Autoimmune Enteropathy

Autoimmune enteropathy is a rare immune mediated small intestinal disorder with severe protracted diarrhoea, villous atrophy and circulating anti enterocyte or anti goblet cell antibodies, unresponsive to dietary elimination.

• Occurs mainly in infants (IPEX syndrome, X linked from FOXP3 mutations, the prototype), but also in adults, often with common variable immunodeficiency, thymoma, or autoimmune disease.
• Associated disorders: type 1 diabetes, thyroiditis, haemolytic anaemia, nephropathy, hepatitis, dermatitis, and cytopenias.
• Other monogenic causes: CTLA4 haploinsufficiency, LRBA deficiency, STAT3 gain of function, IL2RA, STAT5B.
• Drug induced: olmesartan enteropathy, checkpoint inhibitors, idelalisib, mycophenolate.
• Complications: malnutrition, electrolyte disturbance, growth failure, infection, lymphoma.

• Chronic watery diarrhoea (often secretory, persisting during fasting), weight loss, vomiting, failure to thrive, dehydration.
• Extra intestinal autoimmunity: early onset diabetes, eczema, hepatitis, nephritis, cytopenias, thyroid disease.
• Adults: diarrhoea, weight loss, malabsorption, often with immunodeficiency.

Required criteria (Akram)

• Chronic diarrhoea of over 6 weeks, malabsorption.
• Specific histology: partial or complete villous blunting, deep crypt lymphocytosis, increased crypt apoptosis, minimal intraepithelial lymphocytosis.
• Exclusion of other causes: celiac disease (tTG negative, HLA permissive but no response to gluten free diet), food allergy, infection, immunodeficiency.
• Anti enterocyte (AIE 75 kDa) and anti goblet cell antibodies, supportive but not essential.

Other tests

• Immunoglobulins, lymphocyte subsets, FOXP3 expression, genetic panel for primary immunodeficiency, olmesartan history.
• Endoscopy with duodenal and colonic biopsies; capsule endoscopy.
• Stool studies, electrolytes, albumin, vitamins.
• Autoimmune screen (ANA, islet autoantibodies, thyroid antibodies).

• Stop causative drugs (olmesartan).
• Supportive nutrition: oral rehydration, parenteral nutrition for severe malabsorption, elemental diet.
• Immunosuppression:
  • Prednisolone 1 to 2 mg/kg/day (maximum 60 mg), then taper.
  • Budesonide 9 mg daily (adults) for steroid sparing in mild disease.
  • Tacrolimus 0.1 to 0.2 mg/kg/day (trough 5 to 10 ng/mL), sirolimus 1 to 2 mg daily (trough 5 to 10 ng/mL), azathioprine 2 mg/kg, mycophenolate 1 g twice daily, cyclosporine.
  • Infliximab 5 mg/kg, abatacept 10 mg/kg monthly (CTLA4/LRBA deficiency), vedolizumab, rituximab.
• IPEX: haematopoietic stem cell transplantation is the only curative treatment; immunosuppression as a bridge.
• Immunoglobulin replacement for associated immunodeficiency.
• Pneumocystis prophylaxis (co trimoxazole), monitoring of infections and drug levels.
• Treat thymoma (surgical resection) when present.
• Monitor growth, nutrition and extra intestinal autoimmune disease.