IAJPS 2020, 07 (09), 165-168 Anam Sadia et al ISSN 2349-7750

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INDO AMERICAN JOURNAL OF

PHARMACEUTICAL SCIENCES
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Available online at: http://www.iajps.com Research Article

CELIAC DISEASE: FROM PATHOPHYSIOLOGY TO

TREATMENT
1Dr
Anam Sadia, 2Dr Waqas Ahmed,3Dr Shawana Saeed.
1
MBBS,Fatima Jinnah Medical University,Lahore.
2,3
MBBS,Sharif Medical and Dental College,Lahore.
Article Received: July 2020 Accepted: August 2020 Published: September 2020
Abstract:
Celiac sprue is another name of celiac disease. It is a severe inflammatory disorder of small intestine, which is
caused by ingestion of gluten items in susceptible people. This disease is multifactorial and includes
environmental as well as genetic factors. Gluten falls under enviornemntal factors and genetic predisposition is
considered as the major complex histocompatibility region. Celiac disease is not rare anymore and has 1% of
global prevalence. The reason it is not highly recognized is that most of the people do not have classic GIT
symptoms, but they do show some nutritional deficiency or sometimes no symptoms at all. Here, in this review
paper recent data encapsulating epidemiology, clinical presentation and therapeutic management of celiac
disease is presented.
Corresponding author:
Dr. Anam Sadia, QR code
MBBS,Fatima Jinnah Medical University,Lahore.

Please cite this article in press Anam Sadia et al, Celiac Disease: From Pathophysiology To Treatment., Indo
Am. J. P. Sci, 2020; 07(09).

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 IAJPS 2020, 07 (09), 165-168 Anam Sadia et al ISSN 2349-7750

INTRODUCTION: Based upon the given evidence, it is visible that

An aberrant adaptive immune response against genetic factor HLA is among the main but not
gluten containing grains become the cause of sufficient factor for the celiac disease development.
autoimmune disorder, celiac disease, in susceptible But, multitude genetic factors collectively
patients. 1 It was first explained by Samuel Gee in contribute towards this disease. Recently, another
1888, but by 1953 its importance was highlighted genome based study has revealed that 39 non HLA
in the context of pathology. In patients with celiac loci also contribute to celiac disease. 10 one of these
disorder, gluten ingestion causes an enteropathy genes are related to chromosome 19 genetic
impairment of mucosal surface, and, aberrant structure and myosin IXB gene, and may be
nutrient absorption. 2, 3 Various human systems are involved in response towards gluten or gluten free
involved as well as wide range of clinical diet. However, both HLA- DQ8 and HLA- DQ2
manifestations owing to which celiac disease is codifies for heterodimers which are located on
often reffered as a syndrome. Peculiar features like APCs Antigen Presenting Cells. It has been found
complete recovery from mucosal damage or that gluten peptides are present in the intestinal
reversibility of its progression and chronic mucosa on antigen specific t lymphocytes, which
dynamics, in comparison to other autoimmune induce cytokine production and their proliferation.
disorders, are shown by celiac disease. It is • Environmental Factors
depicted that if celiac disease remain undiagnosed Diet plays an important role. The eating pattern in
then it can have serious consequences. Another the early life and viral infections like rotavirus
type of disease, besides celiac disease and wheat might be involved in the celiac disease
allergy, NCGS has been found which is non-celiac development. A medical disease linked
gluten sensitivity. 4 investigation has shown that specific infectious
agents increases the risk of celiac disease
Epidemiology autoimmunity in children. Gluten is composed of
In the recent years, large data have been reported glutenin and prolamines, which are common parts
on celiac epidemiology. Nowadays, celiac disease of human nutrition. The wheat prolamines are
falls in the most prevalent genetically based gliadins, in rye these are secalines and in barely
disorder. Europe is considered its hot hub with a hordeins. It is prosposed that 50mg gluten/ day is
prevalence of 1 to 2%. Despite medical advances, the minimum amount enough to determine the
this disease remains least diagnosed, and its alterations to small intestine in celiac disease
prevalence still remains unclear. 5 It is not known patients.
that either this is owing to screening tool or real
variability of disease prevalence. 6 Other environmental factors include milk feeding
types i.e., breast feeding which can influence the
A multicellular study has shown occurrence rate as small intesteine microenvironment. Moreover,
1 out of 133 in healthy people, and this frequency reduced Bifidobacteria and increased gram
is confirmed in the US, European, Australian and negative bacteria in intestine rises the celiac disease
Asian populations. Moreover, the chances of celiac risks. Heavy metals and bacterial TG in food stuff
disease prevalence ranges from 4.5% in high risk also contribute towards this disease. 11
people to 0.75% in low or not at risk patients.
Celiac Disease: Clinical Presentation
People who are at higher risk include the relatives This disease is highly heterogenous, especially
of patients with this disease, adults or children with when it comes to factors like age, duration and
celiac linked symptoms like abdominal pain, extent of disease as well as the presence of extra
constipation or diarrhea; and adults or children with intestinal comorbidities. Initially it was considered
celiac related disorders like anemia, infertility, aa pediatric disorder, the prevalence is higher in
osteoporosis, Down syndrome, and Diabetes adults.
Mellitus type-1. 7
• Genetic Susceptibility Classical or typical form, it is described by
The most prominent genetic character which common clinical symptoms associated to aberrant
characterizes for 35% of the total celeic disease intestinal absorption. After the introduction of
genetic factor, is the MHC encoding genes for class weaning items containing prolamines, this disorder
II proteins including leukocyte antigen (HLA) DQ occurs between 6 to 18 months of age.
2 and HLA-DQ8. Only 10% patients show HLA- • Atypical Form
DQ8 molecule effect, while 90% subjects express This form is characterized by the presence of extra
HLA_ DQ2 molecules. Only 1 to 3% subjects intestinal symptoms with no or few gastrointestinal
develop the disease while the frequency of celiac symptoms. Usually, the common features of
disease occurrence based on HLA genotype is abnormal absorption are absent and it occurs in
about 30%. 8, 9 older children or adults.

