Collagenous Sprue

Collagenous sprue is a rare malabsorptive enteropathy with villous atrophy and a subepithelial collagen band over 10 micrometres thick. It is nearly always associated with coeliac disease that no longer responds to gluten withdrawal, or with refractory coeliac disease.

It affects mainly women in the fifth to seventh decades, and 5-year survival is about 50% to 60% in the refractory form. Death is from malnutrition, infection, ulcerative jejunitis and enteropathy associated T-cell lymphoma. Some cases are related to drugs (olmesartan) or immunodeficiency.

Pathophysiology.

Chronic immune injury leads to abnormal collagen deposition beneath the epithelium by subepithelial fibroblasts, impairing nutrient transport across the mucosa.

Chronic watery diarrhoea, steatorrhoea, severe weight loss, abdominal pain, oedema from hypoalbuminaemia and deficiency states (anaemia, osteomalacia, neuropathy, coagulopathy). Patients are often malnourished and may need hospital care.

Red flags.

• Severe malnutrition or electrolyte disturbance.
• Abdominal mass, fever or pain (lymphoma).
• Gastrointestinal bleeding or perforation.
• Sepsis.

Duodenal biopsy shows villous atrophy with a thick (over 10 micrometres) subepithelial collagen band, highlighted with trichrome. Confirm coeliac disease (anti-tissue transglutaminase, HLA-DQ2 or DQ8) and exclude olmesartan and other drug enteropathy, tropical sprue, Giardia, common variable immunodeficiency, autoimmune enteropathy and small bowel overgrowth. Send flow cytometry and T-cell receptor clonality for refractory coeliac type 2.

Small bowel imaging and capsule endoscopy or enteroscopy exclude ulcerative jejunitis and lymphoma. Check albumin, calcium, magnesium, B12, folate, iron, vitamin D and bone density.

Differential diagnosis.

• Refractory coeliac disease types 1 and 2.
• Olmesartan associated enteropathy.
• Common variable immunodeficiency.
• Autoimmune enteropathy.
• Tropical sprue.
• Enteropathy associated T-cell lymphoma.

Maintain a strict gluten free diet and stop any implicated drug. Give nutritional support (parenteral nutrition in severe malnutrition) and immunosuppression.

• Budesonide (open capsule): 9 mg orally once daily in the morning for 3 months, then taper to the lowest effective dose; maximum 9 mg daily; monitor for adrenal suppression, infection and bone loss; reduce in moderate hepatic impairment and avoid in severe disease.
• Prednisolone: 0.5 to 1 mg/kg orally once daily (maximum 40 mg daily) for 4 weeks, then taper over 8 weeks; monitor glucose, blood pressure and bone health; reduce in older adults and give gastric protection.
• Azathioprine (steroid sparing): 2 to 2.5 mg/kg orally once daily; maximum 3 mg/kg daily; check thiopurine methyltransferase activity first, and monitor blood counts and liver tests every 2 weeks for 2 months, then every 3 months; reduce the dose in renal impairment and with allopurinol.
• Cyanocobalamin (B12 deficiency): 1,000 micrograms IM on alternate days for 2 weeks, then every 3 months; monitor B12 and haemoglobin; no renal adjustment.
• Folic acid: 5 mg orally once daily for 4 months; maximum 15 mg daily; monitor folate and blood count; check B12 first.

Replace iron, calcium, magnesium and vitamins D, A, E and K as deficient.

Monitoring. Weight, albumin, electrolytes and vitamins every 3 months; repeat biopsy at 6 to 12 months; imaging for lymphoma with new symptoms.

Referral and escalation. Gastroenterology with a coeliac and nutrition service; haematology for suspected lymphoma.