Blastomycosis Workup

  • Author: Basil Varkey, MD, FCCP; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Feb 8, 2011
 

Laboratory Studies

A leukocyte and differential count may show leucocytosis with a left shift, particularly in cases with a pneumonic presentation; however, the test has low sensitivity and specificity.

Pulse oximetry is appropriate in detecting hypoxemia in cases that present as pneumonia.

Arterial blood gases are indicated in the presence of tachypnea, pulmonary infiltrates, and hypoxemia by pulse oximetry.

Sputum microscopy is a simple and inexpensive test that has a high diagnostic yield of more than 75% in patients with a pneumonic presentation. Although overall sensitivity of this test is modest (approximately 40%), in patients with pneumonia or acute respiratory distress syndrome, the sensitivity is much higher (approximately 75%). Place a small sample of freshly expectorated sputum on a slide and digest it with drops of 10% potassium hydroxide. Cover it with a cover slip and examine it under a microscope. Yeasts, 8-20 micrometers in size, with single, broad-based buds, double refractile walls, and multiple nuclei, are extremely characteristic of Blastomyces dermatitidis. This permits the physician to begin treatment without delay.

Microscopy of other fluids (eg, pus from skin lesions, draining fistulas, aspirate from an abscess) can be examined in a manner similar to that described for sputum to detect the fungus.

Microscopic examination of a potassium hydroxide wet mount of pus aspirated or expressed from skin microabscesses, fistulae, or subcutaneous abscesses will reveal characteristic broad-based budding yeast. B dermatitidis also is stained by calcofluor; use of this reagent may improve the sensitivity of microscopic examination of pus.

For sputum culture, isolation and identification of the organism in an appropriate laboratory culture medium provides absolute confirmation of the diagnosis; however, it may be time-consuming since culture observation may occur as early as 5 days or as late as 30 days.

Exoantigen testing and a DNA probe reduce the time for making the final identification from a culture.

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Imaging Studies

Chest radiography findings vary and lack diagnostic specificity. Alveolar infiltrates (eg, consolidation), masslike densities, and nodules are common patterns in order of frequency. Cavitation may be present, and there is no predilection for any lobe. Pleural effusion is uncommon, but pleural thickening adjacent to an infiltrate may be observed. Hilar or mediastinal lymph node enlargement rarely occurs.

Chest CT scanning is not needed in all cases. The test better defines the character and distribution of the abnormalities observed in a roentgenogram and is helpful in identifying mediastinal abnormalities and loculated pleural effusions.

A head CT scan is useful in the detection of brain abscesses.

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Other Tests

Skin testing is not reliable for diagnosis and is not commercially available.

With regard to serologic tests, complement fixation and immunodiffusion tests lack sensitivity and cannot be used to exclude the diagnosis. An enzyme immunoassay (EIA) for antibodies to the A antigen of B dermatitidis is a more sensitive test but lacks specificity. Newer tests that use more specific cell wall antigens, radioimmunoassays (RIAs), and Western blot techniques have improved sensitivity and specificity but are not yet available for widespread clinical use.[9, 10]

DNA probe may be useful in identifying B dermatitidis in formaldehyde-fixed tissue samples.[11]

Antigen detection in serum and urine lacks specificity.

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Procedures

Bronchoscopy (with washings, brushings, and a biopsy) is indicated in the following situations:

  • Absence of sputum
  • Nondiagnostic sputum microscopic examination
  • Undiagnosed pulmonary mass density, atelectasis, or consolidation
  • Hemoptysis

Percutaneous needle or surgical biopsy of the affected organ, such as skin lesions, a subcutaneous nodule, bone, or laryngeal lesion, may be helpful.

Prostatic massage may be necessary. In cases of blastomycosis of the genitourinary tract, the urine collected after a massage is likely to have a higher diagnostic yield.

With regard to lumbar puncture, the diagnostic yield of examination of cerebrospinal fluid is low in CNS blastomycosis; however, ventricular fluid specimens have a higher yield.

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Histologic Findings

The yeast forms are best visualized with a periodic acid-Schiff (PAS) stain, and they are not easily observed with a hematoxylin and eosin (H&E) stain. The methenamine silver and Papanicolaou are other reliable stains. Demonstration of the yeasts is particularly important in blastomycosis that involves sites with squamous epithelium (eg, skin, larynx, trachea) since the hyperplastic response observed in the tissue may simulate squamous cell carcinoma.

Skin lesions of disseminated blastomycosis are characterized by pseudoepitheliomatous hyperplasia of the epidermis, intraepidermal microabscesses, and a suppurating granulomatous reaction in the dermis.

