- Author: Chidinma Chima-Okereke, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
There are no clinical presentations or imaging abnormalities that provide a definitive diagnosis of blastomycosis. Direct visualization of B dermatitidis is essential in order to provide a definitive diagnosis. For most specimens, direct visualization should precede culture to confirm the diagnosis. Sputum specimens processed with 10% potassium hydroxide or a fungal stain are examined first in adolescent and adult patients because these specimens have a high overall yield (approximately 80%). Isolation and identification of the organism on sputum culture provides absolute confirmation of the diagnosis.
With regard to serologic tests, complement fixation and immunodiffusion tests lack sensitivity and cannot be used to exclude the diagnosis. A commonly used test is the commercially available chemiluminescent DNA probe (AccuProbe; GenProbe Inc., San Diego, CA). Although it produces a positive result with all Paracoccidioides brasiliensis species, P brasiliensis is very rare in the United States, so this probe remains useful. P brasiliensis can be differentiated from B dermatitidis by the appearance of the yeast phase. 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.[2, 31]
Skin testing is not reliable for diagnosis and is not commercially available. Antigen detection in serum and urine lacks specificity.
The diagnosis of blastomycosis is more difficult in children. Children with pulmonary disease who are unable to produce sputum may require invasive procedures, such as bronchoscopy with bronchoalveolar lavage, percutaneous needle biopsy of lung, and open lung biopsy, for diagnostic confirmation.
A leukocyte and differential count may show leukocytosis 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 patients with tachypnea, pulmonary infiltrates, and hypoxemia by pulse oximetry.
Chest radiography findings vary and lack diagnostic specificity. Other imaging studies or bronchoscopy may be indicated in select situations.
In patients with extrapulmonary disease, percutaneous needle or surgical biopsy of the affected organ (eg, skin, subcutaneous nodule, bone) may be helpful. Histology and culture of biopsy specimens may reveal the organism. DNA probe may be useful in identifying B dermatitidis in formaldehyde-fixed tissue samples.
Diagnosis of central nervous system blastomycosis is difficult. Lumbar puncture and cerebrospinal fluid analysis may demonstrate a neutrophil predominance, but this is rarely definitive. Ventricular fluid specimens have provided slightly higher rates of culture positivity but are still not sensitive. In one case series, CSF culture identified only 2 out of 22 patients with confirmed blastomycosis meningitis.
Prostatic massage may be necessary to facilitate diagnosis in men with blastomycosis of the genitourinary tract. The urine collected after a prostatic massage is likely to have a higher diagnostic yield.
Sputum microscopy is a simple and inexpensive test, and although the overall sensitivity of this test is modest (less than 40%), the potential for rapid identification of the pathogen makes it a reasonable initial option. In patients with pneumonia or acute respiratory distress syndrome, the sensitivity is much higher (approximately 75%).
Sputum microscopy is performed by placing a small sample of freshly expectorated sputum on a slide digested with 10% potassium hydroxide. Under the microscope, yeasts 8-20 micrometers in size, with single, broad-based buds, double refractile walls, and multiple nuclei, are extremely characteristic of Blastomyces dermatitidis.
Microscopic examination of a potassium hydroxide wet mount can also be performed on aspirated pus, fistulae, or subcutaneous abscesses. These will reveal characteristic broad-based budding yeast. Identification of B dermatitidis by calcofluor staining under a fluorescent microscope is an easy and rapid method of diagnosis. Calcofluor white is a fluorochrome compound that binds to chitin present in the cell walls of B dermatitidis and fluoresces when exposed to short-wavelength UV light from a fluorescent microscope.
Isolation and identification of the organism in an appropriate laboratory culture medium provides absolute confirmation of the diagnosis. The organism can be cultured on brain-heart infusion, potato dextrose agar, potato flake agar, and Sabouraud dextrose agar at room temperature. Cultures may become positive in as few as 5 days or many as 30 days when incubated at 25-30°C. B dermatitidis colonies are creamy white and transform to a brown-gray color as hyphae grow.
B dermatitidis mold has a distinctive “lollipop” appearance with oval conidia, 2-4 μm in diameter at the tips of thin conidiophores. They also have thin septate hyphae, 1-2 μm in diameter.
