CELIAC DISEASE

Question 1

Overview (5)

Answer 1

1- Gluten-sensitive enteropathy
2- Autoimmune condition characterized by an abnormal jejunal mucosa + distal duodenal mucosa; less likely to affect the ileum
3- Mucosa improves when gluten is removed, and it relapses when reintroduced
4- Gluten is contained in wheat, rye, and barely
5- Strong association with HLA class 11 (HLA DQ2 - HLA DQ8)

Question 2

Pathogenesis (5)

Answer 2

1- Alpha-gliadin is the toxic portion of gluten
2- Gliadin is resistant to protease in the small intestinal lumen
3- Epithelial barrier is damaged (as a result of gliadin itself or an infection) —> gliadin passes through and becomes deaminated by tissue trans-glutaminase —> increased immunogenicity
4- Gliadin then interacts with antigen-presenting cells in the lamina propria via HLA DQ2 and HLA DQ8 and activates gluten-sensitive T-cells
5- Villious atrophy, crypt hyperplasia, and increased number of lymphocytes in epithelial cells and lamina propria are typical histological features

Question 3

Clinical Features (4)

Answer 3

1- Presentation can be at any age, but there are 2 peaks:
- Infancy (after weaning on to gluten-containing food)
- Adults (in the fifth decade)
2- Non-specific symptoms: tiredness or malaise or symptoms of small intestine (diarrhea - steatorrhea - abdominal pain or discomfort - anorexia —> weight loss)
3- Physical signs: few and non-specific (related to anemia and nutritional deficiency)
4- Increased incidence of atopy and autoimmune diseases (including T1DM)

Question 4

Investigations (5)

Answer 4

1- Mild anemia present in 50% of cases; almost always folate deficiency, commonly iron deficiency, and rarely vitamin B12 deficiency
2- Serum antibodies
- IgA tissue transglutaminase antibodies: best, increased sensitivity and specificity. False negatives occur in IgA defeciency (2% of celiac patients) —> IgG based tests should be used
- IgA endomysial antibodies are less sensitive
- Antigliadin is another antibody tested in celiac disease
- Serum antibodies for celiac disease should be checked in patients with signs and symptoms of celiac AND as screening for celiac in conditions with increased risk (Down’s syndrome, Turner’s syndrome, first degree relative, IBS, infertility and recurrent miscarriage, Autoimmune diseases e.g. T1DM, Thyroid disease, Autoimmune liver disease, Addison’s disease)
3- Distal duodenal biopsies obtained by endoscopy required for definitive diagnosis:
- Indicated for those with positive serology and those with negative serology but strong suspicion
- Increased number of intraepithelial lymphocytes
- Crypt hyperplasia
- Chronic inflammatory cells in lamina propria
- Villous atrophy (can be seen in tropical sprue, Whipple’s disease, but celiac disease is the commonest cause)
4- Small bowel radiology or capsule endoscopy (only performed if a complication is suspected e.g. lymphoma)
5- Bone densitometry (DEXA SCAN) performed at diagnosis because of increased risk of osteoporosis

Question 5

Management (4)

Answer 5

1- Lifelong gluten-free diet AND correction of any vitamin deficiencies
2- Celiac disease —> hyposplenism —> pneumococcal vaccine given to all patients
3- Monitor recovery and compliance by symptoms and serology testing (undetectable antibodies indicate response). Don’t monitor this with biopsy.
4- Re-biopsy is reserved for patients who do not respond or those with diagnostic uncertainty

Question 6

Complications (2)

Answer 6

1- Increased risk of malignancy:
- Intestinal T cell lymphoma also know as EATL: enteropathy associated T-cell lymphoma + non-Hodgkin lymphoma
- Small bowel cancer
- Esophageal cancer (squamous cell carcinoma)
2- The incidence may be reduced with gluten-free diet