiple
chest X-rays between 1983–2004 showed radiopaque homogenous shadows which were
fleeting in all the zones of the lung (Figs. 1 to 6). Routine blood investigation was done
which showed peripheral eosinophilia (14%). His absolute eosinophil count was also
raised (1,206/mm3). Sputum smear was negative for acid-fast bacilli but was positive for
fungus and culture detected Aspergillus fumigatus (AF). Skin prick test was performed in
which type 1 and type 3 hypersensitivity reaction to AF was detected. Bronchography
was done in 1986 which showed central bronchiectasis (Fig. 7). High-resolution
computed tomography (HRCT) thorax done in 2007 showed bilateral central bronchiectasis
(Figs. 8 and 9). Patient was diagnosed as a case of allergic bronchopulmonary aspergillosis
(ABPA). Patient was put on steroids 0.5 mg/kg body weight daily for 2 weeks which was
tapered off to 0.5 mg/kg body weight alternate day for 6–8 weeks and regular inhaled
medications (LABA + ICS) were also given. He had exacerbations of ABPA on many occasions.
During exacerbations, dose of oral steroids were increased and 6 months of itraconazole
200 mg twice daily was used for 3 months also. Patient has been followed up for 33 years
with recurrent exacerbations.
A B
FIGS. 1A AND B: Chest X-ray showing homogenous opacity in right upper and mid zone
which resolved after 6 weeks of oral steroid treatment.
FIG. 2: Chest X-ray showing homogenous shadow in

left upper zone.
FIG. 3: Chest X-ray showing homogenous shadow in

left mid zone.
Walking Pneumonia Diagnosed as Allergic Bronchopulmonary Aspergillosis 173
A B
FIGS. 4A AND B: Chest X-ray showing homogenous shadow in right mid zone which resolved
after taking oral steroids treatment for 3 weeks.
FIG. 5: Chest X-ray showing homogenous shadow

in right upper and mid zone.
FIG. 6: Chest X-ray showing homogenous shadow

in left mid and lower zone.
FIG. 7: Bronchography showing proximal bronchiec

tasis on the left side.

(HRCT) thorax showing extensive bilateral central
bronchiectasis.
A B
FIGS. 9A AND B: High-resolution computed tomography (HRCT) thorax showing bilateral central
bronchiectasis.
Walking Pneumonia Diagnosed as Allergic Bronchopulmonary Aspergillosis 175
DISCUSSION
Allergic bronchopulmonary aspergillosis (ABPA) is often indolent and may be present for
years before diagnosis. When the diagnosis is made sufficiently early, irreversible lung
damage can be prevented. Although asthma is a common diagnosis, ABPA is diagnosed
infrequently, with the exact prevalence remaining uncertain. ABPA is still under
recognized in India and almost half of the ABPA patients are initially misdiagnosed as
having pulmonary tuberculosis (as happened in our case also).
Specific tests to establish the diagnosis of ABPA should be performed in patients
with asthma who have recurrent infiltrates on chest X-ray with peripheral eosinophilia
(10–20%). In such clinical setting, a skin test with Aspergillus fumigatus (AF) antigen must
be done. If skin test is found to be positive, other tests such as sputum culture of AF, total
serum lgE and lgE or lgG specific to AF and HRCT of thorax for proximal bronchiectasis
must be done to confirm the diagnosis of ABPA.
Currently, oral corticosteroid is the treatment of choice for ABPA, and therapy is
generally long-term. The goal of therapy is to achieve symptom resolution, clearance of
radiographic infiltrates, and establishment of a stable baseline serum level of total IgE.
Usual starting dose of prednisolone is 0.5 mg/kg daily and may be change to alternate-day
dosing with clearance of infiltrates. Along with steroid therapy, baseline therapy including
inhaled corticosteroid and β2 agonists is essential to control asthma.
FURTHER READING
1. Prasad R, Garg R, Sanjay. Walking pneumonia in a patient of bronchial asthma: A clue to the diagnosis
of allergic bronchopulmonary aspergillosis. Pulmon. 2007;9:120-3.
2. Eaton T, Garrett J, Milne D, Frankel A, Wells AU. Allergic bronchopulmonary aspergillosis in the
asthma clinic: A prospective evaluation of CT in the diagnosis algorithm. Chest. 2000;118:66-72.
3. Agarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Allergic bronchopulmonary aspergillosis:
lessons from 126 patients attending a chest clinic in North India. Chest. 2006;130:442-8.
4. Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo
Clin Proc. 2001;76:930-8.
5. Greenberger FA, Patterson R. Diagnosis and management of allergic bronchopulmonary
aspergillosis. Ann Allergy. 1986;56:444-8.
CASE 47
A Case of Allergic Bronchopulmonary

Aspergillosis Presenting as Collapse
Right Upper Lobe
CASE REPORT
A 23-year-old female presented with history of breathlessness since childhood, recurrent
nasal blockage since 3 years for which she underwent functional endoscopic sinus surgery
(FESS) 1 year back. Patient presented with exacerbation of breathlessness. Chest X-ray
and contrast enhanced computerized tomography (CECT) thorax showed collapse of right
upper lobe (Figs. 1 and 2). Routine blood investigation showed peripheral eosinophilia (15%).
Total IgE was elevated (2,248 IU/mL). Specific IgE (24 IU/mL) and IgG against Aspergillus was
elevated (24.78 IU/mL). Spirometry was done which showed obstructive airway disease.
Patient was diagnosed as allergic bronchopulmonary aspergillosis (ABPA) presenting with
collapse. Patient was put on oral prednisolone 0.5 mg/kg body weight daily for 2 weeks
which was tapered off to 0.5 mg/kg body weight alternate day for next 2 weeks and then
tapered to maintenance dose for another 4 months. Patient was advised to take regular
asthma medication (LABA + ICS) and for follow-up regularly. Collapse disappeared after
1 month of treatment with oral steroids (Figs. 3 and 4). Patient improved clinically and her
total IgE came down to 640 IU/mL.
FIG. 1: Chest X-ray showing collapse of right upper lobe.

A Case of Allergic Bronchopulmonary Aspergillosis Presenting... 177
A B
FIGS. 2A AND B: Contrast enhanced computerized tomography (CECT) thorax showing
collapse of right upper lobe.
A B
FIGS. 3A AND B: Chest X-ray after treatment with oral steroids for 1 month.
A B
FIGS. 4A AND B: Contrast enhanced computerized tomography (CECT) thorax after treatment
with steroids for 1 month showing that collapse has disappeared.
DISCUSSION
Allergic bronchopulmonary aspergillosis is often indolent and may be present
for years before diagnosis. When diagnosis is made early and treatment is started,
irreversible lung damage can be prevented. The increasing frequency with which
the diagnosis of ABPA is being made is probably the result of increasing recognition
of the disease entity and perhaps some simplification of the diagnostic criteria. The
diagnostic criteria for ABPA are divided into major and minor ones. The major criteria
includes asthma, fleeting shadows on chest radiograms, immediate cutaneous
reactivity to Aspergillus fumigatus, elevated total serum IgE, precipitating antibodies against
A. fumigatus, peripheral blood eosinophilia, elevated serum IgE and IgG to A. fumigatus,
and central/proximal bronchiectasis with normal tapering of distal bronchi. The minor
criteria are expectoration of golden brownish sputum plugs, positive sputum culture for
Aspergillus species, and delayed skin reactivity to A. fumigatus. A minimum essential
criterion has also been advocated that includes asthma, immediate cutaneous reactivity
to A. fumigatus and central bronchiectasis in the absence of distal bronchiectasis, elevated
total IgE, specific IgE against A. fumigatus. A literature search for ABPA presenting as
opaque hemithorax is rare. In a case series of five patients of lung collapse caused by
ABPA in nonasthmatic by Berkin et al. two cases presented as opaque hemithorax. A
case of total collapse of right lung in a patient with ABPA has been reported from Japan
by Nomura et al. in a 29-year-old man with bronchial asthma. Agarwal et al. described
a 22-year-old female without any prior respiratory symptom history who presented with
respiratory failure secondary to left lung collapse, necessitating rigid bronchoscopy for
diagnosis and management of ABPA. In 8 out of the 19 cases of ABPA in nonasthmatic
patients, bronchogenic carcinoma was initially suspected due to abnormality in the
chest roentgenogram (mostly atelectasis) but bronchoscopy revealed typical mucus
plugs containing macrophages, several eosinophils, fungal hyphae, scaled-off epithelium
(Curschmann spirals), and calcium oxalate crystals. Many times these patients are
confused with tuberculosis and repeatedly treated with antituberculosis drugs. The
radiographs of 100 patients with ABPA were examined to assess the type and distribution
of abnormalities seen during long-term follow-up by Phelan et al. Lobar shrinkage
occurred almost exclusively in the upper zones but other abnormalities were distributed
throughout both lungs. Bronchial wall thickening was the most common lesion and was
usually a permanent finding. Consolidation was most common in the perihilar regions.
Episodes of transient collapse were segmental, lobar or involved a whole lung. Permanent
collapse was always segmental. Massive shadowing, band shadows, and “gloved fingers”
were seen less frequently and cavitation was rare. In some patients, the chest radiograph
was normal between exacerbations of the disease. Pulmonary infiltrates and segmental
collapse are the usual radiological picture, it can rarely present as lung collapse as in our
case. On computed tomography, the mucoid impaction of the bronchial tree generally
shows slightly hyper dense shadow. Computed tomography has a sensitivity of 83% and
a specificity of 92% in detecting central bronchiectasis in patients with ABPA. Computed
tomography appearances can be subdivided into bronchial, parenchymal, and pleural
abnormalities. Bronchial abnormalities include central bronchiectasis, dilated and totally
occluded bronchi, air-fluid levels within the dilated bronchi, bronchial wall thickening,
and parallel-line shadows. Parenchymal abnormalities, which have a predilection for
upper lobes, include consolidation, collapse, and parenchymal scarring. Parenchymal
lesions can extend up to the pleura. The collapse can be managed by aggressive pulmonary
toileting to cause mobilization of secretions by physiotherapy, postural drainage, and/or
bronchoscopy along with treatment with drugs such as corticosteroids and/or antifungal
agents. This patient was treated with oral steroids and responded well. Her collapse
disappeared after 4 weeks of treatment.
FURTHER READING
1. Kumar R, Gaur SN. Prevalence of Allergic bronchopulmonary aspergillosis in patients with bronchial
asthma. Asian Pac J Allergy Immunol. 2000;18:181-5.
2. Kumar R. Mild, moderate and severe forms of allergic bronchopulmonary aspergillosis: a clinical and
serological evaluation. Chest. 2003;124:890-2.
3. Agarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Allergic bronchopulmonary aspergillosis:
lessons from 126 patients attending a chest clinic in north India. Chest. 2006;130:442-8.
4. Agarwal R. Allergic bronchopulmonary aspergillosis: Lessons for the busy radiologist. World J Radiol.
2011;3:178-81.
5. Rosenberg M, Patterson R, Mintzer R, Cooper BJ, Roberts M, Harris KE. Clinical and immunologic
criteria for the diagnosis of ABPA. Ann Intern Med. 1977;86:405-14.
6. Wang JLF, Patterson R, Rosenberg M, Roberts M, Cooper BJ. Serum IgE and IgG antibody activity
against Aspergillus fumigatus as a diagnostic aid in allergic bronchopulmonary aspergillosis. Am Rev
Respir Dis. 1978;117:917-27.
7. Berkin KE, Vernon DR, Kerr JW. Lung collapse caused by ABPA in nonasthmatic patients. Br Med J
(Clin Res Ed). 1982;285:552-3.
8. Nomura K, Sim JJ, Yamashiro Y, Hoshino M, Nakayama H, Hosaka K, et al. Total collapse of the right
lung in a patient with allergic bronchopulmonary aspergillosis. Nihon Kokyuki Gakkai Zasshi.
1998;36:469-72.
9. Agarwal R, Aggarwal AN, Gupta N. A rare cause of acute respiratory failure–allergic bronchopulmonary
aspergillosis. Mycoses. 2011;54:e223-7.
10. Henderson AH. Allergic aspergillosis: review of 32 cases. Thorax. 1968;23:501-12.
11. Glancy JJ, Elder JL, McAleer R. Allergic bronchopulmonary fungal disease without bronchial asthma.
Thorax. 1981;36:345-9.
12. Aubry MC, Fraser R. The role of bronchial biopsy and washing in the diagnosis of ABPA. Mod Pathol.
1998;11:607-11.
13. Molinari M, Ruiu A, Biondi M, Zompatori M. Hyperdense mucoid impaction in ABPA: CT appearances.
Monaldi Arch Chest Dis. 2004;61:62-4.
14. Kumar R. Allergic bronchopulmonary aspergillosis — review of 29 cases. Ind J Tub. 2000;47:237-9.
15. Phelan MS, Kerr IH. Allergic bronchopulmonary aspergillosis: the radiological appearances during
long-term follow-up. Clin Radiol. 1984;35:385-92.
16. Panchal N, Pant CS, Bhagat R, Shah A. Central bronchiectasis in allergic bronchopulmonary
aspergillosis: comparative evaluation of computed tomography of the thorax with bronchography.
Eur Respir J. 1994;7:1290-3.
17. Panchal N, Bhagat R, Pant C, Shah A. ABPA: The spectrum of computed tomographic appearances.
Respir Med 1997;91:213-9.
CASE 48

Aspergillosis Mimicking Tuberculosis
CASE REPORT
A 28-year-old male presented with complaints of breathlessness since childhood and he
presented with exacerbation. He had history of intake of antitubercular drugs from private
practitioner 15 years back for 6 months and he was already taking inhaled salbutamol along
with oral bronchodilators for bronchial asthma. Chest X-ray showed diffuse parenchymal
shadows in both lungs (Fig. 1). High-resolution computed tomography (HRCT) thorax
showed bilateral central bronchiectasis (Figs. 2A and B). His eosinophil count ranged from
8 to 12% on different occasions and total IgE was also raised (6,516.8 IU/mL). Specific IgE
against Aspergillus fumigatus was elevated (38.6 kUA/L). Specific IgG against A. fumigatus was
also raised (170 U/mL). Skin prick test (type 1) was also positive for A. fumigatus. Patient was
diagnosed as a case of allergic bronchopulmonary aspergillosis (ABPA). Patient was put on
oral prednisolone 0.5 mg/kg body weight daily for 2 weeks which was tapered off to 0.5 mg/
kg body weight alternate day for next 2 weeks and then tapered to maintenance dose for
another 3 months (Fig. 3). Patient was advised to take regular asthma medication (LABA + ICS)
and for follow-up regularly.
FIG. 1: Chest X-ray showing bilateral parenchymal

shadows.
A Case of Allergic Bronchopulmonary Aspergillosis Mimicking Tuberculosis 181
A B
FIGS. 2A AND B: High-resolution computed tomography (HRCT) thorax showing
bilateral central bronchiectasis.
FIG. 3: Chest X-ray showing clearing of shadows

after completion of 4 weeks of treatment with oral
prednisolone.
DISCUSSION
CASE 49

Aspergillosis Presenting as
Bilateral Homogenous Shadows
CASE REPORT
A 32-year-old female came to our hospital with complaints of recurrent cough with
expectoration, breathlessness for 20 years, and hemoptysis on and off for 5 years. She was
diagnosed as a case of pulmonary tuberculosis and had received seven courses of anti
tubercular drugs without any response. Sputum smear was negative for acid fast bacilli
(AFB) and GeneXpert was also negative for Mycobacterium tuberculosis. General physical
examination was within normal limits. Examination of the respiratory system showed bilateral
ronchi. Total IgE was raised (2,256 IU/mL). IgE specific for A. fumigatus (200 kUA/L) and IgG
for Aspergillus were raised (65 U/mL). Skin prick test (Type 1) was also positive for Aspergillus
fumigatus. Chest X-ray in 2008 and high-resolution computed tomography (HRCT) thorax
showed bilateral homogenous shadows and bilateral central bronchiectasis respectively
(Figs. 1 and 2). Chest X-ray in 2016 showed clearing of bilateral shadows (Fig. 3). HRCT

showing bilateral homogenous shadows.
A B
C D
FIGS. 2A TO D: High-resolution computed tomography (HRCT) thorax showing
bilateral homogenous shadows.

clearing of bilateral shadows.
A B
central bronchiectasis.
thorax showed bilateral central bronchiectasis (Figs. 4A and B). Patient was diagnosed
as a case of allergic bronchopulmonary aspergillosis (ABPA). Patient was then treated with
oral corticosteroids with a dose of 0.5 mg/kg body weight for 2 weeks and 0.5 mg/kg body
weight alternate day for 3 months and showed marked improvement in clinical, laboratory,
and radiographic findings. Patient is on maintenance dose of steroids along with inhaled
corticosteroids (LABA + ICS) and doing fairly well.
DISCUSSION
CASE 50

Aspergillosis Mimicking
CASE REPORT
A 22-year-old male, nonsmoker presented with complaints of cough and episodic
breathlessness for 7 years, recurrent hemoptysis for 2 years, loss of appetite, and generalized
weakness for 2 years. Sputum for acid fast bacilli (AFB) was negative and based on chest X-ray
in 2003 he was given antitubercular drug for 6 months (2 HREZ/4HR) regularly from a private
practitioner without any response (Fig. 1). Patient had a bout of hemoptysis and deteriorated
radiologically after 6 months but sputum for AFB was negative on three occasions. He had also
received bronchodilators and oral steroids off and on (Fig. 2). On routine blood investigation,
eosinophils were raised (30%); absolute eosinophilic count was raised (3,710/mm3). Total
serum IgE was 34,220 IU/mL. Serum IgG against Aspergillus fumigatus (118 U/mL) and Serum
IgG against A. fumigatus (21.50 U/mL) were raised. High-resolution computed tomography
(HRCT) thorax showed evidence of consolidation with central bronchiectasis (Figs. 3A and
B). Patient was diagnosed as a case of allergic bronchopulmonary aspergillosis (ABPA) and
was given oral steroids 0.5 mg/kg body weight daily for 2 weeks followed by 0.5 mg/kg body
weight alternate day for 6 weeks. All the shadows cleared in 8 weeks duration. Patient was also
given treatment for asthma (LABA + ICS) regularly.
A B
FIGS. 1A AND B: Fleeting pulmonary opacities can be seen on chest X-ray.
FIG. 2: Chest X-ray showing clearing of bilateral

shadows after 8 weeks of treatment with oral steroids.
A B
cental bronchiectasis with consolidation.
DISCUSSION
CASE 51

Aspergillosis with High-density Mucus
Impaction Mimicking Mass Lesion
CASE REPORT
A 36-year-old male presented with complaints of breathlessness since birth, cough with
expectoration since 4 months, hemoptysis on and off for 15 days, fever, and chest pain right
side since 10 days. Patient had received antitubercular treatment (ATT) for 3 months in the
meanwhile and was on inhaled bronchodilators since 5 years. On general examination,
clubbing was present. Chest X-ray showed multiple nodular shadows in right middle zone
(Fig. 1). Computed tomography (CT) thorax showed high-attenuated mucus plugs in right
middle lobe. Routine blood investigation showed eosinophil count 7%. Total IgE was raised
(3,400 IU/mL) and both specific IgE (58 IU/mL) and IgG (113 IU/mL) against Aspergillus
fumigatus were elevated. Fiberoptic bronchoscopy showed lot of mucus plugs in right middle
lobe. Patient was diagnosed as allergic bronchopulmonary aspergillosis (ABPA) with high-
density mucus impaction (Figs. 2A to D). Patient was put on oral prednisolone 0.5 mg/kg
body weight daily for 2 weeks which was tapered off to 0.5 mg/kg body weight alternate
day for next 2 weeks and then tapered to maintenance dose for another 4 months
FIG. 1: Chest X-ray showing multiple nodular

shadows in the right middle lobe.
A B
C D
FIGS. 2A TO D: Computed tomography (CT) thorax showing high-density mucus
impaction in right middle lobe.
FIG. 3: Chest X-ray showing partial resolution of high-attenuated

mucus after treatment with oral steroids for 1 month.
(Figs. 3 and 4). Patient was advised to take regular asthma medication (LABA + ICS) and for
follow-up regularly.
A Case of Allergic Bronchopulmonary Aspergillosis... 189
FIG. 4: Chest X-ray after treatment with oral steroids

showing resolution of high-density mucus impaction.
DISCUSSION
CASE 52

Presenting as a Pulmonary Mass
CASE REPORT
A 38-year-old male, known case of asthma for 15 years, presented with cough with
expectoration, shortness of breath, chest tightness, and fever for 15 days. There was
no history of hemoptysis, expectoration of brownish black mucus plugs or loss of
weight or appetite. On general physical examination, the patient had respiratory rate
of 24 breaths/min without any use of accessory muscles of respiration. Expiratory
polyphonic rhonchi were audible over bilateral lung fields. Examination of rest of the
systems was normal. The patient was prescribed antibiotics and was suspected to have
pulmonary mass by outside doctors on the basis of chest radiograph for which he was
referred to our center. The chest radiograph (Fig. 1) showed an irregular shaped opacity in
right lower zone mimicking pulmonary mass. High-resolution computed tomography (HRCT)
of thorax showed homogenous opacity in right lower lobe resembling pulmonary mass
(Fig. 2) and central bronchiectasis (Fig. 3). Laboratory investigations showed the absolute
FIG. 1: Chest X-ray PA view showing mass like rounded

opacity in the right lower zone.
Allergic Bronchopulmonary Aspergillosis Presenting as a Pulmonary Mass 191
FIG. 2: Contrast-enhanced CT scan of the thorax

showing irregular mass like opacity in right lower
lobe with satellite lesions with central bronchiectasis.
FIG. 3: Contrast-enhanced CT scan of the thorax

(lung window) showing central bronchiectasis.
eosinophil count of the patient was raised (1,120 cells/mm3), total serum immunoglobulin E
(IgE) of the patient was elevated (6,121 kUA/L). Aspergillus-specific immunoglobulin G
(IgG) was elevated (156.80 U/mL) and Aspergillus-specific IgE was elevated (37.30 kUA/L)
and immediate Aspergillus fumigatus skin prick test was positive (Type I). Patient was
diagnosed as allergic bronchopulmonary aspergillosis (ABPA). Patient was treated with
oral corticosteroids with a dose of 0.5 mg/kg body weight for 2 weeks and 0.5 mg/kg body
weight alternate day for 3 months and showed marked improvement in clinical, laboratory,
and radiographic findings (Fig. 4).
FIG. 4: Chest X-ray PA view showing clearing of the

rounded opacity after taking oral corticosteroids for
3 weeks.
DISCUSSION
Allergic bronchopulmonary aspergillosis is a complex immune hypersensitivity reaction
that manifests when the bronchi become colonized by Aspergillus, which causes chronic
inflammation, then bronchiectasis, fibrosis, and ultimately respiratory failure. Although
there are 200 species of Aspergillus (A.), only few such as A. fumigatus, A. flavus, and
A. niger have been reported to cause allergic bronchopulmonary aspergillosis (ABPA).
The Rosenberg criteria are most widely used for diagnosis and include eight major and
three minor criteria. The major criteria include asthma, roentgenographic evidence
of pulmonary opacities, skin test positive for Aspergillus (Type 1 reaction) blood
esonophilia, precipitating antibodies [immunoglobulin G (IgG)] against Aspergillus
fumigator in the serum, elevated serum immunoglobulin E (IgE) levels (>1,000 IU/mL),
central bronchiectasis, and elevated serum A. fumigatus-specific IgG and IgE. The minor
criteria include presence of Aspergillus in sputum, expectoration of brownish black
mucus plugs, and delayed skin reaction to Aspergillus antigen (Type III reaction). If six
of the eight major primary criteria are met, the diagnosis is certain.
Greenberger 1997 criteria do not differentiate into major and minor diagnostic
criteria. Eight diagnostic criteria are laid down to detect ABPA. These criteria are
asthma (mild or severe) or cystic fibrosis, immediate cutaneous reactivity to Aspergillus
antigen, current or previous pulmonary infiltrates, elevated total IgE concentration
(>l mg/L), precipitin antibodies to A. fumigatus, peripheral blood eosinophilia, elevated
serum IgE and/or IgG-against A. fumigatus, and proximal bronchiectasis.
Recently proposed diagnostic criteria for ABPA by International Society for Human
and Animal Mycology (ISHAM) include:
• Predisposing conditions: Bronchial asthma, cystic fibrosis.
• Obligatory criteria (both should be present):
{{ Type I Aspergillus skin test positive or elevated IgE levels against A. fumigatus.
{{ Elevated total IgE levels (>1,000 IU/mL); if the patient meets all other criteria, an
IgE value <1,000 IU/mL may be acceptable.

Allergic Bronchopulmonary Aspergillosis Presenting as a Pulmonary Mass 193
• Other criteria (at least two of three should be present):

{{ Presence of precipitating or IgG antibodies against A. fumigatus in serum
{{ Radiographic pulmonary opacities consistent with ABPA
{{ Total eosinophil counts >500 cells/µL in steroid naıve patients (may be historical).
A wide spectrum of radiographic changes can be seen in patients with ABPA

in
cluding transient migratory radiographic opacities secondary to eosinophilic
pneumonia. HRCT characteristically shows central bronchiectasis, mucus-filled bronchi,
consolidation, and centri-lobular nodules. Other manifestations include segmental
or lobar collapse, pleural effusion, and spontaneous pneumothorax. A characteristic
radiographic finding in ABPA is high-attenuation mucus.
The presentation of ABPA as pulmonary masses (as seen in our patients) is distinctly
uncommon. These masses are usually attributed to mucus plugging of bronchi and distal
accumulation of secretions, as seen in our patient or large bronchocele (mucus-filled
dilated bronchi), which appear as masses but with no proximal obstruction. Another
mechanism is probably inflammatory eosinophilic parenchymal consolidation without
endobronchial involvement, appearing as pseudotumor. Eosinophilic organizing
pneumonia due to adjoining intense bronchial inflammation led to pseudotumor
formation. Though bronchoceles are classically seen in ABPA, reversible bronchoceles
are almost pathognomonic of ABPA. The presence of hyperdense mucus is the most
characteristic (if not pathognomonic) finding of ABPA and occurs in almost 19% of these
patients. The high-attenuation calcium salts generally indicate chronicity and negate an
acute event. In our patient, the quick disappearance of the mass after initiation of treat
ment indicates an acute event which dramatically responded to treatment.
It is important to note that ABPA can be diagnosed in patients without history of
asthma unlike our case. This is particularly important because in these patients, presence
of a lung mass can lead to strong consideration of lung cancer as a diagnostic possibility
and lead to invasive diagnostic procedures to establish an accurate diagnosis. Sanchez-
Alarcos et al. reported a 65-year-old male smoker patient without any history of asthma,
who underwent right upper lobectomy due to the presence of radiological appearance of a
lung mass. The diagnosis of ABPA was delayed for 1 year following surgery.
Allergic bronchopulmonary aspergillosis can present as pulmonary mass lesion and
must be considered in the differential diagnosis in patients presenting with history of
asthma. High-attenuation density within these masses can help narrow the differential
diagnosis. It is important to consider ABPA in the diagnostic algorithm of pulmonary
masses because treatment with glucocorticoids is associated with excellent outcomes, as
seen in our patient.
FURTHER READING
1. Rosenberg M, Patterson R, Mintzer R, Cooper BJ, Roberts M, Harris KE. Clinical and immunologic
criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med. 1977;86:
405-14.
2. Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: Staging
as an aid to management. Ann Intern Med. 1982;96:286-91.
3. Agarwal R, Chakrabarti A, Shah A. Allergic bronchopulmonary aspergillosis: review of literature and
proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013; 43:850-73.
4. Nath A, Khan A, Hashim Z, Patra JK. Prevalence of Aspergillus hypersensitivity and allergic broncho
pulmonary aspergillosis in patients with bronchial asthma at a tertiary care center in North India.
Lung India. 2017;34:150-4.
5. Shah A. Allergic bronchopulmonary and sinus aspergillosis: the roentgenologic spectrum. Front
Biosci. 2003;8:e138-46.
6. Thompson BH, Stanford W, Galvin JR, Kurihara Y. Varied radiologic appearances of pulmonary
aspergillosis. Radiographics 1995;15:1273-84.
7. Cote CG, Cicchelli R, Hassoun PM. Hemoptysis and a lung mass in a 51-year-old patient with asthma.
Chest. 1998;114:1465-8.
8. Sanchez-Alarcos JM, Martinez-Cruz R, Ortega L, Calle M, Rodriguez-Hermosa JL, Alvarez-Sala JL.
ABPA mimicking bronchogenic cancer. Allergy. 2001;56:80-1.
9. Coop C, England RW, Quinn JM. Allergic bronchopulmonary aspergillosis masquerading as invasive
pulmonary aspergillosis. Allergy Asthma Proc. 2004;25:263-6.
10. Lemire P, Trepanier A, Hebert G. Bronchocele and blocked bronchiectasis. Am J Roentgenol.
1970;110:687-93.
11. Maurya V, Gugani HC, Sarma PU, Madan T, Shah A. Sensitization to Aspergillus antigens
and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma. Chest.
2005;127:1252-9.
12. Prasad R, Garg R, Sanjay, Dixit R. A study on prevalence of allergic bronchopulmonary aspergillosis
in patients of bronchial asthma. Internet J Pulm Med. 2008;9:1-6.
13. Agarwal R, Reddy C, Gupta D. An unusual cause of hilar lymphadenopathy. Lung India. 2006;23:
90-2.
CASE 53
Treatment of Tuberculosis in Pregnancy

and Lactation: Case-based Approach
CASE REPORT
Case 1
A 24-year-old lady, having pregnancy of 3 months, presented with newly diagnosed sputum
positive pulmonary tuberculosis. Her liver and renal functions were within normal limits.
Rifampicin, isoniazid, and ethambutol are safe for use in pregnancy. Pyrazinamide is not
confidently recommended, because of lack of evidence for safety. Since she was sputum
positive, and rapid sputum conversion was needed, she could be given four-drug regimen of
rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampicin and
isoniazid for next 4 months, as per World Health Organization (WHO) and International Union
Against Tuberculosis and Lung Disease (IUATLD) recommendation, along with prophylactic
pyridoxine. The neonate should receive vitamin K injection to avoid postnatal hemorrhage.
Case 2
A 24-year-old woman, having pregnancy of 4 months, presented with tuberculous cervical
lymphadenopathy, proved by fine-needle aspiration cytology (FNAC). She also underwent
chest skiagram for any pulmonary lesions, with due precautions for radiation exposure
to her fetus. Her liver and renal functions were within normal limits. Since this lady was
suffering from paucibacillary tubercular condition, pyrazinamide may be avoided. This
lady may be kept on regimen of rifampicin, isoniazid, and ethambutol for 9 months, along with
prophylactic pyridoxine.
Case 3
A 26-year-old lady was suffering from sputum positive pulmonary tuberculosis. She was
receiving four-drug antitubercular regimen consisting of rifampicin, isoniazid, ethambutol,
and pyrazinamide, for last 1 month. While she was on this regimen, she conceived. Since
this lady, was already on effective antitubercular drug regimen, there was very little risk of
disease to fetus. Drugs being used are considered safe in pregnancy, with some doubt about
safety of pyrazinamide. Since she has already taken 1 month of intensive phase of therapy,
she may continue to take same drugs for next 1 month, following which ethambutol and
pyrazinamide may be stopped and rest of drugs to be continued for next 4 months.
DISCUSSION
Isoniazid is considered safe in pregnancy except for some chance of postpartum hepatitis.
The ATS (American Thoracic Society) recommends supplementation of pyridoxine
during pregnancy (25 mg/day). Use of rifampicin and ethambutol is safe in pregnancy.
Data regarding other rifamycins (rifabutin and rifapentine) is insufficient, and thus they
should be cautiously used. Safety regarding pyrazinamide could not be assured but WHO
and IUATLD recommend its use in pregnancy because when used for 6-month regimen,
benefits may outweigh possible risk.
Streptomycin may cause congenital deafness, as this drug interferes with develop
ment of ear. Other injectables such as amikacin, kanamycin, and capreomycin having
pharmacokinetics similar to streptomycin, may also cause fetal nephrotoxicity and
ototoxicity. Ethionamide and prothionamide are contraindicated in pregnancy as they
are found teratogenic in animal studies. Cycloserine crosses placenta and since its
safety in pregnancy is not established, it should be avoided and used only if no other
suitable alternatives are available. Para-aminosalicylic acid (PAS) has been used safely in
pregnancy in past but since no well-designed study has been done to ascertain its safety
in pregnancy, it should be used in absence of any other alternative. Fluoroquinolone,
being toxic and inhibitor of growing cartilage in animals, is to be avoided in pregnancy.
Animal studies demonstrated teratogenicity (retardation of fetal skull ossification) for
clofazimine and crossing of placenta and excretion in milk. However, WHO has approved
this drug safe in pregnancy. Similarly, clarithromycin is not safe in pregnancy as higher
dose has been associated with embryo toxicity. There are no adequate and well-controlled
studies regarding teratogenicity of linezolid in pregnant women. It should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus. Bedaquiline
is not recommended during pregnancy or breastfeeding due to limited data. Reproduction
studies performed in rats and rabbits have revealed no evidence of harm to the fetus. There
are very limited data from the use of delamanid in pregnant women. Studies in animals
have shown reproductive toxicity. Available pharmacokinetic data in animals have shown
excretion of delamanid and/or its metabolites in milk.
Regarding treatment of tuberculosis in a pregnant lady, it is said that treatment of
tuberculosis is far less hazardous than leaving the disease untreated, both with regard
to baby and mother. Tuberculosis in pregnant lady may lead to underweight infant or
congenital tuberculosis. Risk of miscarriage is much higher in active tuberculosis than
risk from the drug treatment, so standard treatment should be given. Treatment regimen
for drug sensitive tuberculosis should include rifampicin, isoniazid, and ethambutol.
Streptomycin should not be used. Opinion regarding use of pyrazinamide is divided, but
WHO and IUATLD recommend its use. ATS does not confidently advocate it. According
to WHO, 6-month regimen based upon isoniazid, rifampicin, and pyrazinamide should
be used whenever possible and ethambutol should be used if a fourth drug is needed
during initial phase. Contrary to this, ATS recommends that pyrazinamide should better
be avoided in pregnancy because of lack of sufficient data for its safety. If pyrazinamide
is not used, duration of treatment should be 9 months. Although isoniazid, rifampicin, and
ethambutol cross the placenta, they are not found to be teratogenic.
Women taking firstline antitubercular drugs should not be asked for termination of
pregnancy, while those on reserve-line drugs should be counseled for possible adverse
effects. Breastfeeding should not be discouraged as amount secreted in milk is insufficient
to cause any toxic or therapeutic effect. Supplemental pyridoxine is recommended for
both nursing mother and her infant, even if no isoniazid is being given to the infant. All
antitubercular drugs could be used during lactation, except fluoroquinolones because
of possible risk. Baby of woman who has taken rifampicin during pregnancy should
Treatment of Tuberculosis in Pregnancy and Lactation: Case-based Approach 197
receive vitamin K at birth to avoid the risk of postnatal hemorrhage as rifampicin may
induce metabolism of vitamin K and hamper hepatic synthesis of vitamin K-dependent
coagulation factors.
Women taking oral hormonal contraceptives should be counseled for possible
contraceptive failure and occurrence of pregnancy, especially in rifampicin-containing
antitubercular treatment regimen because of induction of metabolism of contraceptive
drug by rifampicin. Such ladies should be advised to use nonhormonal contraceptive
during and for 1 month after treatment with rifampicin-containing regimen.
FURTHER READING
1. Prasad R, Singh A, Srivastava R, Hosmane GB, Kushwaha RA, Jain A. Frequency of adverse events
observed with second-line drugs among patients treated for multidrug-resistant tuberculosis.
Indian J Tuberc. 2016;63:106-14.
2. Briggs GG, Freeman RK, Yaffe SJ (Eds). Drugs in pregnancy and lactation, 5th edition. Baltimore:
Williams & Wilkins; 1998. pp. 112-7.
3. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998.
Joint Tuberculosis Committee of the British Thoracic Society. Thorax. 1998;53:536-648.
4. World Health Organization. (2014). Companion handbook to the WHO guidelines for the
programmatic management of drug-resistant tuberculosis. [online] Available from https://apps.
who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdf;jsessionid=FE77DA8527A0
0BEE1871C19426FAEC7B?sequence=1. [Last accessed March, 2020].
5. DOTS PLUS guidelines, Revised National Tuberculosis Control Programme, Central TB Divison
Directorate General Health Services, Ministry of Health & Family welfare, Nirman Bhawan, New
Delhi. Sep 2008;/Revised National Tuberculosis Control Programme. Guidelines on Programmatic
Management of Drug Resistant TB (PMDT) in India. Central TB Division, Directorate General of Health
Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi. May 2012.
6. Franks AL, Binkin NJ, Sinder DE Jr, Rokaw WM, Becker S. Isoniazid hepatitis among pregnant and
postpartum hispanic patients. Public Health Rep. 1989;104:151-5.
7. Frieden T, Espinal M. What is the therapeutic effect and what is the toxicity of antituberculosis drugs?
Toman’s tuberculosis. Case Detection, Treatment and Monitoring, 2nd edition. Geneva: World Health
Organization;2004. pp. 110-21.
8. Harries A. How does treatment of tuberculosis differ in patients with pregnancy, liver disease, or
renal disease? Toman’s Tuberculosis: Case Detection, Treatment and Monitoring, 2nd edition.
Geneva: World Health Organization; 2004. pp. 166-8.
9. Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, et al. ATS/CDC/IDSA Clinical
Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infec Dis. 2016:1-50.
10. World Health Organization. WHO Treatment of Tuberculosis Guidelines, 4th edition. 2009;8:97-8.
11. World Health Organization. (2011). Guidelines for the programmatic management of drug-
resistant tuberculosis, 2011 Update. [online] Available from https://apps.who.int/iris/bitstream/
handle/10665/44597/9789241501583_eng.pdf?sequence=1. [Last accessed March, 2020].
12. World Health Organization. (2016). WHO treatment guidelines for drug-resistant tuberculosis
2016 update. [online] Available from https://apps.who.int/iris/bitstream/handle/10665/250125/
9789241549639-eng.pdf. [Last accessed March, 2020].
13. World Health Organization. Guidelines for the treatment of drug-susceptible tuberculosis and
patient care, 2017 update. [online] Available from http://apps.who.int/iris/bitstream/10665/255052/
1/9789241550000-eng.pdf. [Last accessed March, 2020].
14. World Health Organization. WHO consolidated guidelines on drug resistant tuberculosis treatment.
[online] Available from https://apps.who.int/iris/rest/bitstreams/1211676/retrieve. [Last accessed
March, 2020].
15. Guidelines for the programmatic management of drug-resistant tuberculosis in India 2017. [online]
[Last accessed March, 2020].
16. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society
of America: Treatment of Tuberculosis. Am J Respir Crit Care Med. 2003;167:603-62.
CASE 54
Treatment of Tuberculosis in Renal

