’ Case Report

Bullous pemphigoid in a previously healthy

adolescent: a case report and literature review
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Narmeen Giacaman, MDa,*, Rawan Sami N. Abusaada, MDa, Salem M. Tos, MDa, Mohammad G. Ibdah, MDa,
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Adam M. Reid Mahagney, MDe, Asmaa Rjoob, MDa, Musallam Abukhalil, MDc, Hamza Salimd, Basel Musmard,
Sufyan Zuwahreh, MDb

Introduction: Bullous pemphigoid (BP) is considered the most common bullous autoimmune disorder, characterized by
autoantibodies directed against hemidesmosomes in the skin and mucous membranes. It usually affects elderly individuals in the
sixth through eighth decades of life, with an average age at onset of 65 years. Only a few cases have been reported in children and
teenagers.
Case presentation: Herein, we report a 17-year-old boy who presented with a pruritic vesicular rash on his arms and legs
accompanied by erythema. He was treated at the beginning with topical lotion and acyclovir, but the rash kept deteriorating and
eventually bullae appeared, involving also his mouth. A dermatologist was consulted and diagnosed him with BP, and he was treated
accordingly.
Discussion: BP is the most prevalent autoimmune bullous illness, caused by autoantibodies against hemidesmosomes in the
basement membrane of skin and mucosal surfaces, which in turn attract immune cells, including T-cells and neutrophils, and activate
them, which causes damage to and separation of keratinocytes, resulting in the bullous formation. Diagnosis can be accomplished
by recognizing clinical symptoms supported by histopathological and immunofluorescence testing. Steroids, whether topical or
systemic, are the cornerstone treatment; depending on the extent of the disease, other immunosuppressant drugs can be used as a
second line.
Conclusion: BP manifestations are polymorphic; physicians should keep in mind that they may present with non-bullous, pruritic
lesions, which may persist for some days to several months before bullae appear. Although this disease is rare in the young
population, it should be considered in the differential diagnosis of bullous lesions.
Keywords: bullae, bullous pemphigoid, case report, clinical dermatology

Introduction HIGHLIGHTS
• Bullous pemphigoid is rarely seen in adolescence.
In 1953, Lever introduced the term pemphigoid to describe a • The cutaneous manifestations of bullous pemphigoid are
disease characterized by bullous formation due to subepidermal polymorphic.
detachment to distinguish it from pemphigus, an intraepidermal • It can be misdiagnosed on initial presentation before bullae
blistering disorder brought on by acantholysis. appear.
Only few cases of bullous pemphigoid (BP) were reported in
children and teenagers in the literature, as this disease mainly
affects the elderly in their eighth decade of life and has no preference for either gender[1]. In this case, we describe a patient
with free past medical and surgical history that first presented
a
with pruritic vesicular rash surrounded by erythema on his arms,
College of Medicine, Al-Quds University, Abu Dis, bInternal Medicine Department,
Beit-Jala Governmental Hospital, Bethlehem, cFaculty of Medicine, Islamic University
legs, and trunk for a few days, followed by diffuse skin involve-
of Gaza, Gaza, dAn-Najah National University, Nablus, Palestine and eThe Hebrew ment of bullous lesions. He was treated mainly with topical and
University, Hadassah Medical School, Jerusalem, Israel systemic corticosteroids, which led to significant improvement.
Sponsorships or competing interests that may be relevant to content are disclosed at On follow-up, his lesions healed, and he was back to his
the end of this article. normal life.
*Corresponding author. Address: Al-Quds University, Main Campus, P.O. Box 89,
Abu Dis, Palestine.Te.:+ 970 227 906 06. E-mail: [email protected]
(N. Giacaman). Case presentation
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. This is an
open access article distributed under the Creative Commons Attribution License 4.0 A 17-year-old boy complained of pruritic vesicular rash surrounded
(CCBY), which permits unrestricted use, distribution, and reproduction in any by erythema on his arms, legs, and trunk for few days. He was seen
medium, provided the original work is properly cited. by his family doctor and was diagnosed with chickenpox caused by
Annals of Medicine & Surgery (2023) 85:5039–5042 varicella-zoster virus. The doctor gave him symptomatic treatment
Received 4 October 2022; Accepted 10 June 2023 (calamine lotion) for the pruritis and acyclovir. Two days later, the
Published online 22 July 2023 rash kept getting worse and bullae started to appear; he also
http://dx.doi.org/10.1097/MS9.0000000000000995 developed painful mouth lesions (Fig. 1). The patient was seen by a

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Figure 1. Painful mouth lesions involving the oral mucosa and the soft palate.

dermatologist in his clinic who suspected bullous pemphigoid and for his age, including complete blood count, Thyroid function
sent him to be admitted to our hospital for treatment as the patient tests, basic metabolic panel, liver function tests, and kidney
could not have anything by mouth. function tests. So, he was started on intravenous (i.v.) fluids to
On admission, the patient had stable vital signs but looked prevent dehydration, pantoprazole 40 mg i.v., amoxicillin/cla-
dehydrated with cracked lips and dry skin. Diffuse skin involve- vulanic acid to prevent secondary skin infection, triamcinolone
ment was seen (Figs 2, 3) including axillae, arms, legs, trunk, oral cream for his oral lesions, clobetasol lotion (corticosteroid) for his
mucosal membrane, and the groin area. Nikolsky sign was skin lesions for 2 weeks and methylprednisolone 80 mg IV*1 to
negative on examination. Lab tests were all in the normal range be converted to prednisolone 40 mg once oral intake is tolerated.

