Gastrointestinal Histoplasmosis Causing Intestinal Perforation in a Crohnʼs Disease Patient Taking TNF-alpha Inhibitor

Abstract

66-year-old black woman with history of Crohn's disease presented with diffuse abdominal pain, bloody diarrhea and dyspnea. Her home medications include adalimumab, mercaptopurine and mesalamine. The adalimumab (TNF α inhibitor) was increased to twice per week after a recent hospitalization. Vitals were normal and physical examination revealed clear lungs, diffuse abdominal tenderness. Pertinent laboratory values included: WBC 9000/μL, hemoglobin 9.5 g/dL, potassium of 3.1 mEq/L. Stool was negative for clostridium difficile toxin, ova and parasites. Her chest x-ray showed a nodular pattern while CT chest revealed a diffuse bilateral interstitial thickening. She was empirically started on vancomycin, meropenem and IV steroids. Immunosuppressant medications were held due to pancytopenia. She underwent a bronchoscopy with bronchial wash. While waiting for results, the patient developed a rigid abdomen due to intestinal perforation and was taken for an emergent exploratory laparotomy with ileocolonic resection and ileostomy. Histopathologic analysis of both the resected bowel and bronchial wash specimens revealed histoplasma capsulatum. The serum and urine histoplasma antigen were positive. She was immediately started on a two-week course of IV amphotericin B for disseminated Histoplasmosis with improvement in her cell counts. She was discharged on mesalamine, a tapered dose of steroids, and a 12-month course of oral itraconazole while adalimumab was discontinued. Gastrointestinal involvement occurs in 70-90% of patients with disseminated Histoplasmosis and presents with nausea, vomiting, diarrhea, bleeding, abdominal pain, weight loss, obstruction and perforation. Serum and urine histoplasma antigen are the most sensitive tests. The incidence rate of disseminated histoplasmosis in patients taking TNF-α inhibitors is relatively low with only 1-2 cases per 10,000. TNF-α plays an important role in granuloma formation and sequestration of mycobacterial and fungal pathogens. The current guidelines recommend screening for tuberculosis, hepatitis B and C but not for fungal exposure. First line of treatment is two weeks of IV amphotericin B followed by 12-months of oral itraconazole. Disseminated histoplasmosis should also be considered as differential diagnosis for intestinal perforation in the Crohn's disease patients taking TNF -α inhibitors.