Autoimmune enteropathy (AIE) is an immune-mediated disease, characterized by chronic severe intractable diarrhea.
At least five subtypes of AIE can be recognized: primary AIE (pediatric), syndromic AIE (pediatric), primary (sporadic) AIE of adults, secondary (iatrogenic driven) AIE of adults and paraneoplastic AIE.
Pediatric form: commonly presents as severe and life-threatening diarrhea in infants within the first 6 months of life. Generally exhibit malabsorption and severe weight loss or failure to thrive which does not respond to dietary modification. Endoscopically, the small intestine shows scalloping and fissuring. The syndromic form is associated with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) syndromes. IPEX is caused by loss-of function mutations in FOXP3 gene, which encodes for a transcription factor critical for normal development and function of regulatory T cells. APECED is caused by loss-of-function mutations in the AIRE gene, which encodes a transcription factor that regulates the expression of self-antigens in the thymus.
Histopathology: AIE can largely be grouped into four histologic patterns - active chronic enteritis, celiac-like, graft-versus-host disease-like, and mixed pattern.
Treatment: Challenging and often requires total parental nutrition and systemic steroids, immunosuppressive agents and biological agents. Most children with IPEX receive hematopoietic stem cell transplants.
Prognosis: Depends on the severity of symptoms and the underlying etiology.
References
Umetsu SE, Brown I, Langner C, Lauwers GY. Autoimmune enteropathies. Virchows Arch. 2018;472:55-66.
Singhi AD, Goyal A, Jon M Davison, et al. Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders. Mod Pathol. 2014;27:543-53.
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