Insufficiency: Case-based Approach
CASE REPORT
Case 1
A 33-year-old male weighing 50 kg presented with sputum positive new case of pulmonary
tuberculosis. His liver functions were within normal limits. His renal functions were
deranged with value of blood urea as 98 mg/dL and Serum creatinine as 4 mg/dL. His
creatinine clearance was 18.6 mL/min as calculated by formula as:
Creatinine clearance = [(140 – Age) × Weight in kg]/72 × Serum creatinine (For females
above calculated value is multiplied by 0.85)
He may safely be kept on rifampicin and isoniazid without any modification in dose,
or interval of administration. Creatinine clearance level below 30 mL/min raises risk of
accumulation of pyrazinoic acid and 5-hydroxy pyrazinoic acid, which are metabolites of
pyrazinamide. Thus, it should be given in dose of 1,250 mg (25–35 mg/kg body weight) as
three times a week. Streptomycin and ethambutol should preferably be avoided.
Case 2
A 50-year-old female weighing 45 kg presented with sputum positive pulmonary tuber
culosis. She has previously taken antitubercular drugs irregularly for 4 months. Her liver
functions were within normal limits. Her renal function was deranged, with blood urea
as 84 mg/dL and Serum creatinine as 2.25 mg/dL with creatinine clearance of 25 mL/min.
This lady should be kept on five-drug retreatment regimen. Rifampicin and isoniazid are
safe in usual doses. Pyrazinamide dose should be altered to 1,250 mg three times a week
(25–35 mg/kg body weight). Ethambutol and streptomycin, which should preferably
be avoided in cases of renal insufficiency, need to be given in this case, but their dose
should be modified. Ethambutol could be given in dose of 800 mg three times a week
(15–20 mg/kg body weight), streptomycin dose should also be changed to 500 mg
three times a week (12–15 mg/kg body weight). If this lady undergoes hemodialysis for
management of renal insufficiency, drugs should be given after hemodialysis. Ideally, serum
concentration of drugs should be regularly monitored to prevent toxicity and to ensure
therapeutic drug concentration.
Treatment of Tuberculosis in Renal Insufficiency: Case-based Approach 199
Case 3
A 50-year-old man weighing 50 kg presented with sputum positive pulmonary tuber
culosis. He has previously taken irregular treatment for last 3 years. His sputum culture on
BACTEC was positive for Mycobacterium tuberculosis and bacilli were found resistant to
rifampicin and isoniazid. His liver functions were within normal limits. His renal functions
were deranged with value of blood urea as 74 mg/dL and serum creatinine as 1.05 mg/dL.
His creatinine clearance was 60 mL/min. He could have been kept on reserve line drugs. Since
renal functions are not very much compromised, he may be given ethionamide, cycloserine,
and fluoroquinolone. Injectable drugs (e.g., kanamycin) may be given in dose of 500 mg
thrice a week (12–15 mg/ kg body weight). Para-aminosalicylic acid (PAS) could be used at
dose of 4 g twice a day with hemodialysis. Duration of treatment should be 18–24 months.
Whatever drugs are given, patient should be regularly monitored for serum drug concentration
and renal function, so as to plan and change the medication as and when needed. If this man
undergoes hemodialysis, the drugs should be given after it.
Case 4
A 36-year-old man weighing 58 kg presented with sputum positive pulmonary tuberculosis.
He has previously taken irregular antitubercular treatment. His sputum culture by BACTEC
method was positive for M. tuberculosis, resistant to rifampicin and isoniazid. His liver functions
were within normal limits, but his renal function was impaired with blood urea as 88 mg/dL
and serum creatinine as 3.8 mg/dL. His creatinine clearance was 22 mL/min. He should be kept
on reserve second-line drugs. Severity of renal insufficiency has left us with very little options,
which too are risky. Cycloserine should only be used if this patient undergoes hemodialysis,
in dose of 500 mg three times a week. Dose of ethionamide should be changed to 250 mg
daily (250–500 mg/day). Fluoroquinolone dose should also be changed to 750 mg three
times a week. Dose of injectable drugs should also be changed to 500 mg three times a week
(12–15 mg/kg body weight). PAS is to be avoided. Thioacetazone should not be used.
DISCUSSION
Treatment of tuberculosis in renal insufficiency poses a difficult clinical problem because
various antituberculosis medications are cleared by kidney. On one side, it raises concern
of drug-induced toxicity due to impaired excretion by diseased kidney while on the other
side it raises concern of undertreatment of tuberculosis. In later situation, adequate peak
serum concentration is usually low, and not of therapeutic use. Another issue of concern
is the therapeutic level of antitubercular drugs in patients with end-stage renal disease,
undergoing hemodialysis, which clears some drugs easily than others.
British Thoracic Society advocates dose reduction for drugs which are excreted by
renal route while American Thoracic Society prefers increasing the dosing interval instead
of decreasing the dose. Administration of drugs which are excreted by kidney should be
changed by increasing the dosing interval, if creatinine clearance falls below 30 mL/min
(Table 1). There is paucity of data to guide the dosing recommendation if creatinine
clearance is above 30 mL/min, when standard doses should be prescribed. Rifampicin
and isoniazid are eliminated by liver and they could be given in usual dose. Population
with slow hepatic acetylation of isoniazid could be given supplemental pyridoxine to
prevent peripheral neuropathy. Alteration in dose of ethambutol, which is 80% excreted by
kidney, should be made if creatinine clearance falls below 70 mL/min, to lowest possible
dose, but if it falls after 30 mL/min, it should be given intermittently as three times a
week in dose of 15–20 mg/kg body weight. Pyrazinamide is metabolized in liver but its
TABLE 1: Dosing recommendation for adult patients with renal insufficiency or undergoing
hemodialysis.
Drug Change in Dose and frequency in patients with creatinine
frequency clearance <30 mL/min or those on hemodialysis
Isoniazid No change needed 300 mg daily or 900 mg thrice a week
Rifampicin No change needed 600 mg daily or 600 mg thrice a week
Pyrazinamide Yes 25–35 mg/kg/dose three times a week
Ethambutol Yes 15–25 mg/kg/dose three times a week
Rifabutin No Normal dose can be used, if possible monitor drug
concentrations to avoid toxicity
Rifapentine No No adjustment necessary
Levofloxacin Yes 750–1,000 mg/dose three times a week
Moxifloxacin No No adjustment necessary
Gatifloxacin No 400 mg three times a week
Ofloxacin Yes 600–800 mg/dose three times per week
Cycloserine Yes 250 mg daily or 500 mg three times a week
Terizidone Recommendations not available
Ethionamide No change needed 250–500 mg daily
PAS No change needed 4 g/dose twice daily
Streptomycin Yes 12–15 mg/kg/dose twice or three times a week
Capreomycin Yes 12–15 mg/kg/dose twice or three times a week
Kanamycin Yes 12–15 mg/kg/dose twice or three times a week
Amikacin Yes 12–15 mg/kg/dose twice or three times a week
Clarithromycin Yes Usual dose 500 mg twice daily but can be reduced to
250 mg twice daily
Linezolid No change needed Usual dose is 600 mg twice daily but can be reduced to
600 mg once daily after 4–6 weeks
Clofazimine Yes Begin with 300 mg daily and decreased to 100 mg daily
after 4–6 weeks
Amoxicillin and Yes Dose used is 625 mg twice daily, 1,000 mg should not
clavulanic acid be used
Bedaquiline No No dosage adjustment is required in patients with mild-
to-moderate renal impairment (dosing not established
in severe renal impairment, use with caution)
Delamanid No No dosage adjustment is required in patients with mild-
to-moderate renal impairment (dosing not established
in severe renal impairment, use with caution)
Imipenem/ Yes For creatinine clearance 20–40 mL/min dose 500 mg
cilastatin every 8 h; for creatinine clearance <20 mL/min dose
500 mg every 12 h
Meropenem Yes For creatinine clearance 20–40 mL/min dose 750 mg
every 12 h; for creatinine clearance <20 mL/min dose
500 mg every 12 h
High-dose isoniazid Recommendations not available
(PAS: para-aminosalicylic acid)
metabolites pyrazinoic acid and 5-hydroxypyrazinoic acid are excreted by kidney and thus
drug should be given three times a week in dose of 25–35 mg/kg body weight, to avoid
toxicity, if creatinine clearance falls below 30 mL/min (Table 1). Apart from this, risk of
developing hyperuricemia with pyrazinamide is increased in cases of renal insufficiency.
Since streptomycin is predominantly excreted by renal route and removed by hemodialysis
to a significant extent (about 40%), it should be administered three times a week in dose
of 12–15 mg/kg body weight (Table 1) in patients of renal insufficiency with creatinine
clearance below 30 mL/min, and those on hemodialysis. Since pharmacokinetics of other
aminoglycosides is similar to streptomycin, they need similar modification of dose. Renal
clearance of fluoroquinolones varies from drug-to-drug. It is greater for levofloxacin
than moxifloxacin. Dose adjustment for fluoroquinolones is recommended if creatinine
clearance is <30 mL/min (750–1,000 mg three times a week) ethionamide need no or
little alteration of administration as it is not excreted by kidney but if creatinine clearance
is <30 mL/min, dose of ethionamide should be reduced to 250–500 mg/day (Table 1).
Dose of cycloserine should be modified if creatinine clearance falls below 30 mL/min or
patient is on hemodialysis. It should be changed to 500 mg thrice a week or 250 mg daily
(Table 1); evidence for safety of 250 mg daily dose of cycloserine is not yet established with
regard to neuropathy and 500 mg three times a week is preferred in this regard. Serum
concentrations of drug should be monitored. PAS is not safe in renal disease and should
only be given if no other alternative is available, as it may aggravate metabolic acidosis. If
it is to be given, it should be given at dose of 4 g/dose, twice daily. Thioacetazone, being
excreted in urine, should not be given to patients with renal disease. The pharmacokinetics
of the parent drug linezolid are not altered in patients with any degree of renal insufficiency
but metabolites of linezolid may accumulate in patients with renal insufficiency, with the
amount of accumulation increasing with the severity of renal dysfunction. Therefore, no
dose adjustment is recommended for patients with renal insufficiency. However, given
the absence of information on the clinical significance of accumulation of the primary
metabolites, use of linezolid in patients with renal insufficiency should be weighed
against the potential risks of accumulation of these metabolites. Clofazimine is safe in
patients having renal disease as excretion is mainly through biliary route. In patients
with severe renal impairment, dose of clarithromycin must be reduced. Imipenem is
highly nephrotoxic but addition of cilastatin lessens its toxicity. No dosage adjustment is
required in patients with mild-to-moderate renal impairment with bedaquiline (dosing
not established in severe renal impairment, use with caution). No dosage adjustment is
required in patients with mild-to-moderate renal impairment with delamanid. Dosing
not established in severe renal impairment, use with caution and only when the benefits
outweigh the risks.
Hemodialysis removes the drug before its therapeutic effect, but if the drug is given
sufficient time before hemodialysis, so that it gets time to be distributed throughout the
body, far less drug is likely to be removed. Administration of drug after hemodialysis will
avoid premature removal of drug on one hand and facilitate Directly Observed Treatment
Short Course (DOTS) on the other hand. Premature removal of second-line drugs by
hemodialysis may further aggravate the problem of drug resistance by exposing the
tubercle bacillus to subtherapeutic drug concentration.
Rifampicin, isoniazid, and ethambutol are removed to insignificant extent by
hemodialysis but pyrazinamide is removed to a significant extent. Thus, supplemental
dosing is not needed with isoniazid, rifampicin, and ethambutol, in patients of end-stage
renal disease undergoing hemodialysis. Similar to streptomycin, about 40% of drugs such
as kanamycin, amikacin, and capreomycin are removed from blood, if they are given just
before hemodialysis. Fluoroquinolone and ethionamide are not cleared by hemodialysis
and thus their dose need not be altered in this situation. Usually hemodialysis does not
pose significant problem if drugs are given after the procedure.
Ideally, it is important to monitor serum concentrations of drugs in persons with renal
failure who are taking aminoglycosides, cycloserine or ethambutol to provide effective
therapeutic drug concentration and also to minimize dose-related toxicity. Patients
with renal failure may have other comorbid conditions such as diabetes mellitus and
gastroparesis, which may further complicate the pharmacokinetics of drugs. Presently,
there is no data to guide administration of antitubercular drug use in patients undergoing
peritoneal dialysis, and for this subset of patients, recommendations of hemodialysis are
applicable. The safest regimen that is being advised in patients diagnosed as new cases
of tuberculosis with renal insufficiency is rifampicin, isoniazid, and pyrazinamide for
2 months followed by rifampicin and isoniazid for next 4 months.
FURTHER READING
Thorax. 1998;53:536-648.
3. Companion handbook to the WHO guidelines for the programmatic management of
drug-resistant tuberculosis. [online] Available from https://apps.who.int/iris/bitstream/
handle/10665/130918/9789241548809_eng.pdf;jsessionid=FE77DA8527A00BEE1871C19426FAEC7B
?sequence=1. [Last accessed March, 2020].
4. DOTS PLUS guidelines, Revised National Tuberculosis Control Programme, Central TB Division
Delhi. Sep 2008;Revised National Tuberculosis Control Programme. Guidelines on Programmatic
Management of Drug Resistant TB (PMDT) in India. Central TB Division, Directorate General of
Health Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi. May 2012.
5. Frieden T, Espinal M. What is the therapeutic effect and what is the toxicity of antituberculosis drugs?
Toman’s tuberculosis. Case detection, treatment and monitoring, 2nd edition. Geneva: World Health
Organization; 2004. pp. 110-21.
6. Guidelines for the programmatic management of drug-resistant tuberculosis: Emergency Update
2008. [online] Available from https://apps.who.int/iris/bitstream/handle/10665/43965/978924
1547581_eng.pdf?sequence=1. [Last accessed March, 2020].
8. Held H, Fried F. Elimination of para-aminosalicylic acid in patients with renal insufficiency.
Chemotherapy. 1977;23:405-15.
9. Malone RS, Fish DN, Spiegel DM, Childs JM, Peloquin CA. The effect of hemodialysis on isoniazid,
rifampicin, pyrazinamide and ethambutol. Am J Respir Crit Care Med. 1999;159:1580-4.
11. Strauss I, Erhardt F. Ethambutol absorption, excretion and dosage in patients with renal tuberculosis.
Chemotherapy. 1970;15:148-57.
13. World Health Organization. (2003). Treatment of Tuberculosis. Guidelines for National Programmes.
[online] Available from https://apps.who.int/iris/bitstream/handle/10665/67890/WHO_CDS_
TB_2003.313_eng.pdf;jsessionid=9CC6E4BC3CFCC16371C9B76732A40B77?sequence=1. [Last
accessed March, 2020].
15. World Health Organization. (2011). Guidelines for the programmatic management of drug-
resistant tuberculosis, 2011 Update. [online] Available from https://apps.who.int/iris/bitstream/
16. World Health Organization. (2016). WHO treatment guidelines for drug-resistant
tuberculosis 2016 update. [online] Available from https://apps.who.int/iris/bitstream/hand
le/10665/250125/9789241549639-eng.pdf. [Last accessed March, 2020].
17. World Health Organization. Guidelines for the treatment of drug-susceptible tuberculosis
and patient care, 2017 update. [online] Available from http://apps.who.int/iris/bitstre
am/10665/255052/1/9789241550000-eng.pdf. [Last accessed March, 2020].
18. World Health Organization. WHO consolidated guidelines on drug resistant tuberculosis treatment.
[online] Available from https://apps.who.int/iris/rest/bitstreams/1211676/retrieve. [Last accessed
March, 2020].
[Last accessed March, 2020].
CASE 55
Treatment of Tuberculosis in Liver

Diseases: Case-based Approach
CASE REPORT
Case 1
A 42-year-old man presented with fever, anorexia, cough, and expectoration for 1 month.
He was diagnosed as a new case of sputum positive pulmonary tuberculosis and was kept
on four-drug regimen of rifampicin, isoniazid, ethambutol, and pyrazinamide. After 3 weeks,
he started having vomiting, abdominal pain, and yellowish discoloration of eyes and urine.
His serum bilirubin was 4.4 mg% and serum glutaryl pyruvate transaminase (SGPT) was
272 IU/L. All of his antitubercular drugs should be stopped and he should be investigated for
viral hepatitis. He should be kept on interim regimen considered safe in liver disease, which
should include streptomycin, ethambutol, and fluoroquinolone (other than ciprofloxacin).
Isoniazid is usually tolerated and can be added in author’s opinion. Liver function should be
closely monitored. Hepatotoxic drugs such as rifampicin and pyrazinamide may be tried one-
by-one after liver function comes down to normal, during frequent monitoring. Many of such
patients subsequently tolerate them.
Case 2
A 34-year-old woman with viral hepatitis having hepatitis B surface antigen (HBsAg) positive
presented with sputum positive new case of pulmonary tuberculosis. Her renal functions
were within normal limits. Her serum bilirubin was 7.2 mg% and SGPT was 370 IU/L. Since, this
lady is suffering from chronic active liver disease, all hepatotoxic drugs should be avoided. She
may be kept on regimen of streptomycin, ethambutol, and fluoroquinolone along with an oral
second-line drug, preferably cycloserine for 18–24 months. In case her liver function improves
on repeat test, in author’s experience isoniazid can also be added.
Case 3
A 38-year-old man, alcoholic, and a known case of cirrhosis of liver, weighing 48 kg, presented
as a case of sputum positive pulmonary tuberculosis. He has taken irregular antitubercular
treatment for 3 years, but without response. Current liver function profile showed serum
bilirubin as 2.2 mg/dL, SGPT as 312 IU/L, and serum glutaryl oxalate transaminase (SGOT) as
280 IU/L. His sputum culture on BACTEC was positive for Mycobacterium tuberculosis, resistant
to isoniazid and rifampicin. He should be given reserve antitubercular drugs. Kanamycin, para-
aminosalicylic acid (PAS), and fluoroquinolones except ciprofloxacin are safe. Ethionamide
could be cautiously used, because of risk of drug-induced hepatotoxicity. Isoniazid may
Treatment of Tuberculosis in Liver Diseases: Case-based Approach 205
be given in author’s opinion, along with supplemental pyridoxine. Cycloserine should not
be used because it can lead to seizures, especially in this case of alcohol-related hepatitis.
Thioacetazone, being hepatotoxic, should be avoided. Thus, regimen consists of kanamycin,
isoniazid, PAS, ethionamide, and ofloxacin (K H PAS Ethio Oflo). Duration of treatment should
be 18–24 months. Liver function profile should be monitored frequently. Frequency should be
weekly for 2 weeks and then at 2-weekly interval.
DISCUSSION
Treatment of tuberculosis with deranged liver functions presents with two major clinical
scenarios. First is use of antitubercular drugs in persons with pre-existing liver disease
and second is antitubercular drug-induced hepatotoxicity. Various antitubercular drugs
are potentially hepatotoxic and administration of these drugs may aggravate liver disease
in a patient with compromised liver function. Drugs such as ethambutol, streptomycin,
kanamycin, amikacin, and capreomycin are safe in liver disease as they are neither
significantly metabolized nor toxic to liver.
Drug-induced Hepatotoxicity
It is found that period of latency between start of drug regimen and occurrence of drug-
induced hepatitis is usually 4–9 days. It must be known that about 10–30% of patients
receiving antitubercular therapy may normally have transient rise of bilirubin and liver
enzymes SGPT and SGOT, to about 1–3 times the normal during first 2 months of therapy,
which comes down on continuation of treatment. It is of interest to note that about 10%
of patients, who develop mild transaminase elevation (i.e., 1–2% of all adults treated)
may have severe hepatitis and liver failure until the drug is discontinued. This clinical
condition has case fatality of approximately 10%. Drug-induced hepatitis is considered
when serum level of SGPT or SGOT rises >150 IU/L on >3 occasions, or >250 IU/L on one
occasion, along with values of serum bilirubin >34.2 µmol/L (2 mg%).
Data indicate that incidence of isoniazid-induced clinical hepatitis is lesser than
was previously thought. Hepatitis occurs in 0.6% patients if isoniazid is given alone,
but incidence is 1.6% if it is given with drugs, other than rifampicin. With rifampicin,
incidence of hepatitis is 2.7%. Risk of drug-induced hepatitis increases with age and it is
2% in persons aged 50–64 years. Rate of fatal hepatitis is 0.023%. If it is given to patient
with pre-existing liver disease, it may accumulate in body and further increases risk of
drug-induced hepatitis. Frequent monitoring of serum level of hepatic transaminases is
indicated in this clinical setting.
Patients with alcoholic liver disease are at increased risk of peripheral neuropathy and
should be given pyridoxine prophylactically at dose of 10 mg daily. Rifampicin may cause
normal transient hyperbilirubinemia in 0.6% patients. Incidence of hepatitis is 2.7% if it
is given with isoniazid and it is 1.1%, if given with drug other than isoniazid. Clearance of
rifampicin may be impaired, causing serum levels to rise if it is given to patient with pre-
existing liver disease. Careful monitoring of liver functions is indicated in these patients.
The first-line drugs isoniazid, rifampicin, and pyrazinamide are all associated with
hepatotoxicity. Of the three, rifampicin is least likely to cause hepatocellular damage,
although it is associated with cholestatic jaundice. Pyrazinamide is the most hepatotoxic
of the three first-line drugs. Among the second-line drugs, ethionamide, prothionamide,
and PAS can also be hepatotoxic, although less than any of the first-line drugs. Hepatitis
occurs rarely with the fluoroquinolones.
Chemical structure of ethionamide is similar to isoniazid and it can cause liver toxicity
in about 2% patients and should be cautiously used in pre-existing liver disease. PAS may
cause clinical hepatitis in 0.3% cases. Since, pharmacokinetics of PAS is not significantly
altered in liver disease, it could be used in usual doses and usual regimen. Cycloserine
could be safely used in liver disease, except in case of alcohol-related hepatitis where
it increases risk of seizures. Thioacetazone is hepatotoxic and it should be avoided.
Fluoroquinolones except ciprofloxacin are safe for use in liver disease.
Advanced age, female sex, poor nutritional status, pre-existing liver disease, chronic
alcoholism, Hepatitis B carrier state, and slow acetylator status are considered risk
factors for antitubercular drug-induced hepatitis. Several studies have observed relation
between serum markers for viral hepatitis and antitubercular drug-induced hepatitis. It
has been observed that viral hepatitis complicates treatment more frequently with regimen
containing both rifampicin and isoniazid than in regimen having only one of them or none
of them.
It is often difficult to find the culprit drug, in a multidrug regimen, causing drug-
induced hepatitis. Regarding this practical problem, it is said that, rise in serum
transaminase activity within 15 days of starting regimen is usually attributed to rifampicin
but if it occurs after 1 month, it is usually attributed to pyrazinamide. Whether toxicity is
due to their additive effect, synergistic effect, hypersensitivity phenomenon or direct effect
is still not known. Joint Tuberculosis Committee of British Thoracic Society recommends
that liver functions should be monitored weekly in first 2 weeks and then at 2 weekly
interval in patients who have pre-existing liver disease. Recommendation for frequency of
monitoring liver functions in patients with no known risk factors is not clear.
If a patient on antitubercular therapy develops mild transient elevation of serum
bilirubin or liver enzymes, treatment need not to be stopped as they usually come down on
continuation of treatment. If patient develops hepatitis-related symptoms with significant
elevation of bilirubin and liver enzymes, treatment should be stopped and viral hepatitis
should be ruled out by serology. Drugs should be gradually reintroduced one-by-one
starting from less hepatotoxic drug first, after liver functions come down to normal, with
close monitoring for deterioration.
Antitubercular Treatment with Pre-existing Liver Disease

In case of stable liver disease, all antitubercular drug could be used, but under close
observation for liver functions. In patients with unstable or advanced liver disease, liver
function tests should be done at the start of treatment, if possible. If the serum SGPT level
is >3 times normal before the initiation of treatment, lesser hepatotoxic regimens should
be considered. The alternate regimens are devised on the premise that more unstable or
severe the liver disease is, fewer the hepatotoxic drugs employed. Possible regimens include
those that employ two hepatotoxic drugs (rather than the three in the standard regimen):
(1) where 9 months of isoniazid and rifampicin, plus ethambutol (until or unless isoniazid
susceptibility is documented) is advocated; or (2) where 2 months of isoniazid, rifampicin,
streptomycin and ethambutol is followed by 6–7 months of isoniazid and rifampicin; or (3)
where 6–9 months of rifampicin, pyrazinamide, and ethambutol is administered.
When the liver disease is too serious to permit use of >1 hepatotoxic drug, then a
regimen comprising 2 months of isoniazid, ethambutol, and streptomycin followed by
10 months of isoniazid and ethambutol is preferred. In the extreme case of fulminant
hepatic failure where antitubercular treatment is indispensable, a regimen devoid of any
hepatotoxic drug is prescribed; which is 18–24 months of streptomycin, ethambutol and
a fluoroquinolone. No dosage adjustment is required in patients with mild-to-moderate
hepatic impairment with bedaquiline and delamanid. Dosing and toxicity not well
Treatment of Tuberculosis in Liver Diseases: Case-based Approach 207
established in severe hepatic impairment, use with caution and only when the benefits
outweigh the risks.
FURTHER READING
Thorax. 1998;53:536-648.
3. World Health Organization. (2014). Companion handbook to the WHO guidelines for the
programmatic management of drug- resistant tuberculosis. [online] Available from https://apps.
who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdf;jsessionid=FE77DA8527A0
0BEE1871C19426FAEC7B?sequence=1. [Last accessed March, 2020].
4. DOTS PLUS guidelines, Revised National Tuberculosis Control Programme, Central TB Divison
Delhi. Sep 2008;/Revised National Tuberculosis Control Programme. Guidelines on Programmatic
Management of Drug Resistant TB (PMDT) in India. Central TB Division, Directorate General of Health
Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi. May 2012.
postpartum hispanic patients. Public Health Rep. 1989;104:151-5.
6. Frieden T, Espinal M. What is the therapeutic effect and what is the toxicity of antituberculosis
drugs? Toman’s tuberculosis. Case detection, treatment and monitoring, 2nd edition. World Health
Organization, Geneva. 2004;110-21.
7. Guidelines for the programmatic management of drug resistant tuberculosis. Emergency Update.
2008;9:82-3.
10. Pande JN, Singh SPN, Khilnani GC, Khilnani S, Tandon R. Risk factors for hepatotoxicity from anti
tuberculosis drugs: a case control study. Thorax. 1996;51:132-6.
11. Prasad R, Verma SK, Chaudhary SR, Chandra M. Predisposing factors in hepatitis induced by
antitubercular regimen containing isoniazid, rifampicin and pyrazinamide: A case control study.
Journal of Internal Medicine of India. 2006;9:73-8.
postpartum Hispanic patients. Public Health Rep. 1989;104:151-5.
15. World Health Organization. Guidelines for the programmatic management of drug-resistant
tuberculosis, 2011 Update. [online] Available from https://apps.who.int/iris/bitstream/
16. World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis 2016 update.
eng.pdf. [Last accessed March, 2020].
17. World Health Organization. (2017). Guidelines for the treatment of drug-susceptible tuberculosis
and patient care, 2017 update. [online] Available from http://apps.who.int/iris/bitstre
am/10665/255052/1/9789241550000-eng.pdf. [Last accessed March, 2020].
18. WHO consolidated guidelines on drug-resistant tuberculosis treatment. [online] Available from
https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?ua=1. [Last
Available from https://tbcindia.gov.in/index1.php?lang=1&level=2&sublinkid=4780&lid=3306. [Last
CASE 56
Pulmonary Aspergilloma
Presenting as a Moving Ball
CASE REPORT
A 40-year-old male presented with recurrent hemoptysis for 3 months. He had received
adequate course of antituberculosis drugs for pulmonary tuberculosis. After the complete
course of previous treatment, there was a thin-walled cavity as a residual lesion (open
negative syndrome). His sputum smear was repeatedly negative for acid fast bacilli (AFB)
and his culture was also negative for Mycobacterium tuberculosis but was positive for fungus
and detected Aspergillus fumigatus species. His chest X-ray posteroanterior (PA) view showed
thin-walled cavity with ball inside (Fig. 1). Chest X-ray in different position (left lateral
decubitus and trendelenburg position) showed movement of the fungal ball (Figs. 2A and B).

