Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs.

OBJECTIVE: Coccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona. METHODS: A retrospective chart review identified patients who developed coccidioidomycosis during treatment with DMARDs or BRMs. Patients were seen at least once in a university-affiliated or Veterans Affairs outpatient rheumatology clinic in Tucson, Arizona, between 2007 and 2009. RESULTS: Forty-four patients were identified. Rheumatologic treatment included a BRM alone (n = 11), a DMARD alone (n = 8), or combination therapy (n = 25). Manifestations of coccidioidomycosis included pulmonary infection (n = 29), disseminated disease (n = 9), and asymptomatic positive coccidioidal serologies (n = 6). After the diagnosis of coccidioidomycosis, 26 patients had BRMs and DMARDs stopped, 8 patients had BRMs stopped but DMARD therapy continued, and 10 patients had no change in their immunosuppressive therapy. Forty-one patients had antifungal therapy initiated for 1 month or longer. Followup data were available for 38 patients. BRM and/or DMARD therapy was continued or resumed in 33 patients, only 16 of whom continued concurrent antifungal therapy. None of the patients have had subsequent dissemination or complications of coccidioidomycosis. CONCLUSION: Re-treating rheumatic disease patients with a BRM and/or a DMARD after coccidioidomycosis appears to be safe in some patients. We propose a management strategy based on coccidioidomycosis disease activity.

Discussion: DMARDs and biologic therapies in the management of inflammatory joint diseases.

Therapy for inflammatory joint diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, includes various conventional disease-modifying antirheumatic drugs (DMARDs). These therapeutic agents are termed DMARDs because they have the potential to reduce or prevent joint damage and preserve joint integrity and function. Conventional DMARDs are used as monotherapy or in combination and include methotrexate, leflunomide, azathioprine, ciclosporin, hydroxychloroquine, sulfasalazine, gold and minocycline. Biologic response modifiers, which are based on proteins made by living cells, are newer agents available for the treatment of various inflammatory joint diseases. Biologic therapies now approved for use in inflammatory joint diseases are TNF inhibitors, T-cell modulators and B-cell depleters. They have all been shown to have clinical efficacy and are able to retard structural damage. However, all current immune-modulating therapies also have potential side effects, and the decision to use a particular agent for treatment should be based on a thorough discussion of the benefits and risks with the patient. Newer biologic response modifiers and other immunologic therapies are currently being developed for the treatment of inflammatory joint diseases and are discussed in this review.

Coccidioides immitis fungemia: clinical features and survival in 33 adult patients.

Coccidioides immitis is a fungus endemic to the southwestern United States. Susceptible hosts, including blacks, Hispanics, Filipinos, Native Americans, and those with compromised immunity, may develop disseminated disease, including fungemia. We retrospectively reviewed the records of all patients (n = 33) with Coccidioides immitis fungemia (CIF) at a 550-bed public hospital in Phoenix, Arizona, from 1990 to 2002. This is the largest reported series of CIF. The purpose of the study was to review the incidence, signs, symptoms, and outcomes of CIF. Twenty-nine patients had human immunodeficiency virus infection. CIF was associated with sepsis, end-stage alcoholic liver disease, and diabetes in four patients. Survival was poor; 24 of the 33 patients died within 28 days. CIF manifested as a systemic inflammatory response syndrome with progressive cardiorespiratory failure. Despite fluid loading, infusion of vasoactive agents, and mechanical ventilation with positive end-expiratory pressure, patients typically experienced a rapidly progressive course and death. CIF portends an ominous prognosis and typically occurs in the setting of advanced human immunodeficiency virus or medical or surgical crises.