The hyperplastic epidermis lacks the cytological atypia of squamous cell carcinoma. Intraepidermal abscesses contain abundant neutrophils and organisms; organisms are best visualized with the diastase-digested periodic acid-Schiff staining procedure or with the methenamine silver stain. Yeasts are present extracellularly in the dermis or intracellularly in multinucleated giant cells. Intracellular yeasts are easily identified on routine hematoxylin and eosin-stained sections of skin as punched-out "holes" in cytoplasm of the giant cells. The inflammatory infiltrate is polymorphous, containing lymphocytes, histiocytes, and neutrophils. Tuberculoid granuloma formation is unusual, but if it occurs, it is not accompanied by caseation.

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Contributor Information and Disclosures
Author

Basil Varkey, MD, FCCP  Professor Emeritus, Department of Internal Medicine, Division of Pulmonary and Critical Care, Medical College of Wisconsin; Consulting Pulmonologist, Froedtert Memorial Lutheran Hospital

Basil Varkey, MD, FCCP is a member of the following medical societies: American Association of Physicians of Indian Origin and American College of Chest Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Gregory J Raugi, MD, PhD  Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Peterson, MD  Chief of Medicine, Vice-Chair of Medicine, University of California, San Francisco, School of Medicine; Endowed Professor of Medicine, University of California, San Francisco-Fresno, School of Medicine

Michael Peterson, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD  Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

References
  1. Rooney PJ, Sullivan TD, Klein BS. Selective expression of the virulence factor BAD1 upon morphogenesis to the pathogenic yeast form of Blastomyces dermatitidis: evidence for transcriptional regulation by a conserved mechanism. Mol Microbiol. Feb 2001;39(4):875-89. [Medline].

  2. Chapman SW, Lin AC, Hendricks KA, et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect. Sep 1997;12(3):219-28. [Medline].

  3. Klein BS, Vergeront JM, Weeks RJ, Kumar UN, Mathai G, Varkey B, et al. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin. N Engl J Med. Feb 27 1986;314(9):529-34. [Medline].

  4. Carlos WG, Rose AS, Wheat LJ, et al. Blastomycosis in indiana: digging up more cases. Chest. Dec 2010;138(6):1377-82. [Medline].

  5. Pappas PG, Threlkeld MG, Bedsole GD, Cleveland KO, Gelfand MS, Dismukes WE. Blastomycosis in immunocompromised patients. Medicine (Baltimore). Sep 1993;72(5):311-25. [Medline].

  6. Pappas PG, Pottage JC, Powderly WG, Fraser VJ, Stratton CW, McKenzie S, et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Ann Intern Med. May 15 1992;116(10):847-53. [Medline].

  7. Meyer KC, McManus EJ, Maki DG. Overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome. N Engl J Med. Oct 21 1993;329(17):1231-6. [Medline].

  8. Varkey B. Blastomycosis in children. Semin Respir Infect. Sep 1997;12(3):235-42. [Medline].

  9. Martynowicz MA, Prakash UB. Pulmonary blastomycosis: an appraisal of diagnostic techniques. Chest. Mar 2002;121(3):768-73. [Medline].

  10. Durkin M, Witt J, Lemonte A, Wheat B, Connolly P. Antigen assay with the potential to aid in diagnosis of blastomycosis. J Clin Microbiol. Oct 2004;42(10):4873-5. [Medline]. [Full Text].

  11. Bialek R, Cirera AC, Herrmann T, Aepinus C, Shearn-Bochsler VI, Legendre AM. Nested PCR assays for detection of Blastomyces dermatitidis DNA in paraffin-embedded canine tissue. J Clin Microbiol. Jan 2003;41(1):205-8. [Medline]. [Full Text].

  12. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. Jun 15 2008;46(12):1801-12. [Medline].

  13. Lentnek AL, Lentek IA. Successful management of Blastomyces dematitidis meningitis. Infect Med. 2006;23:39.

  14. Lutsar I, Roffey S, Troke P. Voriconazole concentrations in the cerebrospinal fluid and brain tissue of guinea pigs and immunocompromised patients. Clin Infect Dis. Sep 1 2003;37(5):728-32. [Medline].

  15. Wuthrich M, Warner T, Klein BS. IL-12 is required for induction but not maintenance of protective, memory responses to Blastomyces dermatitidis: implications for vaccine development in immune-deficient hosts. J Immunol. Oct 15 2005;175(8):5288-97. [Medline].

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