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Blastomycosis
Chicago Disease, Gilchrist's disease, North American Blastomycosis
Blastomycosis refers to the disease caused by the endemic dimorphic fungi Blastomyces dermatitidis. The disease is endemic in the southeastern and south central states of North America, along the Mississippi and Ohio Rivers. Outbreaks have been associated with occupational or recreational activities around streams or rivers with high content of moist soil enriched with organic debris and/or rotting wood [1209, 1210]. The infection is acquired via inhalation of the conidia, which transform into the yeast form once in the lungs. After 30 to 45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur. However, at least 50% of primary infections are asymptomatic [1208]. Most cases become manifest during a chronic and indolent phase that may affect the lungs, the skin, the bones, the genitourinary tract and other reticuloendothelial organs [2030]. Blastomycosis may coexist or mimic a bronchogenic carcinoma, and tuberculosis [764, 896, 934, 1583, 2002]. Accidental inoculation may cause primary cutaneous blastomycosis [1289, 1298, 1299, 1522, 2087, 2469].
| CATEGORIES |
NOTES |
| Asymptomatic |
Occurs in about 50% of infections |
| Acute Pulmonary |
Presents as lobar or segmental consolidation that mimics a bacterial pneumonia |
| Chronic Pulmonary |
Radiologic presentations include lobar infiltrates with or without cavitation, mass mimicking bronchogenic carcinoma, or fibronodular infiltrates |
| Skin disease |
Either a verrucous or ulcerative lesion with an indolent course |
| Subcutaneous Nodules |
Cold abscesses commonly associated with systemic manifestations. They are frequently associated with inactive pulmonary or extrapulmonary disease. |
| Bone & Joint Infection |
Most commonly affect long bones, ribs and vertebrae. Lesions are usually osteolytic and well-delineated |
| Genitourinary Tract Infection |
Involvement is seen in 10 to 30% of cases and affects the prostate and epididymis |
| Others |
Almost any other organ can be involved, including the central nervous system, thyroid, pericardium, adrenal glands and gastrointestinal tract |
Special resource: You may also want to refer to the Infectious Disease Society of America-Mycoses Study Group (IDSA-MSG) Practice Guidelines for this disease. It is available at the IDSA website.
Even though spontaneous resolution of pulmonary disease in normal hosts has been reported, therapy is indicated for all clinical presentations of blastomycosis [421, 1881]. Amphotericin B is the drug of choice, particularly for life-threatening pulmonary forms, CNS infections, or cases presenting during pregnancy. A total dose ranging between 1.5 and 2.5 gm must be given to avoid relapse. However, once the patient's condition has stabilized, a regimen with itraconazole (200 to 400 mg/day) can be considered [1993]. For all other mild to moderate presentations, either pulmonary or extrapulmonary, itraconazole at the dose previously mentioned could be used as the first line agent[421, 596]. Ketoconazole at 400 to 800 mg/day is an alternative although is less well tolerated [421]. Fluconazole (800 mg) should be reserved for patients with CNS infection unable to tolerate a full course of amphotericin B [421, 1713]. Hydroxystilbamidine has been used with success in treating the cutaneous form of the disease, but is of limited value in treating other forms of blastomycosis [348, 1034]. Preliminary in vitro data suggest that voriconazole may have a role in the treatment of blastomycosis [686, 1338].
The tissue response is a combination of acute suppurative and granulomatous inflammation. These may vary in relative proportion from one person to another and from one site to another in the same individual. The lung generally has widespread granulomatous inflammation with small areas of abscess formation. Fungi are usually demonstrable at the edge of the abscess. Skin involvement typically shows pseudoepitheliomatous hyperplasia with focal microabscesses in the papillary dermis. The yeast cells are globose to ovoid in shape and approximately 8-15 um in diameter. The single blastoconidium is attached by a broad base to the parent cell. In most instances, predominantly single cells without attached blastoconidia are seen. The cell wall of the yeast is thick and appears doubly refractile.
Direct examination
Clinical material, such as fluids, prostate fluid, sputa, or tissue, is examined in 10% KOH. The fungus usually occurs as a thick-walled, globose yeast that measures 8-15 um in diameter. Some yeast cells have been reported to be up to 30 um in diameter. The fungus may also form yeast cells that are less than 8 um in diameter. Each blastoconidium is attached to the parent cell by a broad base. Owing to their size, the yeasts of Blastomyces dermatitidis could be confused with Coccidioides immitis or Cryptococcus neoformans under some circumstances.
Isolation
Inoculate the clinical material onto Sabouraud glucose agar, brain heart infusion agar, yeast-extract-phosphate agar, and a medium with cycloheximide, and then incubate at 30°C. The cultures should be kept 4 weeks before discarding as negative. Blastomyces dermatitidis grows best on the yeast extract agar or agar containing yeast extract such as Mould Inhibitory Agar (IMA).
The mould form to yeast form conversion is necessary to ensure that the fungus suspected to be B. dermatitidis is not a similar fungus, such as a species of Chrysosporium or Sepedonium. The mould-to-yeast conversion can be readily accomplished by inoculating Kelley's agar or blood agar supplemented with glutamine and then incubating the inoculated tubes at 37°C. The yeast form will begin to develop within a few days. The entire colony does not have to be converted to the yeast form in order to consider the fungus to be B. dermatitidis. An exoantigen technique and a DNA culture confirmation kit are available.
Unknown
Standardized testing procedures are not available. Microbiological resistance has not been demonstrated.
