B. dermatitidis is a thermally dimorphic fungus that grows as a mold in culture, producing hyaline, and branching septate hyphae and conidia. At 37°C or in the host, it converts to a large, singly budding yeast cell (Figure 1). B. dermatitidis causes blastomycosis, a chronic infection with granulomatous and suppurative lesions that is initiated in the lungs, whence dissemination may occur to any organ but preferentially to the skin and bones. The disease has been called North American blastomycosis because it is endemic, and most cases occur in the United States and in Canada. Despite this high prevalence in North America, blastomycosis has been documented in Africa, South America, and Asia. Yet, the vast majority of cases occur in the east ern United States, and among dogs as well as humans.

Fig1. Blastomycosis and B. dermatitidis. A: Note the large, spherical thick-walled yeast cells (8–15 µm in diameter) in this section of a cutaneous abscess. H&E 400×. B: In culture at ambient temperatures, B. dermatitidis produces hyaline, septate hyphae, and single conidia. 400×.

Morphology and Identification

When B. dermatitidis is grown on SDA at room temperature, a white or brownish colony develops, with branching hyphae bearing spherical, ovoid, or piriform conidia (3–5 µm in diameter) on slender terminal or lateral conidiophores (see Figure 1B). Larger chlamydospores (7–18 µm) may also be produced. In tissue or culture at 37°C, B. dermatitidis grows as a thick-walled, multinucleated, spherical yeast (8–15 µm) that usually produces single buds (see Figure 1A). The bud and the parent yeast are attached with a broad base, and the bud often enlarges to the same size as the parent yeast before they become detached. The yeast colonies are wrinkled, waxy, and soft.

Antigenic Structure

 Extracts of culture filtrates of B. dermatitidis contain blastomycin, probably a mixture of antigens. As a skin test reagent, blastomycin lacks specificity and sensitivity. Patients are often negative or lose their reactivity, and false-positive cross-reactions occur in people exposed to other fungi. Consequently, skin test surveys of the population to deter mine the level of exposure have not been conducted. The diagnostic value of blastomycin as an antigen in the CF test is also questionable because cross-reactions are common; however, many patients with widespread blastomycosis have high CF titers. In the ID test, using adsorbed reference anti sera, antibodies can be detected to a specific B. dermatitidis antigen, designated antigen A. More reliable is an enzyme immunoassay for antigen A (see Table 1). The immunodominant motif probably responsible for generating a protective cell-mediated immune response is part of a cell-surface and secreted protein, termed BAD.

Table1. Summary of Serologic Tests for Antibodies to Systemic Dimorphic Pathogenic Fungi

Pathogenesis and Clinical Findings

Human infection is initiated in the lungs. Mild and self-limited cases have been documented, but their frequency is unknown because there is no adequate skin or serologic test with which to assess subclinical or resolved primary infections. The most common clinical presentation is a pulmonary infiltrate in association with a variety of symptoms indistinguishable from other acute lower respiratory infections (fever, malaise, night sweats, cough, and myalgias). Patients can also present with chronic pneumonia. Histologic examination reveals a distinct pyogranulomatous reaction with neutrophils and noncaseating granulomas. When dissemination occurs, skin lesions on exposed surfaces are most common. They may evolve into ulcerated verrucous granulomas with an advancing border and central scarring. The border is filled with microabscesses and has a sharp, sloping edge. Lesions of bone, the genitalia (prostate, epididymis, and testis), and the central nervous system also occur; other sites are less frequently involved. Although immunosuppressed patients, including those with AIDS, may develop blastomycosis, it is not as common in these patients as are other systemic mycoses.

Diagnostic Laboratory Tests

Specimens consist of sputum, pus, exudates, urine, and biopsies from lesions. Upon microscopic examination, wet mounts of specimens may show broadly attached buds on thick-walled yeast cells. These may also be apparent in histologic sections (see Figure 1A). In culture, colonies usually develop within 2 weeks on Sabouraud’s or enriched blood agar at 30°C (see Figure 1B). The identification is confirmed by conversion to the yeast form after cultivation on a rich medium at 37°C, by extraction and detection of the B. dermatitidis-specific antigen A, or by a specific DNA probe. As indicated in Table 1, antibodies can be measured by the CF and ID tests. In the enzyme immunoassay (EIA), high antibody titers to antigen A are associated with progressive pulmonary or disseminated infection. Overall, serologic tests are not as useful for the diagnosis of blastomycosis as they are in the case of the other endemic mycoses.

Treatment

Severe cases of blastomycosis are treated with amphotericin B. In patients with confined lesions, a 6-month course of itraconazole is very effective.

 Epidemiology

Blastomycosis is a relatively common infection of dogs (and rarely other animals) in endemic areas. Blastomycosis cannot be transmitted by animals or humans. Unlike C. immitis and H. capsulatum, B. dermatitidis has only rarely (and not reproducibly) been isolated from the environment, so its natural habitat is unknown. However, the occurrence of several small outbreaks has linked B. dermatitidis to rural river banks.

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