A 73-year-old male patient, with no relevant medical history, had recently been diagnosed with stage IV urothelial cancer. The patient's diagnosis was discussed with a multidisciplinary tumor board, and enfortumab vedotin (1.25 mg/kg body weight on day one and eight of a three-weekly regimen) together with pembrolizumab (200 mg, every 3 weeks) was initiated. After three cycles, the patient developed a checkpoint inhibitor-related pneumonitis. Steroid therapy was initiated, i.e., prednisolone 1 mg/kg body weight/day. The pneumonitis resolved and treatment was rechallenged by only the admission of enfortumab vedotin during the last three cycles.
Following six cycles, the patient was hospitalized due to acute abdominal pain, nausea, vomiting, and diarrhea. An abdominal computed tomography (CT) scan was performed and revealed a diffuse edematous wall thickening of the level of the ileal loops (maximum 1 m in length) and of the rectosigmoid (shown in Fig. 1). Repetitive cultures were positive for Campylobacter-induced enterocolitis. Subsequently, cytomegalovirus (CMV)-induced colitis was also suspected due to fever spikes and high CMV viremia. Nevertheless, no CMV inclusions were noticed on histology of the colon and ileum. Treatment with azithromycin, 500 mg/day, and ganciclovir, 5 mg/kg body weight/12 h, was initiated.
Despite adequate treatment of these infectious complications, the patient deteriorated with persistent high-output diarrhea. Radiological reassessment showed unchanged edematous wall thickening at the level of the preterminal ileal loops. Extensive gastro-intestinal checkup was executed with infectious workup (multiplex PCR panel, CMV PCR), laboratory evaluation (TBC, HIV testing among other), fecal pancreatic elastase, total IgA and tissue transglutaminase IgA, repeat ileocolonoscopy, enteroscopy and esophagogastroduodenoscopy with multiple biopsies. Interestingly, the ileocolonoscopy and enteroscopy showed no mucosal changes in the ileum. Histopathology findings at the level of the colon were normal, while the ileal biopsies showed an enteritis, characterized by a marked inflammatory cellular infiltrate in the lamina propria consisting of neutrophils, lymphocytes, and plasma cells. During this period, blood tests showed a normal renal function, thyroid function, and liver tests.
At this point, grade 3 ICI enteritis (in casu ileitis) was identified, according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). The patient was treated with high-dose corticosteroids without any clinical and radiographic improvement. The following 6 months, he received multiple high doses of infliximab (10 mg/kg body weight), methotrexate, mycophenolate mofetil, and vedolizumab. Different opportunistic infections, such as catheter-related infections and sepsis secondary to bacterial translocation, were treated with antibiotics. A combination of enteral and parenteral nutrition was initiated because of cachexia. Eventually, surgical resection was considered due to persistent signs of obstruction. A presurgery CT enterography still showed extensive ileitis involving multiple segments but also suspected fibrotic strictures with significant prestenotic dilatations (shown in Fig. 2). These fibrotic areas were characterized by abnormally thickened loops with minimal enhancement, no adjacent mesenteric inflammation and demonstrated upstream small bowel dilatation.
During the laparotomy, an 80-cm pathological thickened and inflammatory-appearing ileum segment was resected and an entero-enterostomy was constructed. There were no immediate or late complications following surgery. Histopathology findings of the resected ileum showed a chronic, extensive, ulcerative, and active ileitis with transmural lymphocytic infiltration. Following surgery, the patient was included in a rehabilitation program where he made a full recovery and regained a normal level of exercise capacity.
The CARE Checklist has been completed by the authors for this case report, attached as supplementary material (for all online suppl. material, see https://doi.org/10.1159/000530832).