showing aspergilloma in left upper zone.
Pulmonary Aspergilloma Presenting as a Moving Ball 209
B
FIGS. 2A AND B: Chest X-ray in trendelenburg position and
left lateral decubitus position showing moving fungal ball.
DISCUSSION
Aspergilloma/fungus ball is one of the forms of pulmonary aspergillosis that occurs
commonly in tubercular cavities. The other forms of pulmonary aspergillosis are
allergic bronchopulmonary aspergillosis, chronic necrotizing aspergillosis, and invasive
aspergillosis. Aspergilloma predominantly occurs in the upper lobes, indicating the
predilection for cavity formation at this site. The natural history of aspergilloma varies
from a stable lesion to progression and even spontaneous regression in about 5% of the
cases.
The definitive diagnosis is established by histopathological demonstration of
dichotomously branching hyphae in resected specimen and culture of the tissue
but largely the diagnosis is based on radiological examination. The diagnosis of
aspergilloma is mainly based on the presence of radiological opacity in the cavity with
an air-crescent sign. Adjacent pleural thickening is the earliest sign on chest X-ray
before the fungus ball appears. Isolation of Aspergillus species from sputum, bronchial
washings, and intraoperative or postoperative examination of the fungal ball are other
means of diagnosis. In our case, the diagnosis was established mainly by radiology
and sputum culture. The additional feature in this case was the demonstration of
moving fungal ball.
The most common clinical presentations in aspergilloma are hemoptysis, dyspnea,
with or without fever, chest pain, and weight loss. Up to 25% of patients have massive
hemoptysis. Our patient presented with cough and hemoptysis. Massive hemoptysis is a
common life-threatening complication of aspergilloma, necessitating surgical resection.
Surgery (lobectomy) is the primary choice for treating pulmonary aspergilloma in spite of
the risk of high morbidity and mortality. Systemic antifungal agents such as amphotericin
B and voriconazole have little role in the treatment of aspergilloma. Though the diagnosis
of pulmonary aspergilloma is based on the radiological sign of air-crescent in a cavity, it
can give rise to atypical radiological findings. Sputum and bronchial washing examination
with strong clinical suspicion can help in diagnosis.
FURTHER READING
1. Rippon JW. Aspergillosis. In: Medical Mycology: Pathogenic fungi and the pathogenic Actinomy
cetes, 3rd edition. Philadelphia: WB Saunders Co; 1988. pp. 618-50.
2. Sakarya ME, Ozbay B, Yalcinkaya I, Arslan H, Uzun K, Poyraz N. Aspergillomas in the lung cavities.
East J Med. 1998;3:7-9.
3. Pratap H, Dewan RK, Singh L, Gill S, Avaddadi S. Surgical treatment of pulmonary aspergilloma: A
series of 72 cases. Indian J Chest Dis Allied Sci. 2007;49:23-7.
4. Osinowo O, Softah AL, Zahrani K, Zaharani ME, Al-Mosallami IA. Pulmonary aspergilloma simulating
a bronchogenic carcinoma. Indian J Chest Dis Allied Sci. 2003;45:59-62.
5. Baradkar VP, Mathur M, Kumar S. Uncommon presentation of pulmonary aspergilloma. Indian J Med
Microbiol. 2009;27:270-2.
6. Bennett JE. Aspergillosis. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL,
(Eds). Harrison's Principles of Internal Medicine, 16th edition. USA: Mc-Graw-Hill Companies; 2005.
pp. 1188-9.
CASE 57

and Allergic Aspergillus Sinusitis
CASE REPORT
A 52-year-old married male presented with complaints of recurrent nasal discharge for
25 years, episodic breathlessness, and cough with minimal expectoration of white, thick,
and nonfoul smelling sputum for last 10 years. There was history of recurrent hemo
ptysis for last 6 years. On physical examination, the patient was afebrile with a pulse
rate of 80 beats/min, respiration rate of 20 breaths/min, and a right arm supine blood
pressure of 130/80 mm Hg. There was no cyanosis or clubbing. Chest examination was
unremarkable on inspection, palpation, and percussion. On auscultation, bilateral diffuse
rhonchi were audible. Other systems examination did not reveal any abnormality.
On investigation, total leukocyte count was 10,800/mm3 with eosinophils being 12%
(absolute eosinophil count 1,296/mm3) on differential count. Sputum samples for acid-fast
bacilli were found to be negative on three consecutive days and no pathogenic organisms
were isolated. Chest radiograph (Fig. 1) revealed wine glass like consolidation in left
FIG. 1: Plain chest roentgenogram showing

“V-Y”-shaped (“wine glass”) (arrow) consoli
dation in the left upper zone along with right
perihilar infiltrate (arrowhead).
upper zone along with right perihilar infiltrate. Pulmonary function tests revealed a forced
expiratory volume in first second/forced vital capacity (FEV1/FVC) of 60% of predicted and
a postbronchodilator FEV1 of 1.2 L (66% of predicted) and a change of 310 mL (15%) on
bronchodilator administration. Computed tomography (CT) revealed mucous filled dilated
bronchi, central bronchiectasis and high attenuation mucous (HAM) impact (Figs. 2 and 3).
Skin prick tests with Aspergillus fumigatus antigen showed a positive reaction for
type I hypersensitivity with a wheal size equal to the size of positive control. Total IgE was
5,652 IU/mL (reference range 0–100 IU/mL). Specific IgG and IgE against A. fumigatus by ELISA
were raised (66.30 and 159.90 IU respectively). A diagnosis of allergic bronchopulmonary
aspergillosis (ABPA) was thus established.
Diagnosis of allergic Aspergillus sinusitis (AAS) is based on histopathology and roentgen
ology. X-ray paranasal sinuses showed haziness while CT paranasal sinuses demonstrated
heterogeneous densities and intact bony walls suggestive of allergic fungal sinusitis
(Fig. 4). The patient was advised functional endoscopic sinusoidal surgery (FESS) which
he refused. The patient was then started on a single daily dose of 40 mg prednisolone
(0.5 mg/kg) which was gradually tapered over next 6 months. Inhaled salmeterol with
FIG. 2: High-resolution computed tomography (HRCT) scan (lung window) showing

mucous-filled dilated bronchi (arrow) and extensive bilateral central bronchiectasis
characterized by “signet ring” appearance (arrowheads).
A B
FIGS. 3A AND B: High-resolution computed tomography (HRCT) scan (lung and the
corresponding section on the mediastinal windows) showing high attenuation mucous (HAM)
(arrows) impaction in a patient with allergic bronchopulmonary aspergillosis.
Allergic Bronchopulmonary Aspergillosis and Allergic Aspergillus Sinusitis 213
fluticasone dipropionate 500 µg two times per day from a metered dose inhaler was
also given. During follow-up, total serum IgE levels were reduced and there was a marked
symptomatic improvement. Serial chest X-rays showed radiological improvement and a
repeat CT scan showed clearing of consolidation (Figs. 5 to 7).
FIG. 4: Axial section of the noncontrast computerized tomography of the para nasal
sinuses (CT PNS) showing heterogenous densities, signifying opacification of the
sinuses, with serpiginous areas of increased attenuation which are characteristic of
allergic Aspergillus sinusitis (arrows).
FIG. 5: Plain chest roentgenogram of the same patient

taken 8 months later, showing a nonhomogeneous
consolidation in the right lower zone (arrow). The left-
sided consolidation and right-sided perihilar infiltrate,
seen in Figure 1, have disappeared.
FIG. 6: Plain chest roentgenogram of the same patient taken

18 months after Figure 1, showing re-emergence of a large
consolidation in the left mid and lower zones along with right
mid and lower zones consolidation (arrow). The right-sided
perihilar opacity (arrow) and left upper zone consolidation
have re-emerged (arrowhead).
FIG. 7: Plain chest roentgenogram of the same patient taken

22 months after Figure 1, showing that the shadows described
in Figure 3 have disappeared but a new nonhomogeneous
consolidation has emerged in the left upper and mid zones (arrow).
DISCUSSION
Allergic bronchopulmonary aspergillosis presents as a noninfectious, potentially fatal
inflammatory disease where antigens released by the fungal mycelium provoke an immune
response in long-standing atopic asthmatics. All asthmatics should undergo a skin prick
Allergic Bronchopulmonary Aspergillosis and Allergic Aspergillus Sinusitis 215
test for Aspergillus and those with a positive skin prick test to Aspergillus antigens must be
evaluated for ABPA and AAS should be excluded if there is a recurrent nasal symptoms.
Literature regarding concomitant occurrence of ABPA and AAS is sparse. In one study
concomitant AAS was detected in 13% of the 23 patients of ABPA enrolled. In other study
involving 95 patients with ABPA, 22 had radiological evidence of sinusitis. Nine consented
to surgery, seven of whom were diagnosed as concomitant AAS. Nasal symptoms preceded
chest symptoms in two patients, vice-versa in one, and occurred simultaneously in four. In
our patient, nasal symptoms preceded the chest symptoms.
Radiological findings in cases of ABPA are both interesting and varied. Varied
presentations, both on chest X-ray and CT of the thorax have been reported including
bronchial, parenchymal, and pleural abnormalities. While the diagnosis of AAS is
primarily based on histopathology, roentgenology is essential for the diagnosis. Haziness
of one or more paranasal sinuses is almost always seen on plain roentgenograms.
However, CT offers more reliable information with characteristic features that include
heterogeneous densities and serpiginous areas of increased attenuation on noncontrast
scans. In other series, CT of the paranasal sinuses, carried out in six patients of ABPA with
AAS, revealed mucosal thickening with hyperdense lesions without any bony erosion or
destruction, similar to the presentation in our patient.
Concomitant occurrence of ABPA and AAS seems to be infrequently recognized.
Since asthma and sinusitis are often seen by two different specialties, the occurrence of
AAS in ABPA and ABPA in AAS may easily be overlooked. Early diagnosis, with the help
of roentgenologic techniques, and appropriate therapy could alter the natural history of
these diseases.
FURTHER READING
1. Rosenberg M, Patterson R, Cooper BJ, Roberts M, Harris KE. Clinical and immunological criteria for
the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med. 1977;86:405-14.
2. Bardana EJ Jr, Gerber JD, Craig S, Cianciulli FD. The general and specific humoral immune response
to pulmonary aspergillosis. Amer Rev Resp Dis. 1975;112:799-805.
3. Mroueh S, Spock A. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Chest.
1994;105:32-6.
4. Slavin RG. Allergic bronchopulmonary aspergillosis. Clin Rev Allergy. 1985;3:167-82.
5. Luong A, Marple BF. Allergic fungal rhinosinusitis. Curr Allergy Asthma Rep. 2004;4:465-70.
6. Panchal N, Bhagat R, Pant C, Shah A. Allergic bronchopulmonary aspergillosis: the spectrum of
computed tomography appearances. Respir Med. 1997;91:213-9.
7. Shah A, Panchal N, Agarwal AK. Concomitant allergic bronchopulmonary aspergillosis and allergic
Aspergillus sinusitis: a review of an uncommon association. Clin Exp Allergy. 2001;31:1896-905.
8. Shah A. Allergic bronchopulmonary and sinus aspergillosis: the roentgenologic spectrum. Front
Biosci. 2003;8:e138-46.
CASE 58
Multiple Encysted Effusion

Presenting as Mass Lesion
CASE REPORT
A 30-year-old female came to us with complains of fever, chest pain, and breathlessness
for last 3 months. On general physical examination, there was no significant finding. On
examination of respiratory system, movements were reduced on the right side. There
was stony dullness on percussion and diminished breath sounds on the right side. Chest
X-ray showed multiple pockets of effusion mimicking as mass (Fig. 1). Ultrasound thorax
demonstrated multiple pockets of the fluid. Computed tomography (CT) thorax has also
shown multiple pockets (Figs. 2 and 3). Ultrasound-guided pleural aspiration was done
from one of the large pockets. About 750 mL of straw colored fluid was aspirated which was
exudative and lymphocytic predominant. Pleural fluid culture was negative for any pyogenic
organism and pleural fluid for acid-fast bacilli (AFB) was also negative. Patient was started
on antitubercular drug (rifampicin, isoniazid, pyrazinamide, and ethambutol) along with
40 mg oral prednisolone. Patient improved after 6 weeks when steroid was tapered off.
After 2 months, pyrazinamide and steroids were stopped. Patient improved clinically and
radiologically and her chest X-ray became normal (Fig. 4).

multiple encysted fluid pockets mimicking mass.
Multiple Encysted Effusion Presenting as Mass Lesion 217

multiple fluid pockets.

multiple pockets of fluid.

resolution of shadows after 2 months of treatment.
DISCUSSION
This patient presented with multiple encysted pleural effusion on the right side mimicking
as multiple masses. Pleural fluid loculations develop secondary to the presence of
visceral-to-parietal adhesions that prevent fluid from falling to the dependent portion
of the pleural cavity. Loculations can develop along any portion of the pleural cavity.
The detection of loculations on plain chest radiography depends on the presence of
surrounding aerated lung tissue that outlines the pleural opacity. A single loculated
pocket of pleural effusion can be seen as an oval mass-like structure, a sharply demarcated
convex margin at its interface with the lung and an indistinct margin where it contacts
the chest wall. However, in the setting of a massive pleural effusion and pneumonia with
consolidation, multiloculations cannot typically be seen on plain radiographs. Therefore,
CT scan and/or ultrasound are required to evaluate multiple loculations.
Computed tomography scan has many advantages over plain radiography for
evaluation of patients with unilateral hemithorax opacification. It can potentially
differentiate between pleural and parenchymal lung disease and provide visualization of
underlying lung parenchymal processes that are obscured on the chest radiograph by a
large pleural effusion. Loculated effusions have a lenticular configuration with smooth
margins and relatively homogenous water attenuation. Loculations exert a mass effect,
displace the lung, and cause collapse of the adjacent lung tissue.
Encysted pleural effusions are classified into parietal, diaphragmatic, interlobar,
mediastino-interlobar, mediastinal, and extrapleural. Our patient had multiple encysted
pleural effusions which was also evident on ultrasound thorax and CT scan. Bedside
ultrasound was crucial in making the diagnosis and proceeding with pleural aspiration.
FURTHER READING
1. Stark P. The pleura. In: Taveras J, Ferrucci JT (Eds). Radiology Diagnosis Imaging, Intervention.
Philadelphia: Lippincott; 2000. pp. 1-29.
2. Yang PC, Luh KT, Chang DB, Wu HD, Yu CJ, Kuo SH. Value of sonography in determining the nature
of pleural effusion: analysis of 320 cases. AJR Am J Roentgenol. 1992;159:29-33.
3. Chen HJ, Tu CY, Ling SJ, Chen W, Chiu KL, Hsia TC, et al. Sonographic appearances in transudative
pleural effusions: not always an anechoic pattern. Ultrasound Med Biol. 2008;34:362-69.
4. Lomas DJ, Padley SG, Flower CDR. The sonographic appearances of pleural fluid. Br J Radiol.
1993;66:619-24.
5. Kearney SE, Davies CW, Davies RJ, Gleeson FV. Computed tomography and ultrasound in
parapneumonic effusions and empyema. Clin Radiol. 2000;55:542-47.
6. Fraser RS, Muller NL, Colman N, Pare PD. Fraser and Pare's Diagnosis of Diseases of the Chest.
Philadelphia: Saunders.
7. Goodman LR, Felson B. Felson's Principles of Chest Roentgenology. Philadelphia: Elsevier; 2007.
8. Light RW, Lee YCG. Textbook of Pleural Diseases. Boca Raton: CRC Press; 2016.
9. Shanks SC, Kerley P, Twining EW. A Textbook of X-ray Diagnosis by British Authors. London: Lewis;
1938. p. 411.
CASE 59
A Case of Pulmonary
Alveolar Microlithiasis
CASE REPORT
An 18-year-old male came to the hospital with complains of cough (nonproductive) for
5 days for which chest radiograph was taken (Figs. 1 and 2). Chest radiograph revealed the
presence of dense micronodular opacity (<1 mm), involving both the lungs diffusely giving
classical sandstorm appearance mainly involving the middle and lower zone. High-resolution
computed tomography (HRCT) thorax showed bilateral calcification with increase attenuation
involving alveoli, intra and interlobular septa, fissure and pleura, mainly subpleural in posterior
FIG. 1: Chest X-ray of the patient showing multiple

micronodular opacity involving both lungs.
and basal parts of the lungs. Para-septal emphysema is visible. Hounse field unit measurements
were very high representing areas with calcification and pulmonary function tests were done
(Figs. 2 and 3). Pulmonary function test reports were normal.
FIG. 2: Chest X-ray of the patient after 1 month of

treatment.
A B
FIGS. 3A TO C: High-resolution computed

tomography (HRCT) thorax of the patient
C showing sandstorm appearance.
A Case of Pulmonary Alveolar Microlithiasis 221
DISCUSSION
Pulmonary alveolar microlithiasis (PAM) also known as Harbitz syndrome is an
uncommon disease characterized by numerous small calculi in alveolar spaces with
chronic and deteriorating evolution. Patients may be asymptomatic for many years
and either have normal pulmonary function or mild restrictive pattern and usually
become symptomatic between third and fourth decades. Patients with PAM are
asymptomatic till development of hypoxemia and cor pulmonale. It remains static, while
in some it progresses to pulmonary fibrosis, respiratory failure, and cor pulmonale.
Clinical presen tation includes cough, breathlessness and chest pain, and a lung
disorder with restrictive pattern. Death can occur in midlife. Plain chest X-ray usually
shows diffuse bilateral symmetric micronodular calcification (sandstorm) mainly in
middle and lower zones; apical bullae and black pleural lines. HRCT thorax remains
the imaging technique of choice to diagnose PAM. Lung biopsy reveals presence of
multiple laminated calcospherites within the alveoli of lung parenchyma pathognomonic
of PAM. Extrapulmonary calcifications in PAM include medullary nephrocalcinosis,
nephrolithiasis, calcification of lumbar sympathetic chain, testicles, punctuate calcifica
tions in seminal vesicles, epididymal, and periurethral calcifications causing obstructive
azoospermia.
Lung transplantation is the only effective treatment. Therapeutic bronchoalveolar
lavage (BAL) and corticosteroids are ineffective. Recurrence of disease after lung
transplantation has not been reported yet. Disodium etidronate, known to inhibit
microcrystal growth of hydroxyl appetite, used in the dose of 10 mg/kg/day orally for
1 year can cause considerable regression of calcific densities in PAM because in these
there is deposition of calcium-embedded particles in lung interstitium which are not
dislodged during BAL.
FURTHER READING
1. Prasad R, Garg R, Verma SK, Singhal S, Gupta N. Pulmonary alveolar microlithiasis. Calicut Med
Journal. 2008;6:1-5.
2. Huqun, Izumi S, Miyazawa H, Ishii K, Uchiyama B, Ishida T, et al. Mutations in the SLC34A2 gene are
associated with pulmonary alveolar microlithiasis. Am J Respir Crit Care Med. 2007;175:263-8.
3. Ahmad K, Kumar Gupta M, Dhungel K, Lal Sah P, Ansari S, Kumar Rauniyar R. Pulmonary alveolar
microlithiasis: A rare case report. Iran J Med Sci. 2013;38:267-70.
4. Kashyap S, Mohapatra PR. Pulmonary alveolar microlithiasis. Lung India. 2013;30:143-7.
5. Cluzel P, Grenier P, Bernadac P, Laurent F, Picard JD. Pulmonary alveolar microlithiasis: CT findings.
J Comput Assist Tomogr. 1991;15:938-42.
6. Jonsson ALM, Simonsen U, Hilberg O, Bendstrup E. Pulmonary alveolar microlithiasis: two case
reports and review of the literature. Eur Respir Rev. 2012;21:249-56.
7. Barbolini G, Rossi G, Bisetti A. Pulmonary alveolar microlithiasis. N Engl J Med. 2002;347:69-70.
CASE 60
Hydropneumothorax in Tropical
Pulmonary Eosinophilia
CASE REPORT
A 32-year-old male presented with history of cough and sudden onset of chest pain with
breathlessness for 5 days. There was no history of weight loss, trauma or passing worms in
stool. He was a nonsmoker and nonalcoholic. On examination of the chest, movement was
diminished on the left side. On percussion, stony dullness was found in the left intrascapular
region and hyper-resonance above it. Shifting dullness and succussion splash were also
present. Breath sounds and vocal resonance were diminished on the same side. Chest X-ray
posteroanterior (PA) view dated 26.09.1994 showed evidence of hydropneumothorax on the
left side (Fig. 1). Lateral chest X-ray was not done. Total blood leukocyte count was 10,000/mm3
and absolute eosinophil count was 3,200/mm3. Sputum was persistently negative for acid-
fast bacilli by smear examination. Stool examination did not show any ova or cyst. Urine
examination was normal. Mantoux test using five units of purified protein derivative (PPD) RT
23 showed 6 mm induration.
FIG. 1: Chest X-ray showing hydropneumothorax on

left side.
Hydropneumothorax in Tropical Pulmonary Eosinophilia 223
FIG. 2: Chest X-ray after 3 weeks showing resolution

of hydropneumothorax.
FIG. 3: Chest X-ray on subsequent follow-up after

1 year.
The patient was advised bed rest and prescribed diethylcarbamazine 100 mg thrice daily for
3 weeks. His symptoms improved. A repeat chest X-ray PA view 3 weeks later, on 25/10/1994
(Fig. 2), revealed complete expansion of the left lung. Peripheral blood absolute eosinophil
count decreased to 500/mm3. Subsequent follow-up for 1 year revealed no problem (Fig. 3).
DISCUSSION
Tropical pulmonary eosinophilia usually presents as bouts of cough, wheezing, dyspnea
mostly nocturnal with fever, and other constitutional symptoms. The peripheral blood
shows an absolute eosinophil count above 3,000/mm3 and raised IgE levels. Chest X-ray
shows increased bronchovascular marking with mottling involving the middle and the
lower zones and prominent hila. Unusual radiological presentations such as cavitation,
pleural effusion, and pneumonia have been reported. The present case presenting
as hydropneumothorax is rare in tropical pulmonary eosinophilia. Very few cases of

pneumothorax/hydropneumothorax have been reported.
How pneumothorax can develop in tropical pulmonary eosinophilia is not clear.
It is possible that in the acute stage, when the bronchioles are filled with blood-stained
mucopurulent secretions, airway obstruction occur leading to the formation of air
cysts. These air cysts may rupture and give rise to pneumothorax. The present case of
hydropneumothorax was thought to be due to tropical pulmonary eosinophilia because
of the raised peripheral blood absolute eosinophil count and response to diethyl
carbamazine.
FURTHER READING
1. Prasad R, Tandon S, Kant S, Mukerji PK. Hydropneumothorax in tropical pulmonary eosinophilia. Ind
J Tub. 1996;43:205-6.
2. Vishwanathan R. Pulmonary eosinophilosis. Quart J Med. 1948;17:257.
3. Menon NK. Tropical pulmonary eosinophilia atypical manifestations. Indian J Chest. Dis Allied Sci.
1963;5:231.
4. Mittal OP, Rao MS, Prasad R, Katiyar SK, Singh RP. Tropical pulmonary eosinophilia: Unusual
presentation. Indian J Chest. 1975;17:135-8.
5. Nath J, Jain VK. Atypical presentation of tropical pulmonary eosinophilia. Indian J Chest Dis Allied
Sci. 1978;20:141-4.
6. Khoo FY, Danaraj TJ. The roentogenographic appearance of eosinophilic lung (tropical eosinophilia).
Am J Roentogenology. 1960;83:251-60.
7. Herlinger H. Pulmonary changes in tropical eosinophilia: Brit J Red. 1963;36:889-901.
8. Chaudhry BS, Gupta PK, Gupta PR. Tropical pulmonary eosinophilia: An unusual presentation Indian
J Chest Dis Allied Sci. 1978;20:139-41.
9. Jain VK, Beniwal OP. Unusual presentation of tropical pulmonary eosinophilia. Thorax. 1984;39:
634-5.
10. Jain VK, Beniwal OP. Spontaneous pneumothorax in pulmonary eosinophilia. J Indian Med Assoc.
1985;83:124-5.
CASE 61
Eventration of Diaphragm
CASE REPORT
A 45-year-old male came to us with complains of burning sensation over the precordium
and has no respiratory symptoms. General physical examination revealed no abnormality.
Position of trachea and apex beat was normal. Examination of the respiratory system was
within normal limits except some hyper resonant notes in left infrascapular and mammary
area. Chest X-ray showed elevated left dome of diaphragm and the heart was shifted
toward the right side (Fig. 1). Barium meal was done to find the evidence of any herniation
which was not there and the diaphragm was intact (Figs. 2 and 3). Thus, he was diagnosed
as a case of eventration of diaphragm and no treatment was given. Patient was assured that
there is no significant abnormality and it is a congenital anomaly which generally requires no
treatment.

showing elevated left dome of diaphragm with
shifting of heart toward the right side.

barium meal study in lying down position.

barium meal study in standing position.
DISCUSSION
Eventration of diaphragm is a congenital abnormality due to failure of muscular
development of part or all of one of both hemidiaphragms.. Pathologically it consists of
a thin membranous sheet attached peripherally to normal muscle at the point of origin
from the rib cage. It is generally described as upward displacement of one of side of
diaphragm, usually on left side without break of continuity, permitting one or more of
abdominal organs to occupy position in the thorax.
The condition was first described by Petit (1790). Cru-veilher in 1849 coined the
term eventration for the first time to differentiate this unusual malformation from
diaphragmatic hernia. The eventration was formerly an autopsy finding but it is now
roentgenographs which were proved subsequently to be eventration of diaphragm. Sailor
and Rheim in 1905 collected 13 cases. Bayne-Jones cade made the total number to that
Eventration of Diaphragm 227
date 108 as cited by Verbrycke. Some 300 cases were reported in the literature. Eventration
occurs most commonly on left side. It was also reported rarely on right side by various
authors. Bilateral eventration is very rare. Eventration of diaphragm is of interest not
because it is a rarity and its radiographic feature is sufficiently characteristic to allow the
correct diagnosis to be made with certainty but it may present puzzling problems to those
unfamiliar with the entity and has often led to unnecessary anxiety over treatment and
even needless surgical exploration.
Eventration of diaphragm is a congenital condition, sometimes it is difficult or
impossible to differentiate from diaphragmatic paralysis where marked diaphragmatic
elevation may be attributed to interruption of phrenic nerve by invasive neoplasm or
by surgical section. In many cases, however, there is no way of knowing whether rise
in the dome of diaphragm is caused by congenital absence of muscle or phrenic nerve
paralysis. In infants, for example, hemidiaphragmatic elevation may be attributed to birth
injury as well as to congenital abnormality of muscle and the only method of distinguishing
is by faradic stimulation of phrenic nerve.
Eventration is supposed to be much more infrequent than diaphragmatic hernia,
ratio being 1:37. Eventration is encountered at all ages. Eventration per se as may be
strikingly free from symptoms. Among symptomatic, three types of patients such as
pleuropulmonary, dyspeptic, and cardiac were reported. Korns also observed that
eventration of right hemidiaphragm was 7–8 times less common than that of the left.
Fluoroscopy usually shows marked restricted movement of hemidiaphragm with normal
respiration. On sniffing, paradoxical movement of hemidiaphragm can be seen; reverse
excursion of 2 cm or more can be diagnostic of eventration.
FURTHER READING
1. Prasad R, Nath J, Mukerji PK. Eventration of diaphragm. J Indian Med Assoc. 1986;84:187-9.
2. Agnihotri MS, Jamil Z, Nath J. Localised eventration of the right hemi-diaphragm. Indian J Chest Dis
Allied Sci. 1970;12:124-6.
3. Avnet NL. Roentgenologic features of congenital bilateral anterior diaphragmatic eventration. Am J
Roentgenol Radium Ther Nucl Med. 1962;88:743-50.
4. Chin EF, Lynn RB. Surgery of evenetration of the diaphragm. J Thorac Cardiovasc Surg. 1956;32:6-
14.5.
5. Frazer RG, Pare JAP. Diagnosis of Diseases of the Chest, 2nd edition. Philadelphia: W B Saunders;
1978. pp. 1871-7.
6. Kinzer RE, Cook JC. Lesions of diaphragm, with special references to eventration, report of three
cases. Am J Roentgenol. 1946;52:611-7.
7. Laxdal OE, McDougall HA, Mellin GW. Congenital eventration of the diaphragm. N Engl J Med.
1954;250:401.
8. Vogl A. Small A, Partial eventration of the right diaphragm (congenital diaphragmatic herniation of
the liver). Ann Intern Med. 1955;43:61-82.
CASE 62
Eventration of Diaphragm in a
7-year-old Male
CASE REPORT
A 7-year-old male presented with breathlessness and palpitation off and on for 3 years.
General examination of the patient revealed no abnormality. Examination of the respiratory
system revealed diminished movements on the left lower half of the chest. Trachea was
central and apex beat was 4 cm medial to mid-clavicular line in fifth left intercostal space.
Tympanitic percussion note was present below the level of fourth rib in front and back of
the left side of chest with diminished breath sounds and vocal resonance with occasional
splashing and metallic sound over left half of the chest. Other systems were normal.
Chest X-ray showed thinned out elevated left dome of diaphragm at the level of second rib
anteriorly with shifting of the heart toward right side (Figs. 1 to 4). Fluoroscopic screening of
the chest showed that left dome of the diaphragm was immobile and on sniffing paradoxical
movement of the left diaphragm was present. Barium meal examination was done which
showed elevated dome of diaphragm and abdominal content in the thorax without any
breach in the diaphragm (Figs. 5 to 8). Thus, the diagnosis of eventration was established. As
she was symptomatic, patient was referred for surgery but patient refused. On further follow-
up patient was asymptomatic except some occasional mild breathlessness and palpitation.
FIG. 1: Chest X-ray posteroanterior (PA) showing

elevated left dome on diaphragm.
Eventration of Diaphragm in a 7-year-old Male 229

elevated left dome on diaphragm with shifting of
heart toward right side.
FIG. 3: Chest X-ray PA view showing elevated left dome

on diaphragm with shifting of heart toward right side.
FIG. 4: Chest X-ray left lateral view showing elevated

left dome of diaphragm.
FIG. 5: Barium meal study showing no breach in the



Eventration of Diaphragm in a 7-year-old Male 231

DISCUSSION
Eventration of diaphragm is a congenital abnormality due to failure of muscular develop
ment of part or all of one of both hemidiaphragm. Pathologically it consists of a thin
membranous sheet attached peripherally to normal muscle at the point of origin from
the rib cage. It is generally described as upward displacement of one of side of diaphragm,
usually on left side without break of continuity, permitting one or more of abdominal
organs to occupy position in the thorax.
Cruveilher in 1849 coined the term eventration for the first time to differentiate this
unusual malformation from diaphragmatic hernia. Eventration occurs most commonly on
left side. It was also reported rarely on right side by various authors. Bilateral eventration
is very rare.
Eventration of diaphragm is of interest not because it is a rarity and its radiographic
feature is sufficiently characteristic to allow the correct diagnosis to be made with
certainty but it may present puzzling problems to those unfamiliar with the entity
and has often led to unnecessary anxiety over treatment and even needless surgical
exploration.
Eventration of diaphragm is a congenital condition sometimes it is difficult or im
possible to differentiate from diaphragmatic paralysis where marked diaphragmatic
elevation may be attributed to interruption of phrenic nerve by invasive neoplasm
or by surgical section. In many cases, however, there is no way of knowing whether
rise in the dome of diaphragm is caused by congenital absence of muscle or phrenic
nerve paralysis. In infants, e.g., hemidiaphragmatic elevation may be attributed to
birth injury as well as to congenital abnormality of muscle and the only method of
distinguishing is by faradic stimulation of phrenic nerve. Eventration is supposed to
be much more infrequent than diaphragmatic hernia, ratio being 1:37. Eventration
is encountered at all ages. Eventration per se as may be strikingly free from symptoms.
Among symptomatic, three types of patients having pleuropulmonary, dyspeptic, and
cardiac symptoms were reported.
FURTHER READING
1. Prasad R, Nath J, Mukerji PK. Eventration of diaphragm. J Indian Med Assoc. 1986;84:187-9.
2. Fraser RS, Muller NL, Colman N, Pare PD. Fraser and Pare's Diagnosis of Diseases of the Chest.
Philadelphia: Saunders.
3. Goodman LR, Felson B. Felson's Principles of Chest Roentgenology. Philadelphia: Elsevier; 2007.
4. Kinzer RE, Cook JC. Lesions of diaphragm, with special references to eventration, report of three
cases. Am J Roentgenol. 1946;52:611-7.
CASE 63
A Case of Chilaiditi Syndrome

Mimicking Pleural Effusion
CASE REPORT
A 45-year-old male came to us with chief complaints of mild pain in abdomen for 3 months
and chest pain, and he was suspected as a case of right-side pleural effusion from a private
practitioner. Patient was referred to us for abnormal shadows in the chest X-ray. General
examination was within normal limits. Examination of respiratory system was within normal
limits except presence of hyper-resonant note in right inframammary area. Chest X-ray
posterioranterior (PA) and lateral view showed raised dome of diaphragm on the right side
and there was abnormal gas shadow below the right dome of diaphragm (Figs. 1 and 2).
Ultrasonography (USG) whole abdomen was done to rule out any liver pathology. As he
was practically asymptomatic, diagnosis of chilaiditi syndrome was suspected. Patient was
asked to bring his old X-ray which was done 4 years back which had shown similar findings.
Computed tomography (CT) thorax showed presence of transverse colon between liver and
the diaphragm and the diaphragm was intact (Figs. 3 and 4). Thus, a diagnosis of Chilaiditi
syndrome was made. Patient was not offered any treatment and was consoled that he will not
require any further management.
A B
FIGS. 1A AND B: Chest X-ray posterioranterior (PA) view showing raised dome of
diaphragm right side with abnormal gas shadow.
A B
FIGS. 2A AND B: Chest X-ray lateral view showing presence of abnormal gas
shadow below the right dome of diaphragm.
FIG. 3: Computed tomography (CT) thorax

showing presence of abnormal loop of intestine
between liver and diaphragm.

