Blastomycosis is a systemic pyogranulomatous infection primarily involving the lungs that is caused by inhalation of the infective spores of the diphasic fungus Blastomyces dermatitidis. The organism exists in soil or on forest vegetation in a mycelial form. When the spores (conidia) from the mycelial growth gain entry into the body, usually by inhalation or rarely by direct inoculation, the organism converts into a yeast form. The yeast phase is found in infected tissue, pus, sputum, or other body exudates and is noninfective. The yeast cells are multinucleate, usually 8 to 15 mm in diameter, and are characterized by a thick refractile cell wall and reproduction is by a single broad-based bud.
The ecologic niche for Blastomyces spp. is soil containing decaying vegetation or decomposed wood, with humid conditions fostering its growth. Consequently, a common factor associated with both endemic and epidemic disease is exposure to soil, whether related to work or recreation. Blastomycosis occurs primarily in North America, principally in the Mississippi—Ohio River valleys, the Midwestern states, and in regions bordering the Great Lakes and St. Lawrence River. After North America, blastomycosis has been reported most frequently in Africa, and occasional cases have been identiﬁed in Mexico, Central and South America, India, and the Middle East.
In contrast to the conidia, the yeast forms of B. dermatitidis are more resistant to phagocytosis and killing by polymorphonuclear leukocytes, monocytes, and alveolar macrophages. Conversion to a yeast form likely contributes to infection and persistence of Blastomyces spp., and the capsule and Bad-1, a 120-kd glycoprotein, are major virulence factors expressed in this form.
The major acquired host defense against B. dermatitidis is cellular immunity, although humoral (speciﬁc antibody)-mediated immunity does not appear to confer resistance to or hasten clinical recovery. A variety of Blastomyces antigens are targets of antigen-speciﬁc T lymphocytes and lymphokine-activated macrophages after clinical infection.
Blastomycosis can present as a pulmonary disease, multiple organ involvement (disseminated), or less commonly as extrapulmonary disease only. The incidence of the latter two has declined with the availability of effective therapy to about 18% of patients. Blastomyces lung infection can be an asymptomatic or manifest as acute or chronic pneumonia. Hematogenous dissemination frequently occurs; extrapulmonary disease of the skin, bones, and genitourinary system is common, but almost any organ can be infected, including the central nervous system (CNS).
Acute pneumonia with B. dermatitidis infection resembles inﬂuenza or a bacterial pneumonia. Chronic infection presents as a chronic pneumonia or a potential malignancy. Radiographic manifestations are those of pneumonitis, large and small nodules or masses, cavitation, and diffuse miliary patterns. Lesions may be unilateral or bilateral and involve any or all lobes of the lungs. They may closely simulate a bronchogenic carcinoma in appearance as well as tuberculosis and other pulmonary disorders.
The diagnosis of blastomycosis is made by demonstrating the presence of the causative organism in the patient’s sputum, bronchoscopic specimens, urine, other exudates, or body tissue. Direct visualization of the organism in cytologic and histologic specimens can provide a rapid diagnosis. For pulmonary blastomycosis, direct examination of respiratory specimens is 50% to 90% sensitive, and culture yields the diagnosis in 86% to 100% of cases. Serologic tests are unhelpful; however, an antigen detection test for body ﬂuids has promise.
Although occasional patients with mild to moderate pulmonary blastomycosis can undergo spontaneous cure, most patients need speciﬁc treatment. Both amphotericin B and the azole drugs are active against
B. dermatitidis. Considerations for treatment include the severity of disease, CNS involvement, and the immune competence of the patient. If severe disease, CNS involvement, or immunosuppression is present, intravenous amphotericin B is recommended, preferably as the lipid formulation, for 1 to 2 weeks or until improvement is observed, followed by oral itraconazole for a total 12-month duration of treatment. In mild to moderate disease in an immunocompetent patient without CNS involvement, therapy can be started with oral itraconazole, and the duration can vary between 6 to 12 months. Other azoles, such as ﬂuconazole (high dose) and voriconazole, can also be used if itraconazole is not tolerated or when the CNS is involved because the latter drug has poor CNS penetration. If the patient does not respond to azole therapy, it should be switched to amphotericin B. Adequately treated patients have low relapse rates of less than 10%.