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The dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis/posadasii and the yeast Cryptococcus neoformans share important epidemiologic, mycologic, and clinical characteristics. With the exception of Cryptococcus neoformans var. neoformans, which exhibits no strong geographic predilection, these fungi are found in the soil and other environmental niches of certain endemic regions within the United States, particularly the Mississippi and Ohio River valleys for H. capsulatum and B. dermatitidis, the Southwestern United States for C. posadasii/immitis, and the Pacific Northwest for Cryptococcus neoformans var. gattii (Fig. 133-1). Beyond the United States, areas of high endemicity have been established across all six inhabited continents, lending global significance to these fungal pathogens (Fig. 133-1).1 Additionally, due to global warming, anthropomorphic land utilization, and a world that is increasingly interconnected by the mass migration of people and goods, the geographic extent and epidemiology of endemic fungi are changing. Infection most commonly follows inhalation of aerosolized infectious particles when sites containing the organism are disturbed. Within the human host, these pathogens exist in yeast form and must be distinguished from other pathogenic yeast and from one another based on mycologic characteristics including size, wall thickness, and presence and type of budding, among others important features. Unlike many other fungi that cause disease only in immunocompromised hosts or in those with disrupted mucosal or skin barriers, the dimorphic fungi and Cryptococcus, especially Cryptococcus neoformans var. gattii, can lead to local and disseminated disease in the immunocompetent host. Indeed, the majority of those hospitalized due to infection with endemic mycoses in the United States and up to 20% of HIV-negative patients with Cryptococcus infection have no identifiable immunologic deficits.2 In endemic areas, dimorphic fungal pathogens account for up to 30% of community-acquired pneumonia and respiratory manifestations mimic those of bacterial pneumonia leading to antibiotic misuse, diagnostic delays, and increased morbidity and mortality.3 Both Cryptococcus and the endemic fungi can lead to a wide spectrum of pulmonary manifestations ranging from subclinical and mild respiratory symptoms to acute, subacute, and chronic pneumonias, mediastinal involvement, and acute respiratory failure as well as a variety of pulmonary infiltrates, including nodules, consolidations, cavities, and ground-glass opacities among others. These presentations must be distinguished from other infectious and noninfectious pulmonary processes such as bacterial pneumonia, tuberculosis, lung cancer, and sarcoidosis that may present similarly. Dissemination outside the lungs occurs more commonly in immunosuppressed hosts and is associated with high mortality. In the United States, direct healthcare costs from histoplasmosis, blastomycosis, and coccidioidomycosis alone approach $500 million annually, emphasizing the devastating impact of endemic mycoses and the need for increased awareness, early diagnosis, and effective treatment modalities.4

Figure 133-1

A. Geographic distribution of endemic mycoses in the United States. The area of histoplasmin skin test reactivity in the southwestern United States represents cross-reactivity caused by coccidioidomycosis, not endemic histoplasmosis. World map estimating regions most likely to have ...

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