Specimens for culture may consist of sputum, tracheal aspirates, bronchoalveolar lavage fluid, tissue biopsy samples, cerebrospinal fluid, or urine. Because colonization with B dermatitidis does not occur, detection of the fungus from any sterile site is diagnostic.
Because primary cutaneous blastomycosis has been reported by accidental autoinoculation, clinical laboratory personnel and pathologists should be notified about the possibility of blastomycosis in the differential diagnosis when handling potential infected tissue or body fluid specimens.
Skin Tests and Serodiagnosis
Skin testing and serodiagnosis of blastomycosis using complement fixation (CF) antibodies and immunodiffusion (ID) precipitin bands currently have very limited roles in diagnosis because of poor sensitivity and specificity, and cross-reactivity with other fungi. A recently developed enzyme immunoassay with the A-antigen of B dermatitidis has been shown to be more sensitive than CF and ID tests; however, this test is not available in most commercial laboratories.
Detection of (1→3)-β-d-glucan in serum specimens is of limited benefit in patients with blastomycosis. In one small case series of four patients with Blastomycosis, β-d-glucan was detected in only one patient with disseminated disease.
Chest radiograph findings vary depending on the immune status of the host but, in general, are abnormal in two thirds of cases. In the immunocompetent patient, chest radiography findings can vary but, in many cases, demonstrates lobar or segmental airspace opacities. A focal mass is common with well-defined margins and can range from 5-10 cm in size. These masses may be mistaken for neoplasm. Cavitary lesions are uncommon in immunocompetent patients.
However, in the immunocompromised host, cavitary lesions are more common and disseminated disease can lead to diffuse interstitial infiltrates on the chest radiograph. Pleural effusion is uncommon, but pleural thickening adjacent to an infiltrate may be observed. Hilar or mediastinal lymph node enlargement rarely occurs.
See an example of chest radiography findings in the image below.
Chest computed tomography (CT) is not always necessary, but can provide better definition of the character and distribution of abnormalities observed on a chest radiograph and is helpful in identifying mediastinal abnormalities and loculated pleural effusions. A head CT scan is useful in the detection of brain abscesses.
CT scanning can also be used to detect skeletal involvement in some cases of extrapulmonary blastomycosis. Magnetic resonance imaging is more sensitive for this purpose, however, and a radionuclide bone scan is also an alternative.
Bronchoscopy has a higher sensitivity than sputum examination and yields a positive diagnosis in 92% of patients with pulmonary blastomycosis. 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
Immune Deficiency Workup
In recent years, serious infection with blastomycosis has been recognized increasingly in immunocompromised hosts, especially patients with AIDS. However, other fungal infections, such as progressive disseminated histoplasmosis or cryptococcal meningitis, are more likely to be opportunistic. Blastomycosis is not an AIDS-defining illness and no official recommendations regarding screening for human immunodeficiency virus (HIV) infection in patients diagnosed with blastomycosis are recognized.
The yeast forms of Blastomyces dermatitidis are best visualized with a periodic acid-Schiff (PAS) stain. Methenamine silver and Papanicolaou stains are also reliable.
Demonstration of the yeasts is particularly important in blastomycosis that involves sites with squamous epithelium (eg, skin, larynx, trachea). In these tissues, the fungal infection may provoke a hyperplastic response that simulates squamous cell carcinoma. On the other hand, the hyperplastic epidermis lacks the cytological atypia of squamous cell carcinoma.
Skin lesions of disseminated blastomycosis are characterized by the following histologic features:
Pseudoepitheliomatous hyperplasia of the epidermis
A suppurating granulomatous reaction in the dermis
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 (H&E)–stained sections of skin as punched-out "holes" in cytoplasm of the giant cells. The inflammatory infiltrate is polymorphous, containing lymphocytes, histiocytes, and neutrophils.
On cytologic examination of specimens such as sputum or tissue aspirates, B dermatitidis typically appears as a round, multinucleate yeast ranging from 8-15 μm in diameter, with a broad-based bud.
Granuloma formation is unusual. If it does occur, it generally does not demonstrate caseation or calcification, as is typical of tuberculosis.
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