X-linked agammaglobulinemia (XLA) is caused by mutations in the BTK gene, leading to an arrest in B cell maturation and profound hypogammaglobulinemia. Although immunoglobulin replacement therapy significantly improves survival, adults with XLA may develop complications beyond recurrent bacterial infections, including autoimmunity, bronchiectasis, gastrointestinal inflammation, and, more rarely, opportunistic infections. Despite therapeutic advances, recent data suggest a 5-year survival rate of 75%, with a median age at death of 21 years. Long-term follow-up of adult XLA patients remains critical to anticipate and manage noninfectious and atypical complications.
To report the case of a 40-year-old male with a history of XLA who developed severe diarrhea and cytomegalovirus (CMV) infection.
A 40-year-old man with genetically confirmed XLA (BTK exon 14 deletion, CCTG1335) was referred in January 2025 due to severe, chronic diarrhea and progressive weight loss. His medical history included recurrent infections since childhood, idiopathic juvenile arthritis, and bronchiectasis diagnosed at age 10. He had been receiving regular IgG replacement since then. At presentation, he had lost 10 kg, with >10 bowel movements per day. Endoscopy and capsule studies revealed diffuse villous atrophy, jejunitis, and an ulcerated lesion. Upon admission, he developed anasarca and respiratory failure requiring mechanical ventilation. Bronchoalveolar lavage was positive for CMV by PCR. Ganciclovir was initiated. Despite treatment, the patient experienced multiple complications: catheter-related sepsis, hepatotoxicity, electrolyte imbalances, and persistent diarrhea. Immunoglobulin dosing was intensified to maintain protective levels. Repeat endoscopic biopsies confirmed disseminated CMV enterocolitis. The patient died 44 days after admission.
This case illustrates the potential severity of gastrointestinal and opportunistic complications in adult XLA patients. Chronic diarrhea warrants thorough investigation, including viral studies. CMV reactivation, although rare, can be life-threatening. Multidisciplinary management and vigilant long-term monitoring are crucial for improving outcomes in adults with XLA.