Figure 2. Diffuse skin involvement by bullous pemphigoid. Pictures taken after 4 days in treatment.

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Neutrophil chemotaxis and BM zone destruction are caused by

a dysregulated T cell immune response and the production of
immunoglobulin (Ig)G and IgE autoantibodies against hemi-
desmosomal proteins (BP180 and BP230)[4].
BP is a disease that mainly affects the elderly and is quite rare in
children and adolescents. Dr Patsatsi et al. have published an
impressive review about BP in adolescence. The review included
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nine cases of BP in adolescents, describing aspects as skin lesions

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seen, mucosal involvement, treatment, disease course, and others

in a very comprehensive and tidy table[5]. In addition to the cases,
we decided to report our case as a case of BP diagnosed in an
adolescent to emphasize the importance of keeping BP in any
adolescent presenting with vesicles or bullae. And to remind
clinicians that initially, bullae may not be present and patients
could be misdiagnosed, as our patient was first misdiagnosed and
given treatment for chickenpox.
The diagnosis of BP is based on a combination of clinical
characteristics, histological findings, and immunofluorescence
results; histopathological examination reveals eosinophilic
spongiosis or a subepidermal detachment with eosinophils[6],
immunofluorescence as direct or indirect tests identify linear IgG
and/or C3 deposition at the BM zone[7], and ELISA (enzyme-
linked immunosorbent assay) measure circulating autoantibodies
against BP180 and/or BP230. Direct immunofluorescence test is
considered the gold standard for diagnosis[8].
In the case presented to you, two punch biopsies were taken to
confirm the diagnosis. On histopathological examination, sub-
epidermal acantholytic reaction with blister formation was seen,
mostly in keeping with BP. Moreover, using the direct immuno-
Figure 3. Zoomed in the picture of a bullous. fluorescence test, linear deposition of IgG and complement C3
was seen along the dermal–epidermal junction.
Cutaneous symptoms of BP are variable. The condition fre-
Two punch biopsies were taken and the diagnosis of BP was quently starts with a non-bullous, pruritic phase that can last
confirmed by direct immunofluorescence and histopathological from a few days to many months and is occasionally the first
examination. symptom of BP[9]. During this stage, urticarial or excoriated
Few days into treatment, the patient’s lesions started healing lesions, eczematous plaques, or prurigo-like lesions occur, mak-
and he could tolerate soft food intake. He was discharged on ing accurate diagnosis difficult[10]. As was seen with the patient in
prednisolone 40 mg per day to be tapered for the next 2 months this case, the first presentation consisted of a pruritic vesicular
rash surrounded by erythema without bullae that was mis-
by 5 mg per week before stopping the drug. A week later, the
diagnosed as chickenpox before bullae started to appear.
patient had improved significantly, and his lesions were healing
Classical BP is clinically distinguished by 1–3 cm diameter
well with no new lesions. On follow-up, his lesions healed and he
tense, serous, or hemorrhagic bullae on erythematous or other-
was back to his normal life.
wise normal skin[11]. Severe pruritus is observed in virtually all
The patient presented in this case had free medical and surgical
patients. The condition has a symmetric distribution, and the
history, no family history of autoimmune diseases, and has not
lower abdomen, flexor surfaces of the limbs, groins, and axillae
taken any drug for the past few months since the lesions started.
are common predilection areas[1].
This work has been reported in line with the Surgical CAse
The goal of BP treatment is to halt the progression of new lesions,
REport (SCARE) criteria, which is used by authors, journal edi-
promote cutaneous healing, and alleviate pruritus. Because BP mostly
tors, and reviewers to increase the robustness and transparency in
affects the elderly, therapy must be adjusted to the patient’s comor-
reporting medical and surgical cases[2]. bidities and capacity to self-care in order to minimize probable
consequences and increased morbidity and mortality[12].
The German guideline recommends stage-adjusted treatment
Discussion depending on the affected skin surface area as the best practical
method for treating BP. If involvement is less than 10%, only
The most prevalent autoimmune bullous illness is BP, which is topical glucocorticoid monotherapy is recommended; if partici-
characterized by autoantibodies against hemidesmosomal proteins of pation is greater than 30%, a combination of topical and systemic
the skin and mucous membranes[3]. A distinguishing aspect of the glucocorticoids is recommended. Between 10 and 30% of the
illness is the presence of tissue-bound and circulating autoantibodies time, systemic therapy is an option. Systemic glucocorticoids
directed against structural components of the hemidesmosomes that should be used in severe hypertension and tested in mild
connect basal keratinocytes to the basement membrane (BM)[1]. hypertension[13]. In the case presented, a combination of topical

