P004 Primary colonic histoplasmosis secondary to fecal microbiota transplantation in a patient with ulcerative colitis on anti-TNF alpha
Authors: Krishna Patel , Muhammad Hammami , Florence-Damilola Odufalu , Katie Schroeder 
Published: July 2019

INTRODUCTION:
Histoplasmosis is a mycotic disease that is most common in patients with a weakened immune system, including those on tumor necrosis factor inhibitors. We present a patient with ulcerative colitis (UC) on infliximab, who had recurrent Clostridium difficile infections (CDI) requiring fecal microbiota transplantation (FMT) and subsequently developed primary colonic histoplasmosis.

CASE:
We present a 34-year-old woman from Missouri with ulcerative pancolitis on infliximab complicated by recurrent CDI requiring FMT. She was diagnosed with UC at age 32 (March 2015). She failed Mesalamine, Adalimumab (primary non-responder), and developed Azathioprine-induced pancreatitis. Infliximab later replaced Adalimumab with subsequent dose escalation and frequent courses of Prednisone due to refractory disease. The first CDI was diagnosed March 2016. From initial diagnosis, she had 4 CDI positive stools, in addition to a course of diarrhea that was empirically treated as CDI. She completed 4 courses of oral Vancomycin and 2 courses of Fidaxomicin, with initial response but recurrence of diarrhea shortly after antibiotic completion. Due to recurrent CDI, she underwent FMT in April 2017. Two weeks following FMT, she was diagnosed with a pulmonary embolism. Two weeks later, she presented with high grade fevers, hypotension and altered mental status. Labs were notable for rising liver enzymes (peak values: ALP 1,009 u/L, ALT 120 u/L, AST 293 u/L). Abdominal ultrasound did not show signs of cholestatic or hepatic processes. Symptoms continued to worsen despite steroids, fluid resuscitation and broad-spectrum antibiotics. Her course was further complicated by hematochezia and refractory anemia requiring blood transfusions. Cross sectional imaging demonstrated circumferential wall thickening of the proximal ascending colon to the cecum in addition to the previously identified pulmonary embolism. There was no evidence of pneumonia, hilar/mediastinal lymphadenopathy, ground glass opacity, nodules, masses or cavitary lung lesions. Sigmoidoscopy with biopsies demonstrated diffuse colitis. Qualitative serum CMV PCR and urine Histoplasma were checked and resulted positive. Ganciclovir and Amphotericin B liposome were initiated and within 48 hours, liver enzymes began to improve. However, due to worsening clinical course she eventually underwent total abdominal colectomy and partial proctectomy. Both colonic biopsies from sigmoidoscopy and colectomy were positive for Histoplasma and negative for CMV. She was diagnosed with disseminated histoplasmosis, treated with IV Amphotericin B liposome followed by a course of itraconazole, and she fully recovered. Colonic specimens from 5 months and 12 months prior to FMT were retrospectively reviewed and stained negative for histoplasmosis.

DISCUSSION:
Histoplasmosis in immunocompromised hosts can develop through exogenous exposure or reactivation of latent infection, with the former being more common. Our patient had biopsies from a colonoscopy 5 months preceding FMT which were negative for histoplasmosis, and cross-sectional imaging unrevealing of latent or active pulmonary disease; this suggests that primary colonic histoplasmosis was most likely introduced via FMT, resulting in refractory colitis and requiring total colectomy. Testing FMT donors/stool for histoplasmosis is not standardized and can vary. However, given the frequency of FMT in IBD patients on anti-TNF with recurrent CDI, FMT histoplasmosis screening should be considered.