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Clinical Manifestations and Treatment of Blastomycosis

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Clinical Manifestations and Treatment of Blastomycosis Clinical Manifestations and Treatment of Blastomycosis Joseph A. McBride, MDa,b, Gregory M. Gauthier, MDa,*, Bruce S. Klein, MDa,b,c,* KEYWORDS Blastomycosis Dimorphic fungi Pneumonia Acute respiratory distress syndrome KEY POINTS Blastomyces dermatitidis and Blastomyces gilchristii are the causal agents of blastomycosis. Blastomyces spp infect healthy and immunocompromised hosts. Pulmonary manifestations of blastomycosis range from subclinical infection to acute respiratory distress syndrome. Diagnosis of blastomycosis requires a high degree of clinical suspicion and involves the use of cul- ture and nonculture diagnostic methods. Blastomycosis should be considered in patients who live in or visit regions where Blastomyces is endemic and have unresolving pneumonia despite antibiotic therapy, concomitant pulmonary and cutaneous infection, acute respiratory distress syndrome, or a compatible illness following recognizable risk factors for Blastomyces exposure. INTRODUCTION index of clinical suspicion is essential for prompt diagnosis. Treatment guidelines published by the Blastomyces dermatitidis and Blastomyces gilchris- Infectious Disease Society of America and the tii are the causal agents of blastomycosis. Blasto- American Thoracic Society recommend the use of myces spp are thermally dimorphic fungi that polyene or azole antifungal agents, with selection grow as a filamentous mold in the environment influenced by disease severity, site of infection, and as a yeast in human tissues. Blastomycosis is immunosuppression, and pregnancy. endemic to North America, particularly states/prov- inces bordering the Mississippi, Ohio and St Law- MYCOLOGY rence Rivers, and the Great Lakes. The clinical manifestations of blastomycosis are broad, ranging Recent phylogenic analysis has divided Blastomy- from asymptomatic infection to acute respiratory ces into 2 species, B dermatitidis and B gilchristii.1 distress syndrome (ARDS) and death. Extrapulmo- Blastomyces spp belong to a group of fungi that in- nary dissemination to the skin, bone, and central cludes Histoplasma capsulatum, Coccidioides nervous system can occur. Although culture and immitis and Coccidioides posadasii, Paracocci- non-culture diagnostic tests are available, a high dioides brasiliensis and Paracoccidioides lutzii, Disclosure: The authors have nothing to disclose. a Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Pub- lic Health, 600 Highland Avenue, Madison, WI 53792, USA; b Division of Infectious Disease, Department of Pe- diatrics, University of Wisconsin School of Medicine and Public Health, 1675 Highland Avenue, Madison, WI 53792, USA; c Department of Medical Microbiology and Immunology, University of Wisconsin School of Med- icine and Public Health, 1550 Linden Drive, Madison, WI 53706, USA * Corresponding author. Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792. E-mail addresses: [email protected] (G.M.G.); [email protected] (B.S.K.) Clin Chest Med 38 (2017) 435–449 http://dx.doi.org/10.1016/j.ccm.2017.04.006 0272-5231/17/Ó 2017 Elsevier Inc. All rights reserved. chestmed.theclinics.com Downloaded for Anonymous User (n/a) at University of Wisconsin - Madison from ClinicalKey.com by Elsevier on August 16, 2017. For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved. 436 McBride et al Sporothrix schenckii, and Talaromyces marneffei capsulatum and Cryptococcus, Blastomyces can (formerly Penicillium marneffei). Blastomyces un- grow in bird guano. Although most infections are dergoes a reversible morphologic switch between sporadic, occupational and recreational activities hyphae at 22Cto25C and yeast at 37C. Blasto- that disrupt soil (eg, construction, exploration of myces yeast forms (8–20 mm diameter) are charac- beaver damns or underground forts, use of com- terized by a broad-based bud (4–10 mm) and munity compost piles, clearing brush or cutting doubly refractile cell wall (Fig. 1).2 Although this trees, hunting, canoeing, boating, tubing, fishing) appearance is unique among dimorphic fungi, gi- have all been associated with outbreaks of the ant forms (28–40 mm diameter) have been disease (Table 1).4,5 described and can be confused with Coccidioides Rare autochthonous cases of culture-proven species.3 The mycelial form is characterized by blastomycosis have been reported outside of septate hyphae (1–2 mm diameter) that produce North America. Approximately 100 cases have asexual spores (4–5 mm diameter).2 In contrast been described in 18 African nations, whereas with the yeast, hyphal morphology is not distinct fewer than 10 