Crohn's-like Enteritis in X-Linked Agammaglobulinemia: A Case Series and Systematic Review

Background: X-linked agammaglobulinemia (XLA) is an inherited primary immunodeficiency that usually manifests clinically with recurrent sinopulmonary infections. Gastrointestinal manifestations are mostly driven by acute infections and disturbed mucosal immunity, but there is a notable prevalence of inflammatory bowel disease (IBD). Differentiating between XLA-associated enteritis, which can originate from recurrent infections, and IBD can be diagnostically and therapeutically challenging.

Objective: This study presents a critical appraisal of the clinical, radiological, endoscopic, and histological features associated with XLA-associated Crohn disease (CD)-like enteritis.

Methods: We report 3 cases and performed a systematic review of the literature describing the diagnoses and outcomes.

Results: An XLA-related enteropathy presented in adolescence with an ileocolonic CD-like phenotype without perianal disease. Abdominal pain, noninfectious diarrhea, and weight loss were the most common symptoms. Imaging and endoscopic findings closely resemble CD. However, histologically, it presents without nodular lymphoid hyperplasia and only 2 studies reported the presence of granulomas. In addition, in XLA-associated enteritis, immunohistochemistry showed the absence or marked reduction in B cells and plasma cells.

Conclusions: An XLA-associated enteritis is a distinct pathological process that presents clinically in a manner similar to ileocolonic CD. It is important to evaluate for infectious diarrhea, which is common in XLA and can mimic IBD clinically. Complete multidisciplinary evaluation is, therefore, recommended for XLA patients with persistent gastrointestinal symptoms. Although more research is needed, therapeutic selection for XLA-associated enteritis is like that of IBD, and the possible risk of drug interactions and complications from increasing immunosuppression should be considered.