BLASTOMYCOSIS
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.
TREATMENT
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%.