showing presence of abnormal loop of intestine
between liver and diaphragm.
A Case of Chilaiditi Syndrome Mimicking Pleural Effusion 235
DISCUSSION
Chilaiditi syndrome is a rare condition characterized by transposition of a loop of
large intestine usually transverse colon in between the diaphragm and the liver, visible
on plain abdominal X-ray or chest X-ray normally. This finding is a rare anomaly
incidentally seen on chest or abdominal radiographs, with an incidence of 0.025–0.28%.
Abdominal pain, constipation, vomiting, respiratory distress, anorexia, volvulus, and
obstruction are possible presentations of this syndrome. Predisposing factors for
Chilaiditi syndrome are not clear, but may include increased colonic mobility, chronic
constipation, lax suspensory ligaments, and phrenic nerve injury. Chilaiditi syndrome
can be a self-resolving or can be chronic condition. In the diagnosis of Chilaiditi sign,
the first step is to rule out the possibility of pneumoperitoneum. For the diagnosis to be
made by imaging, the right hemidiaphragm must be displaced superiorly to the liver
by the intestines, pseudo-pneumoperitoneum caused by air in the bowels must be
seen, and the superior aspect of the liver must be positioned below the level of the left
hemidiaphragm. The best imaging modality for visualization is CT scan which carries an
added benefit of ruling out the possibility of diaphragmatic rupture.
No treatment is usually required for an asymptomatic patient. In symptomatic patient,
initial management of Chilaiditi syndrome should include bed rest, intravenous fluid
therapy, bowel decompression, enemas, and laxatives. A repeat radiograph following
bowel decompression may show disappearance of the air below the diaphragm. Thus,
bowel decompression documented by a follow-up radiograph can confirm both the
diagnosis of the condition and the success of the therapy showed the disappearance
of subdiaphragmatic air and repositioning of distended intestine back to the normal
position beneath the liver. If the patient does not respond to initial conservative
management, and either the obstruction fails to resolve or there is evidence of bowel
ischemia, then surgical intervention is indicated.
FURTHER READING
1. Saber AA, Boros MJ. Chilaiditi's syndrome: What should every surgeon know. Am Surg. 2005;71:
261-3.
2. Plorde JJ, Raker EJ. Transverse colon volvulus and associated Chilaiditi’s syndrome: case report and
literature review. Am J Gastroenterol. 1996;91:2613-16.
3. Kamiyoshihara M, Ibe T, Takeyoshi I. Chilaiditi's sign mimicking a traumatic diaphragmatic hernia.
Ann Thorac Surg. 2009;87:959-61.
4. Orangio GR, Fazio VW, Winkelman E, McGonagle BA. The Chilaiditi syndrome and associated volvulus
of the transverse colon. Dis Colon Rectum. 1986;29:653-6.
5. Gurvits GE, Lau N, Gualtieri N, Robilotti JG. Air under the right diaphragm: colonoscopy in the setting
of Chilaiditi syndrome. Gastrointest Endosc. 2009;69:758-9.
6. Blevins WA, Cafasso DE, Fernandez M, Edwards MJ. Minimally invasive colopexy for paediatric
Chilaiditi syndrome. J Pediatr Surg. 2011;46:e33-5.
7. Moaven O, Hodin RA. Chilaiditi syndrome: A rare entity with important differential diagnoses.
Gastroenterology and Herpetology. 2012;8:276-8.
8. Yin AX, Park GH, Garnett GM, Balfour JF. Chilaiditi syndrome precipitated by colonoscopy: a case
report and review of the literature. Hawaii J Med Public Health. 2012;71:158-62.
9. Murphy JM, Maıbaum A, Alexander G, Dıxon AK. Chiliaditi’s Syndrome and obesity: Clinical Anatomy.
2000;13:181-4.
10. Mathews J, Beck GW, Bowley DM, Kingsnorth AN. Chilaiditi's syndrome and recurrent colonic
volvolus: A case report. J R Nav Med Serv. 2001;87:111-2.
11. Chang TY, Tiu CM, Chou YH, Huang LL, Yu C. Hepatodiaphragmatic interposition of the intestine:
Chilaiditi’s Syndrome. Chin J Radiol. 1999;24:101-5.
12. Risaliti A, De Anna D, Terrosu G, Uzzau A, Carcoforo P, Bresadola F. Chilaiditi’s syndrome as a surgical
and nonsurgical problem. Surg Gynecol Obstet. 1993;176:55-8.
13. Flores N, Ingar C, Sánchez J, Fernández J, Lazarte C, Málaga J, et al. The Chilaiditi syndrome and
associated volvulus of the transverse colon, Rev Gastroenterol Peru. 2005;25:279-84.
14. Takahashi K, Ito H, Katsube T, Tsuboi A, Hashimoto M, Ota E, et al. Treatment of Chilaiditi Syndrome
using laparoscopic surgery. Asian J Endosc Surg. 2017;10:63-5.
15. Fomin D, Baranauskaite V, Laima S, Jasulaitis A, Petroška D. Death caused by hepatodiaphragmatic
interposition of colon. J Forensic Sci. 2017;62:247-9.
CASE 64
Multiple Myeloma with

Lung Plasmacytoma
CASE REPORT
A 45-year-old female, nonsmoker was admitted to our department with complaints of right-
sided chest pain and breathlessness for 1 year duration; loss of appetite for 6-month duration;
and about 6 kg weight loss over 4 weeks. The pain was moderate in intensity, constant, and
localized primarily to the upper part of the chest wall both anteriorly and posteriorly. The
pain increased to some extent on movement. She had taken antitubercular drugs for last
6 months without any response. Physical examination revealed pallor. Local examination
revealed about 6 × 6 cm hard swelling, just below right breast, tender, and fixed to underlying
structure. Her chest radiograph revealed opacity in the right lung with lytic lesions over right
clavicle and erosion of the right fifth rib (Fig. 1). Routine investigation showed hemoglobin:
5.1 g%, total leukocyte count: 5,500/mm3, differential count: neutrophils 64%, lymphocyte
34%, eosinophil 2% and platelets count: 1.7 lacs/mm3, serum creatinine 1.9 mg/dL and
24 hours urinary protein 330 mg/dL. Her whole skeletal survey revealed no abnormality
FIG. 1: Chest radiograph revealing opacity in the

right lung with lytic lesions over right clavicle and
erosion of the right fifth rib.
except thorax. A computed tomographic scan of the thorax (CT thorax) revealed soft tissue
mass in the right anterior chest wall with rib destruction and lytic lesions in lateral end of
right clavicle and posterior end of fifth rib suggestive of metastatic deposits (Fig. 2). Thus, a
possibility of metastatic disease was raised. Biopsy of the lung mass revealed atypical plasma
cells arranged in sheets with pulmonary parenchymal cells suggestive of malignant myeloma.
Her skull X-ray revealed multiple lytic lesions (Fig. 3). Serum protein electrophoresis was done
which revealed raised total proteins (11 g/dL) with normal albumin, α-1, α-2, and β globulin
FIG. 2: Computed tomographic scan of the thorax

(CT thorax) revealing soft tissue mass in the right
anterior chest wall with rib destruction and lytic
lesions in lateral end of right clavicle and posterior
end of fifth rib suggestive of metastatic deposits.
FIG. 3: Skull radiograph revealing multiple lytic lesions.

Multiple Myeloma with Lung Plasmacytoma 239
but markedly raised gamma globulin (5 g/dL) and the electrophoresis showed an M-spike
in the β-γ inter zone. Serum immunoglobulin determination revealed markedly raised IgG
immunoglobulin (3,000 g/dL). β-2 microglobulin was 3,815 ng/mL. Urinary examination for
Bence Jones’ proteins was positive. Bone marrow biopsy revealed a hypocellular marrow
with >75% plasma cells and reduced myeloid and erythroid cells. Thus, diagnosis of multiple
myeloma (MM) with lung plasmacytoma was made on the basis of plasma cell infiltration of
the bone marrow, the lytic bone lesions, the presence of monoclonal immunoglobulins in the
serum, and the myeloma plasma cells in the lung mass. The patient was planned to be referred
to the oncology department for chemotherapy but was not willing to undergo any form of
definitive treatment.
DISCUSSION
In multiple myeloma (MM), bone marrow is infiltrated with aggregates of abnormal
plasma cells and that leading to multifocal destructive bone lesions. Extramedullary
plasmacytoma accounts for about 3% of plasma cell malignancies and approximately 80%
of which is in the upper respiratory tract namely oronasopharynx and paranasal sinuses.
But association of MM with lung plasmacytoma is found to be extremely rare.
The most typical thoracic manifestations of MM are bony involvement of the thoracic
cage. While other manifestations are pneumonia, intraparenchymal mass lesions,
mediastinal lymphadenopathy, reticulonodular shadows, interstitial pattern, and intra
pulmonary calcification (details of manifestations are given in Table 1, as reported
by various authors). Despite advances in the diagnosis of MM, it remains an incurable
disease, because the disease follows a relapsing course in majority of patients, regardless
of the treatment regimen or initial response to treatment.
Newly diagnosed patients with good performance status are best treated with
autologous stem cell transplantation. These patients are treated with high dose chemo
therapy (HDCT) with vincristine, melphalan, cyclophosphamide, and prednisone
(VMCP) alternating with vincristine, carmustine, doxorubicin, and prednisone combined
with bone marrow transplantation. It improves the response rate, even free survival,
and overall survival in MM. Induction therapy in patients ineligible for transplantation
(old age, coexisting conditions, and poor physical condition) includes thalidomide in
combination with melphalan and prednisone or melphalan and prednisolone. Recently,
the management of patients with MM has been transformed by introduction of three novel
agents: Thalidomide, lenalidomide, and bortezomib.
The differential diagnoses of MM are metastatic carcinoma, lymphoma, bone
neoplasm, and chronic lymphocytic leukemia.
The prognosis of patients with pulmonary MM is poor. This contrasts with the reports
of long survival rates with primary pulmonary plasmacytomas of the lung.
Table 1: Comparative analysis of pulmonary manifestations in multiple myeloma by various author.
Shin et al. Weber et al. Koss et al. Duggal et al. Oymak et al. Damaj et al. Sullivan et al. Present case
Type Case report Case report Case report Case report Prospective study Prospective study Case report Case report
No. of 2 1 5 1 38 432 1 1
cases • Only 13 had lung • Only 11 had

manifestations lung mani
festations
Age/sex • 71/M 52/F • 4 males and 60/M • 25 males and • 8 males and 3 51/M 45/F
• 68/F 1 female 13 females female
• Ages 50–79 years • Ages 40–80 years • Ages 39–79
years
Chest • Mass Pulmonary • Hilar mass Homogenous • Pneumonia • Pleural Bilateral Mass lesion
radiology • Multiple calcification • Intraparenchymal opacity in • Interstitial involvement hilar lymph
nodule mass UZ+MZ of right shadows • Lung node + lung
lung and erosion • Mass lesions parenchyma nodule
of right sixth rib
• Multiple nodules
Multiple Myeloma with Lung Plasmacytoma 241
FURTHER READING
1. Prasad R, Verma SK Sodhi R. Multiple myeloma with lung plasmacytoma. Lung India. 2011;28:136-8.
2. Longo DL, Anderson KC. Plasma cell disorders. In: Kasper DL, Braunward E, Fauci AS, Hauser SL, Longo
DL, Jameson JL, (Eds). Harrison’s Principles of Internal Medicine, 16th edition. New York: McGraw-Hill;
2005. pp. 657-58.
3. Shih LY, Dunn P, Leung WM, Chen WJ, Wang PN. Localised plasmacytomas in Taiwan: Comparison
between extramedullary plasmacytoma and solitary plasmacytoma of bone. Br J Cancer.
1995;71:128-33.
4. Alexiou C, Kau RJ, Dietzfelbinger H, Kremer M, Spiess JC, Schratzenstaller B, et al. Extramedullary
plasmacytoma: Tumor occurrence and therapeutic concepts. Cancer. 1999;85:2305-14.
5. Sullivan PO, Muller NL. Pulmonary and nodal multiple myeloma mimicking lymphoma. Br J Radiol.
2006;79:e25-7.
6. Ramnik K, Duggal RK, Ramachandran KA. Multiple myeloma with extra medullary dissemination in
the lung. JIACM. 2002;3:93-5.
7. Shin MS. Diverse Roentgenographic manifestations of the rare pulmonary involvement in myeloma.
Chest. 1992;102:946-8.
8. Weber CK, Friedrich JM, Merkle E, Prummer O. Reversible metastatic pulmonary calcification in a
patient with multiple myeloma. Ann Hematol. 1996;72:329-32.
9. Koss MN, Hochholzer L, Moran CA, Frizzera G. Pulmonary plasmacytomas: A clinicopathologic and
immunohistochemical study of 5 cases. Ann Diagn Pathol. 1998;2:1-11.
10. Oymak FS, Karaman A, Soyuer I, Karaman H, Gülmez I, Demir R, et al. Pulmonary and chest wall
involvement in multiple myeloma. Tuberk Toraks. 2003;51:27-32 .
11. Damaj G, Mohty M, Vey N, Dincan E, Bouabdallah R, Faucher C, et al. Features of extramedullary
and extraosseous multiple myeloma: A report of 19 patients from a single center. Eur J Haematol.
2004;73:402-6.
12. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, et al. Antitumor activity of
thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565-71.
13. Richardson P, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of
bortezomaib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609-17.
14. Kushwaha RAS, Verma SK, Mehra S, Prasad R. Pulmonary and nodal multiple myeloma with a pleural
effusion mimicking bronchogenic carcinoma. J Cancer Res Ther. 2009;5:297-9.
CASE 65
Endobronchial Tuberculosis in a
30-year-old Female
CASE REPORT
This patient, nonsmoker, presented with cough with expectoration, fever, chest pain, and
loss of appetite for last 6 months. On general examination, patient was febrile with no
other positive findings and also there were no significant peripheral palpable lymph nodes.
On respiratory system examination, there was diminished air entry on the right infrascapular
area. Examination of abdomen was within normal limit. Chest X-ray posteroanterior (PA) view
showed obstructive pneumonitis in right middle and lower zone (Fig. 1). Contrast enhanced
computed tomography (CECT) thorax showed multiple medi astinal lymph nodes with
evidence of caseation (Figs. 2A and B) with consolidation in right lower lobe (Fig. 3). Fiberoptic
bronchoscopy showed two nodular growths one small and one large nodule in bronchus
intermedius (Figs. 4 and 5). Mucous membrane around nodules was hyperemic. Transbronchial
needle aspiration was done and caseous material came out which was positive for acid-fast bacilli
(Fig. 6). Patient was started with four antitubercular drugs (rifampicin, isoniazid, ethambutol,
and pyrazinamide for 3 months followed by rifampicin, isoniazid for next 9 months) and patient
responded clinically and radiologically to antitubercular drugs (Fig. 7).
FIG. 1: Obstructive pneumonitis right middle and

lower zone.
Endobronchial Tuberculosis in a 30-year-old Female 243
A B
FIGS. 2A AND B: Mediastinal lymphadenitis.
FIG. 3: Pneumonitis right lower lobe.
FIG. 4: Two nodular growths. (For color version, see

Plate 4)
FIG. 5: Close view of nodule. (For color version,

see Plate 5)
FIG. 6: Caseous material after transbronchial

needle aspiration. (For color version, see Plate 5)
FIG. 7: Chest X-ray after antitubercular drugs.
DISCUSSION
CASE 66
Endobronchial Tuberculosis in a
26-year-old female
CASE REPORT
This patient, nonsmoker, known diabetic presented with cough, high fever, and chest pain
for last 15 days. On clinical examination, she was febrile. Examination of the respiratory
system showed evidence of consolidation. Chest X-ray showed evidence of consolidation
in the right upper zone (Fig. 1). Her sputum was repeatedly negative for acid-fast bacillus.
She was prescribed antibiotics for 10 days without any response (Fig. 2) contrast enhance CT
thorax showed mass lesion with central necrosis (Fig. 3). Fiberoptic bronchoscopy showed
edematous and hyperemic tertiary carina near posterior segment of right upper lobe (Fig. 4).
Lumen of the same segment was also reduced. Bronchial aspirate from same segment was
positive for acid-fast bacillus. Patient was given oral hypoglycemic drugs and antitubercular
treatment to which she responded well clinically as well as radiologically.
FIG. 1: Pneumonia right.

FIG. 2: No response after antibiotics.
FIG. 3: Edematous and hyperemic tertiary carina.
FIG. 4: Mass-like lesion with central necrosis.

DISCUSSION
CASE 67
Endobronchial Tuberculosis
in a 44-year-old Female
Presenting as Hemoptysis
CASE REPORT
This patient, nonsmoker, presented with cough, and hemoptysis for last 3 months. On general
examination, there was no significant finding. Examination of the respiratory system revealed
crepitations in the right infraclavicular area. Chest X-ray showed a homogenous shadow in
the paratracheal area of the right upper zone (Figs. 1 and 2). CECT thorax showed triangular
opacity with irregular caseation (Fig. 3). Sputum smear was repeatedly negative for acid-fast
bacilli. Fiberoptic bronchoscopy showed edematous and hyperemic secondary carina near
right upper lobe bronchus which was filled with necrotic material and blood (Fig. 4). Bronchial
aspirate and brush biopsy was positive for AFB and endobronchial biopsy from right upper
lobe was consistent with histology of tuberculosis. She responded clinically and radiologically
with antitubercular drugs.
FIG. 1: Homogenous radio opaque shadow in right

paratracheal area.
FIG. 2: Mass-like shadow in right upper lobe.
FIG. 3: Triangular opacity with irregular caseation.
FIG. 4: Right upper lobe bronchus obstructed

by caseous material and blood. (For color version,
see Plate 6)
DISCUSSION
CASE 68
Endobronchial Tuberculosis
in a 44-year-old Male Presenting as
Recurrent Hemoptysis
CASE REPORT
A 44-year-old male, a bidi smoker 10/day for 20 years presented with cough and recurrent
hemoptysis for last 2 months. General and respiratory system examination was within
normal limits. Chest X-ray was within normal limits (Fig. 1). CT thorax showed consolidation
in left posterior segment (Fig. 2). Sputum smear was repeatedly negative for acid-fast
bacilli. Fiberoptic bronchoscopy (FOB) showed blood clots in left main bronchus. Left lower
lobe bronchial mucous membrane was hyperemic and hypertrophied (Fig. 3). There was a
pit-like ulcer in anteromedial wall of left lower lobe bronchus (Pit and basket-like appearance)
(Fig. 4). Bronchial aspirate was positive for acid-fast bacilli. Endobronchial biopsy from pit-like
ulcer was consistent with histology of tuberculosis. Patient was treated with antituberculosis
drug. FOB could not be repeated as patient was lost to follow-up.
FIG. 1: Normal looking X-ray.

FIG. 2: Consolidation in left posterior segment.
FIG. 3: Hypertrophied and hyperemic mucous

membrane with pit like ulcer. (For color version,
see Plate 6)
FIG. 4: Pit and basket like appearance. (For color

DISCUSSION
CASE 69
A Rare Case of Tuberculous

Endobronchial Sinus
CASE REPORT
A 21-year-old male, nonsmoker presented with fever, dry cough, loss of appetite, and dysphasia
for last 2 months. General physical examination showed pallor. Respiratory examination was
within normal limits. Chest X-ray posteroanterior (PA) view showed mediastinal widening
(Fig. 1). Computed tomography (CT) thorax showed large heterogeneous mass in right
paratracheal and retrotracheal areas (Figs. 2A to C). Fiberoptic bronchoscopy showed bulging
of posterior wall of lower end of trachea near main carina (Fig. 3). There are three sinuses with
blackish margins and with surrounding hyperemia just behind the secondary carina near the
upper lobe bronchus (Figs. 4 and 5). Endobronchial biopsy from the sinuses showed histology
of tuberculosis (Fig. 6).

showing mediastinal widening.
A B
FIGS. 2A TO C: Computed tomography (CT)

thorax showing large heterogeneous mass in
C right paratracheal and retrotracheal areas.
FIG. 3: Fiberoptic bronchoscopy showing bulging

of posterior wall of lower end of trachea. (For color
A Rare Case of Tuberculous Endobronchial Sinus 253
FIG. 4: Fiberoptic bronchoscopy showing tuber

culous sinus. (For color version, see Plate 7)

culous sinus just behind secondary carina.
FIG. 6: Bleeding after endobronchial biopsy. (For

color version, see Plate 8)
DISCUSSION
Endobronchial tuberculosis (EBTB) is defined as a tuberculous infection of the
tracheobronchial tree with microbial and histopathological evidence, with or without
parenchymal involvement. It was shown that it is more common in young woman than
male. Five potential mechanisms were believed to be responsible for the development
of endobronchial infections caused by Mycobacterium tuberculosis: (1) direct invasion
from an adjacent parenchymal focus; (2) implantation of the organisms from infected
sputum; (3) hematogenous spread; (4) erosion of a lymph node inside a bronchus; and
(5) lymphatic drainage from the parenchyma toward the peribronchial region. Since
bronchoscopy is not routinely performed to all patients with pulmonary tuberculosis,
actual incidence of EBTB could not be evaluated. EBTB may mimic diseases such as
bronchial asthma, pneumonia, and lung cancer. EBTB may affect any region of the
tracheobronchial tree. If it affects the middle lobe, it causes collapse, since the entry of
the middle lobe is narrow. This is known as middle lobe syndrome. In elderly patients,
lobar and segmental bronchial invasion were more common whereas in younger patients
involvement of trachea and main bronchi were seen generally and middle lobe syndrome
was more common in elderly. Chung classified forms of EBTB into seven subtypes
by bronchoscopic finding: Actively caseating, edematous-hyperemic, fibrostenotic,
tumorous, granular, ulcerative, and nonspecific bronchitic.
Classical symptoms of EBTB are cough, difficultly expectorated high viscous sputum,
wheezing, fever, chest pain, and hemoptysis. Endobronchial tuberculosis is a severe
situation with high bacilli load and may cause complications with high morbidity such
as bronchial stenosis; early diagnosis and treatment is therefore, mandatory. EBTB
contains rather high amounts of tuberculosis bacilli. Unlike parenchymal diseases, acid-
fast bacilli (AFB) positivity in EBTB is between 16 and 53.3% in most favorable conditions.
Radiological findings of EBTB may vary; different findings such as patchy alveolar
infiltrations, atelectasis, hilar widening, pleural effusion, mass, and cavitary lesions may
be seen.
Bronchoscopy should be performed in suspicious cases such as unexplained
cough, wheezing, dyspnea or hemoptysis. Persistent segmental or lobar collapse, lobar
infiltrations, and obstructive pneumonia findings on chest X-ray examination are also
indications for bronchoscopy. Sputum or bronchial lavage AFB is generally positive in
active caseous type but edematous type is hard to diagnose, and sputum and bronchial
lavage AFB is generally negative; therefore, tuberculosis culture and histopathological
examinations should be performed.
Corticosteroids have been used empirically in the treatment of tuberculosis in an
attempt to prevent fibrosis. However, the value of using corticosteroids for EBTB is
uncertain. Though literature reporting that steroid addition did not help with improve
ment or clinical healing there are literature arguing that oral or inhaled steroids effect
improvement and clinical healing positively in some types of EBTB. Corticosteroids
are likely to be beneficial in earlier stages when hypersensitivity is the predominant
mechanism, but are unlikely to be helpful in more advanced cases when extensive
fibrosis is present. Close follow-up is advisable as stenosis may develop later despite
antituberculosis chemotherapy with or without corticosteroids.
A Rare Case of Tuberculous Endobronchial Sinus 255
FURTHER READING
1. Hoheisel G, Chan B, Chan CH, Chan KS, Teschler H, Costabel U. Endobronchial tuberculosis: diagnostic
features and therapeutic outcome. Respir Med. 1994;88:593-7.
2. Rikimaru T. Endobronchial tuberculosis. Expert Rev Anti Infect Ther. 2004;2:245-51.
3. Chung HS, Lee JH. Bronchoscopic assessment of the evolution of endobronchial tuberculosis. Chest.
2000;117:385-92.
4. Starke JR. Tuberculosis. In: Katz SL, Hotez PJ, Gershon AA, Krugman S (Eds). Krugman’s Infectious
Diseases of Children, 10th edition. St. Louis: Mosby-Year Book Inc.; 1998. pp. 571-604.
5. Kashyap S, Mohapatra PR, Saini V. Endobronchial tuberculosis. Indian J Chest Dis Allied Sci.
2003;45:247-56.
6. An JY, Lee JE, Park HW, Lee JH, Yang SA, Jung SS, et al. Clinical and bronchoscopic features in
endobronchial tuberculosis. Tuberc Respir Dis. 2006;60:532-9.
7. Kurasawa T, Kuze F, Kawai M, Amitani R, Murayama T, Tanaka E, et al. Diagnosis and management of
endobronchial tuberculosis. Intern Med. 1992;31:593-8.
8. Williams DJ, York EL, Nobert EJ, Sproule BJ. Endobronchial tuberculosis presenting as asthma. Chest.
1988;93:836-8.
9. Matthews JI, Matarese SL, Carpenter JL. Endobronchial tuberculosis simulating lung cancer. Chest.
1984;86:642-4.
10. Gupta PP, Gupta KB, Agarwal D. Middle lobe syndrome due to tuberculous etiology: a series of
12 cases. Indian J Tuberc. 2006;53:104-8.
11. Chung HS, Lee JH, Han SK, Shim YS, Kim KY, Han YH, et al. Classification of endobronchial tuberculosis
by the bronchoscopic features. Tuberc Respir Dis. 1991;38:108-15.
12. Um SW, Yoon YS, Lee SM, Yim JJ, Yoo CG, Chung HS, et al. Predictors of persistent airway stenosis in
patients with endobronchial tuberculosis. Int J Tuberc Lung Dis. 2008;12:57-62.
13. Yanardag H, Tetikkurt C, Tetikkurt S, Demirci S, Karayel T. Computed tomography and bronchoscopy
in endobronchial tuberculosis. Can Respir J. 2003;10:445-8.
14. Park EJ, Kim MO, Yang SC, Sohn JW, Yoon HJ, Shin DH, et al. Clinical and bronchoscopic features of
280 patients with endobronchial tuberculosis (1990-2001). Korean J Med. 2003;64:284-92.
15. Kim HJ, Kim HS, Ma JE, Lee SJ, Ham HS, Cho YJ, et al. Clinical characteristics of endobronchial
tuberculosis that develops in patients over 70 years of age. Tuberc Respir Dis. 2007;63:412-16.
16. Kim HC, Kim HS, Lee SJ, Jeong YY, Jeon KN, Lee JD, et al. Endobronchial tuberculosis presenting as
right middle lobe syndrome: clinical characteristics and bronchoscopic findings in 22 cases. Yonsei
Med J. 2008;49:615-9.
17. Qingliang X, Jianxin W. Investigation of endobronchial tuberculosis diagnoses in 22 cases. Eur J Med
Res. 2010;15:309-13.
CASE 70
Endobronchial Polyp Presenting with

CASE REPORT
A 25-year-old female patient, presented with recurrent cough with expectoration and hemo
ptysis for last 10 years. General physical examination was within normal limits. Respiratory
examination revealed normal vesicular breath sounds. Chest X-ray showed collapse of right
middle and lower lobe (Fig. 1). She was given antitubercular drugs for many courses without
any response. Fiberoptic bronchoscopy showed pedunculated polyp obstructing bronchus
intermedius freely moving with respiration (Figs. 2 and 3). Pus was also seen around polyp.
Whole polyp was removed with the help of rigid bronchoscope in two sittings (Fig. 4)
histology which was suggestive of myxomatous polyp.
After 8 months of removal, polyp recurred (Fig. 5) and patient was then advised for surgery
but she was lost to follow-up.
FIG. 1: Collapse of right middle and lower lobe.

Endobronchial Polyp Presenting with Recurrent Hemoptysis 257
A B
FIGS. 2 A AND B: Endobronchial polyp during expiration. (For color version, see Plate 8)
FIG. 3: Endobronchial polyp during inspiration.

FIG. 4: Polyp was removed endobronchially by rigid

bronchoscope in two sittings. (For color version, see
Plate 9)
FIG. 5: Recurrence of endobronchial polyp after

7 months of treatment. (For color version, see Plate 9)
DISCUSSION
Benign fibroepithelial endobronchial polyps are rare among all benign endobronchial
lesions and comprise <2% of all pulmonary tumors. Fibroepithelial polyps are common
benign lesions involving the skin, uterus, ureter, and neck; however, it is rare in the
tracheobronchial tree with very few cases reported in the literature. The etiology is unclear,
but it was thought to be due to inflammation or infection, especially among smokers and
in patients with asthma or chronic obstructive pulmonary disease.
It may be asymptomatic but may present with a myriad of symptoms including
shortness of breath, monophonic wheezing, cough, dyspnea, and hemoptysis or
obstructing features such as recurrent pneumonia and atelectasis.
Histologically, the polyp consists of a lining of squamous epithelium or bronchial
mucosa with a fibrovascular stroma with some inflammatory cells. This histologic
finding can be confused with solitary papilloma of the airways, mostly affecting the
vocal cords and trachea. Squamous papilloma demonstrates papillary architecture with
proliferation of well-differentiated squamous epithelium with associated keratinized
debris covering a connective tissue stalk, although majority are positive for human
papilloma virus.
There is no consensus on the best modality for diagnosis and treatment of fibroepi
thelial polyps. Over the last decade, improved bronchoscopic skills and technology
have aided in avoiding surgery. Removal of the polyp with electrocautery snare not
only helps in the diagnosis but also serves as a superior treatment modality with or
without argon plasma coagulation and laser treatment of the base of the polyp. Recurrence
is rare.
Endobronchial Polyp Presenting with Recurrent Hemoptysis 259
FURTHER READING
1. Tedeschi LG, Libertini R, Conte B. Endobronchial polyp. Chest. 1973;63:110-2.
2. Ushiki A, Yasou M, Tanabe T, Urushihata K, Yamamoto H, Hanaoka M, et al. A rare case of a tracheal
polyp treated with endobronchial resection. Intern Med. 2008;47:1723-6.
3. Dinçer I, Demir A, Akin H, Melek H, Altin S. A giant inflammatory polyp. Ann Thorac Surg.
2005;80:2353-6.
4. Rowalds DT Jr. Fibroepithelial polyps of the bronchus. Dis Chest. 1960;37:199-202.
5. Gurung P, Paoletti L, Doelken P, Melek H, Altin S. Endobronchial fibroepithelial polyp treated by
endobronchial resection. Chest. 2010;138:1378.
6. Amin PB, Baciewicz F. Benign fibroepithelial polyp arising in the bronchus: A case report and review
of the literature. Arch Surg. 2009;144:1081-3.
7. Leiro-Fernandez V, Iglesias-Rio F, Botana-Rial M. Endobronchial fibroepithelial polyp. J Bronchol
Intervent Pulmonol. 2010;17:56-8.
CASE 71
Carcinoid Tumor Presenting with

CASE REPORT
A 26-year-old male, bidi smoker 5 bidi per day for last 6 years presented with cough, fever,
hemoptysis for last 1 year and was misdiagnosed as tuberculosis and was given antitubercular
drugs for 1 year without any response. General examination revealed pallor. Respiratory
system examination revealed diminished breath sounds on left side. Chest X-ray showed
volume reduction on left side (Fig. 1). Computed tomography (CT) thorax revealed a shadow
in left main bronchus (Fig. 2). Fiberoptic bronchoscopy showed a polypoidal growth in left
main bronchus (Fig. 3). Growth was removed with the help of rigid bronchoscope (Fig. 4).
Biopsy of a growth revealed carcinoid tumor.
FIG. 1: Apparently normal X-ray with volume reduc

tion on left side.
Carcinoid Tumor Presenting with Recurrent Hemoptysis 261
FIG. 2: Shadow seen in left main bronchus.
FIG. 3: Fiberoptic bronchoscopy showing multi

lobular tumor in left main bronchus. (For color
FIG. 4: Tumor taken out through rigid bronchoscope.

