eMedicine Specialties > Pulmonology > Infectious Lung Diseases
Coccidioidomycosis: Differential Diagnoses & Workup
Updated: Sep 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Other fungal infections
Lymphoma
Other causes of cough, fever, and fatigue
Old granuloma
Tuberculosis and other granulomatous infections: These are in the differential diagnosis of coccidioidomycosis. Thin- or thick-walled cavities in an asymptomatic patient are suggestive of coccidioidomycosis.
Differential diagnosis of coccidioidomycosis cystic lesions
Blebs
Bullae
Pneumatoceles
Congenital cystic lesions
Traumatic lesions
Pneumocystis carinii pneumonia
Hydatid disease
Differential diagnosis of coccidioidomycosis for focal or multifocal cavitary lesions
Neoplasms (eg, bronchogenic carcinomas and lymphomas), infections, or abscesses
Immunologic disorders such as Wegener granulomatosis and rheumatoid nodule
Pulmonary infarct
Septic embolism
Lymphocytic interstitial pneumonia
Localized bronchiectasis
Differential diagnosis of coccidioidomycosis for diffuse involvement with cystic or cavitary lesions
Pulmonary lymphangioleiomyomatosis
Pulmonary Langerhans cell histiocytosis
Honeycomb lung associated with advanced fibrosis
Diffuse bronchiectasis
Metastatic disease
Workup
Laboratory Studies
General laboratory study results are as follows:
- Normal white blood cell count or mild leukocytosis
- Peripheral eosinophilia (>5%)
- Elevation of erythrocyte sedimentation rate
- Microbiologic culture
- Isolation of C immitis from a clinical specimen establishes the diagnosis.
- Isolation can be from sputum, bronchoalveolar lavage fluid, blood, urine, bone marrow, lymph nodes, urine, skin, bone, and cerebrospinal fluid.
- The organism usually grows within 3-5 days on most routine microbiologic media.
- Laboratory personnel should handle cultures in sealed containers and with caution because the mycelial form isolated from cultures is very infectious.
- Histologic specimens
- Spherules can be seen in tissue specimens using standard stains such as hematoxylin and eosin stain or Papanicolaou stain.
- The identification of spherules on direct examination of sputum also is diagnostic but is less sensitive than cultures (sputum potassium hydroxide [KOH] smear or silver stain [Gomori methenamine silver stain]).
A granuloma with coccidioides immitis spherule (pretracheal lymph node biopsy).
A ruptured Coccidioides immitis spherule (pretracheal lymph node biopsy).
Gomori methenamine silver stain of Coccidioides immitis spherule (pretracheal lymph node biopsy).
Periodic acid-Schiff stain of Coccidioides immitis spherule (pretracheal lymph node biopsy).
- Coccidioidal antibodies
- Immunoglobulin M (IgM) or precipitin antibody is detected in approximately half of all coccidioidal infections within the first week and in approximately 90% by 3 weeks. The IgM antibody fades over several weeks but may reappear under certain circumstances (eg, chronic cavitary coccidiomycosis or systemic reinfection associated with ventriculoperitoneal shunt placement. Methods of IgM detection are as follows:
- Tube precipitin - Older test and not currently in use
- Immunodiffusion tube precipitin - Better specificity; requires more time to perform than latex agglutination or enzyme immunoassay
- Latex agglutination - Rapid and highly sensitive but lacks specificity; higher false-positive rate and positive results require confirmation another test (ie, immunodiffusion tube precipitin)
- Enzyme immunoassay - Highly sensitive but lacks specificity; positive result requires confirmation immunodiffusion
- Immunoglobulin G (IgG) or complement fixation (CF) antibody appears months later and can persist for months or years. CF titers provide a quantitative measure of the immune response to infection and prognostic information with respect to dissemination. CF titers may be not be representative of the severity of infection, with lower titers occurring in patients who are immunosuppressed and unable to mount a response or in patients with overwhelming infection: Methods of IgG detection are as follows:
- Laboratory Branch complement fixation - Older test, supplanted by immunodiffusion complement fixation in most laboratories; some cross-reactivity with other dimorphic fungi
- Immunodiffusion complement fixation - Can be used to test any body fluid, including cerebrospinal fluid; increased titers indicate worsening disease; 4-fold decline in titer associated with therapeutic improvement; disseminated coccidioidomycosis associated with CF titers greater than or equal to 1:16
- Enzyme immunoassay - False positive rates limit use
- Immunoglobulin M (IgM) or precipitin antibody is detected in approximately half of all coccidioidal infections within the first week and in approximately 90% by 3 weeks. The IgM antibody fades over several weeks but may reappear under certain circumstances (eg, chronic cavitary coccidiomycosis or systemic reinfection associated with ventriculoperitoneal shunt placement. Methods of IgM detection are as follows:
- Additional assays to detection of C immitis infection are as follows:
- The urine coccidioidal antigen enzyme immunoassay was developed after cross-reactivity with the histoplasmosis urinary antigen was observed. It is useful in detecting urinary coccidioidal antigen in immunocompromised patients, but its utility in immunocompetent patients is unknown.3
- Polymerase chain reaction (PCR) assay is used to detect a target gene after DNA extraction from biopsy specimens. The utility of PCR in clinical situations is under investigation.4
- Coccidioidin and Spherulin skin tests are no longer available.
Imaging Studies
Chest radiography
The main findings on imaging can be seen on a plain chest radiograph. Typical findings found in previously described clinical syndromes are presented.
