Use of Anti-TNF Agent in Refractory Ulcerative and CMV Colitis: A Case Report

Background: Parenteral glucocorticoids are a well-established treatment for acute severe ulcerative colitis (ASUC) flares in hospitalized patients. Most report symptomatic improvement within 3-5 days of starting treatment. However, for those with no improvement after 5 days, consideration of second-line agents, such as infliximab or cyclosporine, is warranted. We report a case of ASUC and concomitant CMV infection refractory to systemic steroids and ganciclovir, requiring addition of a TNF-alpha inhibitor. Methods: A 40-year-old female with a history of iron-deficiency anemia presented with a 1-month history of abdominal pain and hematochezia. Prior flexible sigmoidoscopy showed moderate inflammation from 25cm to the anal verge, and biopsies were consistent with UC. She was discharged with a 20mg prednisone taper and PO mesalamine. Despite therapy, patient had worsening hematochezia, frequent nocturnal stooling, arthralgias, and weight loss, prompting return to the hospital. On admission, fecal calprotectin was elevated, 248 mcg/g. She was started on IV Solumedrol, 20mg every 8 hours. Results: After 3 days of treatment, her pain and hematochezia were persistent. GI PCR and C. diff testing were negative, and she required blood transfusion for symptomatic anemia. Repeat colonoscopy to the transverse colon showed Mayo 3 left-sided colitis, and biopsies were consistent with UC with moderate inflammatory activity. Biopsied tissue was PCR-positive for CMV infection. Patient was started on IV ganciclovir, 5mg/kg twice daily. Following 3 days of treatment for CMV, symptoms had not improved. After discussing risks/benefits between consulting services, infliximab 10mg/kg was started with significant symptom improvement the following day, with stool frequency decreased to 3-4 daily from 10+. She was discharged on a 40mg prednisone taper and scheduled follow-up for continued induction therapy. With the second dose of infliximab, she reported resolution of abdominal pain and hematochezia. Subsequent fecal calprotectin was undetectable. Conclusions: Initial therapy for acute severe UC is well established, with steroids being first-line treatment. However, 30% of patients with an acute, severe UC flare will not improve with steroids alone, and concomitant infections should be ruled out. This case illustrates the importance of additional testing in UC flares that are refractory to steroids to rule out CMV infection, as well as the role of anti-TNF-alpha agents as adjunctive therapy to steroids and ganciclovir in refractory flares associated with CMV infection. Collaborative management between GI and ID can result in safe usage of TNF-alpha inhibitors in CMV-infected patients requiring therapy escalation in the inpatient setting.