DISCUSSION
CASE 72
Bronchial Carcinoid Presenting as

Recurrent Massive Hemotysis
CASE REPORT
A 22-year-old female patient, presented with recurrent fever, cough with expectoration and
moderate to massive hemoptysis for last 12 years, and was misdiagnosed as pulmonary
tuberculosis by many doctors and had received many courses of antitubercular drugs
without any response. General examination was within normal limits. Respiratory examination
showed decreased breath sound on right side. Chest X-ray showed evidence of right lower
lobe collapse (Fig. 1) which has progressed to collapse of whole right lung (Figs. 2A to C).
Computed tomography (CT) thorax showed heterogeneous enhancing soft tissue mass in
right lung (Figs. 3A and B). Fiberoptic bronchoscopy showed a tumor obstructing right main
bronchus (Fig. 4). Endobronchial biopsy showed bronchial carcinoid.
FIG. 1: Radio-opaque shadow with volume reduction

on right side with collapse of right lower lobe.
Bronchial Carcinoid Presenting as Recurrent Massive Hemotysis 263
A B
C FIGS. 2A TO C: Collapse right lung.
A B
FIGS. 3A AND B: Computed tomography (CT) thorax showing heterogeneous enhancing soft
tissue mass in right lung.
FIG. 4: Tumor obstructing right main bronchus

with distortion of main carina. (For color version, see
Plate 10)
DISCUSSION
Bronchial carcinoids are rare (1 to 2% of all lung cancers in adults), slow-growing
neuroendocrine tumors arising from bronchial mucosa; they affect patients in their
40s to 60s. Carcinoid lung tumors represent the most indolent form of a spectrum of
bronchopulmonary neuroendocrine tumors (NETs) that includes small cell carcinoma of
the lung as its most malignant member, as well as several other forms of intermediately
aggressive tumors, such as atypical carcinoid. Typical carcinoid tumors of the lung
represent the most well differentiated and least biologically aggressive type of pulmonary
NET. These tumors characteristically grow slowly and tend to metastasize infrequently.
However, atypical carcinoid tumors have a more aggressive histologic and clinical picture.
They metastasize at a considerably higher rate and carry a worse prognosis.
Most patients are asymptomatic but some patients present with symptoms of airway
obstruction, including dyspnea, wheezing, and cough. Recurrent pneumonia, hemoptysis,
and chest pain are also common. Paraneoplastic syndromes, including Cushing syndrome
due to ectopic ACTH, acromegaly due to ectopic growth hormone–releasing factor, and
Zollinger–Ellison syndrome due to ectopic gastrin production, are more common than
carcinoid syndrome, which occurs in <3% of patients with the tumor. Carcinoid syndrome
symptoms includes flushing, diarrhea, and bronchospasm. Chronic sequelae of carcinoid
syndrome include telangiectasias, right-sided valvular heart disease, and retroperitoneal
fibrosis.
Diagnosis of bronchial carcinoid is based on bronchoscopic biopsy, but its evaluation
involves chest CT, which reveals tumor calcifications in up to one-third of patients.
Indium-111–labeled octreotide scans are useful for determining regional and metastatic
spread. Increased urinary serotonin and 5-hydroxyindoleacetic acid levels support the
diagnosis, but in most cases these substances are not commonly elevated.
Treatment of bronchial carcinoid is with surgical removal with or without adjuvant
chemotherapy and/or radiation therapy and its prognosis depends on tumor type.
Somatostatin analogs like octreotide (sandostatin) or lanreotide (somatuline) can
Bronchial Carcinoid Presenting as Recurrent Massive Hemotysis 265
be helpful for patients who have carcinoid syndrome or whose tumors can be seen on
somatostatin receptor scintigraphy (octreoscan). Chemo and targeted therapy are also
options. In general, typical carcinoids tend to grow slowly, and chemotherapy is often not
very successful. Five-year survival for well-differentiated carcinoids is >90%; for atypical
tumors, it is 50 to 70%.
FURTHER READING
1. Hindié E. The NETPET Score: Combining FDG and Somatostatin receptor imaging for optimal
management of patients with metastatic well-differentiated neuroendocrine tumors. Theranostics.
2017;7:1159-63.
2. Han B, Sun JM, Ahn JS, Park K, Ahn MJ. Clinical outcomes of atypical carcinoid tumors of the lung and
thymus: 7-year experience of a rare malignancy at single institute. Med Oncol. 2013;30:479.
3. Ha SY, Lee JJ, Cho J, Hyeon J, Han J, Kim HK. Lung parenchymal invasion in pulmonary carcinoid
tumor: an important histologic feature suggesting the diagnosis of atypical carcinoid and poor
prognosis. Lung Cancer. 2013;80:146-52.
4. Zhong CX, Yao F, Zhao H, Shi JX, Fan LM. Long-term outcomes of surgical treatment for pulmonary
carcinoid tumors: 20 years' experience with 131 patients. Chin Med J (Engl). 2012;125:3022-6.
5. Cao C, Yan TD, Kennedy C, Hendel N, Bannon PG, McCaughan BC. Bronchopulmonary carcinoid
tumors: long-term outcomes after resection. Ann Thorac Surg. 2011;91:339-43.
6. Esfahani AF, Chavoshi M, Noorani MH, Saghari M, Eftekhari M, Beiki D, et al. Successful application
of technetium-99m-labeled octreotide acetate scintigraphy in the detection of ectopic adreno
corticotropin-producing bronchial carcinoid lung tumor: a case report. J Med Case Reports.
2010;4:323.
7. Phan AT, Oberg K, Choi J, Harrison LH Jr, Hassan MM, Strosberg JR, et al. NANETS consensus guideline
for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine
tumors of the thorax (includes lung and thymus). Pancreas. 2010;39:784-98.
8. Chong S, Lee KS, Chung MJ. Neuroendocrine tumors of the lung: clinical, pathologic, and imaging
findings. Radiographics. 2006;26:41-57.
9. Hubalewska-Dydejczyk A, Fröss-Baron K, Mikołajczak R, Maecke HR, Huszno B, Pach D, et al. 99mTc-
EDDA/HYNIC-octreotate scintigraphy, an efficient method for the detection and staging of carcinoid
tumours: results of 3 years' experience. Eur J Nucl Med Mol Imaging. 2006;33:1123-33.
10. Chughtai TS, Morin JE, Sheiner NM, Wilson JA, Mulder DS. Bronchial carcinoid—twenty years'
experience defines a selective surgical approach. Surgery. 1997;122:801-8.
11. Ducrocq X, Thomas P, Massard G. Operative risk and prognostic factors of typical bronchial carcinoid
tumors. Ann Thorac Surg. 1998;65:1410-4.
12. Rusch VW, Klimstra DS, Venkatraman ES. Molecular markers help characterize neuroendocrine lung
tumors. Ann Thorac Surg. 1996;62:798-810.
CASE 73
Tuberculous Lympho Tracheal Fistula
CASE REPORT
A 30-year-old nonsmoker male and a known case of diabetes mellitus which was not
properly controlled for last 6 years, presented with dry cough, fever, breathlessness, and loss
of appetite for last 3 months. There was no history of any steroid use or instrumentation in
the past. General examination was normal. Chest X-ray had shown no obvious abnormality
(Fig. 1). CT thorax showed multiple caseating mediastinal lymph nodes (Fig. 2). There was
an additional opening between right and left main bronchus which was inconclusive
(Fig. 3). Fiberoptic bronchoscopy showed fistula at lower end of trachea surrounded by
granulation tissue just before the main carina. Endobronchial biopsy from granulation
tissue showed histology of tuberculosis (Fig. 4). He was given antitubercular drugs for
9 months (HRZE for 2 months) with strict glycemic control on insulin therapy. Patient
improved clinically and radiologically after 11 weeks of treatment. Mediastinal lymph
nodes disappeared at the end of treatment and fistula also healed in the 11 weeks duration
(Figs. 5 to 8). Patient was called for regular follow-up after stopping antitubercular drug and
was asymptomatic. He was strictly advised for effective control of diabetes.
FIG. 1: Chest X-ray with no significant abnormality.

Tuberculous Lympho Tracheal Fistula 267
FIG. 2: Fiberoptic bronchoscopy showing multiple

caseating mediastinal lymph nodes with irregular
tracheal outline.
FIG. 3: Fiberoptic bronchoscopy showing fistulous

track.
FIG. 4: Fiberoptic bronchoscopy showing tracheal

fistula surrounded with granulation tissue. (For
FIG. 5: Chest X-ray after antitubercular treatment (ATT).
FIG. 6: No mediastinal gland.
FIG. 7: Fistula closed.

Tuberculous Lympho Tracheal Fistula 269
FIG. 8: Fiberoptic bronchoscopy showing closure of

fistula. (For color version, see Plate 11)
DISCUSSION
Mycobacterium tuberculosis (MTB) affects lymph nodes of any location, but often
the intrathoracic lymph nodes. Tracheal manifestations of MTB are rare and there
are fewer documented reports. This type of fistula often develops in association with
lymphoma. Tracheo mediastinal tuberculosis can present with or without the evidence
of parenchymal disease on imaging. The course of disease is unpredictable but delay
in medical therapy can increase the risk of further complications. The most common
manifestations are mediastinal lymphadenopathy and tracheal fistula both of which were
seen in this patient. Such patients may be effectively treated with antitubercular therapy
for 6–9 months. Surgery may be necessary in cases of fistula such as stenting, stuffed
prosthesis, myocutaneous flaps, etc. Early diagnosis and treatment is often missed due
to its varied clinical presentation. In this case, patient was experiencing breathlessness
without any parenchymal involvement which raised suspicion. Fiberoptic bronchoscopy
(FOB) showed tracheal fistula and biopsy revealed tubercular etiology. Medical treatment
was initiated and his symptoms subsided in 11 weeks period. Interventional bronchoscopy
approaches should be considered to restore airway patency. Incidence of healing may vary
depending on severity of fistula and time of accurate diagnosis and treatment.
FURTHER READING
1. Pathak V, Shepherd RW, Shojaee S. Tracheobronchial tuberculosis. J Thorac Dis. 2016;8:3818-25.
2. Desai P, Mayenkar P, Northup. TF, Mallela V. Bronchoesophageal fistula due to esophageal
tuberculosis. Case Rep Infect Dis. 2019;2019:6537437.
3. Gomes J, Antunes A, Carvalho A, Duarte R. Dysphagia as a manifestation of esophageal tuberculosis:
a report of two cases. J Med Case Rep. 2011;5:447.
4. Devarbhavi HC, Alvares JF, Radhikadevi M. Esophageal tuberculosis associated with esophagotra
cheal or esophagomediastinal fistula: Report of 10 cases. Gastrointest Endosc. 2003;57:588-92.
5. Macchiarini P. Delamare N, Beuzeboc P, Labussière AS, Cerrina J, Dulmet E, et al. Tracheoesophageal
fistula caused by mycobacteria tuberculosis adenopathy. Ann Thorac Surg. 1993;55:1561-3.
6. Narayanan S, Shiju PV, Majeed KA, Udayabhaskaran V. Tuberculosis presenting as bronchoesopha

geal fistula. IDCases. 2017;8:19-21.
7. Lee JH, Shin DH, Kand KW, Park SS, Lee DH. The medical treatment of a tuberculous tracheo-
oesophageal fistula. Tuber Lung Dis. 1992;73:177-9.
8. Hutchin P, Lindskog GE. Acquired esophagobronchial fistula of infectious origin. J Thorac Cardiovasc
Surg. 1964;48:1-12.
9. Porter JC, Friedland JS, Freedom AR. Tuberculous bronchoesophageal fistulae in patients with the
human immunodeficiency virus: three case report and review. Clin Infect Dis. 1994;19:954-7.
CASE 74
Ruptured Hydatid Cyst Presenting

as Recurrent Hemoptysis
CASE REPORT
A 31-year-old male patient, nonsmoker presented with complaints of recurrent hemoptysis
(mild-to-moderate) for 2 years off and on, fever (low grade) off and on since 2 years, cough with
expectoration off and on for 2 years, chest pain right sided of and on since one and half year.
General examination was within normal limits. Respiratory systemic examination showed
decreased air entry right lower zone. Chest X-ray showed right lower zone heterogeneous opacity
(Fig. 1). In the past history, patient was misdiagnosed as a case of pulmonary TB and was started
on antitubercular therapy for 1 year for which no symptomatic or radiological improvement was
reported. After looking at the chest X-ray, High-resolution computed tomography (HRCT) thorax
was advised which was inconclusive of the diagnosis (Fig. 2). Patient was then planned for
bronchoscopy, which showed a whitish material in the anterior, lateral, and basal segments of
right lower lobe (Figs. 3 to 5). Bronchial aspiration was done and whitish membranous structure
was aspirated which was suggestive of ruptured hydatid cyst (Fig. 6). On the review of previous
chest X-rays and CT thorax, there was a rounded opacity cystic in nature in right lower zone
(Figs. 7 to 12). Patient was then advised for right lower lobe lobectomy in which histopathology
confirmed the diagnosis of ruptured hydatid cyst.

hetrogenous radio opaque shadow.
FIG. 2: CT thorax showing hetrogenous opacity right

lower lobe.
FIG. 3: Fiberoptic bronchocopy showing whitish

material obstructing the right lower lobe bronchus.
FIG. 4: Fiberoptic bronchoscopy showing whitish

material in lower lobe bronchus on right side. (For
Ruptured Hydatid Cyst Presenting as Recurrent Hemoptysis 273

material in lower lobe bronchus on right side (closed
view). (For color version, see Plate 11)
FIG. 6: Whitish membranous material was aspirated

through fiberoptic bronchoscopy.

rounded opacity in right lower zone.

cystic lesion possibly after rupture of hydatid cyst.
FIG. 9: CT thorax showing cystic lesion in right lower lobe.
FIG. 10: CT thorax showing cystic lesion in right

lower lobe.
Ruptured Hydatid Cyst Presenting as Recurrent Hemoptysis 275

rounded shadow in right lower zone.
FIG. 12: CT thorax showing rounded shadow with

cystic appearance in the right lower zone.
DISCUSSION
Hydatid disease is created by metacestode of the larval stage of tapeworm Echinococcus
granulosus. It is characterized by cyst formation in various organs. It is a disease with
worldwide distribution, but most commonly found in several Mediterranean countries,
e.g., New Zealand, Australia, North America, South America, Asia. Liver is the most
common site followed by lungs. Initially the growth is asymptomatic until symptoms
caused by cyst’s space occupying mass effect, mechanical obstruction, rupture or allergic
reactions. Diagnosis of ruptured hydatid cyst is difficult and can be misdiagnosed as
pneumonia, TB, lung abscess, tumor or pneumothorax.
Pulmonary hydatid cyst is most commonly seen in lower lobe of right lung and
is usually solitary. These cysts may initially be asymptomatic and may be diagnosed
incidentally during radiological evaluation for other reasons. On the other hand, hydatid
cyst may be present with chest pain, dyspnea, hemoptysis, and fever. The treatment of
ruptured hydatid cyst is principally surgical; albendazole is given as a compliment to

surgical treatment to avoid recurrence.
Pulmonary hydatid cysts rupture in about one-third of the patient releasing a highly
antigenic fluid in the bronchus which can cause secondary hydatid spread, asphyxia,
anaphylactic shock, hemoptysis, and circulatory collapse. Liver is the most affected organ
followed by lungs.
However, in our case the patient presented with recurrent hemoptysis and was
misdiagnosed as tuberculosis and was started on antitubercular therapy. Diagnosis
was not confirmed by CT scan so the bronchoscopy was performed, which showed
whitish material in the anterior, lateral, and basal segment of right lower lobe. Bronchial
aspiration of whitish membranous structure was done which was suggestive of
ruptured hydatid cyst. Right lower lobe lobectomy confirmed the diagnosis of ruptured
hydatid cyst.
FURTHER READING
1. Bchir A, Hamdi A, Jemni L, Dazza MC, Allegue M, Braham MS, et al. Serological screening for
hydatidosis in households of surgical cases in central Tunisia. Ann Trop Med Parasitol. 1988;82:
271-3.
2. Zhang Q, Huang TM, Li BZ, Li ZL, Liao KX. Misdiagnosis of pulmonary hydatid cyst rupture: report of
38 cases. Zhonghua Jie He He Hu Xi Za Zhi. 2003;26:4746.
3. Kuzucu A, Soysal O, Ozgel M, Yologlu S. Complicated hydatid cysts of the lung: clinical and therapeutic
issues. Ann Thorac Surg. 2004;77:1200-4.
4. Shameem M, Akhtar J, Bhargava R, Ahmed Z, Khan NA, Baneen U. Respiratory Care. 2011;56:863-5.
5. Kaur M, Singh R. Ruptured pulmonary hydatid cyst: The camalote sign. Indian J Clin Practice.
2013;23:856-8.
6. Karimi M, Rostami A, Spotin A, Rouhani S. Ruptured pulmonary hydatid cyst: a case report. J Paracet
Dis. 2017;41:899-902.
7. Basvana GH, Siddesh G, Jayaraj BS, Krishnan MG. A ruptured hydatid cyst of the lung. JAPI.
2007;55:141-45.
8. Rai SP, Panda BN, Ganguly D, Bharadwaj R. Pulmonary hydatid diagnosis and response to hypertonic
saline irrigation and albendazole. Med J Arm Forces India. 2005:61:9-12.
9. Aytac A. Yurdakul Y, Ikizler C, Olga R, Saylam A. Pulmonary hydatid disease: Report of 100 patients.
Ann Thorac Surg. 1977:23:145-51.
10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13:125-33.
CASE 75
A Case of Squamous Cell Carcinoma

Presenting with Cavitation
CASE REPORT
A 53-year-old male, nonsmoker presented with cough with expectoration, fever, and loss of
appetite and weight loss for last 6 months. Patient was prescribed by a private practitioner
anti-TB drugs along with antibiotics for 2 months without any response. General physical
examination was within normal limits. Respiratory examination revealed crepts in right upper
zone. Chest X-ray showed mass-like lesion with cavitation in right upper zone (Figs. 1 and 2).
CT thorax showed mass with cavitation in right upper lobe (Fig. 3). Fiberoptic bronchoscopy
showed tumor obstructing right upper lobe bronchus (Fig. 4). Endobronchial biopsy proved
to be squamous cell carcinoma.
FIG. 1: Rounded opacity in right lung.

FIG. 2: Mass increased in size with cavitation.
FIG. 3: Heterogeneous mass with big area of

necrosis in right lung.
FIG. 4: Tumor obstructing right upper lobe

bronchus. (For color version, see Plate 12)
DISCUSSION
CASE 76
Squamous Cell Carcinoma Presenting with

Cavitating Mass in a Patient of
CASE REPORT
This 65-year-old male patient, bidi smoker 30 bidi per day for 25 years, a known case of
chronic obstructive pulmonary disease for last 5 years presented with hemoptysis. General
physical examination revealed pallor. Respiratory examination revealed harsh vesicular
breath sounds with crepts in right lung. Chest X-ray showed cavity in the right paratracheal
area (Fig. 1). Sputum smear for AFB was negative. Keeping hemoptysis as a symptom and
cavity in the chest X-ray, he was misdiagnosed as sputum negative pulmonary tuberculosis
and was prescribed antitubercular drugs for 6 months ignoring the characteristic computed
tomography (CT) picture of malignant cavity (eccentric and irregular inner wall) without any
response (Figs. 2 and 3). CT thorax done after 6 months showed apart from thick wall cavity
multiple nodules in the opposite lung (Fig. 4). Fiberoptic bronchoscopy showed multinodular
tumor in right main bronchus near main carina (Fig. 5). Endobronchial and brush biopsy
was done and there was bleeding after endobronchial biopsy (Fig. 6). Endobroncial biopsy
showed squamous cell carcinoma.
FIG. 1: Chest X-ray posteroanterior (PA)

view showing cavity in right paratracheal
area.

showing malignant cavity.
FIG. 3: Chest X-ray showing cavity in right para

tracheal area.

showing malignant cavity with multiple nodules in
opposite lung.
Squamous Cell Carcinoma Presenting with Cavitating Mass... 281

nodular tumor. (For color version, see Plate 12)

DISCUSSION
CASE 77
Squamous Cell Carcinoma

Presenting as Lung Abscess
CASE REPORT
A 65-year-old male, bidi smoker 15 bidi per day for 20 years had recurrent streaking for
1 year and ignored it. Two months back he developed cough with moderate amount of
yellow-colored sputum with fever. General physical examination was within normal limits
except for the presence of pallor. Respiratory examination revealed coarse crepts on right
side. Chest X-ray showed radio opaque shadow in right middle and lower zone with volume
reduction (Fig. 1). CT thorax showed abscess in right lower lung with obliteration of right
main bronchus with enlarged paratracheal lymph node (Figs. 2 to 4). Multiple nodular
lesions, some of them cavitating, were seen in both lungs (Fig. 5). Small metastatic deposits
were also seen in right lobe of liver (Fig. 6). Fiberoptic bronchoscopy showed main carina
infiltrated with tumor. Secondary carina between right upper lobe bronchus and bronchus
intermedius was wide and infiltrated (Fig. 7). All the segmental openings of right upper lobe
narrowed and bronchoscope could not be passed further. Multiple nodular lesions seen in left
main bronchus (Fig. 8). Endobronchial and brush biopsy from the right side showed histology
of squamous cell carcinoma.
FIG. 1: Chest X-ray showing radio-opaque shadow

in right mid and lower zone with volume reduction.
Squamous Cell Carcinoma Presenting as Lung Abscess 283
FIG. 2: CT thorax showing paratracheal lymph node.
FIG. 3: CT thorax showing mass with mediastinal

lymph node with multiple nodular lesions.
FIG. 4: CT thorax showing mass with abscess like

picture with nodule in the left lung.
FIG. 5: Mass with abscess like picture with multiple

nodular lesions, one of them is cavitating on left side.
FIG. 6: CT thorax showing secondary in liver.
FIG. 7: Secondary carina near right upper lobe wide

and infiltrated. (For color version, see Plate 13)
Squamous Cell Carcinoma Presenting as Lung Abscess 285
FIG. 8: Multiple nodular lesions in left main bronchus.

DISCUSSION
CASE 78
Squamous Cell Carcinoma Presenting as

Superior Vena Cava Syndrome
CASE REPORT
This patient, 61-year-old male, nonsmoker presented with cough, breathlessness, swelling
over face and upper limbs for last 3 months. On examination, there was engorged neck
veins and fullness of face and chest on the right side (Fig. 1). Patient had pallor. Respiratory
examination revealed reduced vesicular breath sounds on right side. Chest X-ray showed right
paratracheal mass (Fig. 2). CT thorax showed intrathoracic mass (Figs. 3A and B). Fiber optic
bronchoscopy showed engorgement of superficial submucosal veins in trachea and left main
bronchus (Figs. 4 and 5). Posterior wall of lower end of trachea was bulging from outside
compression due to mass. There was no endobronchial growth seen. Transthoracic biopsy of
the mass showed histology of the squamous cell carcinoma.
FIG. 1: Patient with superior vena cava syndrome.

Squamous Cell Carcinoma Presenting as Superior Vena Cava Syndrome 287
FIG. 2: Chest X-ray PA view showing paratracheal mass.
A B
FIGS. 3 A AND B: CT thorax showing intrathoracic mass.
FIG. 4: Fiberoptic bronchoscopic showing engorge-

ment of superficial submucosal veins in trachea and
bulging of posterior wall of lower end of trachea.

ment of superficial submucosal veins in left main
DISCUSSION
CASE 79
Squamous Cell Carcinoma

Presenting as Parahilar Mass
CASE REPORT
A 58-year-old male bidi smoker (15 bidis per day for last 30 years) and known case
of chronic obstructive pulmonary disease for last 6 years presented with recurrent
hemoptysis and loss of appetite for last 7 months. General physical examination revealed
severe pallor. Respiratory examination revealed bilateral harsh vesicular breath sounds.
Chest X-ray showed evidence of chronic obstructive pulmonary disease (COPD) along
with left parahilar shadows (Fig. 1). CT thorax showed mass lesion reducing the lumen
of left main bronchus (Fig. 2). Fiberoptic bronchoscopy showed clotted blood in left
main bronchus (Fig. 3). After the removal of clotted blood, there was a tumor visible in
left main bronchus (Fig. 4). Endobronchial biopsy of the tumor showed squamous cell
carcinoma.
FIG. 1: Chest X-ray showing left parahilar mass.

FIG. 2: CT thorax showing mass involving left

main bronchus.
FIG. 3: Fiberoptic bronchoscopy showing blood

clot filled in left main bronchus. (For color version,
see Plate 15)
FIG. 4: Fiberoptic bronchoscopy showing tumor

arising from medial wall of left main bronchus.
DISCUSSION
CASE 80
Squamous Cell Carcinoma in Chronic

Obstructive Pulmonary Disease Patient
CASE REPORT
A 71-year-old male, cigarette smoker (20 cigarettes/day for last 50 years), and known case of
chronic obstructive pulmonary disease for last 8 years presented with recurrent hemoptysis
(streaking) and loss of appetite for last 4 months. General physical examination was within
normal limits. Respiratory examination revealed bilateral harsh vesicular breath sounds with
crepts in left side. Chest X-ray showed mass in the left middle zone (Fig. 1). CT thorax showed
mass lesion in the left upper lobe (Fig. 2). Fiberoptic bronchoscopy showed tumor obstructing
anterior segment of left upper lobe with thick and edematous adjacent tertiary carina (Fig. 3).
Endobronchial forceps biopsy revealed squamous cell carcinoma (Fig. 4).
FIG. 1: Chest X-ray showing mass lesion in the left

lung.
FIG. 2: CT thorax showing mass lesion in the

left lung.
FIG. 3: Fiberoptic bronchoscopy showing

growth in anterior segment of the left upper
lobe with adjacent thick and edematous carina.
FIG. 4: Endobronchial forceps biopsy. (For color

DISCUSSION
CASE 81
A Case of Squamous Cell Carcinoma

Presenting as Pleural Effusion
CASE REPORT
A 45-year-old nonsmoker but having exposure of biomass fuel (cow dung cake and wood)
for 20 years presented with cough for 9 months, chest pain, breathlessness, and hemoptysis
for last 6 months. Patient had already received 3 months of antitubercular drugs without any
response. General examination revealed pallor. Respiratory examination revealed decrease
breath sounds. Chest X-ray showed effusion left side which has progressed to massive
effusion without mediastinal shift indicating some endobronchial mass other than pleural
effusion on left side (Figs. 1 and 2). CT thorax showed mass with pleural effusion (Fig. 3).
Flexible fiberoptic bronchoscopy showed irregular growth which bled on touch in the left
main bronchus just before its bifurcation (Fig. 4). Endobronchial and brush biopsy of the
growth showed squamous cell carcinoma.
FIG. 1: Chest X-ray showing mass in the left parahilar

area of left lung.
FIG. 2: Chest X-ray showing collapse with effusion

in left lung.
FIG. 3: CT thorax showing mass with necrosis with

pleural effusion.
FIG. 4: Flexible bronchoscopy showing irregular

growth in left main bronchus just before its
bifurcation. (For color version, see Plate 16)
DISCUSSION
CASE 82
Squamous Cell Carcinoma Presenting as

Pleural Effusion in a Patient of Chronic
Obstructive Pulmonary Disease
CASE REPORT
A 53-year-old male, bidi and cigarette smoker (30/day × 30 years), a known case of chronic
obstructive pulmonary disease for last 12 years presented with recurrent streaking, chest
pain, loss of appetite, and change in voice for last 1 month. There was a postauricular hard
lymph node (2 × 2 cm) on left side. Respiratory examination revealed decrease in breath
sounds on left side. Fine needle aspiration cytology of lymph node showed metastasis
from squamous cell carcinoma. Chest X-ray apparently normal looking which progressed to
radiopaque shadow involving the left lung in 1-month duration (Figs. 1 and 2). CT thorax
showed left-side pleural effusion with growth involving mediastinum with mediastinal
lymph node (Figs. 3 and 4). About 300 mL of pleural fluid was aspirated from left side which
was exudative in nature and was negative for malignant cytology. Fiberoptic bronchoscopy
showed irregular growth at carina extending into the medial wall of the right main
bronchus (Figs. 5 and 6). Left main bronchus was infiltrated with tumor till its bifurcation
and secondary carina was also involved (Figs. 7 and 8). Endobronchial and brush biopsy of
the growth showed squamous cell carcinoma.
FIG. 1: Apparently normal looking X-ray.

FIG. 2: Chest X-ray showing radiopaque shadow

in the left lung.
FIG. 3: CT thorax showing left-sided pleural effusion.
FIG. 4: Growth involving mediastinum with

mediastinal lymph node with pleural effusion.
Squamous Cell Carcinoma Presenting as Pleural Effusion in a Patient... 297
FIG. 5: Fiberoptic bronchoscopy showing mul-

tinodular growth at carina. (For color version, see
Plate 16)
FIG. 6: Fiberoptic bronchoscopy showing growth

in the medial wall of the right main bronchus. (For
FIG. 7: Fiberoptic bronchoscopy showing involve

ment of left main bronchus by growth. (For color
FIG. 8: Fiberoptic bronchoscopy showing involvement

of secondary carina at bifurcation of left main bronchus.
(For color version, see Plate 17).
DISCUSSION
CASE 83
Squamous Cell Carcinoma with Osteolytic

Secondaries in Spine
CASE REPORT
A 65-year-old patient, bidi and Ganja smoker (40/day × 30 years), a known case of chronic
obstructive pulmonary disease for last 3 years, presented with recurrent streaking, pain
over back, loss of appetite, and change in voice for last 1 year. General examination showed
pallor. Respiratory examination revealed diminished breath sounds on left side. Chest X-ray
showed collapse of left lung indicating endobronchial lesion (Fig. 1). CT thorax shows mass
in the left lung with osteolytic secondaries in vertebral body (Figs. 2 and 3). Fiberoptic
bronchoscopy showed growth covered with necrotic slough obstructing left main bronchus
just near the main carina (Fig. 4). Endobronchial biopsy of the growth showed squamous
cell carcinoma.
FIG. 1: Collapse of left lung.

FIG. 2: Mass with necrosis left lung.
FIG. 3: Osteolytic secondaries in vertebra.

covered with necrotic slough obstructing left main
bronchus. (For color version, see Plate 18).
DISCUSSION
CASE 84
Squamous Cell Carcinoma Presenting

with Recurrent Hemoptysis
CASE REPORT
A 55-year-old male smoker 40 bidi per day for 25 years, presented with cough, chest pain,
hoarseness of voice, dysphasia and recurrent hemoptysis for 8 months. General examination
revealed pallor. Respiratory system examination revealed decreased breath sounds in right
infraclavicular area. Chest X-ray showed mass in the paratracheal area of the right lung (Figs. 1
and 2). CT thorax showed mass infiltrating trachea (Fig. 3). Fiberoptic bronchoscopy showed
multinodular growth on anterolateral wall of trachea just above the main carina, making
opening of trachea slit like (Fig. 4). Bronchoscope could not be negotiated further. Biopsy
from the growth showed squamous cell carcinoma.

mass in the right paratracheal area.
FIG. 2: Chest X-ray lateral view showing mass in

the right upper lobe.
FIG. 3: CT thorax showing mass infiltrating the trachea.
FIG. 4: Fiberoptic bronchoscopy showing multi-

nodular growth in anterolateral wall of the trachea.
DISCUSSION
CASE 85
Squamous Cell Carcinoma in a Patient of

Presenting as Recurrent Hemoptysis
CASE REPORT
A 58-year-old male, bidi smoker (15/day × for 40 years) presented with cough, recurrent
hemoptysis, and loss of appetite for last 4 months. He was prescribed antitubercular drugs
for 3 months without any response. General physical examination revealed pallor. Respiratory
examination revealed diminished breath sounds with crepts on left side. Chest X-ray showed
left-sided obstructive pneumonitis with mediastinal lymphadenopathy (Figs. 1 and 2).
CT thorax showed left side mass lesion (Figs. 3 and 4). Fiberoptic bronchoscopy showed
multinodular growth covered with necrotic slough obstructing the left main bronchus
(Figs. 5 and 6). Endobronchial and brush biopsy from tumor showed squamous cell carcinoma.
FIG. 1: Chest X-ray showing obstructive pneumonitis

left with mediastinal lymphadenopathy.
FIG. 2: Chest X-ray showing increased obstructive

pneumonitis left with mediastinal lymph nodes.
FIG. 3: CT thorax showing right tracheobronchial

lymph node.
FIG. 4: CT thorax showing mass in left lung.

Squamous Cell Carcinoma in a Patient of Chronic Obstructive Pulmonary Disease... 305
FIG. 5: Fiberoptic bronchoscopy showing multinodular

growth left main bronchus. (For color version, see Plate 18)

growth with necrotic slough. (For color version, see Plate 19)
DISCUSSION
Squamous cell carcinoma (SCC) of the lung represents 30% of all non-small cell lung
carcinomas (NSCLC). SCC is the second most frequent type of NSCLC. It is formed
from round cells that replace injured or damaged cells in the lining of the bronchi. SCC
usually spread to bones, adrenal glands, the liver, and brain. The main cause of NSCLC
is cigarette, bidi, and other forms of smoking, and the risk is directly proportional to the
duration of exposure to smoking. About 25% of lung cancer in India occurs in nonsmokers.
The principal nonsmoking factor is the use of biomass fuel including coal. Nonsmokers
develop a disease in which genetic abnormalities are more relevant, with tumor cell
proliferation largely depending on epidermal growth factor receptor (EGFR). In smokers,
however, EGFR is wild type whereas a mutation of the K-Ras oncogene is very common.
Different tests are used to diagnose lung cancer and determine whether it has spread
to other parts of the body. These tests include imaging tests, laboratory tests, and biopsies.
Different imaging tests a person might undergo include chest X-ray, CT (computed
tomography or CAT) scan, MRI (magnetic resonance imaging) scan, PET (positron
emission tomography) scan, and bone scan.
If lung cancer is suspected, sputum cytology may be performed. Sputum cytology is
more likely to help to diagnose lung cancers that start in the major airways of the lung such
as most squamous cell lung cancer. Only a biopsy can provide a definite diagnosis of lung
cancer. Having enough tissue available for biomarker (mutation, genomic, or molecular)
testing can also be an important consideration.
The staging system used for squamous cell lung cancer is the TNM system, where the
combination of the values assigned to a patient's cancer is based on three measures: T
(tumor), N (node), and M (metastasis)—to determine the cancer's stage. Stages range
from 0 to IV. The higher the stage number, the more advanced the cancer.
There are a number of treatment options for squamous cell lung cancer which depend
on the stage of the cancer, the patient’s overall health including how well the organs of
the patient's body are functioning, and the patient's preferences. Approved treatment
options for squamous cell lung cancer include surgery, radiation therapy, chemotherapy,
angiogenesis inhibitors, and immunotherapy. Most often, the platinum-based drugs
cisplatin or carboplatin are combined with another chemotherapy drug like gemcitabine
for squamous cell lung cancer treatment.
The 5-year survival rate of NSCLC is only ~15% as the majority of the patients have
advanced-stage disease at diagnosis and the treatment options are limited. Approximately
60–70% of the patients have advanced-stage disease at diagnosis.
The presence of EGFR mutations is a predictor of response to TKI treatment (gefitinib
and erlotinib). Erlotinib is a tumor kinase inhibitor of EGFR and is currently approved
for the treatment of metastatic NSCLC after failure of at least one prior chemotherapy
regimen, as maintenance therapy in patients with stable disease after 4 cycles of standard
first line platinum-based chemotherapy, and as a first-line treatment in the presence of
activating EGFR mutations.
FURTHER READING
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018:
GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA
Cancer J Clin. 2018;68:394-424.
2. Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R. EUROCARE Working Group.
EUROCARE-4: Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J
Cancer. 2009;45:931-91.
3. GlobocanIndia. [online] Available from https://gco.iarc.fr/today/data/factsheets/populations/356-
india-fact-sheets.pdf. [Last accessed March, 2020].
4. Prasad R, Srivastava A N, VermaSK. Clinico-pathological profile of bronchogenic carcinoma among
females in North India. Indian J Chest Dis Allied Sci. 2015;57:161-63.
5. ICMR. Consolidated Report of the Hospital Based Cancer Registries Bengaluru, India; 2016. [online]
Available from http://www.ncdirindia.org/Download/AR_2016_2017.pdf. [Last accessed March,
2020].
6. Population Based Cancer Registries. National Centre for Disease Informatics and Research. [online]
Available from http://www.ncdirindia.org/cancersamiksha/reg_Rates.aspx. [Last accessed March,
2020].
7. Shepherd FA, Pereira Rodrigues J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in
previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123-32.
Squamous Cell Carcinoma in a Patient of Chronic Obstructive Pulmonary Disease... 307
8. Neal JW. The SATURN trial: The value of maintenance erlotinib in patients with non-small-cell lung
cancer. Future Oncol. 2010;6:1827-32.
9. Prasad R, James P, Kesarwani V, Gupta R, Pant MC, Chaturvedi A, et al. Clinicopathological study of
bronchogenic carcinoma. Respirology. 2004;9:557-60.
10. Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, et al. Efficacy and safety
of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-
cell lung cancer with poor prognosis (TITAN): A randomized multicentre, open-label, phase 3 study.
Lancet Oncol. 2012;13:300-8.
11. Johnson BE, Jänne PA. Epidermal growth factor receptor mutations in patients with non-small cell
lung cancer. Cancer Res. 2005;65:7525-9.
12. Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular
subtypes and therapeutic opportunities. Clin Cancer Res. 2012;18:2443-51.
13. Kader I, Strong M, George M. Skull destruction from intracranial metastasis arising from pulmonary
squamous cell carcinoma: a case report. J Med Case Rep. 2013;7:28.
CASE 86
Adenocarcinoma Presenting as a
Recurrent Pleural Effusion
CASE REPORT
A 53-year-old male, cigarette smoker (15/day for 30 years) presented with chest pain, right
side and recurrent pleural effusion on the right side for last 6 months. He had received
antitubercular drugs for 6 months without any response. General examination was within
normal limits. Respiratory examination revealed decreased breath sounds in right lung. Chest
X-ray showed parahilar mass in right lung with moderate pleural effusion (Fig. 1). Further chest
X-ray also showed pleural effusion and multiple nodular shadows suggesting secondaries.
(Figs. 2 and 3). CT thorax also showed multiple secondaries with mass and pleural effusion
(Figs. 4 and 5). Fiberoptic bronchoscopy showed widening and infiltration of secondary
carina near right upper lobe bronchus with narrowed right upper lobe bronchus (Figs. 6 to 8).
Middle lobe opening is also narrowed. Pleural fluid cytology was positive for malignant cells.
Endobronchial biopsy from secondary carina showed adenocarcinoma.
FIG. 1: Parahilar mass in the right lung with pleural

effusion.
Adenocarcinoma Presenting as a Recurrent Pleural Effusion 309
FIG. 2: Parahilar mass in the right lung with

multiple secondaries.
FIG. 3: Pleural effusion on right side has increased.
FIG. 4: Mass in the right lung with pleural effusion.

