Cytomegalovirus and Crohn's disease as competing causes of small bowel inflammation after double-lung transplantation.

Background: Cytomegalovirus (CMV) infection remains a significant cause of morbidity following solid organ transplantation, most frequently affecting the gastrointestinal tract. In transplant recipients presenting with diarrhea, alternative etiologies such as inflammatory bowel disease (IBD) should be considered. The emergence of antiviral resistance poses a therapeutic challenge, and molecular testing for resistance-associated mutations is essential in cases of treatment failure. Case presentation: A lung transplant recipient developed chronic diarrhea leading to functional intestinal failure. CMV infection was identified in intestinal biopsies and initially managed with two courses of valganciclovir. Due to persistent symptoms, genotypic analysis was performed, revealing UL97 mutations conferring ganciclovir resistance. Sequential therapy with foscarnet, maribavir, and letermovir achieved virological clearance, but diarrhea persisted. Small bowel enteroscopy with biopsies showed ongoing mucosal inflammation and minimal residual CMV activity. These findings were consistent with ganciclovir-resistant CMV enteritis coexisting with de novo Crohn's disease. The patient was commenced on standard biological therapy for Crohn's disease, resulting in marked clinical improvement and recovery. Conclusion: This case illustrates the diagnostic challenge of distinguishing CMV enteritis from de novo Crohn's disease and determining the primary driver of the clinical presentation.