GastroenterologyTier 2Disease (DEADMAN)

Autoimmune enteropathy and IPEX syndrome

Description

Autoimmune enteropathy is severe, treatment-refractory diarrhoea/malabsorption from autoimmune destruction of the intestinal mucosa; IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) is the classic, most severe genetic cause, from FOXP3 gene mutations impairing regulatory T cell function

IPEX syndrome is rare, X-linked, presenting in male infants with a severe, early-onset multisystem autoimmune phenotype; autoimmune enteropathy can also occur in older children/adults, sometimes without an identified genetic cause

FOXP3 is essential for the development and function of regulatory T cells (Tregs), which normally suppress autoreactive immune responses - its loss (IPEX) removes this suppression, allowing autoimmune attack against multiple organs, with the gut, endocrine pancreas/thyroid, and skin most classically affected

Classic IPEX triad: severe enteropathy (villous atrophy, intractable diarrhoea), endocrinopathy (most commonly neonatal/early-onset type 1 diabetes, also thyroiditis), and dermatitis (eczema-like) - presenting in early infancy in affected males
Small bowel biopsy shows severe villous atrophy with an intense inflammatory infiltrate, resembling but distinguishable from coeliac disease on specific immunohistochemical/clinical grounds (notably the lack of response to gluten withdrawal)
Autoantibodies against gut epithelial antigens (e.g. anti-enterocyte, anti-goblet cell antibodies) can support the diagnosis; genetic testing (FOXP3) confirms IPEX specifically

Immunosuppression (corticosteroids, calcineurin inhibitors, or other steroid-sparing agents) to control the autoimmune process
Haematopoietic stem cell transplantation is potentially curative for IPEX syndrome, given the underlying defect is in a haematopoietic cell lineage (Tregs), and is considered in severe cases given the otherwise poor prognosis
Nutritional support (often including parenteral nutrition in severe enteropathy) alongside immunosuppression

Type 1 diabetes (early-onset, in the IPEX context), autoimmune thyroiditis, eczema/dermatitis, other autoimmune cytopenias

Untreated IPEX syndrome carries a poor prognosis in infancy without transplantation, given the severity of the multisystem autoimmune process - early recognition (severe enteropathy plus endocrinopathy plus dermatitis in a male infant) is important to enable timely consideration of curative transplantation

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