Autoimmune Colitis and Subsequent CMV-induced Hepatitis After Treatment With Ipilimumab

Ipilimumab, a humanized CTLA-4 antibody, improves overall survival in patients with metastatic melanoma. However, immune-related adverse effects occur in about 65% of ipilimumab-treated patients and have to be adequately managed. A 55-year-old patient developed grade 3 autoimmune colitis 7 weeks after initiation of ipilimumab treatment and subsequently hepatitis with grade 3 elevation of transaminases and gamma-glutamyl transferase. Colitis manifested with up to 18 watery and bloody stools per day and severe attacks of abdominal pain. After exclusion of infectious causes, immunosuppression with corticosteroids was initiated. Because of recurrent abdominal pain, spontaneous perforation of the colon had to be excluded. Elevated liver function tests (grade 3 CTCAE) occurred and differential diagnosis included immune-mediated, toxic, and viral hepatitis. It is interesting to note that, not an immune-mediated but a cytomegalovirus-induced hepatitis was diagnosed by serum blood tests and liver biopsy and was subsequently successfully treated. Careful elaboration of the patient under immunotherapy was essential as further immunosuppression mandatory for autoimmune hepatitis would have worsened the viral hepatitis. In conclusion, cytomegalovirus reactivation should be included in the differential in patients under immunotherapy with checkpoint inhibitors and has to be considered as a cause for morbidity.