Background/Purpose: Coccidioidomycosis (valley fever) is an endemic fungal infection in the Southwestern United States which typically causes a self-limited pulmonary illness. Patients with rheumatic disease on immunosuppressive medication, including methotrexate and tumor necrosis factor (TNF) antagonists, are at higher risk of more severe infection or dissemination. Currently, there are no guidelines for management of coccidioidomycosis in patients on disease-modifying antirheumatic drug (DMARD) or biologic response modifier (BRM) therapy.

Methods: A retrospective chart review identified patients at two centers in Tucson, Arizona, who developed coccidioidomycosis while on DMARD or BRM therapy. Review emphasized disease manifestations, antifungal therapy and duration, as well as management of BRM/DMARD therapy.

Results: Sixty-six patients who developed coccidioidomycosis while on DMARD and/or BRM therapy were identified.  Forty-four of these have been previously reported, and their charts were re-reviewed for an additional 12 months of follow-up. Twenty-two new patients were identified. Rheumatologic treatment included BRM alone (18), DMARD alone (15), or combination therapy (33). Eighteen patients were on oral prednisone at the time of diagnosis, with doses ranging from 3 to 40 mg daily (median 10 mg). Manifestations of coccidioidomycosis were asymptomatic positive serologies (15), pulmonary illness (41), and dissemination (10). At the time of coccidioidomycosis diagnosis, 35 patients held all BRM and DMARD therapy, 9 patients held BRM but continued DMARD therapy, and 22 patients had no change in immunosuppressive therapy. Most patients (54) received antifungal therapy, usually for 3 months or longer.

Follow-up data were available for 56 patients. BRM and/or DMARD therapy was continued or resumed in 45 patients, of whom 17 continued concurrent antifungal therapy. Three patients with disseminated disease restarted BRM therapy. The most common reasons for continuing antifungal therapy were persistent positive serology or disseminated disease. The most common reason for stopping antifungal therapy was a negative serology. Follow-up for patients who stopped antifungal therapy or were never treated is 2 to 119 months (median 18 mos). One patient on DMARD and corticosteroid therapy died soon after diagnosis of severe disseminated coccidioidomycosis despite antifungal therapy. Another patient with coccidioidal meningitis had relapse of disease, possibly related to non-adherence to antifungal therapy. Otherwise, there have been no cases of subsequent dissemination or complications to date.

Conclusion: Continuing or restarting DMARD and/or BRM therapy after coccidioidomycosis appears to be safe in some patients with appropriate monitoring. If coccidioidomycosis is asymptomatic and rheumatic disease is active, continuation of DMARD and/or BRM can be considered. Patients with symptomatic infection should stop immunosuppressive therapy and continue antifungal therapy until the coccidioidomycosis is under control.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/an-update-of-management-of-coccidioidomycosis-in-patients-on-biologic-response-modifiers-and-disease-modifying-antirheumatic-drugs/