FIG. 5: CT scan showing secondaries in lungs with

pleural effusion on the right side.
FIG. 6: Secondary carina near right upper lobe is

wide and infiltrated obliterating right upper lobe
FIG. 7: Middle lobe bronchus narrowed. (For color

Adenocarcinoma Presenting as a Recurrent Pleural Effusion 311

DISCUSSION
CASE 87
Adenocarcinoma in
a 65-year-old Nonsmoker Female
CASE REPORT
A 65-year-old, nonsmoker female presented with cough, chest pain, breathlessness, loss of
appetite, and weight loss for last 11 months. General examination revealed severe pallor.
Respiratory examination revealed absent breath sounds in left lung. Chest X-ray showed left-
side pleural effusion (Fig. 1). In the 11 months duration, hemorrhagic pleural fluid was done.
which was negative for malignant cells. She was diagnosed as a case of pleural effusion left
side and was given antitubercular drugs for 6 months from outside without any response
(Fig. 2). CT thorax showed pleural effusion with mass (Fig. 3). Fiberoptic bronchoscopy showed
infiltration with mucosal edema in the medial wall of left main bronchus near the lingular
opening. Nearby tertiary carina was also infiltrated and edematous (Fig. 4). Endobronchial
and brush biopsy from infiltrated area showed adenocarcinoma.
FIG. 1: Chest X-ray showing left-sided pleural effusion.

Adenocarcinoma in a 65-year-old Nonsmoker Female 313
FIG. 2: Pleural effusion increased in spite of

6 months antitubercular treatment (ATT).
FIG. 3: Pleural effusion with mass.
FIG. 4: Infiltrated bronchial wafll and edematous

tertiary carina. (For color version, see Plate 20).
DISCUSSION
CASE 88
A Case of Adenosquamous Cell Carcinoma

in a 40-year-old Male
CASE REPORT
A 40-year-old nonsmoker male presented with cough, chest pain for 8 months, and
hemoptysis for 1 month. He had an enlarged hard lymph node (2 cm) in left supraclavicular
area. Respiratory examination revealed crepts in left infraclavicular area. Fine needle
aspiration cytology of the lymph node showed metastatic squamous cell carcinoma (SCC).
Chest X-ray showed radio opaque shadow in left lower zone (Fig. 1). CT thorax showed mass
in left lung with multiple nodular shadows suggestive of secondaries (Figs. 2 and 3 ). Fiber
optic bronchoscopy showed widened anterior part of main carina. Lower lobe bronchus is
narrowed and full of blood. After saline wash there were multiple nodular growth on the wall of
left lower lobe bronchus (Fig. 4). Endobronchial biopsy showed histology of adenosquamous
carcinoma.
FIG. 1: Radio opaque shadow in left lower zone.

A Case of Adenosquamous Cell Carcinoma in a 40-year-old Male 315
FIG. 2: Mass in left lung.
FIG. 3: Secondaries in lungs.
FIG. 4: Tumor with blood in left lower lobe

DISCUSSION
Lung adenocarcinoma is a subtype of non-small cell lung cancer (NSCLC). Lung
adenocarcinoma is categorized as such by how the cancer cells look under a microscope.
Lung adenocarcinoma starts in glandular cells, which secrete substances such as mucus
and tends to develop in smaller airways, such as alveoli. Lung adenocarcinoma is usually
located more along the outer edges of the lungs. Lung adenocarcinoma tends to grow
more slowly than other lung cancers. Lung adenocarcinoma accounts for 40% of all lung
cancers. It is found more often in women. Younger people (aged 20–46) who have lung
cancer are more likely to have lung adenocarcinoma than other lung cancers. At the
present time, around 85% of lung cancers are NSCLC, and of these, over 50% are lung
adenocarcinomas.
Different tests are used to diagnose lung cancer and determine whether it has spread
to other parts of the body. Some of these tests can also help to decide which treatments
might work best. Steps and tests used in diagnosing lung adenocarcinoma include
imaging tests, laboratory tests, and biopsy of a tissue which is the only way to confirm a
diagnosis of lung cancer. The staging system used for lung adenocarcinoma is the TNM
system, where the combination of the values assigned to a patient’s cancer on three
measures: T (tumor), N (node), and M (metastasis)—determine the cancer's stage. Stages
range from 0 to IV. The higher the stage number, the more advanced the cancer.
Approved treatment options for lung adenocarcinoma include surgery, radiation
therapy, chemotherapy, targeted therapies, angiogenesis inhibitors, and immunotherapy.
Epithelial growth factor receptor (EGFR) mutations are most common in people with lung
adenocarcinoma, and are more common with lung cancer in nonsmokers, and in women.
The prognosis of patients with advanced NSCLC is poor and their 1-year survival
rate after cytotoxic chemotherapy is only 29%. Development of epidermal growth factor
receptor tyrosine kinase inhibitors (EGFR-TKIs) dramatically improves the prognosis
of certain patients. Patients with EGFR-mutant advanced NSCLC receiving EGFR-TKIs
have a median overall survival (OS) more than twice as long as those not receiving
EGFR-TKIs. The 5-year survival rate of patients with EGFR-mutant metastatic lung
adenocarcinoma treated with EGFR-TKIs is 14.6%. The 5-year survival rate of localized
NSCLC is 60%, for regional it is 33%, and for distant it is 6%.
FURTHER READING
1. American Cancer Society. What is Non-Small Cell Lung Cancer? [online] Available from https://www.
cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html.
2. National Cancer Institute. Non-Small Cell Lung Cancer Treatment (PDQ®)—Patient Version. [online]
Available from https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq.
3. Chen Z, Fillmore M, Hammerman PS, Kim CF, Wong K-K . Non-small cell lung cancers: a heterogeneous
set of diseases. Nat Rev Cancer. 2014;14:535-46.
4. Lung Cancer: Metastatic—Non-Small Cell Lung Cancer. NCCN Guidelines for Patients. Version 3.2019.
[online] Available from https://www.nccn.org/patient/guidelines/lung-metastatic. [Last accessed
February, 2020].
5. Cancer.Net. Lung Cancer–Non-Small Cell: Stages. [online] Available from http://www.cancer.net/
cancer-types/lung-cancer-non-small-cell/stages. [Last accessed February, 2020].
6. Hirsch FR, Suda K, Wiens J, Bunn PA Jr. New and emerging targeted treatments in advanced non-
small-cell-lung-cancer. Lancet. 2016;388:1012-24.
A Case of Adenosquamous Cell Carcinoma in a 40-year-old Male 317
7. Lung Cancer: Early and Locally Advanced—Non-Small Cell Lung Cancer. NCCN Guidelines for
Patients. Version 3.2019. [online] Available from https://www.nccn.org/patients/guidelines/lung-
early-stage. [Last accessed February, 2020].
8. Non-Small Cell Lung Cancer. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).
Version 4.2019. [online] Available from https://www.nccn.org/professionals/physician_gls/pdf/nscl.
pdf. [Last accessed February, 2020].
9. Cancer.Net. Understanding Targeted Therapy. [online] Available from https://www.cancer.net/
navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-
targeted-therapy. [Last accessed February, 2020].
10. Lovly C. Combating acquired resistance to tyrosine kinase inhibitors in lung cancer. Am Soc Clin
Oncol Educ Book. 2015:e165-73.
11. National Cancer Institute. Angiogenesis inhibitors. [online] Available from https://www.cancer.gov/
about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet. [Last accessed
February, 2020].
12. National Cancer Institute. Biological therapies for cancer. [online] Available from https://www.cancer.
gov/about-cancer/treatment/types/immunotherapy/bio-therapies-fact-sheet. [Last accessed
February, 2020].
13. National Cancer Institute. Immunotherapy to Treat Cancer. [online] Available from https://www.
cancer.gov/about-cancer/treatment/types/immunotherapy. [Last accessed February, 2020].
CASE 89
Small-cell Carcinoma Presenting as

Pleural Effusion in a Patient of COPD
CASE REPORT
A 51-year-old male, bidi smoker 20 bidi per day for 25 years, a known case of chronic
obstructive pulmonary disease for last 4 years, had developed recurrent hemoptysis for last
1 year. General examination was within normal limits. Respiratory examination revealed
decrease in breath sounds with crepts in left infrascapular area. Chest X-ray showed mass in
left parahilar area (Figs. 1 and 2). Chest X-ray lateral view showed rounded opacity (Fig. 3).
CT thorax showed large mass in left lower lobe infiltrating mediastinum with multiple
mediastinal lymphadenopathy with pleural effusion with multiple bullae (Figs. 4 and 5).
Fiberoptic bronchoscopy showed bulging of posterior wall of trachea in lower part. Main
carina was short and wide and infiltrated (Fig. 6). Right endobronchial tree showed evidences
of chronic bronchitis, the lumen of left main bronchus was narrowed and medial wall of left
main bronchus was infiltrated in whole of its length (Figs. 7 and 8). Endobronchial biopsy
showed histology of small-cell carcinoma.

showing mass in left parahilar area.
Small-cell Carcinoma Presenting as Pleural Effusion in a Patient of COPD 319

showing mass in left parahilar area which has
increased.
FIG. 3: Chest X-ray lateral view showing rounded

opacity.
FIG. 4: CT thorax showing intrathoracic mass

with mediastinal lymphadenopathy with pleural
effusion.
FIG. 5: CT thorax showing multiple bullae.
FIG. 6: Main carina is short and wide and infiltrated.

FIG. 7: Multiple nodules over medial wall of left

main bronchus. (For color version, see Plate 21)
Small-cell Carcinoma Presenting as Pleural Effusion in a Patient of COPD 321
FIG. 8: Infiltration of the left main bronchus. (For

DISCUSSION
CASE 90
Small-cell Carcinoma with

Secondaries in Brain
CASE REPORT
A 51-year-old male, cigarette smoker 20 cigarette/day for 30 years presented with weakness
in both limbs, hemoptysis, hoarseness of voice, dysphasia, loss of weight, and appetite for
3 months. General examination revealed pallor. Respiratory examination revealed harsh
vesicular breath sounds. Chest X-ray showed mass in the left lung which is centrally placed
(Fig. 1). CT thorax showed mass in left lung (Fig. 2). Fiberoptic bronchoscopy showed tumor
obstructing left upper lobe bronchus (Fig. 3). Endobronchial biopsy showed small cell
carcinoma. MRI brain showed secondaries in brain (Fig. 4). Thus, the patient was diagnosed
as small cell lung cancer extensive disease. Patient was advised for chemotherapy but family
members refused for any further treatment. Prognosis was explained to family members.
FIG. 1: Chest X-ray showing mass in left lung.

Small-cell Carcinoma with Secondaries in Brain 323
FIG. 2: CT thorax showing mass in left lung.
FIG. 3: Tumor obstructing left upper lobe bronchus.

FIG. 4: MRI brain showing secondaries in brain.
DISCUSSION
CASE 91
Small-cell Carcinoma in a Patient of

CASE REPORT
A 53-year-old male, bidi smoker 15 bidi per day for 40 years, a known case of chronic obstruc
tive pulmonary disease presented with fever, loss of appetite, and hoarseness of voice for
2 months. General physical examination was within normal limits. Respiratory examination
revealed bilateral harsh vesicular sounds with occasional crepts. Chest X-ray posteroanterior
(PA) view showed emphysematous changes with left hilar mass which has increased in size
rapidly (Figs. 1 and 2). Fiberoptic bronchoscopy showed evidence of chronic bronchitis in
both endobronchial tree with infiltration of posterior wall of left upper lobe bronchus reducing
its lumen (Figs. 3 and 4). Endobronchial and brush biopsy showed histology of small-cell
carcinoma. There was no other evidence of distant metastasis. Patient was diagnosed as a case
of small cell lung cancer limited stage. Patient was treated with six cycles of chemotherapy
with cisplatin and etoposide with partial response. After that patient was lost to follow-up.

emphysematous changes with left hilar mass which
has increased in size.
Small-cell Carcinoma in a Patient of Chronic Obstructive Pulmonary Disease 325

showing emphysematous changes with left hilar
prominence which has increased.
FIG. 3: Main carina deviated to left side. (For color

FIG. 4: Infiltration in the walls of left upper lobe

DISCUSSION
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises
within the lung, although it can occasionally arise in other body sites such as the cervix,
prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small-cell
carcinoma has a shorter doubling time, higher growth rate, and earlier development
of metastases. Small-cell lung cancer (SCLC) represents approximately 13% of all
newly diagnosed lung cancers. SCLC is a very aggressive disease characterized by early
locoregional and distant metastases. Small-cell lung carcinoma has long been divided
into two clinicopathological stages including limited stage (LS) and extensive stage (ES).
The stage is generally determined by the presence or absence of metastases, whether or
not the tumor appears limited to the thorax, and whether or not the entire tumor burden
within the chest can feasibly be encompassed within a single radiotherapy portal. In
general, if the tumor is confined to one lung and the lymph nodes close to that lung,
the cancer is said to be limited stage. If the cancer has spread beyond that, it is said to
be extensive stage. In cases of limited stage-SCLC, combination chemotherapy (often
including cyclophosphamide, cisplatin, doxorubicin, etoposide, vincristine, and/or
paclitaxel) is administered together with concurrent chest radiotherapy (RT). Chest RT has
been shown to improve survival in LS-SCLC. In ES-SCLC, platinum-based combination
chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms
such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases
(BM), which in small-cell lung carcinoma typically have a rapid, if temporary, response to
whole brain radiotherapy. Response rates are high even in extensive disease, with between
15 and 30% of subjects having a complete response to combination chemotherapy and the
vast majority having at least some objective response.
Over 10% of SCLC patients have brain metastasis at initial diagnosis; >50% will develop
BM within 2 years. BM are detected in up to 80% of all patients at autopsy. After primary
treatment, prophylactic cranial irradiation (PCI) has been established as standard of care in
SCLC patients responding to initial therapy. In 2018, the FDA approved nivolumab to treat
patients with metastatic SCLC who failed to respond to platinum-based chemotherapy
and at least one other first line of treatment.
The median survival is 14–16 months for patients with limited disease and 8-11 months
for those with extensive disease are alive with good treatment. 20–40% of patients with
limited disease and 5% of patients with extensive disease are alive at 2 years. The 5-year
survival rates for SCLC range between 3.6 and 32.2% for women, and between 2.2 and
24.5% for men. Relative 5-year survival rate for both sexes has increased from 3.6% in 1975
to 6.7% in 2014. In limited stage disease, relative 5-year survival rate (both sexes, all races,
all ages) is 21.3%; The prognosis is far more grim in ES small-cell lung carcinoma where
5-year relative survival rate (both sexes, all races, all ages) is 2.8%.
Usually, SCLC is rarely mistaken for carcinoids, with the exception of small biopsy
materials. There are also certain differences in the clinical background and profiles
according to the subgroup of neuroendocrine (NE) tumors. Unlike carcinoids, SCLC
is markedly associated with a history of smoking. Carcinoids tend to occur in younger
patients (mean age 45–50 years), whereas the high-grade NE tumors affect older patients
(mean age 65 years). The former are capable of distant metastases in <20% of cases (most
commonly to liver and bones), and SCLC tends to metastasize to the brain, liver, adrenal
glands, and bone with higher frequency. Due to the low response rates for chemo- and
radiotherapy, surgical resection is primarily used in the treatment of carcinoids whereas
the standard treatment for limited-stage SCLC includes combined chemoradiotherapy
due to high sensitivity.
Small-cell Carcinoma in a Patient of Chronic Obstructive Pulmonary Disease 327
FURTHER READING
1. Auperin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial
irradiation for patients with small-cell lung cancer in complete remission. Prophylactic cranial
irradiation overview collaborative group. N Engl J Med. 1999;341:476-84.
2. Gustafsson BI, Kidd M, Chan A, Malfertheiner MV, Modlin IM. Bronchopulmonary neuroendocrine
tumors. Cancer. 2008;113:5-21.
3. Rekhtman N: Neuroendocrine tumors of the lung: an update. Arch Pathol Lab Med. 2010;134:
1628-38.
4. Ou SH, Ziogas A, Zell JA. Prognostic factors for survival in extensive stage small cell lung cancer
(ED-SCLC): the importance of smoking history, socioeconomic and marital statuses, and ethnicity. J
Thorac Oncol. 2009;4:37-43.
5. Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The Eighth Edition Lung Cancer Stage Classiﬁcation.
Chest. 2017;151:193-203.
6. Asamura H, Kameya T, Matsuno Y, Noguchi M, Tada H, Ishikawa Y, et al. Neuroendocrine neoplasms
of the lung: a prognostic spectrum. J Clin Oncol. 2006;24:70-6.
7. Pelosi G, Rodriguez J, Viale G, Rosai J. Typical and atypical pulmonary carcinoid tumor over diagnosed
as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer
patients. Am J Surg Pathol. 2005;29:179-87.
8. Gaspar LE, Mehta MP, Patchell RA, Burri SH, Robinson PD, Morris RE, et al. The role of whole brain
radiation therapy in the management of newly diagnosed brain metastases: a systematic review
and evidence-based clinical practice guideline. J Neurooncol. 2010;96:17-32.
9. Capizzello A, Peponi E, Simou N, Ntaskagiannis D, Tasiou I, Kamina S, et al. Pure small cell literature
review. Case Rep Oncol. 2011;4:88-95.
10. El Maalouf G, Rodier JM, Faivre S, Raymond E. Could we expect to improve survival in small cell lung
cancer? Lung Cancer. 2007;57:30-4.
CASE 92
Large Cell Carcinoma Presenting as

Parahilar Mass in a Patient of COPD
CASE REPORT
A 61-year-old male patient, bidi smoker (20/day for 30 years) presented with cough, breath
lessness, loss of appetite, and weight loss for last 4 months. General examination revealed
clubbing. Respiratory examination revealed bilateral harsh vesicular sound with rhonchi
with occasional crepts in left side. He was misdiagnosed as tuberculosis and prescribed
antitubercular drugs for 5 months without any response. Chest X-ray showed parahilar mass
with nodular shadows in left lower zone (Fig. 1). CT thorax showed parahilar mass with
multiple nodular shadows in left lower lobe (Figs. 2 and 3). Fiberoptic bronchoscopy showed
tumor covered with necrotic slough in left main bronchus (Fig. 4). Endobronchial and brush
biopsy from tumor showed large cell carcinoma.
FIG. 1: Parahilar mass with nodular

shadows in left lower zone.
Large Cell Carcinoma Presenting as Parahilar Mass in a Patient of COPD 329
FIG. 2: Parahilar mass.
FIG. 3: Nodular shadows in left lower zone.
FIG. 4: Tumor obstructing left main bronchus.

DISCUSSION
CASE 93
Large-cell Carcinoma Presenting with

Massive Pleural Effusion
CASE REPORT
This 51-year-old male patient, bidi smoker 10 bidi per day for 25 years presented with cough
breathlessness, chest pain, and loss of appetite for 6 months. General physical examination
was within normal limits. Respiratory examination revealed absent breath sounds on left
side. Chest X-ray and CT thorax showed massive pleural effusion left side (Figs. 1 and 2)
which was aspirated and was exudative in character with lymphocytic predominant. Levels
of adenosine deaminase (ADA) was 56 IU/mL and pleural fluid cytology was negative for
malignant cell. He was diagnosed as a case of tubercular pleural effusion, antitubercular drugs
were given emperically for 2 months without any response. Chest X-ray showed increased
fluid on the left side (Fig. 3). CECT thorax showed cavitating large mass in the left lung
(Figs. 4 and 5) and there was radiolucent shadow in the liver suggestive of secondaries
(Fig. 6). Fiberoptic bronchoscopy showed that secondary carina between left upper lobe
bronchus and lower lobe bronchus is thickened (Fig. 7). Tertiary carina is thick and infiltrated
(Fig. 8). Endobronchial and brush biopsy showed large cell carcinoma.

showing massive pleural effusion with mediasti-
nal shift to the opposite side.
Large-cell Carcinoma Presenting with Massive Pleural Effusion 331
FIG. 2: CT thorax showing mass and effusion on

the right side.

showing increased pleural effusion on the left side.
FIG. 4: CT thorax showing mass with necrosis.

FIG. 5: CT thorax showing mass with necrosis with

small pleural effusion.
FIG. 6: CT thorax showing secondaries in liver.
FIG. 7: Fiberoptic bronchoscopy showing thick

secondary carina. (For color version, see Plate 23)
Large-cell Carcinoma Presenting with Massive Pleural Effusion 333
FIG. 8: Fiberoptic bronchoscopy showing tertiary

carina thick edematous and infiltrated. (For color
DISCUSSION
Large-cell carcinoma (LCC) is a heterogeneous group of undifferentiated malignant
neoplasms that lack the cytologic and architectural features of small-cell carcinoma
(SCLC) and glandular or squamous differentiation. LCC is categorized as a type of
non-small cell lung carcinoma (NSCLC) which originates from epithelial cells of the
lung. LCC is, in effect, a “diagnosis of exclusion,” in that the tumor cells lack light
microscopic characteristics that would classify the neoplasm as a small-cell carcinoma,
squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung
cancer. Large-cell carcinoma is differentiated from SCLC primarily by the larger size of the
anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of “salt-and-pepper”
chromatin.
Clinical signs and symptoms resemble those of other types of NSCLC. Most tumors
develop as peripheral lung masses, except for basaloid carcinomas, which usually
form centrally located masses. Histologically, large cell carcinomas consist of sheets
and nests of large cells with vesicular nuclei, prominent nucleoli, and moderate or
abundant amounts of cytoplasm.
One clinically significant subtype is “large-cell neuroendocrine carcinoma” (LCNEC),
which is believed to derive from neuroendocrine cells. In addition, a “subvariant” called
“combined large-cell neuroendocrine carcinoma”, is recognized under the new system.
Treatment of LCC includes surgery, chemotherapy, radiotherapy, adjuvant therapy, and
with immunotherapy as other varieties of non small cell lung cancer.
FURTHER READING
1. Fernandez FG, Battafarano RJ. Large-cell neuroendocrine carcinoma of the lung. Cancer Control.
2006;13:270-5.
2. Cotran RS, Kumar V, Fausto N, R SL, Abbas AK, Robbins SL. Robbins and Cotran pathologic basis of
disease. St. Louis: Elsevier Saunders; 2005. p. 762.
3. Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA. Comparison of aspects of smoking among
the four histological types of lung cancer. Tob Control. 2008;17:198-204.
4. Muscat JE, Stellman SD, Zhang ZF, Neugut AI, Wynder EL. Cigarette smoking and large cell carcinoma
of the lung. Cancer Epidemiol Biomarkers Prev. 1997;6:477-80.
CASE 94
Pulmonary Langerhans Cell Histiocytosis

in a 15-year-old Nonsmoker Male
CASE REPORT
A 15-year-old nonsmoker male presented with complaints of nonproductive cough on
and off for 10 years and breathlessness which was progressive for 3 years. Patient had a
history of antitubercular drugs 2 years back which he took for complete 6 months but with
no improvement. General examination was within normal limits except for presence of
Grade 4 clubbing (Fig. 1). On respiratory examination, there was presence of fine crepts
bilaterally. Routine investigations were within normal limits. Chest X-ray showed diffuse
bilateral reticulonodular opacities with cysts (Figs. 2A and B). High-resolution computed
tomography (HRCT) thorax showed multiple thin-walled cysts with area of honeycombing
diffusely involving bilateral lung predominantly upper and middle lobe on right side with
destruction of normal lung parenchyma and showed reticular pattern. Inter, intralobular,
septal, and peribronchovascular thickening was seen (Figs. 3A to C). 2D Echo showed mild
tricuspid regurgitation with mild pulmonary arterial hypertension. Oral prednisolone 30
mg daily was given for a period of 8 weeks and then it was gradually tapered and patient
had responded clinically. After 4 months, patient was advised for lung biopsy, to prove the
diagnosis, but patient was lost to follow-up.
FIG. 1: Patient showing clubbing of fingers. (For

Pulmonary Langerhans Cell Histiocytosis in a 15-year-old Nonsmoker Male 335
A B
FIGS. 2A AND B: Chest X-ray posteroanterior (PA) view showing diffuse reticulonodular opacities.
A B
FIGS. 3A TO C: CT thorax showing diffuse

C multiple cysts bilaterally.
DISCUSSION
Pulmonary Langerhans cell histiocytosis (PLCH) is a relatively uncommon lung disease
that generally occurs in smokers. The pathologic hallmark of PLCH is the accumulation
of Langerhans and other inflammatory cells in small airways, resulting in the formation
of nodular inflammatory lesions. While cellular inflammation is prominent in early
disease, more advanced stages are characterized by cystic lung destruction, cicatricial
scarring of airways, and pulmonary vascular remodeling. Pulmonary function is
frequently abnormal at presentation. Imaging of the chest with HRCT scanning may show
characteristic nodular and cystic abnormalities. Lung biopsy is obligatory for a definitive
diagnosis, although may not be required in instances where imaging findings are highly
characteristic. A role for interleukin-17 (IL-17) especially IL-17A as a mediator of important
cellular pathobiologic events pertinent to LCH has been proposed. About two-thirds of
patients are symptomatic at presentation. Dyspnea and unproductive cough are the
most common symptoms at the time of diagnosis. Constitutional symptoms including
fever, sweats, and weight loss occur in 15–20%. Chest pain usually signifies pneumothorax
or rib involvement. Pneumothorax occurs in about 15% of patients. Hemoptysis is
uncommon. In 10–15% of adults diagnosed with PLCH, symptoms due to extrapulmonary
disease may be present. These include polyuria and polydipsia due to diabetes insipidus,
pain which may be attributed to skeletal involvement, or skin rashes due to cutaneous
disease.
The chest X-ray is almost always abnormal. Reticulonodular infiltrates are predomi
nant in early disease whereas cystic lesions are more dominant in advanced disease.
Radiological changes in advanced disease can be difficult to differentiate from advanced
emphysema. Nodular or reticulonodular involvement is characteristically diffuse,
predominantly involving upper and middle lobes with relative sparing of lung bases. Lung
volumes on chest X-ray are usually normal or increased. HRCT should be obtained in
every patient, as in many cases it can differentiate PLCH from other cystic lung diseases
such as lymphangioleiomyomatosis (LAM), Birt–Hogg–Dubé syndrome, or emphysema.
Smoking cessation may lead to regression of disease or stabilization of symptoms
although some individuals will have disease progression despite smoking cessation.
There are hardly any biological markers to predict which patient will improve and
who will continue to get worse despite smoking cessation. Pharmacotherapy with
immunosuppressive medication should be considered for all adult patients with severe
disease, or patients in whom progressive decline in lung function occurs. Corticosteroids
in the form of prednisone 0.5–1.0 mg/kg daily with slow tapering over months is given
to treat patients with progressive disease. Other immunosuppressive agents such as
chlorodeoxyadenosine (also known as cladribine or 2-CDA), cyclophosphamide, and
methotrexate, have been used to treat progressive disease. Lung transplant can be an
option in selected patients with progressive disease despite smoking cessation and a trial
of immunosuppressive therapy.
Spontaneous pneumothorax can be an initial manifestation in approximately
15% of patients and seems to be more frequent in younger patients. Pneumothorax is
usually unilateral, although rare cases of spontaneous bilateral pneumothoraces have
been reported. Recurrence is usually ipsilateral but can occur in contralateral lung.
Small pneumothoraces may be managed conservatively. Surgical management is
recommended for any patient with recurrent pneumothorax or a single moderate to
large pneumothorax, since the rate of recurrence with a conservative approach (chest
tube drainage without pleurodesis) is unacceptably high. Pulmonary hypertension is a
common and under-recognized complication. Progressive vascular involvement may
occur in a minority of patients despite relative stability of pulmonary parenchymal
lesions. In addition to appropriate trials of vasodilator therapy, patients with moderate-
to-severe pulmonary hypertension may benefit from anticoagulation and supplemental
oxygen to correct underlying hypoxemia.
The survival of adults with PLCH is shorter than that in the general population. Several
factors have been associated with poor outcome including extremes of age, prolonged
constitutional symptoms, multiorgan involvement, extensive cysts and honeycombing
on the radiograph, severely reduced diffusing capacity, obstructive physiology on lung
Pulmonary Langerhans Cell Histiocytosis in a 15-year-old Nonsmoker Male 337
function testing, prolong treatment with steroid therapy, and associated pulmonary
hypertension. The presence of pulmonary hypertension, can reliably predict prognosis in
the individual patient. Respiratory failure accounts for a substantial proportion of deaths
in end-stage disease.
FURTHER READING
1. Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, et al. Contemporary classification
of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations.
Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997;29:157-66.
2. Komp DM. Historical perspectives of Langerhans cell histiocytosis. Hematol Oncol Clin North Am.
1987;1:9-21.
3. Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH. Clinical outcomes of pulmonary
Langerhans'-cell histiocytosis in adults. N Engl J Med. 2002;346:484-90.
4. Arico M, Girschikofsky M, Genereau T, Klersy C, McClain K, Grois N, et al. Langerhans cell histiocytosis
in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer. 2003;39:
2341-8.
5. Salotti JA, Nanduri V, Pearce MS, Parker L, Lynn R, Windebank KP. Incidence and clinical features of
Langerhans cell histiocytosis in the UK and Ireland. Arch Dis Child. 2009;94:376-80.
6. Alston RD, Tatevossian RG, McNally RJ, Kelsey A, Birch JM, Eden TO. Incidence and survival of
childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998. Pediatr blood
cancer. 2007;48:555-60.
7. Travis WD, Borok Z, Roum JH, Zhang J, Feuerstein I, Ferrans VJ, et al. Pulmonary Langerhans
cell granulomatosis (histiocytosis X). A clinicopathologic study of 48 cases. Am J Surg Pathol.
1993;17:971-86.
8. Schonfeld N, Frank W, Wenig S, Uhrmeister P, Allica E, Preussler H, et al. Clinical and radiologic
features, lung function and therapeutic results in pulmonary histiocytosis X. Respiration. 1993;60:38-
44.
9. Braier J, Latella A, Balancini B, Castanos C, Rosso D, Chantada G, et al. Outcome in children with
pulmonary Langerhans cell Histiocytosis. Pediatr Blood Cancer. 2004;43:765-9.
10. Odame I, Li P, Lau L, Doda W, Noseworthy M, Babyn P, et al. Pulmonary Langerhans cell histiocytosis:
A variable disease in childhood. Pediatr Blood Cancer. 2006;47:889-93.
11. Seely JM, Salahudeen S, Cadaval-Goncalves AT, Jamieson DH, Dennie CJ, Matzinger FR, et al.
Pulmonary Langerhans Cell Histiocytosis: A comparative study of computed tomography in children
and adults. J Thorac Imaging. 2010.
CASE 95
A Case of Chronic Hypersensitivity

