Zelalem Temesgen MD
Essentials of Diagnosis
Both clusters and sporadic cases of blastomycosis have been reported. Outdoor activities in proximity to waterways as well as exposure to dust from construction and excavation have been noted as possible risk factors for acquiring infection.
Infection begins with inhalation of conidia of the mycelial phase of the organism. In the lungs, the fungus converts to its yeast phase. Inflammatory response occurs in the form of polymorphonuclear leukocyte infiltration followed by macrophage infiltration and granuloma formation. The infection can spread via the bloodstream and lymphatic system to distant sites. Cellular immunity is the major protecting factor in preventing progression of disease in blastomycosis.
B dermatitidis may cause disease in virtually every organ of the body. The most common clinical syndromes associated with blastomycosis are described in the following sections (Box 71-1).
Pulmonary blastomycosis characteristically presents as an acute or chronic pneumonitis.
Symptomatic acute pulmonary infection presents similarly to an acute bacterial pneumonia with fever, chills, and productive cough, with or without hemoptysis or pleuritic chest pain.
This syndrome is also associated with significant mortality. In one report, only 13 of 29 patients survived. Although also seen in immunocompetent individuals, it is much more often encountered in immunocompromised individuals, including those with AIDS. Large amounts of B dermatitidis are easily recovered from respiratory cultures, and examination of lung tissue will show histopathological changes characteristic of ARDS, as well as the presence of a large number of the causative organisms. Aggressive therapy with large doses of amphotericin B (0.7–1.0 mg/kg) should be initiated promptly, and many patients require mechanical ventilatory assistance. Survivors may regain good pulmonary function.
BOX 71-1 Clinical Syndromes in Blastomycosis in Adults and Children
Extrapulmonary disease is usually seen in conjunction with pulmonary infection and is the result of hematogenous dissemination of B dermatitidis. The exception is primary cutaneous blastomycosis, which occurs as a result of accidental inoculation in the laboratory, during autopsy, or after dog bites.
Cutaneous blastomycosis is the most commo manifestation of extrapulmonary blastomycosis (40%–80% of reported cases). Areas of the body not covered by clothing are sites of predilection, but lesions can occasionally be found on mucocutaneous surfaces. The skin lesions start as papules or pustules but later advance to form either verrucous (ie, fungating, heaped up) or ulcerative lesions. The verrucous lesions, both by their gross and microscopic (hyperplasia, acanthosis) appearance, may be mistaken for cancer. Other differential diagnosis includes skin lesions caused by other fungi (eg, Histoplasma capsulatum, Coccidioides immitis, and Sporothrix schenckii), as well as lesions caused by nocardiosis and atypical mycobacteria (eg, Mycobacterium marinum). Both types of skin lesions may be present in the same patient.
Bone involvement represents the second most frequent manifestation of extrapulmonary disease, having been reported in ≤ 25% of extrapulmonary cases. The most commonly affected bones are the vertebrae, pelvis, sacrum, ribs, and long bones, but any bone can be involved. The usual presenting symptoms consist of soft tissue abscesses or chronic draining sinuses adjacent to areas of osteomyelitis. Vertebral disease, with involvement of the vertebral body and development of large paraspinal abscesses, may be indistinguishable from tuberculosis. The typical radiographic appearance is a well-circumscribed osteolytic lesion.
Vertebral disease may be indistinguishable from tuberculosis. In addition, differential diagnosis includes bacterial osteomyelitis, osteomyelitis caused by other fungi, and a Brodie abscess.
Blastomycosis of the genitourinary tract follows skin and bone infection in the frequency of its extrapulmonary involvement. Men are more prone to be infected than women. Prostatic involvement is the most common presentation, followed by epidydimoorchitis. Symptoms include urinary obstruction with an enlarged and tender prostate and pyuria.
Yield of cultures may be improved by collection of urine after prostatic massage. In women, both endometrial infection as a result of sexual contact with a man with blastomycosis on the penis and tuboovarian abscess after hematogenous dissemination have been reported.
Central nervous system blastomycosis is an uncommon complication of disseminated disease. It presents either as an abscess or meningitis. Abscesses present as mass lesions, either intracranially or in an epidural location. Meningitis is difficult to diagnose. Cerebrospinal fluid evaluation is usually not diagnostic. Culture of ventricular fluid may on occasion yield the organism. Cultures of large volumes of spinal fluid increase the likelihood of a positive culture.
