1. Coeliac Disease (CD)
By Dr. Zahoor

2. Coeliac Disease Coeliac Disease (Gluten Sensitive Enteropathy)
Coeliac Disease (CD) is an immunologically mediated disorder in which there is inflammation of mucosa of the upper small bowel (duodenum and jejunum) that improves when gluten is withdrawn from the diet and relapses when gluten is reintroduced
Up to 1% of population is affected

3. Coeliac Disease (Gluten Sensitive Enteropathy)
What is Gluten?
Gluten is the protein content of the cereals, present in Wheat, Barley, Rye and Oat
Prolamins (seed protein) – damaging factors
Gliadin – from wheat
Hordeins – from Barley
Secalins – from Rye

4. Rye
Barley
Wheat
Oats

5. Coeliac Disease (Gluten Sensitive Enteropathy)
Gluten protein present in wheat, barley, rye can not be digested by pepsin, chymotrypsin because of their high glutamine and proline contents, therefore, remain in the intestine lumen triggering immune response
Immunology
Gliadin peptides pass through epithelium in small intestine and bind to antigen presenting cells

6. Coeliac Disease (Gluten Sensitive Enteropathy)
Antigens present in cells interact with CD4 T- cell ( T- helper cell) in the lamina propria
These CD4 T-cell produce interferon and also interact with B-cell to produce antibodies
Gliadin peptide also causes release of interleukin – 15 from entrocytes, activating entroepethilial lymphocytes

7. Coeliac Disease (Gluten Sensitive Enteropathy)
This inflammatory cascade releases metalloproteinases and other mediators that contribute to the VILLIOUS ATROPHY and CRYPT HYPERPLASIA, which are typical of Coeliac disease.
Mucosa of proximal small bowel (duodenum and jejunum) is predominantly affected. Mucosal damage decreases towards ileum.

8. Pathophysiology of Coeliac Disease

9. Coeliac Disease (Gluten Sensitive Enteropathy)
Genetic Factors
Increase incidence of Coeliac Disease occurs in families but exact mode of inheritance is not known
Over 90% of patients will have HLA-DQ2
Environmental Factors
Rota virus infection in infancy increases the risk

10. Coeliac Disease (Gluten Sensitive Enteropathy)
Clinical Features
Coeliac Disease can present at any age
In infancy, it sometimes appears when gluten containing foods are introduced
In adult, peak age of diagnosis is 5th decade with F > M. Many patients are asymptomatic (silent) and come to attention because of routine blood test e.g. raised MCV, or iron deficiency in pregnancy

11. Coeliac Disease (Gluten Sensitive Enteropathy)
Symptoms
These are non-specific e.g. tiredness and malaise associated with anaemia
GI Symptoms
May be absent or mild
Diarrhoea, Steatorrhea, abdominal pain and weight loss – suggest more severe disease
Mouth ulcer, angular stomatitis are frequent and can be intermittent

12. Coeliac Disease (Gluten Sensitive Enteropathy)
Neuropsychiatric symptoms of anxiety and depression occur
Neurological symptoms
Paraesthesia, Ataxia, Muscle weakness, polyneuropathy occur
Other Symptoms – Infertility
Rare complications
Tetany
Osteomalacia, Osteoporosis
Gross mal nutrition with peripheral edema

13. Coeliac Disease (Gluten Sensitive Enteropathy)
Association with other autoimmune disease
There is increased incidence of autoimmune diseases associated with CD, like
- Thyroid disease
- Type I Diabetes Mellitus
- Sjogren’s syndrome

14. Coeliac Disease (Gluten Sensitive Enteropathy)
Other Associated Diseases with CD
Inflammatory bowel disease
Primary Biliary cirrhosis
Chronic liver disease
Interstitial lung disease
Epilepsy

16. Coeliac Disease Consider Differential Diagnosis - Giardiasis
- Chronic pancreatitis
- Lactose intolerance
- Irritable bowel syndrome
- Crohn disease

17. Coeliac Disease (Gluten Sensitive Enteropathy)
Diagnosis
Small bowel biopsy
Histology
Shows subtotal villous atrophy
Crypt hyperplasia with inflammatory cells, increased lymphocyte and plasma cells in the lamina propria

18. Coeliac Disease (Gluten Sensitive Enteropathy)
Diagram showing normal and subtotal villous atrophy
Normal Mucosa
Subtotal Villous Atrophy in CD

19. Coeliac Disease (Gluten Sensitive Enteropathy)
Causes of Subtotal Villous Atrophy

20. Coeliac Disease (Gluten Sensitive Enteropathy)
Diagnosis (cont)
Endoscopy
Endoscopy shows absence of mucosal folds, mosaic pattern of mucosal surface
Serology
Endomysial and anti tissue transglutaminase antibodies – sensitivity is more than 90%
IgA antibodies

21. Coeliac Disease (Gluten Sensitive Enteropathy)
Diagnosis
HLA typing
HLA - DQ2 ( gene marker) is present in % cases ( on chromosome-6 )
HLA – DQ8 is present in about 8%

22. Coeliac Disease (Gluten Sensitive Enteropathy)
Other investigation
Folate deficiency is common and causes macrocytosis (Vitamin B12 deficiency is rare)
Iron deficiency is common
Blood film may show microcytosis and macrocytosis, hyper segmented polymorphonueclear leukocytes
Howell – Jolly bodies due to splenic atrophy

23. Howell – Jolly bodies in a blood smear stained with Giemsa
Note: Howell-Jolly bodies are histological finding. It is basophilic nuclear remanants (cluster of DNA) in circulating erythrocytes.

24. Coeliac Disease (Gluten Sensitive Enteropathy)
Investigations (cont)
Biochemistry
Low calcium and high phosphate – Osteomalacia
Hypoalbuminaemia

25. Coeliac Disease (Gluten Sensitive Enteropathy)
Investigation (cont)
Radiology
Small bowel follow through may show dilatation of small bowel with slow transit
Bone densitometry (DXA) – should be performed due to risk of Osteoporosis
Capsule endoscopy

26. Coeliac Disease (Gluten Sensitive Enteropathy)
Treatment and Management
Gluten free diet for life
Elimination of wheat, barley, rye ,oats
NOTE – Diet produces clinical improvement within days or weeks. Morphological improvement takes months
Replacement of minerals and vitamins
E.g. Iron, folic acid, calcium, vitamin D
Pneumococcal vaccination – once every 5 years (because of splenic atrophy)

27. Coeliac Disease (Gluten Sensitive Enteropathy)
Complications
Very rarely, T-cell lymphoma
Ulcerative jejunitis – present with fever, abdominal pain, perforation and bleeding
Diagnosis for these Complications
MRI
Laparoscopy with small bowel biopsy
Barium studies

28. Coeliac Disease (Gluten Sensitive Enteropathy)
Treatment for Ulcerative Jejunitis
Steroids
Immunosuppressive agents Azathioprine

29. Coeliac Disease (Gluten Sensitive Enteropathy)
Association with Coeliac Disease
Dermatitis herpetiformis – blistering sub - epidermal eruption of skin associated with Coeliac disease. It is extremely itchy appears on forearm, knees, buttocks and back.

30. Dermatitis herpetiformis at the forearm, elbow region and on the hand

31. Thank you