confirmed autochthonous cases and requires molecular confirmation or transition have been reported in India.6,7 Blastomyces is to yeast for identification. not considered endemic to Central America, South America, Europe, Australia, or Asia outside India. GEOGRAPHIC DISTRIBUTION AND The epidemiology of blastomycosis in North EPIDEMIOLOGY America is based mainly on retrospective studies and passive surveillance. Within endemic zones, Knowledge about the geographic distribution and 6 American states (Arkansas, Louisiana, Michigan, epidemiologic risks is important for including blas- Minnesota, Missouri, and Wisconsin) and 2 Cana- tomycosis in the differential diagnosis in patients dian provinces (Manitoba and Ontario) require with pulmonary, cutaneous, bone, and central ner- reporting of new cases. In North America, the vous system (CNS) infections. In North America, annual incidence of blastomycosis ranges from Blastomyces is endemic to the midwestern, 0.2 to 1.94 cases per 100,000 persons.8–11 Several south-central, and southeastern regions of the hyperendemic regions exist, including Kenora, United States and 4 Canadian provinces from Sas- Ontario (117.2 human cases per 100,000 popula- katchewan to Quebec (Fig. 2). In the endemic re- tion); Eagle River, Wisconsin (101.3 per 100,000); gion, Blastomyces is not uniformly distributed; it Vilas County, Wisconsin (40.4 per 100,000); inhabits an ecologic niche that is characterized Washington Parish, Louisiana (6.8 per 100,000); by forested, sandy soils with an acidic pH, decay- and central/south-central Mississippi (>5 per ing vegetation or organic material, and rotting 100,000).12–15 The true incidence of blastomycosis wood located near water sources.4 Similar to H is likely greater than the reported numbers. Reli- able skin and serologic tests are not available. Moreover, approximately 50% of infected persons have subclinical or asymptomatic illness.4 Thus, epidemiologic data are limited to patients with clinically apparent infection that is diagnosed and reported. In the United States from 2007 to 2011 a total of 4688 patients in 46 states were hospital- ized for blastomycosis.16 Most of these patients were hospitalized in the state in which they resided; however, 8% of patients were admitted to hospitals outside of known endemic regions.16 Most blastomycosis cases occur in adults, with less than 13% occurring in the pediatric popula- tion.5,17 Similar to histoplasmosis and coccidioi- domycosis, blastomycosis epidemiologic studies of adults show a slight male predominance. Blas- tomyces is a primary fungal pathogen because it causes invasive disease in immunocompetent hosts; most patients with blastomycosis are immunocompetent. Patients who are immuno- Fig. 1. B dermatitidis yeast. Broad-based budding compromised by solid organ transplant (SOT), yeast at 37C. Arrow points to the broad-based bud be- tumor necrosis factor-alpha (TNF-a) inhibitors, tween mother and daughter cells. Scale bar is 10 mm. malignancy, or human immunodeficiency virus Downloaded for Anonymous User (n/a) at University of Wisconsin - Madison from ClinicalKey.com by Elsevier on August 16, 2017. For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved. Manifestations and Treatment of Blastomycosis 437 Fig. 2. Map of the distribution of endemic and epidemic blastomycosis in North America. Cross-hatching denotes geographic distribution of cases. Circled numbers denote location of epidemics referred to in Table 1. (Ó OpenStreetMap contributors.) (HIV)/AIDS (acquired immunodeficiency syn- host (37C) convert to pathogenic yeast, which drome) can develop more severe disease.18–22 evades host immune defenses to cause infection. The higher incidence of blastomycosis in some Moreover, conidia phagocytized by lung macro- ethnic groups, including aboriginal ethnicity in phages are able to survive and convert into Canada and Hmong populations in Wisconsin, yeast.25 This intracellular lifestyle is not unique may signal genetic predisposition.9,23 to Blastomyces; other dimorphic pathogens, including H capsulatum, Coccidioides spp, and Paracoccidioides spp, show similar intracellular PATHOGENESIS preferences. For fungi such as H capsulatum and The Phase Transition Cryptococcus neoformans, survival in macro- The ability to convert from mold to yeast is an phages promotes dissemination; however, it is essential event in the pathogenesis of all dimor- unknown whether B dermatitidis uses this so- phic fungi, including Blastomyces spp. This called Trojan horse method for extrapulmonary morphologic shift or phase transition is primarily dissemination.26 influenced by a change in temperature and is a The development of molecular tools to geneti- complex process involving
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