Disseminated Histoplasmosis Associated With Anti-Tumor Necrosis Factor Alpha Therapy: A Case Series

Abstract

Introduction: Anti-tumor necrosis factor alpha (anti-TNF-α) therapy is effective and widely used in the treatment of inflammatory bowel disease and autoimmune rheumatic disease. The immunosuppressive effects of anti-TNF agents are well known; however, in rare cases disseminated fungal infections have been reported.1 We present two patients who developed disseminated histoplasmosis after initiation of anti-TNF-α therapy. Case 1: A 47 year old male, who was recently initiated on methotrexate followed by adalimumab for psoriatic arthritis, was admitted for fever, cough and transaminitis. No clear etiology was ascertained and he progressed to acute respiratory failure and acute liver failure. A computed tomography (CT) of his chest reported diffuse ground-glass opacities. Antivirals, antifungals, including amphotericin B, and steroids were added to antibiotics without improvement. Given the unclear etiology of his multi-organ failure, a liver biopsy was performed; however, the patient expired the following morning. A urine Histoplasma antigen returned positive two days after. The biopsy demonstrated poorly formed granulomas with yeast forms, consistent with Histoplasma capsulatum. Case 2: A 30 year old male, on infliximab and 6-mercaptopurine for his Crohn's disease, was hospitalized for fever and dyspnea. Initial labs indicated leukopenia. A chest x-ray (CXR) demonstrated right upper lobe bullous changes. The patient was started on antibiotic and antifungal therapy. His liver enzymes were uptrending throughout his hospitalization. A urine histoplasma antigen returned positive and therapy was adjusted to liposomal amphotericin B followed by oral itraconazole. A lumbar puncture showed no evidence of central nervous system (CNS) involvement and oral itraconazole therapy was continued. The patient improved steadily on therapy and was in remission when evaluated a few months later. Discussion: While the majority of Histoplasma infections are clinically silent in patients with a normal immune system, patients in endemic areas receiving anti-TNF-α therapy are at an increased risk for developing severe histoplasmosis infection.2 The treatment-related impaired cellular immune response, can allow disseminated histoplasmosis to occur, resulting in multi-organ failure or even death.1Symbol3 As histoplasmosis is an endemic fungal infection, further research should focus on 1) determining which patients are at highest risk and 2) the role of antifungal prophylaxis.Symbol