Enteropathy in inborn and acquired errors of immunity: histological patterns and clinical correlates

Enteropathy is a significant and under-recognised complication of inborn errors of immunity (IEI), frequently misclassified as inflammatory bowel disease (IBD) or coeliac disease due to overlapping and non-specific histopathological findings. Diagnostic criteria remain poorly defined, contributing to substantial diagnostic delay and associated morbidity.

We conducted a structured literature review and established the AT-SEA (Adult Tertiary Severe Enteropathy Audit) working group, a collaborative network of Australian clinical immunologists operating under the Clinical Immunogenomics Research Consortium Australasia (CIRCA), to characterise the clinicopathological features of IEI-associated enteropathy across a multicentre cohort.

Twenty-eight patients were identified. Moderate or severe disease was present in 89%, with malabsorption in 71% and protein-losing enteropathy in 43%. Across 48 biopsy reports, the most frequent histopathological patterns were coeliac-like changes (including villous atrophy, increased intraepithelial lymphocytes and crypt hyperplasia), IBD-like changes, reduced or absent plasma cells, graft versus host disease (GVHD)-like changes or increased apoptotic bodies and intraepithelial neutrophilia. Seventy-seven percent of patients demonstrated two or more concurrent patterns. Increasing histological complexity correlated significantly with clinician-assessed disease severity (Kruskal-Wallis p=0.042).

IEI-associated enteropathy is characterised by overlapping and evolving histopathological patterns rather than discrete subtypes. The co-occurrence of multiple patterns should prompt consideration of an underlying IEI.