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References
348. Busey, J. F. 1972. Blastomycosis. 3. A comparative study of 2-hydroxystilbamidine and amphotericin B therapy. Am Rev Respir Dis. 105:812-8.
421. Chapman, S. W., R. W. Bradsher, G. D. Campbell, P. G. Pappas, and C. A. Kauffman. 2000. Practice guidelines for the management of patients with blastomycosis. Clin. Infect. Dis. 30:679-683.
596. Dismukes, W. E., R. W. Bradsher, G. C. Cloud, C. A. Kauffman, S. W. Chapman, R. B. George, D. A. Stevens, W. M. Girard, M. S. Saag, C. Bowles-Patton, and the NIAID Mycoses Study Group. 1992. Itraconazole therapy for blastomycosis and histoplasmosis. Am. J. Med. 93:489-497.
686. Espinel-Ingroff, A. 1998. In vitro activities of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J. Clin. Microbiol. 36:198-202.
764. Frean, J., L. Blumberg, and M. Woolf. 1993. Disseminated blastomycosis masquerading as tuberculosis. J Infect. 26:203-6.
896. Green, G. S., W. V. Leary, and G. Sanchez. 1969. Disseminated North American blastomycosis: report of a fatal case of four weeks' duration, imitating bronchogenic carcinoma. South Med J. 62:202-6.
934. Guler, N., A. Palanduz, U. Ones, A. Ozturk, A. Somer, N. Salman, and I. Yalcin. 1995. Progressive vertebral blastomycosis mimicking tuberculosis. Pediatr Infect Dis J. 14:816-8.
1034. Hermans, P. E., and T. F. Keys. 1983. Antifungal agents used for deep-seated mycotic infections. Mayo Clin Proc. 58:223-31.
1208. Klein, B. S., J. M. Vergeront, and J. P. Davis. 1986. Epidemiologic aspects of blastomycosis, the enigmatic systemic mycosis. Semin Respir Infect. 1:29-39.
1209. Klein, B. S., J. M. Vergeront, A. F. DiSalvo, L. Kaufman, and J. P. Davis. 1987. Two outbreaks of blastomycosis along rivers in Wisconsin. Isolation of Blastomyces dermatitidis from riverbank soil and evidence of its transmission along waterways. Am Rev Respir Dis. 136:1333-8.
1210. Klein, B. S., J. M. Vergeront, R. J. Weeks, U. N. Kumar, G. Mathai, B. Varkey, L. Kaufman, R. W. Bradsher, J. F. Stoebig, and J. P. Davis. 1986. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin. N Engl J Med. 314:529-34.
1289. Landay, M. E., and J. Schwarz. 1971. Primary cutaneous blastomycosis. Arch Dermatol. 104:408-9 passim.
1298. Larsh, H. W., and J. Schwarz. 1977. Accidental inoculation blastomycosis. Cutis. 19:334-5, 337.
1299. Larson, D. M., M. R. Eckman, R. L. Alber, and V. G. Goldschmidt. 1983. Primary cutaneous (inoculation) blastomycosis: an occupational hazard to pathologists. Am J Clin Pathol. 79:253-5.
1338. Li, R. K., M. A. Ciblak, N. Nordoff, L. Pasarell, D. W. Warnock, and M. R. McGinnis. 2000. In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum. Antimicrob. Agents Chemother. 44:1734-1736.
1522. Mercurio, M. G., and B. E. Elewski. 1992. Cutaneous blastomycosis. Cutis. 50:422-4.
1583. Morse, H. G., W. P. Nichol, D. M. Cook, N. K. Blank, and T. T. Ward. 1983. Central nervous system and genitourinary blastomycosis: confusion with tuberculosis. West J Med. 139:99-103.
1713. Pappas, P. G., R. W. Bradsher, C. A. Kauffman, G. A. Cloud, C. J. Thomas, G. D. Campbell, Jr., S. W. Chapman, C. Newman, W. E. Dismukes, and National Institute of Allergy and Infectious Diseases Mycoses Study Group. 1997. Treatment of blastomycosis with higher doses of fluconazole. Clin. Infect. Dis. 25:200-205.
1881. Recht, L. D., J. R. Philips, M. R. Eckman, and G. A. Sarosi. 1979. Self-limited blastomycosis: a report of thirteen cases. Am Rev Respir Dis. 120:1109-12.
1993. Saag, M. S., R. J. Graybill, R. A. Larsen, P. G. Pappas, J. R. Perfect, W. G. Powderly, J. D. Sobel, W. E. Dismukes, and the Mycoses Study Group Cryptococcal Subproject. 2000. Practice guidelines for the management of cryptococcal disease. Clin. Infect. Dis. 30:710-718.
2002. Saliba, N. A. 1967. Pulmonary blastomycosis complicating miliary tuberculosis. J Ky Med Assoc. 65:672-4 passim.
2030. Sarosi, G. A., and S. F. Davies. 1979. Blastomycosis. Am Rev Respir Dis. 120:911-38.
2087. Sharma, A. K., and P. Narang. 1997. Primary cutaneous inoculation blastomycosis with some unusual features [letter]. Australas J Dermatol. 38:101-2.
2469. Yen, A., R. C. Knipe, and S. K. Tyring. 1994. Primary cutaneous blastomycosis: report of a case acquired by direct inoculation of a bullous pemphigoid lesion. J Am Acad Dermatol. 31:277-8.
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