Pneumonitis in a 30-year-old Male
CASE REPORT
A 30-year-old nonsmoker male, farmer by occupation came to us with chief complaints of
cough (productive in nature) on and off for 2 years more since last 1 month and progressive
dyspnea since last 6 months with no history of orthopnea and paroxysmal nocturnal
dyspnea (PND). He has a past history of antitubercular treatment for smear negative
pulmonary tuberculosis for 6 months. General physical examination was within normal
limits except for the presence of clubbing. Respiratory examination revealed bilateral end
inspiratory crepts. Chest X-ray showed diffuse poorly defined nodular shadows with areas
of ground-glass opacity (Fig. 1). CT thorax showed multiple centrilobular nodules 2–4 mm
in diameter throughout the lung fields, with some areas of ground-glass radiodensities,
especially in the lower lobes (Figs. 2A to D). Routine blood investigation was within normal
limits. Rheumatology panel was negative for all markers. Pulmonary function test revealed
decrease in diffusion capacity of lungs for carbon monoxide (DLCO) (38%) with normal forced
FIG. 1: Chest X-ray at the time of presen

tation.
A Case of Chronic Hypersensitivity Pneumonitis in a 30-year-old Male 339
A B
C D
FIGS. 2A TO D: CT thorax showing multiple centrilobular nodules with areas of
ground-glass radiodensities in the lower lobes.
expiratory volume in 1 second (FEV1) forced vital capacity (FVC) ratio (76%), normal FEV1(72%)
and decrease in FVC (28%) suggestive of restrictive lung disease. Transbronchial lung
biopsy (TBLB) shows alveolar macrophages and multinucleated giant cells consistent with
diagnosis of hypersensitivity pneumonitis (HP). Bronchial aspirate was also sent for cytology
which showed benign columnar epithelial cells, heavy infiltration of neutrophils, and few
macrophages. Thus, a diagnosis of HP was made. Patient was put on oral prednisolone 40
mg for first 2 weeks which was gradually tapered over next 4 weeks. Patient showed dramatic
response to corticosteroid treatment.
DISCUSSION
Hypersensitivity pneumonitis (HP) is a rare immune system disorder that affects
the lungs. It is an inflammation of the alveoli (airspaces) within the lung caused by
hypersensitivity to inhaled organic dusts. An imperative feature of HP is the great
unevenness of susceptibility among exposed inhabitants and the seeming resistance to
illness of most exposed persons. Farmer’s lung and Bird breeder’s are the most common
type of HP.
The disease may be acute, subacute, or chronic as per categorization. Acute clinical
presentation includes transient fever, hypoxemia, myalgias, arthralgias, dyspnea, and
cough that occur 2–9 hours after exposure to specific antigen and resolve in 12–72 hours
without definitive treatment. Subacute or intermittent disease may result from repetitive
exposures and manifest as productive cough, dyspnea, fatigue, and weight loss. The
chronic entity present with a gradual onset of cough, dyspnea which are troublesome for
the patient with few constitutional symptoms such as fatigue, and weight loss. Symptoms
have a gradual course and are usually present for months to years. Long-term exposure to
low amounts of bird antigens is associated with chronic HP.
In acute HP, chest radiographs show diffuse micronodular interstitial pattern in the
lower and middle lung zones. In high-resolution CT scans, ground-glass opacities or
diffusely increased radiodensities are present. Pulmonary function tests reveals mostly
restrictive patterns, sometimes may also show mixed patterns with reduced diffusion
capacity of lungs for carbon monoxide (DLCO). In chronic HP, chest radiographs show
progressive fibrotic changes with loss of lung volume particularly affecting the upper
lobes. Nodular or ground glass opacities are not present.
Lung biopsies can be diagnostic in cases of chronic HP, and may help to propose the
diagnosis and strengthen the search for a particular allergen. The best treatment is to avoid
the aggravating allergen, as chronic exposure can cause irreversible damage to the lung
parenchyma. Corticosteroids help to control symptoms.
FURTHER READING
1. Girard M, Lacasse Y, Cormier Y. Hypersensitivity pneumonitis. Allergy. 2009;64:322-34.
2. Salisbury ML, Gu T, Murray S, Gross BH, Chughtai A, Sayyouh M, et al. Hypersensitivity pneumonitis:
Radiologic phenotypes are associated with distinct survival time and pulmonary function trajectory.
Chest. 2019;155:699-711.
3. Vasakova M, Morell F, Walsh S, Leslie K, Raghu G. Hypersensitivity Pneumonitis: Perspectives in
Diagnosis and Management. Am J Respir Crit Care Med. 2017;196:680-9.
4. Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J
Respir Crit Care Med. 1994;150:967-72.
5. Richerson HB, Bernstein IL, Fink JN, Hunninghake GW, Novey HS, Reed CE, et al. Guidelines for the
clinical evaluation of hypersensitivity pneumonitis. Report of the Subcommittee on Hypersensitivity
Pneumonitis. J Allergy Clin Immunol. 1989;84:839-44.
6. Monkare S, Haahtela T. Farmer's lung—a 5-year follow-up of eighty-six patients. Clin Allergy.
1987;17:143-51.
7. De Vuyst P, Dalphin JC. Occupational interstitial lung diseases. Rev Prat. 2007;57:2266-76.
8. Gupta A, Rosenman KD. Hypersensitivity pneumonitis due to metal working fluids: Sporadic or
under reported? Am J Ind Med. 2006;49:423-33.
9. Hodgson MJ, Bracker A, Yang C, Storey E, Jarvis BJ, Milton D, et al. Hypersensitivity pneumonitis in a
metal-working environment. Am J Ind Med. 2001;39:616-28.
10. Rosenman KD. Asthma, hypersensitivity pneumonitis and other respiratory diseases caused by
metalworking fluids. Curr Opin Allergy Clin Immunol. 2009;9:97-102.
11. Adkinson NF, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FER, et al. Middleton's
Allergy: Principles & Practice, 6th edition. Missouri: Mosby; 2007.
12. Vourlekis JS, Schwarz MI, Cherniack RM, Curran-Everett D, Cool CD, Tuder RM, et al. The effect
of pulmonary fibrosis on survival in patients with hypersensitivity pneumonitis. Am J Med.
2004;116:662-8.
CASE 96
A Case of Cryptogenic Organizing

Pneumonia in a 60-year-old Female
CASE REPORT
A 60-year-old female, housewife by occupation came to us with complains of progressive,
persistent breathlessness for 4 months. There is no history of orthopnea/paroxysmal
nocturnal dyspnea (PND). She also complained of cough (nonproductive) for 4 months. She
also has type 2 diabetes mellitus (T2DM) and is on treatment for last 5 years but it is poorly
controlled. She is a known hypertensive for 7 years. She has a history of hypothyroidism for
5 years. General physical examination was within normal limits. Respiratory examination
revealed bilateral infrascapular end inspiratory crepts. Routine Blood investigation was
within normal limits. Rheumatoid panel workup was done which came negative. Chest
X-ray showed nonspecific patchy areas of consolidation (Fig. 1). Computed tomography (CT)
FIG. 1: Chest X-ray showing patchy areas of consoli

dation at time of presentation.
A B C
D E F
FIGS. 2A TO F: Computed tomography (CT) thorax showing areas of peripheral, peribronchial
consolidation at the time of presentation.
FIG. 3: Chest X-ray after 1 month of oral steroid

treatment.
thorax showed peripheral peribronchovascular areas of ground-glass opacity and consoli

dation (Fig. 2). Spirometry showed FEV1/FVC 78% and FVC was 40% with 79% carbon monoxide
diffusing capacity (DLCO) suggestive of restrictive lung disease. Patient was diagnosed as a
case of cryptogenic organizing pneumonia (COP) and was put on oral steroid 0.75 mg/kg for
2 weeks followed by 0.5 mg/kg for next 4 weeks and showed dramatic response to treatment
both clinically and radiologically within 6 weeks (Figs. 3 to 5).
A Case of Cryptogenic Organizing Pneumonia in a 60-year-old Female 343
FIG. 4: Chest X-ray after completion of treatment.
A B C
D E F
FIGS. 5A TO F: Computed tomography (CT) thorax showing resolution on completion of
treatment.
DISCUSSION
Cryptogenic organising pneumonia (COP) is a form of idiopathic interstitial pneumonia
characterized by lung inflammation and scarring that obstructs the small air-ways and
alveoli The three main imaging characteristic patterns of COP are multiple alveolar
opacities (typical COP), solitary opacity (focal COP) and infiltrative opacities (infiltrative
COP). It represents with flu like symptoms such as cough, fever, malaise, fatigue, and
weight loss. It often affects adults and middle-aged persons (40–60 years). The exact
underlying cause is unknown. Radiologically it presents with unilateral or bilateral
patchy areas in all lung zones usually peripheral, subpleural, peribronchovascular. The
diagnosis of COP cough relies on apical clinicoradiological and pathological features
and exclusion of any recognized cause. Lung biopsy is preferred method to confirm the
diagnosis. The differential diagnosis of COP includes community-acquired pneumonia,
idiopathic interstitial pneumonias, hypersensitivity pneumonitis and chronic eosinophilic
pneumonia and sarcoidosis. Spontaneous remissions have been described for patients
with mild symptoms and minimal radiographic and PFT abnormalities. Majority of
patients with progressive symptoms and diffuse radiographic involvement are treated
with oral glucocorticoids resulting in marked improvement in symptoms. British Thoracic
Society guidelines recommend initiating prednisone at a dose of 0.75 to 1 mg/kg per day
and weaning over 6 to 12 months. The prognosis of typical cough with patchy alveolar
opacities is usually excellent with corticosteroid treatment as happens in this case.
FURTHER READING
1. Shen L, Liu J, Huang L, Zhang Y, Xiao X, Yu H. Cryptogenic Organizing Pneumonia Presenting as a
Solitary Mass: Clinical, Imaging, and Pathologic Features. Med. Sci. Monit. 2019;25:466-74.
2. Saito Z, Kaneko Y, Hasegawa T, Yoshida M, Odashima K, Horikiri T, et al. Predictive factors for relapse
of cryptogenic organizing pneumonia. BMC Pulm Med. 2019;19:10.
3. Oliveira DS, Araújo Filho JA, Paiva AFL, Ikari ES, Chate RC, Nomura CH. Idiopathic interstitial
pneumonias: review of the latest American Thoracic Society/European Respiratory Society
classification. Radiol Bras. 2018;51:321-7.
4. Baha A, Yıldırım F, Köktürk N, Galata Z, Akyürek N, Demirci NY, et al. Cryptogenic and secondary
organizing pneumonia: Clinical presentation, radiological and laboratory findings, treatment, and
prognosis in 56 cases. Turk Thorac J. 2018;19:201-8.
5. Neelambra AN, Acharya V, Sundararajan S. Cryptogenic Organizing Pneumonia with Sarcoidosis
Overlap: An Atypical Case Study. Case Rep Med. 2018;2018:4316109.
6. Godbert B, Clement-Duchêne C, Regent D, Martinet Y. [Do all cryptogenic organizing pneumonias
require lung biopsy and steroid treatment?]. Rev Mal Respir. 2010;27:509-14.
CASE 97
A Case of Drug-induced Interstitial Lung

Disease in a 63-year-old Female
CASE REPORT
A 63-year-old female, doctor by occupation came to our OPD with complaints of progres
sive breathlessness for 1 month [not associated with orthopnea and paroxysmal nocturnal
dyspnea (PND)] and nonproductive cough for 1 month. She is a nonsmoker and there
is no history of diabetes mellitus and hypertension. There is no history of arthralgia,
morning stiffness, Raynaud’s phenomenon, photosensitivity, dry skin, oral ulcers, and digi
tal ulceration. On detailed history, patient had been treated for adenocarcinoma colon
and was given oxaliplatin, 5-FU, and leucovorin chemotherapy for six cycles which was
completed 4 months ago. General physical examination was within normal limits. Respiratory
examination revealed bilateral end inspiratory crepts. Chest X-ray showed reticulonodular
shadows, mainly confined to both lower zones (Fig. 1). High-resolution CT thorax showed
interseptal thickening with patchy consolidation and reticulonodular shadows along with
subpleural honeycombing mainly confined to bases (Fig. 2). Routine blood investigation
and rheumatoid panel was negative. Blood gas analysis revealed hypoxemia (pO2 36).
Spirometry showed decrease in diffusing capacity of lung for carbon monoxide (DLCO)
test (40%), normal forced expiratory volume in one second/forced vital capacity (FEV1/FVC),
and decreased FVC (56%) suggestive of restrictive lung disease. After careful examination
and excluding other causes of interstitial lung disease (ILD), drug-induced ILD (DIILD) due
to oxaliplatin was diagnosed and patient was started on deflazacort 30 mg BD and after
2 weeks tapered to 6 mg OD over 6 months while monitoring clinical, physiological, and
radiological measures (Figs. 3A and B). Further patient was put on maintenance dose with
Deflazacort 1 mg alternate day. Follow-up spirometry after 3 months treatment revealed
normal study (FVC 99% DLCO 79%). Treatment was stopped after completion of 1 year.
After a year of treatment chest X-ray. CT thorax improved (Figs. 4A and B) and spirometry
showed normal study. Patient improved symptomatically and radiologically on completion of
treatment. On regular follow-up for next 5 years, she remained asymptomatic.
FIG. 1: Chest X-ray showing diffuse reticulonodu-

lar shadow at time of presentation.
FIG. 2: CT thorax showing interseptal thickening

with patchy consolidation, reticulonodular infil-
trates with subpleural honeycombing.
A B
FIGS. 3A AND B: Chest X-ray and CT thorax after 3 months of treatment showing
complete resolution.
A Case of Drug-induced Interstitial Lung Disease in a 63-year-old Female 347
A B
FIGS. 4A AND B: Chest X-ray and CT thorax after 1 year of treatment.
DISCUSSION
Drug-induced lung injury may involve the airways, lung parenchyma, mediastinum,
pleura, pulmonary vasculature, and/or the neuromuscular system. The most common
form of drug-induced lung toxicity is DIILD. A large number of drugs are involved in
the etiology of drug-induced interstitial lung disease (DIILD). DIILD can be caused by
chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive
agents. Oxaliplatin, a third-generation platin derivative, acts via interruption of DNA
synthesis. This drug has demonstrated activity in patients with resected colorectal cancer
as well as for patients with stage IV colorectal cancer. There are no distinct physiologic,
radiographic or pathologic patterns of DIILD, and the diagnosis is usually made when a
patient with interstitial lung disease (ILD) is exposed to a medication known to result in
lung disease. In this particular case HRCT thorax features were quite similar to idiopathic
interstitial fibrosis (IPF), but patient has history of exposure to drug oxaliplatin. Though
HRCT was suggestive of IPF but it was drug induced that is why patient responded
dramatically and patient’s X-ray and CT thorax became normal and patient remained
asymptomatic and normal in subsequent 5 year follow-up. Treatment is avoidance of
further exposure and systemic corticosteroids in patients with progressive or disabling
disease.
FURTHER READING
1. Chen C, Chen C-H, Liao W-C, Liang S-J, Tu C-Y. Fibrotic hypersensitivity pneumonitis induced by
oxaliplatin: A unexpected but serious side effect in treating colorectal cancer. Am J Respir Crit Care
Med. 2018;197:A6648.
2. Flieder D, Travis W. Pathologic characteristics of drug-induced lung disease. Clin Chest Med.
2004;25:37-45.
3. Nemery B, Bast A, Behr J, Borm PJ, Bourke SJ, Camus PH, et al. Interstitial lung disease induced by
exogenous agents: factors governing susceptibility. Eur Respir J. 2001;18:30S-42S.
4. Davies E, Green C, Talor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in
hospital in-patients. A prospective analysis of 3695 patient-episodes. PLoS One. 2009;4:e4439.
5. Wu T, Jen M, Bottle A, Molokhia M, Aylin P, Bell D, et al. Ten-year trends in hospital admissions for
adverse drug reactions in England 1999-2009. J R Soc Med. 2010;103:239-50.
6. Limper A, Rosenow E. Drug-induced interstitial lung disease. Curr Opin Pulm Med. 1996;2:396-404.
7. Coultas D, Zumwalt R, Black W, Sobonya RE. The epidemiology of interstitial lung diseases. Am J
Respir Crit Care Med. 1994;150:967-72.
8. Mendez J, Nardous H, Hartman T, Ryu JH. Chronic nitrofurantoin-induced lung disease. Mayo Clin
Proc. 2005;80:1298-302.
9. Kudoh S, Kato H, Nishiwaki Y, Fukuoka M, Nakata K, Ichinose Y, et al. Interstitial lung disease in
Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care
Med. 2008;177:1348-57.
10. Miyakoshi S, Kami M, Yuji K, Matsumura T, Takatoku M, Sasaki M, et al. Severe pulmonary
complications in Japanese patients after bortezomib treatment for refractory multiple myeloma.
Blood. 2006;107:3492-4.
CASE 98
A Case of Idiopathic Pulmonary Fibrosis

Misdiagnosed as Bronchial Asthma
CASE REPORT
A 63-year-old male smoker came to our OPD with complaints of nonproductive cough and
progressive breathlessness for 3 years. He had decreased appetite for 10 days and fever
(low grade) for 5 days. There was no history of hemoptysis or joint pain. General physical
examination revealed clubbing and cyanosis. Respiratory examination revealed tachypnea
and bilateral end inspiratory crepts. Chest X-ray revealed bilateral reticulonodular opacity
in lower zones distributed asymmetrically which has increased with passage of time. CT
thorax revealed patchy, predominantly peripheral, subpleural, and bibasilar reticular
opacities (Figs. 1 and 2). Lung function test revealed reduced forced vital capacity (FVC)
[1.3 (48% predicted) with normal forced expiratory volume in 1 second (FEV1), FEV1/FVC
ratio and reduced diffusion lung capacity for carbon monoxide (CO) (43%)]. Rheumatoid
panel was within normal limits. Patient was earlier misdiagnosed as bronchial asthma and
was put on inhaled steroid for a period of 3 years without any response. In due course of time
patient chest, X-ray and CT thorax progressively deteriorated. Blood gas analysis revealed
hypoxemia (pO2 45%). Patient was diagnosed as a case of idiopathic interstitial pneumonia
and was diagnosed as idiopathic pulmonary fibrosis. Patient was put on oral corticosteroids,
FIG. 1: Chest X-ray showing reticular opacities in

bilateral lower zone.
azathioprine, and N-acetylcysteine according to the guidelines for management of

idiopathic pulmonary fibrosis (IPF) prevalent at that time and was given long-term oxygen
therapy. Follow-up CT thorax showed presence of extensive honeycombing (small, round
translucencies with a density equal to that of air), traction bronchiectasis, and thickened
interlobular septae (Fig. 3). Follow-up spirometry showed decline in FVC (29%). However,
the disease progressively increased and patient died in 2005. This was a case of IPF which
did not respond to any treatment and patient died in 7 years’ time.
A B
C
FIGS. 2A TO C: CT thorax showing honeycombing, traction bronchiectasis, and
septal thickening.
A B
FIGS. 3A AND B: CT thorax showing extensive honeycombing with reticular
pattern with tractional bronchiectasis.
A Case of Idiopathic Pulmonary Fibrosis Misdiagnosed as Bronchial Asthma 351
DISCUSSION
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease in which progressive
fibrosis and scarring of the lung parenchyma lead to symptoms such as dyspnea on
exertion, dry cough, and eventually leading to respiratory failure. The clinical symptoms
of IPF are nonspecific. Progressive dyspnea and dry cough are predominant clinical
features found in most patients of IPF. Symptoms like these can be shared with a range
of pulmonary and cardiac diseases. The most prominent symptom in IPF is dyspnea
which has a gradual onset and is often progressive. Constitutional symptoms can occur
but are uncommon. Some of these systemic symptoms consist of weight loss, low-grade
fevers, fatigue, arthralgias, or myalgias. In most patients with IPF, the physical examination
reveals fine bibasilar inspiratory crackles (Velcro crackles). Additionally, digital clubbing is
seen in 25–50% of patients with IPF. Pulmonary hypertension is a common comorbidity in
patients with idiopathic pulmonary fibrosis and an estimated 20–40% of patients with IPF
who are evaluated or listed for lung transplantation have pulmonary hypertension at rest.
The chest radiograph shows peripheral reticular opacities (netlike linear and curvilin
ear densities) predominantly at the base of lung. Honeycombing (coarse reticular pattern)
and volume loss in lower lobes has also been seen. On high-resolution computed
tomography (HRCT) imaging, IPF is characterized by patchy, peripheral, subpleural, and
bibasilar reticular opacities. Ground-glass opacities can be found but are less extensive
than reticular abnormalities.
A restrictive ventilatory defect is characteristically present in patients with IPF. Vital
capacity, functional residual capacity, total lung capacity, and forced vital capacity (FVC)
all are reduced. Prognostication in IPF depends on serial assessments of FVC. Patients who
have >10% decline in FVC (percent predicted) over 6 months, have a 2.4-fold increased
risk of death. Furthermore, in patients who do not desaturate to <88% during a 6-minute
walk test (6MWT), the only strong predictor of mortality is a progressive decline in FVC
(>10% after 6 months). About 70–90% of all patients with IPF have shown increased
numbers of neutrophils in bronchoalveolar lavage (BAL) fluid and increased numbers
of eosinophils in BAL fluid are found in 40–60% of all patients with IPF. A surgical lung
biopsy offers the best sample which distinguishes usual interstitial pneumonia from other
idiopathic interstitial pneumonias.
Treatment consists of antifibrotics (pirfenidone/nintedanib), long-term oxygen
therapy, and symptomatic treatment. When antifibrotic drugs were not available, treat
ment consisted of combination of oral corticosteroids, N-acetylcysteine, and azathioprine.
Studies later on revealed that corticosteroids and other drugs were of little to no help
in providing symptomatic relief to the patient. Although the life span of IPF patient is
between 3–5 years from the onset of disease, but this patient remained alive for >7 years.
Lung transplantation can also be offered to the patient of IPF.
FURTHER READING
1. Raghu G, Remy-Jardin M, L. Myers J, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic
pulmonary fibrosis. An official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care
Med. 2018;198:44-65.
2. Cerri S, Sgalla G, Richeldi L, Luppi F. Occurrence of idiopathic pulmonary fibrosis during
immunosuppressive treatment: A case report. J Med Case Rep. 2016:10:127.
3. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. INPULSIS Trial Investigators.
Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071-82.
4. King TE Jr., Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial
of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083-92.
5. The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, azathioprine, and
N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366:1968-77.
6. King TE, Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378:1949-61.
7. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/
ALAT statement: idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and
management. Am J Respir Crit Care Med. 2011;183:788-824.
8. Spagnolo P, Del Giovane C, Luppi F, Cerri S, Balduzzi S, Walters EH, et al. Non-steroid agents for
idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2010;9:CD003134.
9. Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, et al. Treatment of idiopathic pulmonary
fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013;158:641-9.
10. Schunemann HJ, Jaeschke R, Cook DJ, Bria WF, El-Solh AA, Ernst A, et al. An official ATS statement:
grading the quality of evidence and strength of recommendations in ATS guidelines and
recommendations. Am J Respir Crit Care Med. 2006;174:605-14.
11. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic
pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174:810-6.
12. Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, et al. Acute exacerbation of
idiopathic pulmonary fibrosis: an international working group report. Am J Respir Crit Care Med.
2016;194:265-75.
CASE 99
A Case of Rheumatoid Arthritis-associated

Interstitial Lung Disease
CASE REPORT
A 56-year-old smoker male (20 bidi per day for 35 years), known case of rheumatoid
arthritis came to us with complaints of cough with expectoration for 1 year, progressive
breathlessness for 1 year, fever for 1 month, right side chest pain referred to ipsilateral
shoulder for 15 days, and decreased appetite for 15 days. General examination revealed
clubbing and pallor. Metacarpophalangeal and interphalangeal joints were stiff, swollen,
and painful. Respiratory examination revealed end inspiratory crepts on left side and
reduced breath sound on right side. Chest X-ray revealed diffuse reticular infiltrates with
right side subpulmonic effusion (Fig. 1). X-ray both hands were suggestive of rheumatoid
arthritis (Fig. 2) Patient was on antitubercular treatment by a private practitioner outside
for last 4 weeks without any improvement. Routine blood investigation was within normal
limits. Rheumatoid arthritis (RA) panel workup revealed positive RA factor (452 IU/mL) and
positive antinuclear antibody (ANA) test. Pleural fluid was aspirated which was exudative
in nature. Pleural fluid was negative for AFB and was positive for RA factor. Pleural fluid
cytology revealed a background of necrotic debris, spindle-shaped macrophages, and
multinucleated histiocytes suggestive of rheumatoid pleural effusion. CT thorax revealed
FIG. 1: Chest X-ray showing diffuse reticular

infiltrates with right-sided pleural effusion.
honeycombing with areas of ground glass occupying basal and subpleural region
(Figs. 3 to 5). Thus, a diagnosis of rheumatoid arthritis-associated interstitial lung disease
(RA-ILD) with right-sided pleural effusion was made and patient was put on corticosteroid
treatment. Patient was evaluated after 6 weeks. Pleural effusion disappeared and patient
improved symptomatically.
FIG. 2: X-ray both hands suggestive of rheumatoid arthritis.
FIG. 3: HRCT thorax showing increased reticular

marking with ground glass shadows.
A Case of Rheumatoid Arthritis-associated Interstitial Lung Disease 355
FIG. 4: HRCT thorax showing with honeycombing

with areas of ground glass shadows.
FIG. 5: CT thorax revealed honeycombing with areas

of ground glass occupying basal and subpleural region.
DISCUSSION
Interstitial lung disease (ILD) is one of the common complications of rheumatoid
arthritis (RA) contributing to significantly increased morbidity and mortality. In an
estimate, nearly 50% of RA patients will develop some form of respiratory abnormality
during their lifes pan. Numerous pulmonary complications have been listed which are
associated with RA but the most debilitating respiratory disease remains rheumatoid
arthritis-associated interstitial lung disease (RA-ILD). Pulmonary function test and
more specifically the diffusing capacity of lung for carbon monoxide (DLCO) test,
appears to be the most sensitive test available to screen for the presence of RA-ILD.
Patients with RA have a reduced DLCO, a purely restrictive defect is found in 5–15%
of patients on spirometry. Mortality and morbidity is associated with greater articular

involvement, presence of rheumatoid nodule, pleuropulmonary involvement, and
systemic complications such as myocarditis, pericarditis. Pleural effusion is exudative
with low glucose and low pH. Pleural fluid cytology reveals necrotic debris and spindle
cell macrophages. High-resolution computed tomography (HRCT) thorax shows
the presence of bibasilar, symmetrical, ground glass infiltrates, increased reticular
markings, or honeycombing which is highly suggestive of ILD. Other relevant findings
consist of pleural involvement, rheumatoid nodules, bronchiectasis, emphysema, or
even bronchiolitis with or without consolidation. Usual interstitial pneumonitis (UIP)
is the principal histological finding in RA-ILD affecting >50% of patients. Bronchiolitis
obliterans-organizing pneumonia (BOOP) occurs less frequently in about 10% of
patients and it carries good prognosis as Nonspecific interstitial pnuemonia (NSIP).
Hallmark features on HRCT include subpleural consolidation with patchy ground
glass infiltrates. Treatment comprises of oral corticosteroids, disease-modifying anti
rheumatic drugs (DMARDs), biologics (e.g., infliximab, etanercept, rituximab), and
other conservative measures.
FURTHER READING
1. Hamblin MJ, Horton MR. Rheumatoid arthritis-associated interstitial lung disease: Diagnostic
dilemma. Pulm Med. 2011;2011:872120.
2. Iqbal K, Kelly C. Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective
review. Ther Adv Musculoskelet Dis. 2015;7:247-67.
3. Airo P, Danieli E, Rossi M, Frassi M, Cavazzana I, Scarsi M, et al. Intravenous cyclophosphamide for
interstitial lung disease associated to systemic sclerosis: results with an 18-month long protocol
including a maintenance phase. Clin Exp Rheumatol. 2007;25:293-6.
4. Assayag D, Elicker B, Urbania T, Colby T, Kang B, Ryu J, et al. Rheumatoid arthritis-associated
interstitial lung disease: radiologic identification of usual interstitial pneumonia pattern. Radiology.
2014;270:583-8.
5. Aubart F, Crestani B, Nicaise-Roland P, Tubach F, Bollet C, Dawidowicz K, et al. High levels of anti-
cyclic citrullinated peptide autoantibodies are associated with co-occurrence of pulmonary
diseases with rheumatoid arthritis. J Rheumatol. 2011;38:979-82.
6. Barskova T, Gargani L, Guiducci S, Randone S, Bruni C, Carnesecchi G, et al. Lung ultrasound for the
screening of interstitial lung disease in very early systemic sclerosis. Ann Rheum Dis. 2013;72:390-5.
7. Becerra G, Cambridge M. Safety and efficacy of rituximab in patients with rheumatoid arthritis and
lung involvement. Ann Rheum Dis. 2013;72:A450-A450.
8. Bonella F, Costabel U. Biomarkers in connective tissue disease-associated interstitial lung disease.
Semin Respir Crit Care Med. 2014;35:181-200.
CASE 100
A Case of Combined Pulmonary

Fibrosis and Emphysema
CASE REPORT
A 75-year-old male came to us with complaints of progressive breathlessness for 6 months
which was insidious in onset, exertional in nature, and gradually increased from MMRC
Grade 2 to Grade 4 at presentation. No diurnal or postural variation was present. There was
no history of orthopnea, paroxysmal nocturnal dyspnea, and wheeze. He has a history of
type 2 diabetes mellitus (T2DM) for 7 years and is on oral hypoglycemic agents since then
and was adequately controlled. On clinical examination pulse rate is 100 beats/min and
regular. Respiratory rate is 28/min blood pressure is 126/78 mm Hg. Temperature was 98°F,
SpO2 was 90% at room air. On general examination, there was the presence of clubbing.
Respiratory examination revealed bilateral basal end inspiratory crepts. Chest X-ray revealed
the presence of reticular infiltrates bilaterally with cystic shadows (Fig. 1). High-resolution
computed tomography (HRCT) thorax revealed the presence of upper-lobe centrilobular and
paraseptal emphysema with multiple bullae and lower-lobe honeycombing with subpleural
reticular opacities and traction bronchiectasis (Figs. 2 and 3). Spirometry with diffusing
FIG. 1: Chest X-ray revealed the presence of reticular