BLASTOMYCOSIS & AIDS
Blastomycosis is an uncommon infection among patients with AIDS and is not recognized as an AIDS-defining opportunistic infection according to present Centers for Disease Control guidelines. When it occurs, it is a late manifestation of HIV infection, usually affecting individuals with prior diagnosis of an AIDS-defining illness and CD4 lymphocyte counts of < 200 cells/mm3. It can present either with disease limited to the lungs and pleura or with disseminated infection involving multiple visceral organs. There is also more frequent involvement of the central nervous system. Cutaneous lesions appear to be less common.
A higher frequency of diffuse interstitial or miliary pattern is noted on chest radiograms. Relapse is common, necessitating chronic maintenance treatment to prevent recurrent disease.
BLASTOMYCOSIS IN OTHER IMMUNOCOMPROMISED HOSTS
Blastomycosis has been reported to cause infection in other immunocompromised patients including patients on long-term glucocorticoid treatment, solid-organ transplant recipients, patients with hematological malignancies, patients with disorders of neutropenia, patients demonstrating humoral immune dysfunction, and patients with combined immunologic dysfunction. Infection in these individuals differs from that of normal hosts in several ways. The pulmonary involvement is more extensive; a greater frequency of progression to respiratory failure and ARDS is observed.
Diffuse interstitial alveolar changes and pleural effusions are much more common than in normal hosts. Multiple visceral organ disease, with or without central nervous system involvement, is also more common.
Blastomycosis is diagnosed by identification and isolation of the organism in tissue, exudate, or histopathologic sections.
Acute pulmonary infection caused by B dermatitidis sometimes resolves spontaneously without specific therapy. However, it is not possible to determine which patients will progress to serious infection or develop extrapulmonary disease. For this reason, many authorities recommend treating all cases of active blastomycosis. If withholding treatment is considered, extrapulmonary disease should be excluded. If treatment is withheld, patients must be carefully monitored for a prolonged period for evidence of relapse, progression, or extrapulmonary infection.
Amphotericin B is the drug of choice for immunocompromised patients, including those with AIDS, patients with life-threatening infections, and patients with central nervous system disease (Box 71-2). Because relapse of blastomycosis after amphotericin therapy is dose related and rarely occurs in patients who had received > 1.5 g of the drug, a total cumulative dose of amphotericin between 1.5 and 2.5 g is recommended.
BOX 71-2 Treatment of Blastomycosis in Adults and Children
Itraconazole, a triazole antifungal agent, is the drug of choice for those patients who do not require amphotericin B (see above). It should be used at a dose of 200 mg/d orally. The dose can be increased to 400 mg/d for persistent or progressive disease. A minimum of 6 months of therapy is recommended by most authorities.
Ketoconazole, another oral antifungal agent with a similar mechanism of action to itraconazole, may be used at a dose of 400 mg/d by mouth. Doses of ≤ 800 mg/d may be required for persistent and unresponsive disease. Treatment should be continued for ≥ 6 months.
Both itraconazole and ketoconazole require gastric acid for absorption. There are significant drug-drug interactions with drugs such as terfenadine, rifampin, phenytoin, and carbamazepine. In addition, neither itraconazole nor ketoconazole is excreted in the urine as an active drug. Therefore treatment of genitourinary blastomycosis with these agents may be inadequate.
Fluconazole, another triazole antifungal agent, has been shown to be moderately effective in the treatment of non–life-threatening blastomycosis at a dose of 200–400 mg/d.
Patients with AIDS and immunocompromised patients with ongoing immunosuppression require chronic oral maintenance treatment (eg, itraconazole, 200 mg/d) to prevent recurrence.
Surgery may be indicated for evacuation of large abscesses, diagnostic biopsy, or removal of central nervous system mass lesions, or débridement of devitalized and necrotic bone in patients with osteomyelitis refractory to pharmacotherapy.
The mortality rate for blastomycosis in HIV-infected patients is much higher than the mortality rate from blastomycosis in the general population. In one report, of 24 patients with HIV and blastomycosis, 15 (63%) had disseminated disease, and 13 (54%) died as a result of their infection. Previous reports have suggested a mortality rate of ~ 10% in those with disseminated blastomycosis but without concomitant HIV infection.
BOX 71-3 Control of Blastomycosis
Prevention & Control
Individuals residing in endemic areas who are at increased risk (eg, immunocompromised or HIV-infected individuals) should avoid activities associated with acquiring infection, such as exposure to dust, construction, or excavation. AIDS patients with blastomycosis who have completed initial therapy should receive lifelong suppressive treatment with itraconazole (Box 71-3).
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