eMedicine Specialties > Dermatology > Fungal Infections
Coccidioidomycosis: Differential Diagnoses & Workup
Updated: Jun 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Rarely, disseminated coccidioidomycosis with cutaneous involvement may clinically mimic a cutaneous T-cell lymphoma.14
Workup
Laboratory Studies
- At microscopic analysis, C immitis spherules can be visualized by staining biopsy samples with hematoxylin and eosin or Gomori methenamine-silver stain. Sputum or bronchoalveolar-lavage samples are stained with hematoxylin and eosin or Papanicolaou stain. The high sensitivity of the staining permits detection of small numbers of spherules. Direct examination of stained specimens of the spherules is more rapid than other methods and may speed the diagnosis.
- Culturing is more sensitive than other methods. C immitis grows well on most mycologic or bacteriologic media within 5-7 days of incubation. Aerobic conditions are required. Culturing procedures for C immitis are tedious and require experienced personnel and special laboratory containment facilities. Do not attempt culturing unless these provisions are in place because of the risk of infecting laboratory personnel with the airborne arthrospores. The recovery of Coccidioides species by culture and confirmation using the AccuProbe nucleic acid hybridization method by GenProbe is a sensitive and specific diagnostic method.15 The designation of Coccidioides species as a potential agent of bioterrorism mandates strict regulation of their transport and inventory.
- Serologic testing is most frequently used to diagnose primary infections. Most of the available tests are highly specific for an active infectious process. Minimally reactive test results are often diagnostically important and should not be dismissed as insignificant findings. A negative serologic test result does not exclude a coccidioidal infection. The performance of 1 or more serologic tests over the course of 2 months increases the sensitivity, especially for recently acquired C immitis infection.
- With tube precipitation (TP) antibody testing, immunoglobulin M (IgM) is most adept at forming immune precipitants, and these reactions can be detected early after the onset of infection. This test is sometimes called the IgM test. The antigen responsible for this reaction is a polysaccharide from the fungal cell wall. In as many as 95% of patients, TP antibodies are detected at some point within the first 4 weeks after symptoms appear. Within 7 months after the onset of self-limited disease, TP antibodies are detected in less than 5%.
- Complement-fixing (CF) antibody testing may be helpful. Because immunoglobulin G (IgG) is the immunoglobulin that is usually involved in forming immune complexes, this test is sometimes called the IgG test. Compared with TP antibodies, CF antibodies are identified later and persist for longer periods in early coccidioidal infections. CF antibodies can be present in various body fluids, and their detection in the cerebrospinal fluid is especially important in the diagnosis of coccidioidal meningitis. A titer of 1:16 or greater is commonly associated with extrathoracic dissemination. Higher titers reflect more extensive coccidioidal infection, and increasing CF antibody concentrations are associated with a worsening disease process.16
- Antibodies detected by using the original TP or CF testing can also be detected by means of alternative procedures called immunodiffusion tube precipitation (IDTP) or immunodiffusion complement-fixing (IDCF) tests, respectively. Both tests are at least as sensitive as their original counterparts.
- An enzyme-linked immunoassay for coccidioidal antibodies is commercially available. The test kit enables the specific detection of IgM or IgG antibodies. Positive results are highly sensitive for coccidioidal infection; however, false-positive results are possible, especially with the IgM enzyme immunoassay. Currently, enzyme immunoassay results should be confirmed with IDTP, IDCF, or CF tests before they are considered diagnostic.
- Bialek et al reported on the use of polymerase chain reaction with chemiluminescent DNA probes, targeting multicopy genes, for identifying clinical isolates of Coccidioides species.17
Imaging Studies
- Chest radiography may be used to detect granulomas and cavities.18
- In cases with severe headache, magnetic resonance imaging may be required to evaluate possible meningitis.
- Radionuclide bone scanning can be used to assess for bone lesions in the disseminated form of the disease or to evaluate bone pain.
Other Tests
- Skin testing: In current practice, test is available in the United States for assessing the cellular immune response in persons with coccidioidomycosis. Recent data suggest that archived coccidioidin retains its potency and specificity and that in vitro tests of coccidioidal immunity may have utility in the measurement of coccidioidal cellular immunity.
- A dermal delayed-type hypersensitivity reaction to coccidioidin is highly specific for coccidioidal infection. However, a positive result may not be related to currently acquired disease because, in most persons, this skin test result remains positive for life after infection.
- Although skin test results are useful for epidemiologic studies, the test has important limitations when it is used as a screening procedure for recent infections with C immitis.
- In patients in whom coccidioidomycosis is diagnosed with the help of other tests, the results of skin testing may have prognostic significance.
- With skin testing, the induration of the skin is measured at 24 hours and 48 hours after coccidioidin is injected intradermally. An induration greater than 5 mm is considered reactive. Erythema at the injection site does not aid in the diagnosis of coccidioidomycosis.
Procedures
- Nonhealing skin lesions may need to be evaluated by means of biopsy.
- When patients present with new complaints of focal discomfort or swelling, appropriate imaging methods or biopsy (if necessary) should be performed.
- Lumbar puncture may be required to evaluate the possibility of meningitis in patients with severe headaches.
- Increased cerebrospinal fluid pressure, increased WBC counts, increased protein levels, and decreased glucose levels are common findings in patients with meningitis.
- Occasionally, eosinophils are prominent in the cerebrospinal fluid.
- An effusion that develops in a joint can be aspirated to determine the cell counts and for culturing.
Histologic Findings
Cutaneous coccidioidomycosis with verrucous nodules tends to have an overlying hyperplastic epidermis with a dermal granuloma. Characteristic spores may be evident in the granuloma. Caseation necrosis may also be present.
Primary inoculation disease results in a dense, mixed, inflammatory dermal infiltrate with occasional giant cells and the formation of small abscesses. Spores may be evident, though hyphae are less likely to be present.
The occasionally associated erythema nodosum has typical histologic features, with no alterations suggestive of coccidioidomycosis. The same is true of erythema multiforme, which is less commonly linked to coccidioidomycosis.
More on Coccidioidomycosis |
| Overview: Coccidioidomycosis |
 Differential Diagnoses & Workup: Coccidioidomycosis |
| Treatment & Medication: Coccidioidomycosis |
| Follow-up: Coccidioidomycosis |
| References |
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Further Reading
Keywords
Valley fever, San Joaquin Valley fever, Coccidioides immitis, C immitis, arthroconidia, primary cutaneous coccidioidomycosis, respiratory infection, coccidioidal pneumonia, coccidioidal meningitis
