P-018 YI Primary Gastrointestinal Histoplasmosis Complicating Vedolizumab Therapy in Crohn's Patients

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Abstract

Background:

Vedolizumab (VDZ) is a gut-selective monoclonal antibody against α4β7-integrin, an adhesion molecule expressed on the surface of gut-specific lymphocytes which mediates leukocyte trafficking to the gut. We present 2 patients who developed primary gastrointestinal histoplasmosis (GIH) on VDZ therapy with the first submitted as a case report to American College of Gastroenterology (ACG) meeting but now updated to include post treatment findings. Since a second similar case was found at our institution, we found this relevant for physicians to acknowledge the possibility that VDZ may play a role in GIH as none have been previously reported in the literature.

Methods:

Not applicable for case reports.

Results:

Case 1: A 38 year old Caucasian male with severe ileo-colonic Crohn's disease (CD) diagnosed 20 years ago treated with conventional therapy as well as infliximab, adalimumab and natalizumab failed to induce remission. He achieved clinical remission after starting VDZ and oral prednisone 40 mg with a successful taper after colonoscopy showed moderate to severe inflammation along the terminal ileum (TI) and entire colon (edema, erythema, friability, granularity, ulcerations and scattered pseudopolyps). Colonoscopy a year later showed significant improvement in endoscopic appearance (few scattered pseudopolyps, scarring surrounded by normal mucosa) however with 3 new multilobulated cecal polyps. Pathology confirmed microscopic inflammation and Histoplasma identified with Grocott's Methenamine Silver (GMS) stain, and no evidence of systemic infection was found. After 3 months of therapy with itraconazole, a follow up colonoscopy showed moderately severe disease involving the terminal ileum and colon but resolution of histoplasmosis as no organisms was identified on histology.

Results:

Case 2: A 31 year old Caucasian male diagnosed with ileocolonic CD complicated with ileocecal inflammatory stenosis 10 years ago had previously failed or was intolerant to treatments with azathioprine, adalimumab, and infliximab. Prior to initiating treatment with VDZ, and a successful 1 month prednisone taper, colonoscopy revealed severe inflammation with ulceration in the cecum and ascending colon. Of note, histology was negative for fungal organisms. Approximately 3 months later, he complained of high fevers ranging from 101 to 104oF. Computed tomography of the chest, abdomen and pelvis did not show any pulmonary involvement but findings compatible with infectious or inflammatory colitis of the right colon with prominent mesenteric and retroperitoneal lymphadenopathy. Gastrointestinal stool panel was negative for infections. Urine Histoplasmosis Ag was strongly positive at 5.44 ng/mL. A repeat colonoscopy revealed severe right sided disease with GMS staining positive for Histoplasmosis. Within 5 days of initiating itraconazole, his fevers resolved and he is completing a 12 weeks treatment course.

Conclusions:

GIH occurs in about 70% of cases with disseminated Histoplasmosis and frequently involves TI and cecum. Evidence suggests that VDZ may increase risk of Clostridum difficile infection and cytomegalovirus colitis but no data reports a link to fungal infections. This is the first case series of primary GIH reported with VDZ use. It is unclear if the gut specific nature of the drug may play a role in causing primary GIH instead of secondary disease. Providers should be vigilant of fungal infections among patients on biologics.

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