Background/Purpose: In the Southwestern United States, coccidioidomycosis (valley fever) is an endemic fungal infection which typically causes a self-limited pulmonary illness. Immunosuppressed patients, including those with rheumatic disease on disease-modifying antirheumatic drugs (DMARD) or biologic response modifiers (BRM), are at higher risk of more severe infection. The routine practice at our institution is to screen patients for coccidioidomycosis before initiating BRM therapy, and then annually thereafter. Through this process, patients have been identified with asymptomatic positive serologies.  This is concerning as it indicates recent active infection in these patients. There are currently no guidelines regarding the management of these patients; however, a recent retrospective study proposed continuing antirheumatic therapy rather than stopping it.

Methods: A prospective chart review at two centers in Tucson, Arizona identified patients who developed coccidioidomycosis while on DMARD or BRM therapy. Several of those patient had asymptomatic illness as defined as a positive serology found on surveillance labs, not ordered in response to symptoms, and no concurrent signs or symptoms of active disease. Patients were seen at least once between 2007 and 2014. Review emphasized management of BRM/DMARD therapy, as well as antifungal therapy and duration.

Results: Seventy one patients with rheumatic disease were diagnosed with coccidioidomycosis, and 18 of them had positive serologies and no symptoms. Most (16/18) had rheumatoid arthritis, 1 had psoriatic arthritis, and 1 had dermatomyositis. Fifteen patients were identified during routine annual surveillance, and three were identified during pre-BRM therapy screening. Six patients were on BRM alone, 10 on BRM with a DMARD, and 2 on a DMARD alone. Three patients were also on prednisone. All but 6 patients continued their antirheumatic therapy. BRM therapy was restarted in 5 of these patients, most resuming therapy within 1 month of infection (range 0.5 – 12 mos). One did not resume therapy due to osteonecrosis of the jaw. Six patients received fluconazole, duration ranging from 6 to 73 months (median 30.5 mos). One of these patients remains on fluconazole for persistently positive serologies (42 mos.).  Eight patients neither reduced antirheumatic therapy, nor started antifungal treatment. The median follow up is 31.5 months, and no patients have developed symptomatic illness.  Three patients have been lost to follow up.

Conclusion: Positive coccidioidomycosis serologies are concerning in asymptomatic patient as they indicate a recent active infection. At present, the optimal screening interval and management in patients with rheumatic disease remains unclear. This series supports the management strategy of continuing BRM therapy in patients with asymptomatic disease.  It also suggests that antifungal therapy may be reserved for those with persistently positive serologies. Future studies are needed to determine the significance of positive serologies in immunosuppressed patients with rheumatic disease, and the safest management strategy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/management-of-asymptomatic-coccidioidomycosis-in-patients-with-rheumatic-disease/