infiltrates bilaterally with cystic shadows.
A B
FIGS. 2A AND B: HRCT thorax showing upper-lobe centrilobular and paraseptal emphysema
with multiple bullae and lower-lobe honeycombing with subpleural reticular opacities and
traction bronchiectasis.
FIG. 3: HRCT thorax showing honeycombing with cyst.
capacity of lung for carbon monoxide (DLCO) test showed normal values of forced expiratory
volume in one second (FEV1), normal forced vital capacity (FVC), normal FEV1/FVC ratio, and
decreased DLCO 33%. Combined with the HRCT picture and the lung function report, the final
diagnosis of combined pulmonary fibrosis with emphysema (CPFE) was made.
DISCUSSION
In 2005, Cottin et al. originally put forward a defined syndrome termed “combined
pulmonary fibrosis and emphysema (CPFE)”, which is characterized by heavy smoking
history, exercise hypoxemia, upper lobe emphysema and lower lobe fibrosis, unexpected
subnormal lung volumes, and severe reduction of carbon monoxide transfer. High-
resolution computed tomography (HRCT) is an obligatory tool to diagnose this syndrome.
CPFE is commonly complicated by pulmonary hypertension, acute lung injury, and
lung cancer which suggests poor prognosis. Other than lung transplantation, there is
A Case of Combined Pulmonary Fibrosis and Emphysema 359
little to no treatment or less effective treatment for CPFE patients with severe pulmonary
hypertension.
When pulmonary function tests (PFTs) demonstrate normal or near-normal
spirometry and lung volumes but a severely diminished diffusing capacity of lung for
carbon monoxide (DLCO), the diagnosis of the CPFE syndrome should be taken into
consideration in such settings especially in a current or former smoker. In a retrospective
review of patients with severe abnormalities in gas exchange on PFTs, defined as a carbon
monoxide transfer coefficient, of 40% predicted, 16% had CPFE while remaining had
emphysema, interstitial lung disease, or pulmonary arterial hypertension. These PFT
patterns should raise suspicion for CPFE syndrome but may also be explained by other
abnormalities such as pulmonary vascular disease, emphysema, and some forms of
interstitial lung disease.CPFE also has been recognized in the lung cancer population,
being present in 101 of 1,143 (8.9%) consecutive patients with lung cancer in a study
by Usui et al. Diagnosis of CPFE should be considered in those patients with severe
breathlessness and normal or near-normal spirometry and those with oxygen require
ments out of proportion to spirometric abnormalities as in this case. In such cases, full
PFTs and HRCT thorax can establish the presence of CPFE syndrome. Characteristic
radiologic findings in the CPFE syndrome include upper-lobe emphysema and lower-
lobe interstitial fibrotic changes. The emphysema in CPFE comprises bullous, paraseptal,
and centrilobular changes and is characteristically distributed in the upper lobes.
Honeycombing and reticular abnormalities are frequent but areas of ground glass
attenuation can be seen in most patients. Occasionally, ground glass attenuation is the
only abnormality suggesting the likelihood of interstitial lung disease and in this setting
biopsy is essential. Smoking is almost universal in reported cases of CPFE, ground
glass attenuation may be indicative of smoking-related interstitial lung diseases such
as desquamative interstitial pneumonia. Incidentally, lung nodules or masses may be
found in patients with CPFE because the prevalence of lung cancer in this population
appears to be high. Diagnosis of the CPFE syndrome is established after HRCT imaging
in combination with pathology. Lung biopsy is rarely required. There is no definitive
treatment for the CPFE syndrome at present. The first recommended treatment for COPD
and IPF is smoking cessation, which should be encouraged for CPFE as well because it
may halt the progression of disease. In order to reduce acute exacerbations and infections,
patients are suggested to recieve a long-term oxygen therapy and take vaccination against
influenza viruses and streptococcus pneumonia. Oxygen therapy is known as the most
definitive treatment for hypoxemia and pulmonary hypertension in CPFE. For those who
have an obstructive or mixed ventilation dysfunction, the use of inhaled bronchodilators
provides some symptomatic relief. Cottin et al. recommended the use of N-acetylcysteine
(1.8 g/day) in CPFE but there was limited evidence for its efficacy. The main causes of
death in CPFE are severe pulmonary hypertension, hypoxemia, pulmonary infections, and
lung cancer. The key predictor of mortality is pulmonary hypertension.
FURTHER READING
1. Cottin V, Le Pavec J, Prévot G, Mal H, Humbert M, Simonneau G, et al. Pulmonary hypertension
in patients with combined pulmonary fibrosis and emphysema syndrome. Eur Respir J. 2010;35:
105-11.
2. Kiakouama L, Cottin V, Glerant JC, Bayle JY, Mornex JF, Cordier JF. Conditions associated with severe
carbon monoxide diffusion coefficient reduction. Respir Med. 2011;105:1248-56.
3. Katzenstein AL. Republished: smoking-related interstitial fibrosis (SRIF): pathologic findings and
distinction from other chronic fibrosing lung diseases. Postgrad Med J. 2014;90:597-602.
4. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/
ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and
management. Am J Respir Crit Care Med. 2011;183:788-824.
5. Papiris SA, Triantafillidou C, Manali ED, Kolilekas Likurgos. Combined pulmonary fibrosis and
emphysema. Expert Rev Respir Med. 2013;7:19-31.
6. Ryerson CJ, Hartman T, Elicker BM, Ley B, Lee JS, Abbritti M, et al. Clinical features and outcomes
in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis. Chest.
2013;144:234-40.
7. Lin H, Jiang S. Combined pulmonary fibrosis and emphysema (CPFE): an entity different from
emphysema or pulmonary fibrosis alone. J Thorac Dis. 2015;7:767-79.
INDEX
Page numbers followed by f refer to figure, and t refer to table.
A Aorta, arch of 7f
Aortography 42f
Abdominal diseases 49
Aorto-pulmonary window, lymph nodes of 99f,
Acetylene 75
100
Achalasia
Apgar scores 2
cardia 167
Aplasia 36
primary 169
Appetite, loss of 47, 125, 146, 242, 251, 277, 303,
Acid-fast bacilli 8, 18, 21, 22, 39, 41, 48, 60, 74,
312, 328, 330
85, 103, 110, 119, 131, 136, 148, 155, 159,
Artery, pulmonary 86
182, 216
Aspergilloma 209
smear 34, 67
pulmonary 208
Acid-fast bacteria 115, 117
Aspergillosis, invasive pulmonary 5
Acne 53
Aspergillus fumigatus 19, 88, 94, 171, 175, 178,
Acquired immune deficiency syndrome 16
180, 185, 191, 208, 212
Actinomyces israelii 83
Aspiration pneumonia 15
Actinomycosis, pulmonary 83
Asthma 190
Activated partial thromboplastin time 73
bronchial 34
Acute pneumococcal pneumonia 68
uncontrolled 167
Adenocarcinoma 308, 312
Atoll sign 5
Adenosine deaminase 22, 74
Autosomal dominant polycystic kidney
levels of 330
disease 87
Adenosquamous cell carcinoma 314
Agenesis 36
Allergic Aspergillus sinusitis 211, 212 B
Allergic bronchopulmonary aspergillosis 88, Bacilli Calmette-Guérin 62
91, 96, 171, 175, 176, 178, 180, 182, 185, 187, Barium meal study 230f, 231f
190-192, 211, 212f, 214 Bedaquiline 162, 163, 200
Alveolar microlithiasis, pulmonary 221 Benign fibroepithelial endobronchial
American Thoracic Society 196 polyps 258
Amikacin 162-163, 200 Bilateral homogenous shadows 182f, 183f
Amoxicillin 44, 162, 200 Bilateral multiple cavitary opacities 5f
Anemia 77 Bilateral parenchymal shadows 180f
Aneurysm rupture 49 Bilateral pleural effusion 54f, 73f, 74f, 77f, 78f
Angel’s wing appearance 40 resolution of 79f
Angiotensin-converting enzyme 48 Biomass fuel 293
Anthrax 49 Bird breeder’s 339
Anticoagulant 49 Bleeding 85
Antinuclear antibody test 353 after endobronchial biopsy 253f, 281f, 311f
Antiretroviral therapy 107 disorder 49
Antitubercular drugs 32, 104f, 129, 139, 162, Blood counts 81
244f Bone
dose of 107t marrow biopsy 11
Antitubercular therapy 22, 23f, 24, 24f, 106 scan 306
Antitubercular treatment 32, 56f, 103, 112f, Bony tumor 49
122f, 123, 124f, 126f, 134f, 136, 137f, 206, Borderline lepromatous leprosy 60, 63
268f, 313f Brain metastases, treatment of 326
Breast carcinoma 49 radiograph 4f, 15f, 18, 19f, 26, 27f, 36, 38, 38f,
Breathlessness 10, 54, 67, 77, 88, 93, 171, 180, 68f, 79f, 77f, 81f, 82f, 85f, 237f
216, 222, 228, 286, 312, 328, 330 roentgenogram 211f
progressive 14, 345, 349, 357 skiagram 94f
Bronchial carcinoid 262, 264 serial 95f
diagnosis of 264 wall, angiosarcoma of 49
treatment of 264 X-ray 22, 24f, 34, 41f, 47f, 61f, 89f, 103f-105f,
Bronchial disease 16 112f, 116f, 118f, 122f, 126f, 132f-138f,
Bronchiectasis 14, 71 142f-145f, 147f-149f, 155f-158f, 172f,
bilateral 16f, 91f 176f, 180f-183f, 187f-190f, 208f, 209f,
coexistence of 70 216f, 219, 223f, 226f, 229f, 233f, 244f,
Bronchiolitis obliterans-organizing 251, 262, 266f, 271, 273f-275f, 279f, 282f,
pneumonia 356 289f, 291f, 293f, 296f, 301f-304f, 312f,
Bronchoalveolar lavage 5, 9, 21, 39, 67, 99, 221, 318f, 322f, 325f, 330f, 335f, 341f, 346f,
351 349f, 357f
Ziehl–Neelsen staining of 74 Chilaiditi syndrome 233, 235
Bronchodilators 81 management of 235
Bronchography 174f Chondrosarcoma, retroperitoneal 49
Bronchopulmonary neuroendocrine
Choriocarcinoma 49
tumors 264
Chronic obstructive pulmonary disease 28, 70,
Bronchoscopy 82
71, 81, 93, 279, 289, 291, 295, 299, 303, 318,
Brucella 49
324
Burning sensation 225
Chylothorax 56-58, 58t, 78, 79
bilateral 54, 56f, 77
C
Cilastatin 162, 163, 200
Capreomycin 162-164, 200 Cirrhosis 56
Carbohydrate, high 78 Clavulanate 162
Carbon monoxide 340, 349 Clavulanic acid 200
diffusion capacity for 26, 27 Clofazimine 62, 162, 163, 200
lung for 338
Combined large-cell neuroendocrine
Carcinoid lung tumors 264
carcinoma 333
Carcinoid syndrome 264
Combined pulmonary fibrosis and
chronic sequelae of 264
emphysema 357, 358
Carcinoid tumor 260
Computed tomography 2, 7, 7f, 35, 169, 218
Carcinoma, bronchogenic 10, 49, 78
Conglomerate mass 40
Carmustine 239
Conglomerate silicosis 38, 39
Castleman disease 56
Cavity, malignant 280f Connective tissue diseases 49
Central bronchiectasis 184f, 191f Constant pain 46
Cerebrospinal fluid 106, 164 Contact dermatitis 53
Cervical lymphadenopathy 55 Contrast-enhanced computed tomography 97,
Cervix 326 167, 242
Chemotherapy, high-dose 239 Corticosteroids 340
Chest computed tomography 5 Cough 7, 14, 26, 30, 34, 41, 44, 93, 133, 146,
Chest 155, 159, 185, 219, 222, 245, 247, 249, 260,
computed tomography of 19, 19f, 20f, 38, 39f 262, 277, 286, 301, 303, 312, 314, 328, 330,
contrast-enhanced computed tomography of 353
5, 5f, 99, 99f-101f, 168f nonproductive 334, 345, 349
high-resolution computed tomography of productive 70, 81, 339
16f, 26, 26f recurrent 88, 256
infiltrates resolution of 134f, 135f, 137f, 138f Cushing syndrome 264
pain 1, 7, 115, 216, 242, 245, 301, 308, 312, Cyclophosphamide 13
314, 330 Cycloserine 121, 143, 156, 162, 163, 200
right-sided 237 Cystic shadows 357f
sudden onset of 222 Cysts, diffuse multiple 335f
Index 363
D Exertional dyspnea 16
Expectoration 30, 41, 155, 159, 242, 256,
Deficient thyroid transcription factor-1 36
262, 353
Delamanid 162, 163, 200
Extensive bilateral central bronchiectasis 174f,
Dengue hemorrhagic fever 49
212f
Densities, heterogeneous 213f
Extensively drug-resistant tuberculosis 136,
Dermatitis, exfoliative 51f, 52f
159, 161f
Diabetes mellitus 88, 110, 266
Extralobar sequestration 42
insulin-dependent 18
type 1 18
type 2 341
F
Diaphragm 228f Fairy ring sign 5
eventration of 225, 226, 228, 231 Familian lymphedema 56
raised dome of 118 Farmer’s lung 339
Diaphragmatic hernia 49 Fatigue 339
Differential leukocyte count 55, 77 Feeding, oral 78
Diffuse reticulonodular opacities 335f Fever 7, 77, 133, 142, 146, 155, 159, 216, 242,
Disease-modifying antirheumatic drugs 356 251, 260, 277
Doxorubicin 239 high-grade 67
Drug sensitive and drug resistant tuberculosis, low-grade 30, 93, 99
treatment of 106 moderate to high grade 44
Drug susceptibility test 155, 159, 161f recurrent 262
Dry cough 10, 67, 99, 142, 251 Fiberoptic bronchoscopy 39, 95, 253f, 261f, 269,
Dysphasia 251, 301, 322 269f, 272f, 273f, 281f, 290f, 291, 292f, 297f,
Dyspnea 339 298f, 300f, 301, 302f, 303, 305f, 312, 332f,
progressive exertional 81 333f
Fibrosis
E idiopathic
interstitial 347
Echinococcus granulosus 275
pulmonary 349, 351
Edema, pulmonary 68
progressive massive 38
Embolism, pulmonary 139
Filirasis 56
Emphysema
Fine-needle aspiration cytology 9, 11, 195
bilateral centrilobular 28f
Fingers, clubbing of 334f
paraseptal 358f
First-line antitubercular treatment 136f, 147f
Empyema 58t
Fistula, closure of 269f
thoracis 58
Flexible bronchoscopy 294f
Endobronchial biopsy 251, 262, 308, 314, 318
Fluoroquinolones 162
specimen, Gram’s stain of 82f
Forced expiratory volume 27
Endobronchial brush 39
Forced vital capacity 27, 339, 351, 358
Endobronchial polyp 256, 257f
Functional endoscopic
recurrence of 258f
sinus surgery 176
Endobroncial biopsy 279
sinusoidal surgery 212
Epidermal growth factor receptor 305
Fungal ball 19f, 89f, 90f, 209, 209f
Episodic breathlessness 34, 185
Erythrocyte sedimentation rate 85
Escherichia coli 86 G
Esophagectomy 79 Gastrointestinal tract 326
Estimated glomerular filtration rate 36 Gatifloxacin 162, 200
Etanercept 356 GeneXpert 99, 125, 136, 146, 155, 159
Ethambutol 23, 107, 108, 112, 113, 115, 119, Gentamicin 44
123, 133, 136, 137, 155, 156, 162, 163, 195, Glandular hypertrophy 31
206, 200, 216 Gomori methenamine silver staining 8, 8f,
Ethane 75 93
Ethionamide 32, 121, 156, 162, 163, 200 Gorham’s syndrome 56
chemical structure of 206 Gram’s stain 82f
Ewing sarcoma 49 Granulation tissue 267f
Ground-glass International Society for Human and Animal

radiodensities 339f Mycology 192
shadows 354f, 355f International Union Against Tuberculosis and
Gynecomastia 30f, 31f, 32 Lung Disease 195
drug-induced 30 Interstitial lung disease 347, 355
isoniazid-induced 30 drug-induced 345, 347
Interstitial pneumonia, nonspecific 5
H Interstitial pneumonitis, drug-induced 5
Halo sign 96 Intralobar sequestration 49
reversed 5 Invasive fungal pneumonias, diagnosis of 5
Hands, dorsum of 61f Isoniazid 30, 32, 107, 108, 112, 113, 115, 119,
Heart surgery, congenital 79 123, 133, 136, 142, 155, 195, 196, 200, 216
Heller’s myotomy, modified 169 high-dose 162, 163, 200
Hemangioma, pleural 49
Hemoptysis 88, 247, 256, 260, 314, 322 J
moderate to massive 262 Jugular venous pressure 22
recurrent 7, 41, 208, 249, 256, 260, 271,
301, 303 K
Hermaphroditism 32 Kanamycin 119, 121, 125, 129, 134, 144f, 150f,
High-density mucus impaction 189f 156, 162-164, 200, 204
High-resolution computed tomography 28, Kaposi’s sarcoma 15, 56
180, 190, 212, 219, 351, 358 Kawasaki disease 49
Hilar lymphadenopathy, bilateral 48f Klebsiella pneumonia 49
Histamine phosphate 88 Klinefelter syndrome 32
Hodgkin’s lymphoma 49
Human immunodeficiency virus 4, 22, 24, 70 L
Hydatid cyst
pulmonary 275, 276 Lactation 195
rupture of 271, 274f Langerhans cell histiocytosis,
Hydatid disease 275 pulmonary 334, 335
Hydrocarbons 75 Large-cell carcinoma 328, 330, 333
Hydropneumothorax 22, 222f Larynx and cutaneous tuberculosis,
resolution of 223f tuberculosis of 63
Hypernephroma 49 Left hilar mass 324f
Hypertension 88, 110 Left lung, collapse of 299f
Hypoalbuminemia 54, 77 Left pleural cavity 55
Hypoplasia 35f, 36 Lepra reaction 61f, 64
pulmonary 86 Leprosy 62, 63
Hypothyroidism 56 diagnosis of 64
tuberculosis coinfection 64t, 65t
I Leukemia 49
Imipenem 162, 163, 200 acute lymphoblastic 56
Immune Levofloxacin 137, 143, 156, 162, 163, 200
reconstitution inflammatory syndrome 24 Linezolid 162, 163, 200
system disorder 339 Lipoid pneumonia 5
Infarction, pulmonary 5, 49 Liver 85
Infection cirrhosis 49
pleuropulmonary 49 disease 204
recurrent 46 pre-existing 206
Inflammatory cells 335 function test 159
Infliximab 356 Lobectomy 210
Infrapulmonary effusion, right-sided 117, 117f Low fat medium chain triglycerides 78
International Agency for Research on Lowenstein–Jensen culture 55
Cancer’s 29 Lower lobe hypoplasia 34
Index 365
Lung Mitogen-activated protein kinase 36

abscess 45f, 282 Modern antitubercular chemotherapy
adenocarcinoma 316 regimens 53
agenesis of 36 Modified Medical Research Council Scale 26
biopsy 340, 344 Moxifloxacin 156, 162, 163, 200
transbronchial 339 Mucopurulent expectoration 7
disease, restrictive 339 Mucormycosis 8
following lung abscess, herniation of 44 aseptate hyphae of 8f
function data 27t pulmonary 4, 7, 8
hernia 45 Multidrug-resistant tuberculosis 107, 119, 121,
diagnosis of 45 123, 125, 127, 129, 131, 133, 134f, 137f, 142,
injury, drug-induced 347 146, 155, 156f, 157f
intralobar sequestration of 41 primary 121
plasmacytoma 237 regimen 133, 159
Lymph node 269, 314 treatment 100f, 135f, 143f-145f, 148f-150f,
fine-needle aspiration cytology of 295 156f, 157f, 160f
mediastinal 101f, 283f, 296f, 304f Multinodular growth 302f, 305f
multiple caseating mediastinal 267f Multiple bullae 320f
paratracheal 283f Multiple encysted fluid pockets mimicking
resolution of 23f mass 216f
tracheobronchial 304f Multiple myeloma 12, 237, 239, 240t
Lymphadenitis, mediastinal 243f diagnosis of 239
Lymphadenopathy, mediastinal 23f, 303, Multiple nodular
303f, 319f lesions 282, 283f-285f
Lymphangioleiomyomatosis 56 opacities 38f
Lymphocytes 47 shadows 187f
Lymphoma 49 Multisystem disorder 101
Lymphomatoid granulomatosis 5 Mycobacterium tuberculosis 24, 38, 42, 47, 55,
99, 110, 119, 121, 123, 125, 127, 129, 131,
M 133, 134, 136, 143, 147, 155, 159, 182, 199,
Magnetic resonance angiography 43 204, 208, 269
Magnetic resonance imaging 11, 169 Myelolipoma, mediastinal 49
thoracic angiography 35f Myofibroblastoma 49
Malignancy, pleuropulmonary 49
Mammary tissue hyperplasia, bilateral N
benign 31
Nasal blockage, recurrent 176
Mantoux test 167
Nasal discharge, recurrent 211
Mass
Neoplasm 88
heterogeneous 278f
Neuroendocrine tumors 326
intrathoracic 287f, 319f
Neutrophils 47
left parahilar 289f
parahilar 289, 308f, 309f, 328f, 329f Nocardia asteroides 94
paratracheal 287f Nodal multiple myeloma 10
pulmonary 81, 190 Nodule 244f
Massive hemotysis, recurrent 262 multiple 280f
Mediastinal fibrosis, radiation-induced 56 Non-Hodgkin’s lymphoma 49
Mediastinal nodes 49 Non-small cell lung
Meig’s syndrome 49 cancer 316
Melanoma, malignant 49 carcinoma 305, 333
Meropenem 162, 163, 200
Mesothelioma, malignant 49 O
Metastasis 49 Obstructive pneumonitis 242f, 303f, 304f
Metastatic squamous cell carcinoma 314 Octreoscan 265
Micafungin 21 Ofloxacin 200
Miliary tuberculosis 67 Oral corticosteroids 101f, 356
Oral steroids 188f Prednisone 239

treatment 172f, 173f Pregnancy 195
Orthopnea, history of 338, 341 unusual complication of 1
Osteosarcoma 49 Prophylactic cranial irradiation 326
Ovarian tumors 49 Prostate 326
Protein 55
P high 78
Pancreatitis Prothionamide 162, 163
acute 49 Pseudoachalasia 169
chronic 49 Pseudochylothorax 58, 58t
Para-aminosalicylic acid 119, 163, 196, 199, 204 Pseudomonas aeruginosa 71, 82
Para-aortic lymphadenopathy 55 Pulmonary aspergillosis, chronic
Paracoccidioidomycosis, pulmonary 5 necrotizing 18-20
Para-nasal sinuses, noncontrast computerized Pulmonary function test 71, 359
tomography of 213f Purified protein derivative 22, 48, 60
Paratracheal area, right 301f Pyrazinamide 23, 30, 107, 108, 112, 113, 123,
Parenchymal opacity 48f 133, 134, 136, 137, 142, 143, 155, 156, 162,
Paroxysmal nocturnal dyspnea 338, 341, 345 163, 200, 206, 216
Pericardial effusion, resolution of 24f
Phenol 75 R
Pit and basket like appearance 250f Red blood cell count 47
Pleural cavity, right 55 Renal failure 32
Pleural effusion 293, 296f chronic 49
left-sided 47f, 312f Renal insufficiency 198
massive 330, 330f Respiratory distress 46
recurrent 308 Rheumatoid arthritis 353, 354f, 355
right-sided 353f associated interstitial lung disease 353
sarcoidosis-related 49 diagnosis of 354
Pleural fluid 27, 55 Rhizopus oryzae 5
adenosine deaminase activity 106 Rifabutin 200
characteristics of 55t Rifampicin 107, 108, 112, 113, 119, 123, 133,
cholesterol 55 136, 142, 155, 200, 206, 216
culture 55 Rifapentine 200
triglyceride 58 Right upper lobe, collapse of 176, 176f
Pneumoconiosis 39 Rituximab 356
Pneumocystis carinii infection 14
Pneumonia 139, 245f S
bacterial 49 Sabouraud dextrose agar 8
community-acquired 67, 68 Sandstorm appearance 220f
cryptogenic organising 5, 341, 344 Sarcoidosis 47, 49, 56, 101
Pneumonitis pulmonary 5
chronic hypersensitivity 338 Scabies 53
hypersensitivity 339 Scanty sputum 26
usual interstitial 356 Semi-invasive pulmonary aspergillosis 20
Pneumothorax 2 Sequestration, pulmonary 42
primary spontaneous 2 Serum glutaryl pyruvate transaminase 204
right-sided 1f Signet ring appearance 212f
spontaneous 1 Silicosis 39
treatment of 2 Sinus
Positron emission tomography scan 306 signifying opacification of 213f
Postcoronary artery bypass grafting 49 tuberculous 253f
Potassium hydroxide 8 Small-cell
Potters rot 39 carcinoma 318, 322, 324, 326, 333
Prednisolone 62 lung cancer 326
oral 181f Spine, magnetic resonance imaging of 11
Index 367
Sputum positive pulmonary tuberculosis 129, Total lung capacity 27

195 Trachea, anterolateral wall of 302f
Squamous cell carcinoma 279, 282, 286, 289, Traction bronchiectasis 350f
293, 295, 299, 301, 303, 305 Transbronchial needle aspiration 244f
Streptomycin 107, 108, 112, 113, 115, 119, 123, Trimethoprim 97
133, 136, 162, 163 Tropical pulmonary eosinophilia 222, 223
Subclavian vein 56 Tubercle bacillus 201
Subpulmonic pleural effusion 118 Tuberculosis 22, 24, 40, 54, 62, 63, 65, 105, 107t,
Sugar 55 113, 163
Sulfamethoxazole 97 concomitant pulmonary 60
Superficial submucosal veins 287f, 288f endobronchial 242, 245
Superior vena cava prevalence of 69
syndrome 49, 286 pulmonary 5, 7, 51, 119, 123, 147f
thrombosis of 56 retreatment pulmonary 110
Swelling treatment of 106, 195, 198, 199, 204
over face 286 tuberculosis, bilateral pulmonary 127, 131
upper limbs 286 Tuberculous lymphotracheal fistula 266
Systemic lupus erythematosus 49 Tumor
malignant 49
T multinodular 281f
Tachypnea 93 pleural 49
Terizidone 162, 163, , 200
Testosterone production, enzyme U
defects of 32 Ultrasonography 35, 100, 233
Thalassemia intermediate 49 Uremic pleuritis 49
Thalidomide 62
Thioacetazone 32, 108, 162 V
Thoracic aorta 42f Velcro crackles 351
Thoracotomy 2 Video-assisted thoracic surgery 43
posterolateral 43 Video-assisted thoracoscopic surgery 2
Thorax Vincristine 239
computed tomography of 10, 11f, 23f, 35f, 36, Voice, hoarseness of 301, 322
41, 44, 45f, 60, 62f, 74f, 78, 187, 188f, 211f, Voriconazole 21
217f, 233, 234f, 238, 252f, 260, 262, 343f
contrast-enhanced computed tomography of W
85, 177f, 184f, 191f
high-resolution computed tomography of Wegener’s granulomatosis 5
88, 91f, 148f-150f, 171, 174f, 181f, 183f, Weight loss 125, 146, 277, 312, 322, 328, 339
186f, 220f, 271, 334, 356, 357 White blood cell count 22
Thromboembolism, pulmonary 49
Thrombotic microangiopathies 49 Z
Thyrotoxicosis 32 Ziehl–Neelsen stain 8, 55, 93, 96f
Toluene 75 modified 82, 83, 97
Total leukocyte count 55, 67, 73 Zollinger–Ellison syndrome 264
PLATE 1
FIG. 2: Gomori methenamine silver (GMS) staining from fine needle aspiration sample
showing broad randomly branched and aseptate hyphae of mucormycosis. (Case 1)
A B
FIG. 1A AND B: Revealed exfoliative dermatitis. (Case 15)
PLATE 2
A B
FIGS. 2A TO C: Image showing exfoliative

C dermatitis. (Case 15)
A B
FIGS. 1A TO C: (A and B) Revealed skin lesions

over face, forearm, and dorsum of hands due to
type-II lepra reaction. (C) Revealed exfoliative
skin lesions over forearm due to type-II lepra
C reaction. (Case 17)
PLATE 3
FIG. 2: Gram’s stain of the endobronchial biopsy specimen. Photomicro

graph showing thin, filamentous, branching gram-positive organisms
with a neutrophil-rich background (Gram's stain × 20). (Case 22)
A B C
FIGS. 1A TO C: (A) Chest radiograph [posteroanterior (PA) view] showing veiled opacity in left
hemithorax with shift of the mediastinum to the same side and both the diaphragms at the same
level; (B) Axial CT thorax at tracheal bifurcation level showing hypoplastic lung parenchyma on the
left side; and (C) Bronchoscopy image showing the small caliber opening of the left main bronchus.
(Case 23)
A B C
FIGS. 2A TO C: Axial CT thorax showing: (A) Absence of left pulmonary artery (arrow shows right
pulmonary artery); (B) 3D-reconstruction image showing right-sided aortic arch and four branches
arising from it; and (C) Enlarged bilateral kidneys with multiple cysts and thinning of parenchyma.
(Case 23)
PLATE 4
FIG. 4: Lactophenol cotton blue mount of sputum un-

der magnification 40× showing acute angle branching
septate hyphae of Aspergillus species. (Case 25)
A B
FIGS. 5A AND B: Ziehl–Neelsen (Z–N) staining and Gomori Methenamine Silver (GMS) mount
of sputum under magnification 400× and 1,000× respectively showing long delicate branched
filaments that are weakly acid fast and beaded pattern suggestive of Nocardia species. (Case 25)
FIG. 4: Two nodular growths. (Case 65)

PLATE 5
FIG. 5: Close view of nodule. (Case 65)
FIG. 6: Caseous material after transbronchial needle

aspiration. (Case 65)
FIG. 4: Mass-like lesion with central necrosis. (Case 66)

PLATE 6
FIG. 4: Right upper lobe bronchus obstructed by

caseous material and blood. (Case 67)
FIG. 3: Hypertrophied and hyperemic mucous mem

brane with pit like ulcer. (Case 68)
FIG. 4: Pit and basket like appearance. (Case 68)

PLATE 7
FIG. 3: Fiberoptic bronchoscopy showing bulging of

posterior wall of lower end of trachea. (Case 69)

culous sinus. (Case 69)
FIG. 5: Fiberoptic bronchoscopy showing tuberculous

sinus just behind secondary carina. (Case 69)
PLATE 8
FIG. 6: Bleeding after endobronchial biopsy. (Case 69)
A B
FIGS. 2 A AND B: Endobronchial polyp during expiration. (Case 70)
FIG. 3: Endobronchial polyp during inspiration.

(Case 70)
PLATE 9
FIG. 4: Polyp was removed endobronchially by rigid

bronchoscope in two sittings. (Case 70)
FIG. 5: Recurrence of endobronchial polyp after

7 months of treatment. (Case 70)

lobular tumor in left main bronchus. (Case 71)
PLATE 10
FIG. 4: Tumor taken out through rigid bronchoscope.

(Case 71)
FIG. 4: Tumor obstructing right main bronchus with

distortion of main carina. (Case 72)
FIG. 4: Fiberoptic bronchoscopy showing tracheal

fistula surrounded with granulation tissue. (Case 73)
PLATE 11
FIG. 8: Fiberoptic bronchoscopy showing closure of

fistula. (Case 73)
FIG. 3: Fiberoptic bronchocopy showing whitish

material obstructing the right lower lobe bronchus.
(Case 74)

material in lower lobe bronchus on right side. (Case 74)
PLATE 12

material in lower lobe bronchus on right side (closed
view). (Case 74)
FIG. 4: Tumor obstructing right upper lobe bronchus.

(Case 75)
FIG. 5: Fiberoptic bronchoscopy showing multinod

ular tumor. (Case 76)
PLATE 13
FIG. 7: Secondary carina near right upper lobe wide

and infiltrated. (Case 77)
FIG. 8: Multiple nodular lesions in left main bronchus.

(Case 77)
PLATE 14
FIG. 1: Patient with superior vena cava syndrome. (Case 78)

ment of superficial submucosal veins in trachea and
bulging of posterior wall of lower end of trachea.
(Case 78)

ment of superficial submucosal veins in left main
bronchus. (Case 78)
PLATE 15
FIG. 3: Fiberoptic bronchoscopy showing blood clot

filled in left main bronchus. (Case 79)
FIG. 4: Fiberoptic bronchoscopy showing tumor aris

ing from medial wall of left main bronchus. (Case 79)
FIG. 3: Fiberoptic bronchoscopy showing growth in

anterior segment of the left upper lobe with adjacent
thick and edematous carina. (Case 80)
PLATE 16
FIG. 4: Endobronchial forceps biopsy. (Case 80)
FIG. 4: Flexible bronchoscopy showing irregular

growth in left main bronchus just before its bifur
cation. (Case 81)
FIG. 5: Fiberoptic bronchoscopy showing multinod-

ular growth at carina. (Case 82)
PLATE 17
FIG. 6: Fiberoptic bronchoscopy showing growth in

the medial wall of the right main bronchus. (Case 82)
FIG. 7: Fiberoptic bronchoscopy showing involve

ment of left main bronchus by growth. (Case 82)
FIG. 8: Fiberoptic bronchoscopy showing involve-

ment of secondary carina at bifurcation of left main
bronchus. (Case 82)
PLATE 18

covered with necrotic slough obstructing left main
bronchus. (Case 83)

growth in anterolateral wall of the trachea. (Case 84)

nodular growth left main bronchus. (Case 85)
PLATE 19

nodular growth with necrotic slough. (Case 85)
FIG. 6: Secondary carina near right upper lobe is

wide and infiltrated obliterating right upper lobe
bronchus. (Case 86)
FIG. 7: Middle lobe bronchus narrowed. (Case 86)

PLATE 20
FIG. 4: Infiltrated bronchial wall and oedematous

tertiary carina. (Case 87)
FIG. 4: Tumor with blood in left lower lobe bronchus.

(Case 88)
PLATE 21
FIG. 6: Main carina is short and wide and infiltrated.

(Case 89)
FIG. 7: Multiple nodules over medial wall of left

main bronchus. (Case 89)
FIG. 8: Infiltration of the left main bronchus. (Case 89)

PLATE 22
FIG. 3: Tumor obstructing left upper lobe bronchus.

(Case 90)
FIG. 3: Main carina deviated to left side. (Case 91)
FIG. 4: Infiltration in the walls of left upper lobe

bronchus. (Case 91)
PLATE 23
FIG. 4: Tumor obstructing left main bronchus. (Case 92)
FIG. 7: Fiberoptic bronchoscopy showing thick

secondary carina. (Case 93)
FIG. 8: Fiberoptic bronchoscopy showing tertiary

carina thick edematous and infiltrated. (Case 93)
PLATE 24
FIG. 1: Patient showing clubbing of fingers. (Case 94)

100 Cases in Pulmonary Medicine

Uploaded by

Copyright:

Available Formats

100 Cases in Pulmonary Medicine

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

100 Cases in Pulmonary Medicine

Uploaded by

Copyright:

Available Formats

00 Cases in

Nikhil Gupta MBBS MD (Medicine)

JAYPEE BROTHERS MEDICAL PUBLISHERS

First Edition: 2020

Diagnostic problems faced by a clinician remain the most exciting challenges in

Surinder K Jindal MD FCCP FAMS FNCCP

It occurred to me that presentation of interesting cases in a concise format would

As a senior author of this book, I wish to acknowledge my indebtedness to a number

1. Spontaneous Pneumothorax: An Unusual Complication of Pregnancy 1

2. Pulmonary Mucormycosis Presenting as Reversed Halo Sign 4

3. Pulmonary Mucormycosis Mimicking as Pulmonary Tuberculosis 7

4. Pulmonary and Nodal Multiple Myeloma with a

5. Bronchiectasis as a Cause of Unexplained Breathlessness in

6. Progressive Increase in Cavitation with the Evolution of

7. Pericardial Effusion as a Paradoxical Response to Therapy for

8. Occupational Emphysema Following Long-term Exposure to Metal 26

11. Ischemic Cavitation in Conglomerate Silicosis 38

12. Intralobar Sequestration of Lung 41

13. Herniation of Lung Following Lung Abscess in a Child: A Case Report 44

14. Hemorrhagic Pleural Effusion Secondary to Sarcoidosis 47

15. Exfoliative Dermatitis Secondary to Ethambutol and Pyrazinamide 51

16. Bilateral Chylothorax in a Young Female Secondary to Tuberculosis 54

17. Concomitant Pulmonary Tuberculosis and Borderline Leprosy with

18. Community-Acquired Miliary Pneumonia Mimicking as

19. Coexistence of Bronchiectasis and Chronic Obstructive

20. Bilateral Hemorrhagic Pleural Effusion due to Kerosene Aspiration 73

21. Bilateral Chylothorax in a Child after Mild Trauma 77

22. An Unusual Case of Actinomycosis Presenting as a Pulmonary Mass 81

23. A Rare Case of Congenital Anomaly Presenting as Hemoptysis 85

24. Allergic Bronchopulmonary Aspergillosis with Aspergilloma

25. A Rare Coexistence of Pulmonary Nocardiosis and Aspergillosis in

26. Necrotizing Mediastinal Lymph Nodes in Sarcoidosis 99

27. New Case of Pulmonary Tuberculosis with Radiological Clearing

28. Case of Retreatment Pulmonary Tuberculosis Presented as Mass Lesion 110

29. Left-sided Infrapulmonary Effusion 115

30. Right-sided Infrapulmonary Pleural Effusion 117

31. Multidrug-resistant Tuberculosis Treated with Injection

32. Primary Multidrug-resistant Tuberculosis Treated with

33. Multidrug-resistant Tuberculosis Treated on Emperical Grounds 123

34. Multidrug-resistant Tuberculosis Treated with

35. Multidrug-resistant Tuberculosis under Treatment with

36. Multidrug-resistant Tuberculosis Treatement with

37. Multidrug-resistant Tuberculosis under Treatment with

38. Multidrug-resistant Tuberculosis Treated with

39. Extensively Drug-resistant Tuberculosis Treated with

40. Multidrug-resistant Tuberculosis (Pre XDR-TB) Treated

41. Multidrug-resistant Tuberculosis Treated with CAT IV Regimen 146

42. Extensive Drug-resistant Tuberculosis Treated as

43. Multidrug-resistant Tuberculosis Following Adverse Drug Intolerance

44. Extensively Drug-resistant Tuberculosis Treated as

45. Achalasia Cardia Presenting as Uncontrolled Asthma 167

46. Walking Pneumonia Diagnosed as Allergic

47. A Case of Allergic Bronchopulmonary Aspergillosis

48. A Case of Allergic Bronchopulmonary Aspergillosis

49. A Case of Allergic Bronchopulmonary Aspergillosis Presenting as

50. A Case of Allergic Bronchopulmonary Aspergillosis

51. A Case of Allergic Bronchopulmonary Aspergillosis with

52. Allergic Bronchopulmonary Aspergillosis Presenting as

53. Treatment of Tuberculosis in Pregnancy and

FIG. 3: Chest X-ray posteroanterior (PA) after adding steroid to anti