Coeliac Disease (CD) By Dr. Zahoor

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Coeliac Disease (CD)By Dr. Zahoor

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Coeliac DiseaseCoeliac 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in which there is inflammation of mucosa of the upper small bowel (duodenum and jejunum) that improves when gluten is withdrawn from the diet and relapses when gluten is reintroduced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

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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

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BarleyRye

Oats Wheat

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•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

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•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

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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.

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Pathophysiology of Coeliac Disease

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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

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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

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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

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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

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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

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Other Associated Diseases with CD•Inflammatory bowel disease •Primary Biliary cirrhosis •Chronic liver disease•Interstitial lung disease •Epilepsy

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

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Diagnosis•Small bowel biopsy Histology •Shows subtotal villous atrophy•Crypt hyperplasia with inflammatory

cells, increased lymphocyte and plasma cells in the lamina propria

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Diagram showing normal and subtotal villous atrophy

Normal Mucosa Subtotal Villous Atrophy in CD

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Causes of Subtotal Villous Atrophy

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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

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DiagnosisHLA typing•HLA - DQ2 ( gene marker) is present in 90 - 95%

cases ( on chromosome-6 )•HLA – DQ8 is present in about 8%

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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

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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.

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Investigations (cont)

Biochemistry•Low calcium and high phosphate –

Osteomalacia•Hypoalbuminaemia

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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

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Treatment and Management• Gluten free diet for life Elimination of wheat, barley, rye ,oatsNOTE – 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)

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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

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Treatment for Ulcerative Jejunitis•Steroids •Immunosuppressive agents Azathioprine

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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.

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

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Thank you

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Coeliac Disease (CD) By Dr. Zahoor