FOCUSED REVIEWS Update on the Diagnosis of Pulmonary Coccidioidomycosis Joshua Malo 1 , Carmen Luraschi-Monjagatta 1 , Donna M. Wolk 2,3,4 , R. Thompson 2 , Chadi A. Hage 5 , and Kenneth S. Knox 1 1 Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, and 2 Department of Pathology, University of Arizona Health Network, Tucson, Arizona; 3 BIO5 Institute, University of Arizona, Tucson, Arizona; 4 Geisinger Health Systems, Danville, Pennsylvania; and 5 Indiana University Health, Thoracic Transplant Program, Indianapolis, Indiana Abstract Coccidioidomycosis is a common cause of community-acquired pneumonia in the southwest United States, Mexico, and South America. The disease has seen a marked increase in incidence in the western United States in the last decade and can be acquired by individuals who travel even briefly through an endemic area, presenting a diagnostic dilemma for clinicians who are not familiar with the disease. The clinical and radiographic manifestations of pulmonary coccidioidomycosis often mimic those of other causes of pneumonia. However, because treatment recommendations and the potential for chronic sequelae of acute infection differ substantially from those for bacterial community-acquired pneumonia, accurate, timely diagnosis of coccidioidomycosis is paramount. A number of diagnostic tests are available with varying sensitivity and specificity, making the approach complex. Radiographic features, although nonspecific, sometimes demonstrate patterns more suggestive of coccidioidomycosis than bacterial community- acquired pneumonias. A routine blood count may reveal eosinophilia. Serologic testing is used most widely but may be negative early in the course of disease, potentially leading to misdiagnosis with subsequent inappropriate treatment and follow-up. The sensitivity of serologic testing is lower in immunocompromised patients, a population at the highest risk for developing severe disease. When clinically appropriate, other biologic specimens, such as sputum, bronchoalveolar lavage fluid, or lung biopsies, may allow for rapid, definitive diagnosis. In light of the significantly increased incidence and complexities in diagnosis of coccidioidomycosis, we examine the diagnostic approach and provide examples of classic clinical and radiographic presentations, discuss the utility of serologic testing, and suggest algorithms that may aid in the diagnosis. Keywords: fungal lung diseases; serologic tests; coccidioidomycosis; cavitary lung diseases; eosinophilic lung diseases (Received in original form August 27, 2013; accepted in final form December 11, 2013 ) Correspondence and requests for reprints should be addressed to Joshua Malo, M.D., Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85724. E-mail: [email protected] Ann Am Thorac Soc Vol 11, No 2, pp 243–253, Feb 2014 Copyright © 2014 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201308-286FR Internet address: www.atsjournals.org Coccidioidomycosis, often referred to as valley fever, is a common cause of community- acquired pneumonia in endemic areas of the southwest United States (including California), Mexico, and parts of South America (1, 2). Over the past decade, a dramatic increase in the incidence of coccidioidomycosis has been observed, particularly in endemic areas (3), necessitating a greater understanding of the various clinical presentations and overall diagnostic approach. Most infections are acquired through soil disruption and subsequent inhalation of airborne arthroconidia. As such, “haboob” sand storms near Phoenix, Arizona and military training exercises in California are frequent culprits of outbreaks (4). Coccidioides spp. do not infect via person-to-person transmission but are highly infectious to laboratory personnel. Studies show that immunocompetent and immunocompromised patients are susceptible to infection (5–8), making discussions about “cocci” an everyday occurrence. Epidemiology Recent data indicate significant increases in the incidence of pulmonary coccidioidomycosis within the United States in the last decade. In endemic areas in the United States, the incidence has increased from 5.3 per 100,000 population in 1998 to 42.6 per 100,000 population in 2011, with a total of 111,717 cases reported to the CDC nationally during this time period (3). Cases reported outside of endemic areas are typically associated with prior travel to those regions. For this reason, deaths due to coccidioidomycosis have been reported throughout the United States (9) (Figure 1). Exposure History Although the major exposure risk factor is travel to an endemic area, recent reports suggest that cases may be acquired de novo outside of these areas, implicating climate Focused Reviews 243
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