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Overlooked Causes of Community Acquired Pneumonia View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Respiratory Medicine (2012) 106, 769e776 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/rmed REVIEW Endemic mycoses: Overlooked causes of community acquired pneumonia Chadi A. Hage a,*, Kenneth S. Knox b, Lawrence J. Wheat c a Pulmonary-Critical Care and Infectious Diseases, Indiana University and Richard L. Roudebush VA Medical Center, 1481 W. 10th St., 111P-IU, Indianapolis, IN, USA b University of Arizona, Tucson, AZ, USA c MiraVista Diagnostics and Mirabella Technologies, Indianapolis, IN, USA Received 31 October 2011; accepted 10 February 2012 Available online 3 March 2012 KEYWORDS Summary Community acquired The endemic mycoses are important but often overlooked causes for community acquired pneumonia; pneumonia. Delays in recognition, diagnosis and proper treatment often lead to disastrous Endemic mycosis; outcomes. This topic is not usually discussed in reviews and guidelines addressing the subject Histoplasmosis; of community acquired pneumonia. In this review we discuss the three major endemic mycoses Coccidioidomycosis; in North America that present as community acquired pneumonias; Coccidioidomycosis, Histo- Blastomycosis plasmosis and Blastomycosis. We discuss their epidemiology, clinical presentations, methods of diagnosis and current treatment strategies. Published by Elsevier Ltd. Contents Introduction . ........................................................................770 Coccidioidomycosis ................................................................770 Epidemiology ................................................................770 Clinical . .................................................................770 Radiographic ................................................................770 Diagnosis . .................................................................771 Management ................................................................771 Blastomycosis . .................................................................772 Epidemiology ................................................................772 * Corresponding author. Tel.: þ1 317 988 3811; fax: þ1 317 988 3976. E-mail address: [email protected] (C.A. Hage). 0954-6111/$ - see front matter Published by Elsevier Ltd. doi:10.1016/j.rmed.2012.02.004 770 C.A. Hage et al. Clinical ....................................................................772 Radiographic . ...............................................................772 Diagnosis ...................................................................772 Management . ...............................................................773 Histoplasmosis ...................................................................773 Epidemiology . ...............................................................773 Clinical ....................................................................773 Radiographic . ...............................................................773 Diagnosis ...................................................................773 Management . ...............................................................774 Funding . ...........................................................................774 Conflict of interest statement . ...........................................................774 References ..........................................................................774 Introduction symptomatic cases 95% experience a self-limited infection that resolves after several weeks. Approximately 1% of The endemic mycoses are important but often overlooked patients will have disseminated infection with the most common extra thoracic sites being skin, soft tissue, bone, causes for community acquired pneumonia (CAP). Of note is 6 that they often occur outside of the traditional endemic and meninges. Symptoms of acute infection resemble bronchitis or pneumonia and are indistinguishable from area. For example, in a review of endemic mycoses among 3,4,7 the elderly, one quarter of cases of coccidioidomycosis other causes of community acquired pneumonia, occurred outside the southwest United States.1 Not only are Table 1. In retrospective studies, patients with coccidioi- the endemic mycoses common causes for hospitalizations, domycosis were less likely to have cough and sputum they are often severe, fatal in nearly 10% of cases.2 production but more likely to have eosinophilia, pleurisy, myalgia, rash, and fatigue than patients without coccidi- Surprisingly, deaths occurred overwhelmingly (87%) in 4,5 nonimmunocompromised subjects. The failure to consider oidomycosis. Eosinophilia occurs in a quarter of cases and and delay in testing for the