Blastomycosis

Published on 18/03/2015 by admin

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Blastomycosis

Wanda Sonia Robles and Mahreen Ameen

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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(From Lebwohl, M.G., 2003. The Skin and Systemic Disease: A Color Atlas, second ed. Churchill Livingstone, with permission from Elsevier.)

Blastomycosis is a systemic, suppurative granulomatous infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. It is acquired by inhalation of the conidia which are transformed into the yeast form in the lungs. It is an endemic mycosis that is most prevalent in the North American continent, particularly in the states that border Mississippi and Ohio rivers, and the Great Lakes region. Cases have also been reported in Latin America, Africa, the Middle East and India. Consequently, the term ‘North American blastomycosis’ is now obsolete. Point source epidemics have been reported in endemic regions relating to recreational activities in wooded areas along waterways.

Blastomycosis is associated with a spectrum of disease ranging from subclinical infection to an acute or chronic pneumonia. Most cases are restricted to the respiratory system, and many are asymptomatic. Extrapulmonary infection occurs in 25–40% of cases, and most commonly affects the skin. Cutaneous manifestations range from papules to verrucous and ulcerative lesions. The bones, genitourinary system and central nervous system (CNS) may also be involved. Dissemination occurs more frequently in the immunocompromised, such as organ transplant recipients and those with HIV infection. The immunocompromised are at high risk of CNS involvement and adult respiratory distress syndrome. Their prognosis is poor and therefore they require aggressive management. There are also rare reports of primary cutaneous blastomycosis acquired after accidental inoculation, and in some cases infection has been self-limiting.

Management strategy

In the immunocompetent individual, acute pulmonary blastomycosis may be mild and self-limiting. However, all diagnosed cases are treated in order to prevent extrapulmonary dissemination. Itraconazole is the drug of choice for the treatment of non-CNS infection that is not life-threatening. A loading dose of 200 mg three times daily for 3 days followed by 200 mg once or twice daily for 6 to 12 months is recommended. Serum itraconazole levels should be measured 2 weeks after commencement of treatment. Ketoconazole (400–800 mg daily) and fluconazole (400–800 mg daily) are second line agents as they have lower efficacy against blastomyces. In addition, long-term treatment with ketoconazole is associated with adverse effects. The new generation azoles, voriconazole and posaconazole, have demonstrated activity against B. dermatitidis in in vitro and animal studies. There have been reports of the successful use of voriconazole in the treatment of CNS blastomycosis. Amphotericin B is the treatment of choice for those who fail on treatment with azoles, severe infection, the immunosuppressed, in pregnancy, and with CNS involvement. The experience to date has been largely with the use of amphotericin B deoxycholate. Liposomal amphotericin B is recommended for CNS infection as it achieves higher CNS penetration and is better tolerated with prolonged therapy. After an initial response with amphotericin B, step-down therapy to an azole is common practice.

Specific investigations

Definitive diagnosis of blastomycosis is based on the identification of characteristic thick-walled, broad-based budding yeasts by direct examination of tissue or the isolation of Blastomyces in culture. Specimens for direct microscopy in 10% KOH can be skin scrapings, pus from skin lesions, sputum, and biopsy tissue from any lesion suspicious of infection. Successful culture of sputum, tissue biopsy specimens, cerebrospinal fluid or urine produces a white mould at 25°C on Sabouraud’s agar, and a brown wrinkled colony at 37°C on blood agar. Histopathology of infected tissues reveals a pyogranulomatous response without caseation, and pseudoepitheliomatous hyperplasia. A Blastomyces antigen assay is available to test urine, blood and other fluids, but it is not always specific. Antibody assays are non-specific and insensitive.

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