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 Giacaman et al. Annals of Medicine & Surgery (2023) Annals of Medicine & Surgery

and systemic glucocorticoids was used as more than 30% of the Research registration unique identifying number
skin surface area was affected. (UIN)
The recommendations prescribe or may explore the following
additional medications: cyclosporine, cyclophosphamide, plas- Not applicable.
mapheresis/immunoapheresis, sulfonamides, topical tacrolimus,
TNF (tumor necrosis factor) inhibitors, and other biologic Guarantor
agents[12-14]. According to the updated S2K guidelines for BP
kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 01/03/2024

management, Immunosuppressive treatments, such as metho- Sufyan Zuwahreh.

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trexate, azathioprine, mycophenolate mofetil, or mycophenolate

acid, may be advised in the event of contraindications or resis- Provenance and peer review
tance to corticosteroids. In treatment-resistant cases, intravenous
immunoglobulins and B-cell-depleting therapy may be explored. Not commissioned, externally peer-reviewed.
Dupilumab and omalizumab have lately demonstrated encoura-
ging outcomes too[15].
Acknowledgements
The authors thank the patient and his family.
Conclusion
In conclusion, although uncommon at a young age, BP must be References
kept in mind when putting the list of differential diagnoses of a
[1] Miyamoto D, Santi CG, Aoki V, et al. Bullous pemphigoid. An Bras
young patient presenting with vesicles or bullae. Dermatol 2019;94:133–46.
In addition, clinicians should keep BP in mind when facing [2] Agha RA, Franchi T, Sohrab C, et al. The SCARE 2020 guideline:
cutaneous lesions, as the cutaneous manifestations of BP are updating consensus Surgical CAse REport (SCARE) guidelines. Int J Surg
polymorphic. So, it can initially present as non-bullous, pruritic 2020;84:226–30.
[3] Bağcı IS, Horváth ON, Ruzicka T, et al. Bullous pemphigoid. Autoimmun
lesions which may persist for some days to several months before
Rev 2017;16:445–55.
bullae appear and sometimes remain the only sign of BP. [4] Di Zenzo G, Thoma-Uszynski S, Fontao L, et al. Multicenter prospective
study of the humoral autoimmune response in bullous pemphigoid. Clin
Immunol 2008;128:415–26.
Ethical approval [5] Patsatsi A, Kyriakou A, Werth VP. Bullous pemphigoid in adolescence.
Pediatr Dermatol 2019;36:184–8.
The study is exempt from ethical approval in our institution. [6] Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification
of pemphigus and bullous pemphigoid. Autoimmun Rev 2014;13:
477–81.
Consent [7] Ujiie H, Nishie W, Shimizu H. Pathogenesis of bullous pemphigoid.
Dermatol Clin 2011;29:439–46; ix.
Written informed consent was obtained from the patient’s par- [8] Schmidt E, Zillikens D. Pemphigoid diseases. Lancet 2013;381:320–32.
ents for the publication of this case report and accompanying [9] Di Zenzo G, Marazza G, Borradori L. Bullous pemphigoid: physio-
pathology, clinical features and management. Adv Dermatol 2007;23:
images. A copy of the written consent is available for review by 257–88.
the Editor-in-Chief of this journal on request. [10] Lamb PM, Abell E, Tharp M, et al. Prodromal bullous pemphigoid. Int J
Dermatol 2006;45:209–14.
[11] Cozzani E, Gasparini G, Burlando M, et al. Atypical presentations of
Sources of funding bullous pemphigoid: clinical and immunopathological aspects.
Autoimmun Rev 2015;14:438–45.
No funding or grant support. [12] Eming R, Sticherling M, Hofmann SC, et al. S2k guidelines for the
treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid.
J Dtsch Dermatol Ges 2015;13:833–44.
Author contribution [13] Feliciani C, Joly P, Jonkman MF, et al. Management of bullous pem-
phigoid: the European Dermatology Forum consensus in collaboration
N.G.: study concept or design; N.G., R.S.N.A., S.M.T., M.G.I., with the European Academy of Dermatology and Venereology. Br J
Dermatol 2015;172:867–77.
A.M.R.M., A.R., M.A., H.S., and B.M.: writing the manuscript; [14] Venning VA, Taghipour K, Mohd Mustapa MF, et al. British Association
N.G., S.M.T., and S.Z.: review and editing the manuscript. of Dermatologists’ guidelines for the management of bullous pemphigoid
2012. Br J Dermatol 2012;167:1200–14.
[15] Borradori L, Van Beek N, Feliciani C, et al. Updated S2 K guidelines for
Conflicts of interest disclosure the management of bullous pemphigoid initiated by the European
Academy of Dermatology and Venereology (EADV). J Eur Acad
The authors declare that they have no conflicts of interest. Dermatol Venereol 2022;36:1689–704.

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