endemic mycoses contributes to may suggest coccidioidal pneumonia or prompt further the poor outcome. testing. Although resolution is the norm, chronic progres- sive, often apical cavitary pneumonia resembling tubercu- losis may occur, and peripheral cavities can rupture causing Coccidioidomycosis pneumothorax or pyopneumothorax. Pleural manifestations are more prominent in coccidioidomycosis than other Epidemiology endemic fungal diseases. Coccidioidomycosis is a common fungal cause of community acquired pneumonia in the southwest endemic areas,3e5 Radiographic Table 1. Most infections are acquired through soil disrup- The radiologic findings of acute coccidioidomycosis are tion and subsequent inhalation of airborne arthroconidia. diverse and nonspecific. Pulmonary infiltrates are identified As such, “haboob” sand storms near Phoenix, Arizona as in the majority of patients, and pleural effusions and well as military training exercises in California are frequent adenopathy are common,8 Table 1. Pulmonary nodules and culprits of outbreaks. cavities are identified in less than 5% of cases. Immuno- suppressed patients may manifest a diffuse “miliary” Clinical pattern.9 CT scans are more sensitive, identifying effusions, Coccidioidomycosis mimics bacterial causes of CAP in hilar lymph nodes, micronodular infiltrates, and multifocal healthy individuals and immunocompromised patients. ground glass infiltrates more readily. Mediastinal and hilar About 60% of people infected are asymptomatic, and of adenopathy is common, but not to the degree that is seen Table 1 Epidemiologic, clinical and radiographic characteristics. Parameter Coccidioidomycosis Blastomycosis Histoplasmosis Exposure history Sand storms, construction, Outdoor activity near Exposure to soil containing military exercises, often dry waterways bat or bird droppings, period following rainy seasons usually unrecognized Clinical findings Respiratory symptoms, fever, Respiratory symptoms, Respiratory symptoms, fever, fatigue, eosinophilia skin or bone lesions arthralgia Chest radiographs/CT Focal and diffuse infiltrates, Lobar consolidation, Focal, diffuse or cavitary cavities, pleural effusion, diffuse infiltrates, infiltrates, hilar or mediastinal adenopathy, micronodular infiltrates nodular infiltrates lymphadenopathy Endemic mycoses CAP 771 in some patients with acute histoplasmosis. Lymph nodes 100% were judged to be true positives in one14 but 82% were and nodules exhibit varying degrees of uptake on PET scans. regarded as false positive in another15 report. An isolated Small non-calcified nodules are common residua of acute positive IgM should be confirmed by additional diagnostic Coccidioides that can be confused with malignancy. testing.14 Additionally, the antibody test may be falsely Nodules may evolve into thin walled cavities by shelling out negative early in the course of infection or in immunosup- the nodule contents. These cavities usually resolve but may pressed patients11,12,16e18 False negative EIA was noted in be sanctuary for secondary infection or mycetoma, or may 13% of healthy patients and 33% of immunosuppressed cause pneumothorax or hemoptysis. patients, declining to 5% and 17%, respectively when confirmatory tests were performed.16 Antibody tests also Diagnosis may be negative early in the disease,16 as noted in half of In a large proportion of community acquired pneumonia cases in one study.11 Thus, negative antibody tests cannot patients in the endemic area, diagnostic testing for exclude coccidioidomycosis.19 coccidioidomycosis is not performed.3 In a large retro- Coccidioides galactomannan antigen testing is available spective cohort, patients more likely to be tested for in select reference laboratories. Antigenuria was detected coccidioidomycosis were adults and immunosuppressed in 50% of patients with moderate20 and 71% with moderate patients. Patients who experienced symptoms for >14 to severe disease, among whom tests for antibodies were days, manifest a rash, or had chest pain were also more positive in 54%.10 Antigenemia was detected in 73% of likely to be tested.3 patients with mild to moderate disease, identifying an Rapid diagnosis can be achieved by cytopathologic additional 29% of cases that would have been missed if only examination of respiratory specimens in patients with lung urine was tested.20 Thus, the greatest sensitivity may be infiltrates or cavitary disease, positive in one quarter10,11 to achieved by testing both urine and serum. Antigen also has two-thirds of cases,8,12 Table 2. Simultaneous trans- been detected in BAL in patients with negative results in bronchial biopsy may increase the diagnostic yield.12 urine.11 Nodules may be biopsied to exclude malignancy.13 In Real-time PCR targeting
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