This document discusses Celiac disease, an autoimmune disorder caused by a reaction to gluten. It covers the epidemiology, pathophysiology involving genetics and tissue transglutaminase. Signs and symptoms include diarrhea, abdominal pain, and malnutrition. Diagnosis involves blood tests for tissue transglutaminase antibodies and biopsy of the small intestine. Treatment is a lifelong gluten-free diet, while refractory cases may require steroids or immunosuppressants. Complications can include intestinal cancer or lymphoma if untreated. Prognosis is excellent with a gluten-free diet.

1. CELIAC DISEASE
Dr. Jan Muhammad Afridi
Professor
Deptt of Child Health
KMC/MTI KTH

2. General Learning Outcomes:
 Learn the pertinent aspects of the history and physical exam relative to
Celiac disease.
 To learn the presenting signs and symptoms of Celiac disease.
 Learn the patho-physiology ,diagnosis, differential diagnosis and
treatment of Celiac disease.

3. Specific Learning Objectives
 By the end of this one hr lecture The Medical student will be able to:
 To define Celiac disease
 Pathogenesis of Celiac disease
 Genetics of Celiac disease
 Clinical manifestation Celiac disease
 Laboratory and histo-pathological findings
 Differential diagnosis
 Treatment of Celiac disease

4. Celiac Disease
 Celiac disease is an autoimmune disorder of the small intestine that occurs in
genetically predisposed people of all ages from middle infancy.
 Celiac disease Is caused by a reaction to gliadin, a gluten protein found in wheat,
rye and barley.
 This condition has several other names including:
 celiac sprue,
 non-tropical sprue,
 endemic sprue,
 gluten-sensitive enteropathy

5. Epidemiology
 The Prevalence Of Clinically Diagnosed Disease Is 0.05–0.27%
 Prevalence in children 0.33 and 1.06%
 Prevalence in adults 0.18–1.2%

6. Pathophysiology
 Celiac disease appears to be polyfactorial, both in that more than one
genetic factor can cause the disease and also more than one factor is
necessary for the disease to manifest in a patient.

7. 1. Genetics
 The vast majority of celiac patients have one of two types of HLA
DQ
 Two of these variants—DQ2 and DQ8—are associated with celiac
disease
 The reason these genes produce an increase in risk of celiac disease
is that the receptors formed by these genes bind to gliadin peptides
more tightly than other forms of the antigen-presenting receptor.

8. 2. Tissue Transglutaminase
 Anti-transglutaminase antibodies to the enzyme tissue
transglutaminase (tTG) are found in an overwhelming majority of
cases.
 Tissue transglutaminase modifies gluten peptides into a form that
may stimulate the immune system more effectively.

9. 3. Villous Atrophy & Malabsorption
 The inflammatory process, mediated by T cells, leads to disruption
of the structure and function of the small bowel's mucosal lining, and
causes malabsorption as it impairs the body's ability to absorb
nutrients, minerals and fat-soluble vitamins A, D, E and K from
food.
 Lactose intolerance may be present due to
The decreased bowel surface.
 Reduced production of lactase but typically resolves once the condition is
treated.

10. 4. Risk Modifiers
 Infection by Rota virus
 Human intestinal adeno virus
 Timing of the exposure to gluten in childhood is an important risk
modifier
 Prolonging breastfeeding until the introduction of gluten-containing
grains into the diet is associated with a 52% reduced risk of
developing celiac disease in infancy

11. Signs & Symptoms
1. GIT:
 Diarrhoea which is pale, voluminous and malodorous
 Abdominal pain and cramping, bloatedness with abdominal distention
 lactose intolerance
 adenocarcinoma and lymphoma of small bowel
 Ulcerative jejunitis and stricturing
 Celiac Crisis and the Role of Steroid

12. 2. Malabsorption-related
 Weight loss
 Fatigue
 Anemia
 Abnormal coagulation due to deficiency of vitamin K,
 Bacterial overgrowth
 Calcium and vitamin D malabsorption (and compensatory secondary
hyperparathyroidism) may cause osteopenia (decreased mineral content of the
bone) or osteoporosis (bone weakening and risk of fractures)

13. 3. Miscellaneous
 IgA deficiency
 an increased risk of infections and autoimmune disease
 Dermatitis herpetiformis; this itchy cutaneous condition has been linked to a
transglutaminase enzyme in the skin, features small bowel changes identical to
those in celiac disease and occurs more often (in 2%) in patients with celiac
disease.
 Epilepsy, ataxia (coordination problems), myelopathy, peripheral neuropathy,
and schizophrenia
 Growth failure and/or pubertal delay
 Miscarriage and infertility.
 Hyposplenism (a small and under active spleen)

14. Conti…
 Other Auto-immune Disorders
 diabetes mellitus type 1
 autoimmune thyroiditis
 primary biliary cirrhosis
 microscopic colitis

15. DIAGNOSIS

17. Routine Lab Test
 Full blood count
 Electrolytes
 Calcium
 Vitamin B12 and
 Folic acid
 levels Prothrombin time

18. Serologic Test
 Tissue transglutaminase (TTG) antibodies
 Antibodies against endomysium
 Antibodies against reticulin (ARA) or gliadin (AGA)
 Guidelines recommend that a total serum IgA level is checked in parallel, as
coeliac patients with IgA deficiency may be unable to produce the antibodies on
which these tests depend

19. Endoscopy
 Endoscopic still of duodenum of patient with celiac disease
showing scalloping of folds.

20. Histopathology
 The classic pathology changes of celiac disease in the small bowel are
categorized by the "Marsh classification"
 Marsh stage 0: normal mucosa
 Marsh stage 1: increased number of intra-epithelial
lymphocytes, usually exceeding 30 per 100
enterocytes
 Marsh stage 2: proliferation of the crypts of Lieberkuhn
 Marsh stage 3: partial or complete villous atrophy
 Marsh stage 4: hypoplasia of the small bowel architecture

21. Differential Diagnosis
 Cow milk protein allergy
 Giardiasis
 Tropical sprue
 Other malabsorption syndromes

22. Treatment
By diet:
 Presently, the only effective treatment is a lifelong GLUTEN FREE DIET
 Rice, soyabean, potato and corn flour are safe
 No medication exists that will prevent damage, or prevent the body from
attacking the gut when gluten is present.
 Strict adherence to the diet allows the intestines to heal, leading to resolution of
all symptoms in most cases and, depending on how soon the diet is begun, can
also eliminate the heightened risk of osteoporosis and intestinal cancer

23. Refractory Disease
This May be Because
 The disease has been present for so long that the intestines are no longer able to heal on
diet alone
 The patient is not adhering to the diet
 Because the patient is consuming foods that are inadvertently contaminated with gluten
 In this case steroids and immuno-suppresents should be considered . Also Steroid is to
be given in celiac crisis

24. Complications
 Intestinal T-cell lymphoma
 Carcinoma of small intestine
 Ulcerative jejunitis
 Complications of nutritional deficiency
 Anemia
 Osteoporosis
 Osteomalacia
 Peripheral neuropathy

25. Prognosis
 Prognosis is Excellent if properly diagnosed and treated
 In some patients it becomes refractory to gluten withdrawal and it carries a poor
prognosis
 These patients may have developed ulcerative jejunitis or T-cell lymphoma(10%
of patients)

26. COUNSELING