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• Silent Form As some specifically targeted diet might also

It is characterized by histological abnormalities and contain tiny amounts of gluten in them, specific
serological issues without prominent clinical considerations must be taken into account for its
symptoms. This subtype is often present in subjects diet recommendation. In minority of patients
with family history of celiac disease, or patients affected by RCD, GFD is ineffective. It shows
with associated autoimmune (type 1 diabetes) or higher mortality rate in comparison to RCD type 1,
genetic disorders (Williams syndrome or Down’s owing to more severe malnutrition along with risk
syndrome). of overt lymphoma development. These disease
• Latent Form forms require immunosuppressant and
This subtype has characteristics associated with corticosteroids, like cyclosporine or azathioprine
previous asymptomatic celiac disease. No villous which can improve symptoms in most patients.
atropy or histology abnormalities are prominent in Furthermore, these drugs might increase the risk of
it, but has positive serology. Troncone et al has overt T cell lymphoma progression, so it is
postulated that increased level of endomysial advisable to use drugs and agents in chemotherapy
antibodies in these subjects can act as predictor of with caution.
disease progression. 12 • Gluten Degrading Enzymes
• Potential Form Enzyme supplement treatment including bacterial
Persons who have never diagnosed with celiac prolyl endopeptidase has been proposed to enhance
disease, the word potential is used for those gluten digestion in the GIT and to destroy T cell
patients, but they show appropriate genetic epitopes. Prolyl endopeptidase are peoline specific
background (HLA- DQ2/DQ8), normal or mildly enzymes which have the ability to cleave gluten
aberrant histology and positive serology. peptides. These are under clinical trials on two drug
• Refractory Form candidates, ALV003 and AN-PEP (Aspergillus
The presence of malabsorptive symptoms and niger prolyl-endoprotease. Recent data based on
villous atrophy persistent for 1 year after gluten these trials has depicted that therapy with AL V003
free diet defines this refractory form. Many eradicate the peripheral blood T cell response in
refractory form patients do not response to gluten celiac patients. The current triasl with this therapy
free diet, while others might respond but recurrence is showing positive outcomes with reduced
of symptoms and intestinal damage is prominent. symptoms in patients with typically induced by
This form has two different types; “Type 1” gluten. AN-PEP is an anzyem which can thrive in
showing normal intraepithelial lymphocyte count stomach acidic pH and degrades gluten peptides
and “Type 2” showing abnormal intraepithelial effectively. Therefore this enzyme might show
lymphocyte count. 13 promising outcomes in the long run. 14
• Modified Grains
Celiac disease can affect person of any age, but the These can be introduced either by selective grain
two peak ranges are less than 6 years old and 4 th or breeding of early wheat species or using siRNA
5th decade. Classical presentation is frequent in technology to mutate or silence immunostimulatory
pediatric and occurs in early life, 6 to 24 months, sequenece. 15
while atypical one occurs at later age in adults or • Blocking gluten entry across the intestinal
children with age greater than 5 years. epithelium
Zonulin inhibitor larazotide (AT-1001) modifies
Current Treatments of Celiac Disease and corrects intestinal barrier defects. It is currently
• Life Long Gluten Free Diet studied to treat celiac patients. It is observed that
The current treatment is the life long gluten free patients treated with AT-1001 had improvement in
diet, as clinical improvement can be achieved symptom score, less pro-inflammatory production
within a few weeks and mucosal damage recovers and autoantibody response, less urinary nitrate
in 1 to 2 years. Patients with this disease have excretion as comparison to placebo controls. 16
damaged surface of epithelial cells and brush • Rho/Rho kinase inhibition
border lactase deficiency, milk and dairy products The increase in intestinal permeability depends
are advised to avoid in the first week of therapy. upon Rho kinase (ROCK) activity. ROCK is
Gluten free multivitamin are also recommenede to known to regulate axon growth, tight junction
overcome nutritious deficiency. structure and function. The drug can be used to
reverse gluten dependent increase in intestinal
Early diagnosis and treatment is beneficial in permeability or ROCK inhibition in these patients.
pediatric celiac disease, as later on some Vaccines and immunotherapy are under testing
complications are irreversible: abnormal dentition, phase, so these are not discussed in this review
osteoporosis, growth retardation. Prolonging breast paper.
feeding and delaying the introduction of gluten diet
in babies might lower the risk of this disease.

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CONCLUSION: 8. Sollid LM, Markussen G, Ek J, Gjerde H,

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