Blastomycosis is a systemic pyogranulomatous infection, involving primarily the lungs, that arises after inhalation of the conidia of Blastomyces dermatitidis. Pulmonary blastomycosis varies from an asymptomatic infection to acute or chronic pneumonia. Hematogenous dissemination occurs frequently. Extrapulmonary disease of the skin, bones, and genitourinary system is common, but almost any organ can be infected.
B. dermatitidis is the asexual state of Ajellomyces dermatitidis. Two serotypes have been identified on the basis of the presence or absence of the A antigen. B. dermatitidis exhibits thermal dimorphism, growing as the mycelial phase at room temperature and as the yeast phase at 37°C. Primary isolation is most dependable for the mycelial phase incubated at 30°C. Definitive identification usually requires conversion to the yeast phase at 37°C or, more commonly, the use of nucleic acid amplification techniques (e.g., AccuProbe, Gen-Probe, San Diego, CA) that detect mycelial-phase growth. Yeast cells are usually 8–15 μm in diameter, have thick refractile cell walls, are multinucleate, and reproduce by a single, large, broad-based bud.
Most cases of blastomycosis have been reported in North America. Endemic areas include the southeastern and south-central states bordering the Mississippi and Ohio river basins, the midwestern states and Canadian provinces bordering the Great Lakes, and a small area in New York and Canada along the St. Lawrence River. Outside North America, blastomycosis has been reported most frequently in Africa.
Early studies of endemic cases indicated that middle-aged men with outdoor occupations were at greatest risk. Reported outbreaks, however, do not suggest a predilection according to sex, age, race, occupation, or season. B. dermatitidis probably grows as microfoci in the warm, moist soil of wooded areas rich in organic debris. Exposure to soil, whether related to work or recreation, appears to be the common factor associated with infection.
After inhalation, the conidia of B. dermatitidis are susceptible to phagocytosis and killing in the lungs by polymorphonuclear leukocytes, monocytes, and alveolar macrophages. This phagocytic response represents innate immunity and probably explains the high frequency of asymptomatic infections in outbreaks. Conidia that escape phagocytosis rapidly convert to the yeast phase in tissue. The greater resistance of the thick-walled yeast form to phagocytosis and killing probably contributes to infection. This yeast-phase conversion also induces the expression of the 120-kDa glycoprotein BAD-1, which is an adhesin, an essential virulence factor, and the major epitope for humoral and cellular immunity. The primary acquired host defense against B. dermatitidis is cellular immunity mediated by antigen-specific T cells and lymphokine-activated macrophages.
Approach to the Patient: Blastomycosis
Whether acute or chronic, blastomycosis mimics many other disease processes. For example, acute pulmonary blastomycosis may present with signs and symptoms indistinguishable from those of bacterial pneumonia or influenza. Chronic pulmonary blastomycosis most commonly mimics malignancy or tuberculosis. Skin lesions are often misdiagnosed as basal cell or squamous cell carcinoma, pyoderma gangrenosum, or keratoacanthoma. Laryngeal lesions are frequently mistaken for squamous cell carcinoma. Thus, the clinician must maintain a high index of suspicion and perform a careful histologic evaluation of secretions or biopsy material from patients who live in or have visited regions endemic for blastomycosis.
Acute pulmonary infection is usually diagnosed in association with point-source outbreaks and is accompanied by the abrupt onset of fever, chills, pleuritic chest pain, arthralgias, and myalgias. Cough is initially nonproductive but frequently becomes purulent as disease progresses. Chest radiographs usually reveal alveolar infiltrates with consolidation. Pleural effusions and hilar adenopathy are uncommon. Most patients diagnosed with pulmonary blastomycosis have chronic indolent pneumonia with signs and symptoms of fever, weight loss, productive cough, and hemoptysis. The most common radiologic findings are alveolar infiltrates with or without cavitation, mass lesions that mimic bronchogenic carcinoma, and fibronodular infiltrates. Respiratory failure (adult respiratory distress syndrome) associated with miliary disease or diffuse pulmonary infiltrates is more common among immunocompromised patients, especially those in the late stages of AIDS (Chap. 189). Mortality rates are ≥50% among these patients, and most deaths occur within the first few days of therapy.
Skin disease is the most common extrapulmonary manifestation of blastomycosis. Two types of skin lesions occur: verrucous (more common) and ulcerative. Osteomyelitis is associated with as many as one-fourth of B. dermatitidis infections. The vertebrae, pelvis, sacrum, skull, ribs, or long bones are most frequently involved. Patients with B. dermatitidis osteomyelitis often present with contiguous soft-tissue abscesses or chronic draining sinuses. In men, blastomycosis may involve the prostate and epididymis. Central nervous system (CNS) disease occurs in <5% of immunocompetent patients with blastomycosis. In AIDS patients, however, CNS disease has been reported in ~40% of cases, usually presenting as a brain abscess. Less common forms of CNS disease are cranial or spinal epidural abscess and meningitis.
Definitive diagnosis of blastomycosis requires growth of the organism from sputum, pus, or biopsy material. A presumptive diagnosis is made by visualization of the characteristic broad-based budding yeast in clinical specimens. Serologic diagnosis of blastomycosis is of limited usefulness because of cross-reactivity with other fungal antigens.
A Blastomyces antigen assay that detects antigen in urine and serum is commercially available (Mira Vista Diagnostics, Indianapolis, IN). Antigen detection in urine appears to be more sensitive than serum antigen detection. This antigen test may be useful for monitoring of patients during therapy or for early detection of relapse. Molecular identification techniques, including DNA probe hybridization, are commercially available but are currently used only to supplement traditional methods of diagnosis.
The Infectious Diseases Society of America has published guidelines for the treatment of blastomycosis. Selection of an appropriate therapeutic regimen must be based on the clinical form and severity of the disease, the immune status of the patient, and the toxicity of the antifungal agent ...