Coeliac Disease (CD) By Dr. Zahoor

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in which there is inflammation of mucosa of the upper small bowel (duodenum and jejunum) that improves when gluten is withdrawn from the diet and relapses when gluten is reintroduced Up to 1% of population is affected

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

Rye Barley Wheat Oats

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

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

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.

Pathophysiology of Coeliac Disease

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

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

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

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

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

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

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

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

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

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

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

Coeliac Disease (Gluten Sensitive Enteropathy) Diagnosis HLA typing HLA - DQ2 ( gene marker) is present in 90 - 95% cases ( on chromosome-6 ) HLA – DQ8 is present in about 8%

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

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.

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

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

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)

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

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

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.

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

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