948. Histoplasmosis Complicating Tumor Necrosis Factor-α (TNF) Blocker Therapy
Session: Poster Abstract Session: Clinical Mycology
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Histoplasmosis is a cause of serious infection among patients receiving TNF blocker therapy. The safety of discontinuation of antifungal treatment after a favorable clinical response remains undetermined.

Methods: We retrospectively reviewed records of patients diagnosed with histoplasmosis while receiving TNF blocker therapy in 18 centers. Cases had clinical signs and symptoms attributable to fungal infection and at least one of the following: growth of Histoplasma capsulatum from the affected site, histopathologic demonstration of morphologic forms consistent with H. capsulatum, and/or positive urine or serum Histoplasma antigen by means of an enzyme-linked immunoassay.

Results: We identified 90 cases during the study period (2000-2010). Mean age was 46 years (range, 9 to 82). 58% were female. 67% were receiving infliximab, 23% adalimumab, and 10% etanercept. 53% had rheumatoid arthritis, 35% inflammatory bowel disease, and 7% psoriasis. Median duration of treatment with TNF blockers prior to diagnosis of histoplasmosis was 17 months. 80% had pulmonary involvement, and 76% disseminated disease. Disease was mild in 27% of cases, moderate in 50%, and severe in 18%. Urine Histoplasma antigen was positive in 88%. Two patients with severe disease died within 4 weeks after diagnosis. Among patients discontinuing biologic therapy, 14 were diagnosed with probable immune reconstitution inflammatory syndrome.

Half of the patients received amphotericin B. All patients received azole treatment which was given for a median duration of 12 months. TNF blocker therapy was continued in 5 patients. One of them relapsed. Six patients had urine Histoplasma antigen levels >2 ng/mL at completion of antifungal treatment and none of them relapsed. Overall, relapse occurred in 6/90 (7%) cases. One was on antifungal treatment at the time of relapse. TNF blocker therapy was resumed in 23/85 (27%) cases at a median time of 12 months. For all surviving patients, histoplasmosis was in remission at last follow-up.

Conclusion: Patients who develop histoplasmosis while receiving TNF blocker therapy commonly present with disseminated disease. Elevated Histoplasma antigen levels at completion of antifungal treatment do not necessarily portend relapse.

Subject Category: M. Mycology including clinical and basic studies of fungal infections

Paschalis Vergidis1, Chadi A. Hage2, Maha A. Assi3, Kenneth S. Knox4, Randall C. Walker1 and L Wheat, MD5, (1)Mayo Clinic, Rochester, MN, (2)Indiana University, Indianapolis, IN, (3)University of Kansas School of Medicine, Wichita, KS, (4)University of Arizona, Tucson, AZ, (5)MiraVista Diagnostics, Indianapolis, IN


P. Vergidis, None

C. A. Hage, None

M. A. Assi, None

K. S. Knox, None

R. C. Walker, None

L. Wheat, MiraVista Diagnostics: President, Salary

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