108 An Inflammatory Bowel Disease Mimicker: Ocrelizumab-Induced Immunosuppression Leading to Fulminant Cytomegalovirus and Herpes Simplex Virus Infection

Introduction: Ocrelizumab is a recombinant monoclonal antibody approved for the treatment of multiple sclerosis in adults through the targeting of CD-20 on B-lymphocytes. Through depleting peripheral B-cell populations whilst maintaining their stem cell progenitors, this humanized antibody has significant efficacy in controlling multiple sclerosis activity. There have been cases in the literature of colitis and enteritis caused by ocrelizumab, with clinical and histological findings highly mimicking IBD. Rarely, however, the immunosuppressive nature of ocrelizumab can predispose patients to life-threatening opportunistic infections. Case Presentation: A 65-year-old female presented for generalized weakness, multiple falls, and diarrhea. She reported numerous watery stools for 3 weeks as well as left lower quadrant abdominal pain. She had initially been seen at an outside hospital 2 weeks prior for these symptoms and was treated for unspecified colitis with a course of doxycycline followed by ciprofloxacin. Her history included a prior total colectomy with ileorectal anastomosis for suspected familial adenomatous polyposis syndrome but eventual negative genetic testing, multiple sclerosis on long-term ocrelizumab twice a year, paroxysmal atrial flutter on Eliquis status-post multiple ablations and eventual pacemaker placement, iritis on azathioprine, and coronary artery disease status-post drug eluting stent to the left anterior descending artery. Upon presentation, pertinent labs showed: sodium 128, blood urea nitrogen 57, creatinine 2.63, alkaline phosphate 262, alanine aminotransferase 164, aspartate aminotransferase 167. C-reactive protein was 12.8 and fecal calprotectin was 732. Clostridium difficile toxin and gastrointestinal pathogen panel were negative. Computed tomography showed bowel wall thickening and edema near the site of her ileocolonic anastomosis. A colonoscopy showed diffuse moderate inflammation characterized by altered vascularity, congestion, scattered superficial erosions and ulcers 30–60 cm proximal to the anus with normal mucosa between said erosions/ulcers. The ileorectal anastomosis was unable to be definitively visualized at 25 cm. The rectum appeared normal. Rectal pathology showed focal epithelial denudation and crypt loss, suggestive of ischemic changes. Small bowel biopsies showed extensive ulceration with acute and chronic inflammation. Both cytomegalovirus (CMV) immunohistochemistry and herpes simplex virus (HSV) 1–2 immunohistochemistry were positive. Ganciclovir and acyclovir were started. Steroids were considered but only initiated temporarily. The patient’s hospital course was complicated by multiorgan failure requiring continuous renal replacement therapy and maximal therapy on 4 pressors as well as profound pancytopenia refractory to blood and cryoprecipitate. Despite best efforts, the patient continued to decompensate resulting in comfort care measures being initiated after family discussion. Discussion: There are scattered case reports of ocrelizumab-induced colitis and, even more rarely, ocrelizumab-induced enteritis, characterized by CD19 and CD20 B-cell depletion on immunohistochemistry. Management of enteritis in patients on ocrelizumab is challenging, as they mimic both clinical and histopathological features of inflammatory bowel disease (e.g. ulcerations, cryptitis, crypt abscesses, etc.). Steroid treatment is mainstay; however, given this medication’s immunosuppressive nature, opportunistic infections should remain high on the differential even in the absence of profound B-cell depletion on histology. It is suspected that our patient’s 4-year-long duration of ocrelizumab played a key role in altering gut architecture and immunogenicity, creating the conditions favorable to CMV and HSV infection.