P-003 New Diagnosis of Crohn’s Colitis 6 weeks After Fecal Microbiota Transplantation (FMT)

Abstract

BACKGROUND: The pathophysiology of IBD is incompletely understood, but believed to result from a combination of genetic, immune, and environmental factors. The role of microbial dysbiosis has become increasingly recognized as an important element in disease development. We report the first case of newly diagnosed Crohn's disease post-FMT for recurrent Clostridium difficile infection (CDI). METHODS: A 41 year old female with Irritable Bowel Syndrome (IBS) and a family history of lymphocytic colitis (mother) presented with nausea, vomiting, diarrhea and abdominal pain, which resolved with ciprofloxacin and metronidazole for presumed "gastroenteritis." Colonoscopy 1 month later showed diffuse edema and erythema, but multiple random biopsies of the colon were normal. Four months later, she was hospitalized with fatigue, vomiting, diarrhea, and fevers. CT scan showed pancolitis. C. difficile toxin PCR was positive. She improved on IV metronidazole and oral vancomycin. Two weeks later, she was hospitalized with the same symptoms, diagnosed with CDI, and treated with metronidazole and vancomycin for 3 weeks. One year after initial presentation, she developed another recurrence of CDI, following ciprofloxacin for pyelonephritis. Symptoms resolved with oral vancomycin pulse-dosed over 6 weeks. She developed her 4th CDI after azithromycin for a sinus infection and again improved on vancomycin, which was continued until 3 days prior to FMT. Donor material was an investigational whole stool microbiota suspension. FMT was delivered by sigmoidoscopy which revealed mild patchy erythema and edema of the sigmoid, and normal histology. At follow-up phone contacts 24 hours and 1 week post-FMT, she was asymptomatic. Six weeks post FMT, she developed diarrhea, hematochezia, and severe abdominal pain. Stool C. difficile PCR was negative x 2. CT scan showed pancolitis. RESULTS: Colonoscopy showed discontinuous areas of bleeding, deeply ulcerated mucosa, severe inflammation and segmental pseudopolyps. The terminal ileum was normal. Histology revealed chronic inactive colitis with crypt architectural distortion, mildly increased lamina propria lymphocytosis, and crypt dropout, and non-necrotizing granulomas. No microorganisms or fungi were seen. Special stains including GMS and AFB for fungi and acid fast bacilli were negative. Stool testing sent after the colonoscopy for culture, E. coli O157 H7, giardia/ cryptosporidium and C. difficile PCR were negative. She was treated with prednisone with improvement in fatigue, arthralgia and abdominal symptoms and has since initiated infliximab. CONCLUSIONS: This appears to be a new diagnosis of Crohn's colitis 6 weeks post-FMT for recurrent CDI. Based on the temporal relationship to FMT, this adverse event is possibly related. Transmission of an unidentified agent via FMT may have precipitated inflammation and immune dysregulation. Alternatively, repeated CDI and courses of antibiotics could have shifted the gut microbiota to a state of dysbiosis contributing to the emergence of IBD in this patient who may be genetically predisposed. It is less likely that this represents another infectious process, as multiple stool studies and histologic stains have been negative. Although FMT is generally considered a safe and effective therapy for recurrent CDI, this case association highlights the need for further research on FMT as well as monitoring for short- and long-term adverse events.