Always a Suspect: CMV in Ulcerative Colitis

Abstract

In June 2011, a 60-year-old white woman with history of ulcerative colitis presented with severe bloody diarrhea, reporting up to 12 bowel movements per day, vomiting and fatigue. She had initially presented with painless diarrhea and urgency 14 years ago. After the initial colonoscopic and histologic diagnosis of ulcerative colitis, she was placed on tapering doses of steroids and eventually on 100 mg of 6-mercaptopurine (6-MP). Over the next 5 years, she was treated for intermittent flares of ulcerative colitis with oral steroids in addition to 6-MP. Colonoscopy performed for a flare 6 years ago revealed viral inclusions in the cecal and rectal biopsies, consistent with cytomegalovirus (CMV). Serum IgG and IgM levels were elevated at 50.1 and 3.1, respectively. She was treated with ganciclovir 900 mg for 6 weeks in addition to 6-MP and prednisone, with subsequent clearance of histologic CMV inclusions. Over the next 5 years, she had a total of six colitis flares which were treated with short courses of steroids. However, because of an episode of pancreatitis in October 2006, 6-MP was discontinued in favor of methotrexate 12.5 mg weekly. Infliximab infusions were included in her regimen in March 2011 and were continued every 8 weeks thereafter. Her past medical history was otherwise significant for hepatitis A, hypothyroidism, hyperlipidemia, sclerosing cholangitis (for which she was treated with ursodeoxycholic acid 900 mg orally daily) and Sjogren’s syndrome. She was a non-smoker and non-drinker and worked as a librarian. Upon presentation in June 2011, her physical examination revealed a pale woman with a soft, non-distended, non-tender abdomen with positive bowel sounds. She was re-started on 40 mg of prednisone with continuation of methotrexate and infliximab; severe diarrhea persisted. Colonoscopy revealed severe ulcerative colitis with several large nodules suggestive of ‘‘dysplasia-associated lesion or mass’’ (DALM) (Fig. 1). Biopsies revealed high-grade dysplastic epithelium in the sigmoid and rectal nodules (Fig. 2). Viral inclusion bodies specific to CMV were observed with conventional histology and with immunohistochemal stains (Fig. 3). Infliximab infusions were stopped in favor of ganciclovir 900 mg given orally twice daily for 6 weeks. After one week of therapy, bowel movements decreased to 5–6 per day, her fatigue improved, but her hematocrit decreased by 4 points to 28.8 %. Intravenous iron was initiated to treat iron deficiency. Ten days after stopping ganciclovir, her hematocrit normalized. Upon follow-up colonoscopy 4 months later, severe ulcerative colitis with more dysplastic nodular lesions in several locations were identified. Because of this, she underwent a laparascopically-assisted total proctocolectomy with an end-ileostomy. The specimen revealed welldifferentiated adenocarcinoma in the cecum and sigmoid colon. Sixty-two lymph nodes identified were negative. When seen at follow up 2 months post colectomy, she felt more energetic and had discontinued prednisone, infliximab and methotrexate. Ursodeoxycholic acid was continued as the treatment for her primary sclerosing cholangitis. S. Kommareddy C. L. Chun W. Rogers G. Triadafilopoulos El Camino Hospital, Mountain View, CA, USA