Autoimmune Enteropathy
Introduction
Autoimmune enteropathy (AIE) is a rare, immune-mediated disorder characterized by intractable diarrhea, malabsorption, and immune-driven injury to the intestinal mucosa. First described in 1982, AIE predominantly affects infants but may present at any age. Because of its severity and resistance to dietary measures, prompt recognition and immunosuppressive therapy are essential.[1][2]
Epidemiology
AIE is exceedingly rare, with an estimated prevalence of <1 per 100,000 children, most presenting before six months of age. Adult cases comprise a small but growing proportion in the literature.[3][2]
Pathogenesis
AIE involves dysregulation of intestinal immune tolerance:
- Loss of regulatory T-cell function permits autoreactive lymphocytes to damage enterocytes and goblet cells.[2][4]
- Circulating anti-enterocyte and antigoblet-cell antibodies are detected in 85–87% of cases, supporting a humoral component.[4]
- Monogenic syndromes such as IPEX (FOXP3 mutation) and APECED (AIRE mutation) underscore genetic susceptibility and regulatory T-cell defects.[2][4]
Clinical Presentation
Patients typically present with:
- Severe, high-output diarrhea refractory to dietary modification
- Malnutrition and failure to thrive, often requiring total parenteral nutrition (TPN)
- Electrolyte disturbances due to fluid losses
- Extraintestinal autoimmune features including endocrinopathies, dermatitis, and hepatic or renal involvement.[5][4]
Diagnosis
Histology
Small-bowel biopsy reveals partial to total villous atrophy, crypt apoptosis, goblet and Paneth cell loss, and lymphocytic infiltration.[2]
Serology
Anti-enterocyte antibodies are a supportive but not definitive marker, present in ~14–87% of patients.[6][4]
Exclusion
Clonal T-cell receptor studies exclude refractory celiac disease, while negative celiac serologies and lack of response to a gluten-free diet distinguish AIE.[3][6]
Treatment
Nutritional Support
- Early TPN is often required to address severe malabsorption and growth failure.[4]
First-Line Immunosuppression
Steroid-Sparing Agents
- Azathioprine, 6-mercaptopurine, cyclosporine, and tacrolimus are used for steroid-dependent or refractory disease.[4]
Biologic Therapies
- Infliximab, adalimumab, and vedolizumab have shown efficacy in steroid-resistant cases, with response rates up to 85% in small series.[3]
Targeted Molecular Therapy
- Identification of pathogenic variants (CTLA4, LRBA, STAT3/STAT1) enables precision therapy (e.g., abatacept, JAK inhibitors), achieving durable remission in over 60% of genetically characterized adults.[6]
Advanced Therapies
- Bone marrow or mesenchymal stem cell infusions have yielded short-term benefit in isolated reports.[3]
- Small-bowel transplantation is a last-resort option for refractory, life-threatening disease.[3]
Prognosis and Follow-Up
Despite aggressive therapy, AIE carries significant morbidity from malnutrition, infections, and immunosuppression. Early genetic diagnosis and endoscopic monitoring are recommended to guide therapy adjustments and detect complications such as lymphoma.[6][4]
Conclusion
Autoimmune enteropathy is a rare but severe cause of chronic diarrhea and malabsorption in infants and adults. A high index of suspicion, histopathologic confirmation, and early initiation of immunosuppressive therapy are critical. Advances in genetic characterization and targeted treatments offer hope for improved outcomes in refractory cases.
Cincinnati Children’s Hospital and Children’s Hospital of Philadelphia provide multidisciplinary care, emphasizing immunosuppression, nutritional support, and long-term monitoring for this complex disorder.[7][5]
- https://en.wikipedia.org/wiki/Autoimmune_enteropathy
- https://www.pathologyoutlines.com/topic/smallbowelautoimmuneenter.html
- https://acr.amegroups.org/article/view/11119/html
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3912565/
- https://www.cincinnatichildrens.org/health/a/autoimmune-enteropathy
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10165659/
- https://www.chop.edu/conditions-diseases/autoimmune-enteropathy
- https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/autoimmune-enteropathy/
- https://www.sciencedirect.com/science/article/pii/S0893395222018464
- https://www.reviveresearch.org/blog/autoimmune-enteropathy-its-impact-on-the-human-body/
- https://www.nicklauschildrens.org/conditions/autoimmune-enteropathy
- https://www.sciencedirect.com/science/article/pii/S0896841121000172
- https://onlinelibrary.wiley.com/doi/full/10.1002/aid2.13234
