Cryptosporidiosis in inborn errors of immunity: a single center cohort and review of the literature

BACKGROUND: Severe intestinal or hepatobiliary cryptosporidiosis affects patients with inborn errors of immunity (IEI), particularly those with CD40 ligand or CD40 deficiency, major histocompatibility complex class II deficiency, interleukin-21 receptor deficiency, and DOCK8 deficiency. Susceptibility to Cryptosporidium reflects defects in lymphocyte development, activation, and effector function. METHODS: We conducted a retrospective chart review of IEI patients with cryptosporidiosis, focusing on 17 individuals with chronic infection who underwent hematopoietic cell transplant (HCT), to characterize their clinical course, diagnostic evaluation, management, and outcomes. A literature review was also performed to summarize current knowledge of cryptosporidiosis in IEI patients. RESULTS: Patients frequently presented with secondary sclerosing cholangitis, posing significant diagnostic and therapeutic challenges. Molecular diagnostic assays offered higher sensitivity than conventional microscopy. Antiparasitic agents had limited efficacy against hepatobiliary disease. Durable immune reconstitution through HCT remained the mainstay of management, though it carries risk, especially in patients with established liver disease. Prophylactic strategies for at-risk individuals remain underexplored but should include exposure avoidance and consideration of antiparasitic prophylaxis. CONCLUSIONS: Cryptosporidium-related sclerosing cholangitis imposes a substantial disease burden in susceptible IEI patients, underscoring the importance of early recognition and proactive management, particularly timely immune reconstitution in this population.