- Author: Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH; Chief Editor: Mark R Wallace, MD, FACP, FIDSA more...
The diagnosis of paracoccidioidomycosis is most commonly made through the visualization of typical yeast cells in tissue, wet preparations (eg, sputum), or superficial scrapings (eg, skin lesions). Cultures should be obtained, but are limited by low sensitivity. Cerebrospinal fluid (CSF) studies are nonspecific, and mycologic examination (smears and culture) is usually negative. Blood culture results are typically negative, but recovery of P lutzii from blood has recently been reported.
Other laboratory studies
Patients with juvenile paracoccidioidomycosis can have anemia, hypergammaglobulinemia, and eosinophilia.
Pulmonary function tests
These may reveal obstructive abnormalities.
Wet mount of sputum or lesional material
In more than 90% of patients, potassium hydroxide (KOH) preparation of sputum or lesional material reveals large, multiple budding yeasts (blastoconidia) (2-30 µm in diameter) diagnostic for paracoccidioidomycosis. The typical pathognomonic features are large, thick-walled, spherical yeast cells with multiple peripheral buds encircling the central cell (pilot's wheel or mariner's wheel). This appearance helps to differentiate Paracoccidioides from Blastomyces dermatitidis and all other yeasts. (See the image below.)
Histologic examination reveals a granulomatous reaction with epithelioid and giant cells in association with a severe inflammatory infiltrate. Yeast with the characteristic pilot's wheel configuration may be found within giant cells or free in the inflammatory infiltrate. In skin and mucous membrane lesions, pseudoepitheliomatous hyperplasia with intraepidermal abscesses may be seen. Caseous necrosis is seen within the lymph nodes. A diffuse tissue reaction is typically seen in the juvenile form.
Paracoccidioides can be recovered on fungal media (eg, Sabouraud dextrose agar) but may require 20-30 days for growth. The fungus grows as a mold at room temperature; conversion to the typical yeast form by growth at 35-37°C is required for confirmation of the diagnosis.
Serologic testing is not available in the United States (or outside endemic areas) and may be negative in patients infected with P lutzii infection.
Double-agar gel immunodiffusion can be used for screening, diagnosis, and treatment follow-up. The most-used test, with a sensitivity of greater than 80% and a specificity of more than 90%, it detects circulating Paracoccidioides antibodies.
Complement fixation test
This test is useful but technically cumbersome. It has a quantitative nature that allows evaluation of patient response to treatment, but it may cross-react with Histoplasma capsulatum antigens.
This test is similar to immunodiffusion with regard to sensitivity and specificity. Counter immunoelectrophoresis can be a useful test in endemic areas that are resource poor, as it does not require a power supply or buffers.
These tests (eg, enzyme-linked immunoassay [ELISA]) are used to detect circulating antibodies in the patient's serum. Most ELISA tests detect antibodies to gp43, and newer assays report a sensitivity of 95% and a specificity of 93%. Cross-reactivity is also possible in patients with histoplasmosis or lobomycosis.
These tests (eg, Western blot) detect circulating antibodies to gp43 in the serum in 100% of patients and circulating antibodies to gp70 in 96% of patients.
Novel and emerging technologies
Monoclonal antibodies to antigenic compounds of P brasiliensis have increased sensitivity. The antigen gP43 reacts with the sera of almost all patients infected with P brasiliensis, but it also shows positivity in patients with histoplasmosis. Because of specific protocols needed in the development and purification of the antigen, it is typically only used in a research setting or at larger referral centers.
Synthetic peptides mimicking P brasiliensis innate antigens have been studied as cheaper and more sensitive and specific alternatives to current serologic testing. However, they are still under investigation.
Polymerase chain reaction (PCR) diagnosis has been reported in experimental settings and holds the potential for a more sensitive and specific methodology for the diagnosis of paracoccidioidomycosis.
The paracoccidioidin skin test, if available, provides little diagnostic value. A positive skin test result indicates prior exposure, but it does not necessarily indicate current disease. The test may be useful prognostically because the conversion from an anergic result to a positive result is associated with a good prognosis in patients with severe paracoccidioidomycosis. Skin testing may also be an excellent tool for epidemiologic study of this disease.
Imaging to evaluate the extent of lymphadenopathy is warranted, and the patient should also be evaluated for possible obstruction or compression of structures secondary to lymphadenopathy. If clinically indicated, bone scanning can be performed to evaluate bone lesions.
Chest radiography and chest CT scanning should be considered. Chronic paracoccidioidomycosis patients without respiratory symptoms may have lung fibrosis. Chest radiography may show a nodular-interstitial, bilateral, and diffuse lung infiltrate in chronic paracoccidioidomycosis. CT scanning may also be useful.
If clinically indicated, CT scanning or magnetic resonance imaging (MRI) of the brain should be obtained to evaluate CNS involvement. Consider imaging suspected affected areas.
In patients with active paracoccidioidomycosis, chest radiography reveals interstitial infiltrates (in 64% of cases) or mixed lesions with linear and nodular infiltrates. Lesions are frequently bilateral and symmetrical.
Most changes occur in the central and basal portions of the lungs; the apices are usually spared. Cavities are frequent, but hilar adenopathy is rare.
Chronic pulmonary sequelae can present as fibrosis, bullae, and emphysematous areas. Chronic cor pulmonale can cause right ventricular hypertrophy.
CT scanning and MRI
CT scanning of the chest may help delineate disease and rule out coexisting pathology (eg, tuberculosis, malignancy). In CNS disease, features on CT and MRI scans are nonspecific and similar to those seen in other granulomatous diseases (solitary or multifocal parenchymal lesions).
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