Human immunodeficiency virus infection mimicking very early onset inflammatory bowel disease

Abstract Very early onset inflammatory bowel disease (VEO‐IBD), defined as diagnosis before 6 years of age, is often associated with immune dysregulation and monogenic etiologies; however, infectious mimics may be overlooked in low‐prevalence regions. We report a 4‐year‐old male with poor weight gain, intermittent diarrhea, elevated fecal calprotectin, and persistently elevated erythrocyte sedimentation rate. Endoscopy showed diffuse friable colonic mucosa, and biopsies demonstrated focal active colitis with mild crypt distortion. He was diagnosed with VEO‐IBD and treated with mesalamine, infliximab, adalimumab, and upadacitinib, with incomplete response. At age 7, he was hospitalized with fever, cytopenias, and pulmonary infiltrates; human immunodeficiency virus (HIV) testing was positive, with Pneumocystis jirovecii pneumonia and cytomegalovirus viremia. After discontinuing immunosuppression and initiating antiretroviral therapy, gastrointestinal symptoms and inflammatory markers improved. HIV‐associated colitis can closely mimic VEO‐IBD, and progressive lymphopenia should prompt evaluation for secondary immunodeficiency.