Coeliac disease

Coeliac disease is a chronic, systemic autoimmune disorder that primarily affects the small intestine. It occurs in genetically predisposed individuals who develop an inappropriate immune response to gluten, a protein found in wheat, barley, and rye. The ingestion of gluten triggers inflammation and immune-mediated damage to the intestinal mucosa, leading to villous atrophy, impaired nutrient absorption, and a wide spectrum of gastrointestinal and extraintestinal manifestations. It is both a digestive and systemic condition that, if left untreated, can lead to significant complications such as osteoporosis, infertility, neurological problems, and an increased risk of certain malignancies.

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Pathophysiology

The underlying mechanism of coeliac disease involves both genetic and immunological factors:

• Genetic predisposition: The vast majority of patients carry the HLA-DQ2 or HLA-DQ8 haplotypes. However, not everyone with these genes develops the disease, indicating additional environmental and immune triggers.

• Gluten exposure: Gluten peptides resist complete digestion and reach the small intestine, where they interact with tissue transglutaminase (tTG). tTG modifies gluten peptides into negatively charged forms, enhancing their binding to HLA-DQ2/DQ8 molecules on antigen-presenting cells.

• Immune activation: This triggers an inappropriate T-cell–mediated immune response, leading to mucosal inflammation, villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.

• Systemic involvement: The immune activation extends beyond the gut, explaining extraintestinal manifestations such as dermatitis herpetiformis, anemia, neurological symptoms, and liver enzyme abnormalities.

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Clinical Features

1. Gastrointestinal manifestations:

• Chronic diarrhea or steatorrhea

• Abdominal bloating, cramping, or pain

• Flatulence

• Nausea and vomiting

• Constipation (sometimes, especially in children)

2. Nutritional deficiencies and metabolic effects:

• Iron-deficiency anemia unresponsive to oral iron therapy

• Folate and vitamin B12 deficiency

• Fat-soluble vitamin deficiencies (A, D, E, K)

• Weight loss and failure to thrive (especially in children)

• Osteopenia and osteoporosis from vitamin D and calcium malabsorption

3. Extraintestinal features:

• Dermatitis herpetiformis: intensely itchy papulovesicular rash, typically on elbows, knees, and buttocks

• Neurological problems: ataxia, peripheral neuropathy, headache, seizures

• Reproductive issues: infertility, delayed puberty, recurrent miscarriages

• Fatigue, depression, and irritability

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Diagnosis

1. Serology:

• Anti-tissue transglutaminase IgA (tTG-IgA): most sensitive and specific test

• Anti-endomysial antibody (EMA-IgA)

• Total serum IgA (to exclude IgA deficiency, which may cause false negatives)

• Deamidated gliadin peptide antibodies (DGP-IgG): useful in young children and IgA-deficient patients

2. Genetic testing:

• HLA-DQ2 and HLA-DQ8 testing: absence effectively rules out the disease, but presence alone is not diagnostic.

3. Small bowel biopsy (gold standard):

• Duodenal biopsy via endoscopy reveals villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.

4. Gluten challenge (in special cases):

• Used when diagnosis is unclear or when the patient is already on a gluten-free diet.

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Treatment

The cornerstone of treatment is a lifelong strict gluten-free diet (GFD). Complete elimination of wheat, barley, and rye is essential. Even small amounts of gluten (e.g., contamination from kitchen utensils) can trigger inflammation.

1. Dietary management:

• Gluten-free substitutes: rice, maize, quinoa, buckwheat, potato, millet, and certified gluten-free oats.

• Avoid processed foods containing hidden gluten (soups, sauces, salad dressings, beer, soy sauce).

• Support from dietitians specializing in coeliac disease is crucial.

2. Symptomatic and supportive treatment:

• Iron supplementation: ferrous sulfate 325 mg orally once to three times daily for iron-deficiency anemia.

• Folic acid: 5 mg once daily for folate deficiency.

• Vitamin B12: cyanocobalamin 1000 mcg intramuscularly every month or orally 1000 mcg daily (depending on severity).

• Vitamin D and calcium supplementation: cholecalciferol (Vitamin D3) 800–2000 IU daily and calcium carbonate 500–1000 mg daily for bone health.

• Bisphosphonates (e.g., alendronate 70 mg once weekly) may be considered in osteoporosis.

3. Refractory coeliac disease (rare, persistent symptoms despite strict GFD):

• Corticosteroids: Prednisone (20–40 mg/day orally, tapered gradually).

• Immunosuppressants: Azathioprine (1–2.5 mg/kg/day orally) or Cyclosporine (3–5 mg/kg/day orally). These are reserved for severe, treatment-resistant cases.

• Referral to specialized centers for evaluation of complications such as enteropathy-associated T-cell lymphoma (EATL).

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Complications

If untreated or poorly controlled, coeliac disease may lead to:

• Osteoporosis and fractures

• Malnutrition and severe anemia

• Infertility and miscarriage

• Neurological impairment

• Dermatitis herpetiformis

• Small bowel adenocarcinoma

• Enteropathy-associated T-cell lymphoma (EATL)

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Prognosis

With strict adherence to a gluten-free diet, most patients achieve complete mucosal healing and resolution of symptoms within 6–24 months. Risk of complications significantly decreases. Lifelong monitoring by healthcare professionals, including periodic nutritional assessment and bone density scans, is recommended.

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Key Points for Patients

• Coeliac disease is lifelong and cannot be “outgrown.”

• Even trace gluten exposure can cause harm, even if symptoms are not obvious.

• Regular follow-up with healthcare providers ensures early detection of complications.

• Support groups and educational resources can improve adherence and quality of life.