Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease.

Cavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due to the poor sensitivity of serological tests and rarity of culture from sputum. A pathologic and clinical analysis was performed of 21 consecutive patients with surgically resected cavities that proved to be coccidioidomycosis. Ten patients (48%) had serological evidence of Coccidioides infection, and 1 patient cultured Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was made in the remaining 10 patients (48%) upon microscopic examination of tissue. The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated in 4 cases (19%). The cavity wall showed chronic inflammation and occasional giant cells but no granulomas and no microorganisms. The cavity contents included a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%) cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic bronchiolitis in all cases; satellite granulomas with diagnostic spherules were variably present. The histopathology of cavitary coccidioidomycosis is strikingly variable depending on what area is sampled by biopsy, and microorganisms may be rare. This may explain the high rate of failure of diagnosis by fine needle aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be aware of these findings, as this disease is now diagnosed worldwide.

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.

Pulmonary nocardiosis in cystic fibrosis.

BACKGROUND: The treatment of Nocardia species found in the sputum of cystic fibrosis patients is of unknown value. METHODS: We conducted a retrospective analysis of the impact of directed oral antibiotic therapy against Nocardia spp. isolated from the sputum of 17 cystic fibrosis patients over a 10-year period. Pulmonary Function Tests were used as the clinical indicator of the disease state and the data were analyzed by general linear mixed model statistics with univariate analysis. RESULTS: Pulmonary Function Test values of all patients studied showed no significant difference before, during, or after the antibiotic treatment period. Treatment groups did not differ from non-treatment groups. This held true for Forced Expiratory Volume over 1 s and Functional Vital Capacity analysis. In addition, individual patient analysis did not reveal any trends or outliers. CONCLUSIONS: Oral antibiotic therapy of cystic fibrosis patients colonized with Nocardia does not appear to affect clinical outcome. This suggests that deferring therapy may be an acceptable alternative and justifies conducting a future placebo controlled trial. In addition, this study model may be useful in analyzing the effect of therapy on other rare and difficult organisms, such as fungi and mycobacteria in the cystic fibrosis population.