- Primary pulmonary coccidioidomycosis
- Asymptomatic patients may have a normal chest radiograph or may have residual abnormalities of a previous infection. Findings include parenchymal scarring, pleural thickening, calcified and uncalcified nodules, and lymph nodes. Calcifications occur in the minority (<15%) of lesions.
- Findings in asymptomatic patients include infiltrates (lobar, segmental, or subsegmental) indistinguishable from those seen with acute pneumonia.
- Hilar adenopathy is uncommon in bacterial pneumonia but is seen in approximately 20-25% of patients. The constellation of an infiltrate and adenopathy in a patient from an endemic area should raise suspicion for coccidioidal pneumonia. Paratracheal or mediastinal adenopathy can also be seen, and its appearance is often a precursor to disseminated disease.
- Pleural effusions can be seen in 5-15% of patients, more often left sided, transudative, and eosinophilic on analysis.
- Empyema can also occur, with diagnosis confirmed with thoracentesis.
- Bronchopleural fistulas and secondary spontaneous pneumothoraces have also been reported.
- Diffuse pneumonia is unusual and may represent a large inhalation of arthrospore or severe underlying immunodeficiency. Findings may suggest acute respiratory distress syndrome or a miliary pattern with multiple, small, bilateral nodular densities. This pattern is also seen in disseminated disease.
- Chronic pulmonary coccidioidomycosis
- Most primary coccidioidal infection resolves spontaneously, but approximately 5% of patients may develop pulmonary disease that persists beyond 3 months.
- Dense segmental and lobar consolidation, unifocal or multifocal, sometimes bilateral with cavitary regions, are the most common findings on imaging.
- Findings may resemble those seen in pulmonary tuberculosis, with associated infiltrates and fibrosis.
- Bronchiectasis may be seen in 1-2% of patients.
- Pulmonary nodules
- This is one of the most common findings on imaging and usually represents the evolution of the infiltrate to a nodule.
- Nodules can be solitary or multiple, more often in the upper lobes and usually 1-2 cm. Rarely, nodules can be as large as 6 cm.
- Calcification is uncommon, occurring in less than 15% of cases.
- Nodules may have the typical appearance of a granuloma, with smooth, well-circumscribed edges, but they can be indistinguishable from a malignant lesion.
- CT imaging may provide better definition of the nodule.
- Fluorodeoxyglucose positron-emission tomography (FDG-PET) scans may demonstrate intense uptake in nodules, similar to malignancy, but uptake may also be mild.
Coccidioidomycosis nodule, left upper lobe.
- Cavitary pulmonary coccidioidomycosis
- Cavities develop as a result of central necrosis in the granulomas or areas of consolidation.
- Cavities may be thin walled or thick walled and are seen more often in the lung apices.
- A solitary, thin-walled cavity is a common residual finding of coccidioidal infection.
- Many thin-walled cavities on plain chest radiographs are actually thick-walled cavities when visualized on CT scans.
- Cavities smaller than 2.5 cm often spontaneously resolve. Large cavities (>5 cm) may persist and be subject to hemorrhage (hemoptysis), colonization with Aspergillus (mycetoma), and pneumothorax.
Thin-walled coccidioidomycosis cavity, right upper lobe.
- Disseminated pulmonary coccidioidomycosis
- Diffuse, bilateral, small nodular densities reminiscent of miliary tuberculosis can be seen in patients with overwhelming disease, either as a result of hematogenous or endobronchial spread.
- Mediastinal adenopathy is often seen as bulky paratracheal adenopathy. This is often seen in patients who are eventually diagnosed with disseminated coccidioidomycosis.
- Other manifestations seen in thoracic imaging include an enlarged cardiac silhouette representing pericardial involvement and a pericardial effusion.
Coccidioidomycosis, bilateral mediastinal adenopathy.
Chest CT scanning
All of the findings seen on chest radiographs can be better visualized on a chest CT scan. Chest CT scanning better defines some abnormalities that may be suggested by plain chest radiography. Examples are as follows:
- Airway disease - Endotracheal or endobronchial coccidioidal granulomas
- Mediastinal adenopathy (paratracheal and mediastinal)
- Pericardial disease
- Pulmonary nodules
- Cavitary disease and pneumatoceles
- Mycetomas residing in chronic cavities
- Pleural effusion and empyema
- Hydropneumothorax
- Bronchiectasis
Coccidioidomycosis nodule, left upper lobe
Thin-walled coccidioidomycosis cavity, right upper lobe.
Chronic coccidioidomycosis pneumonia, lingula.
Chronic persistent coccidioidomycosis cavity, left upper lobe.
Other Tests
- Head CT scanning or brain MRI
- Basilar meningeal enhancement is typical of coccidioidal meningitis.
- Obstructing hydrocephalus may be seen and is the initial sign of meningeal involvement.
- Cerebral infarctions can also be seen in coccidioidal meningitis.
- Bone scanning: This scan is sensitive for identifying sites of dissemination (eg, skull, hands, feet, spine, tibia).
- FDG-PET scanning
- FDG-PET scanning can help identify areas of active coccidioidal infection. Intense diffuse uptake is seen in patients with disseminated coccidioidomycosis.
- Solitary nodules may have uptake indistinguishable from malignancy.
- Long-standing granulomas may have little or no uptake.
Procedures
- Bronchoscopy
- Bronchoscopy is a useful diagnostic procedure in suspected coccidioidal infection if results from other studies (sputum, serologies) are not diagnostic.
- Bronchoscopy may be able to double the yield (compared with sputum) in patients with parenchymal infiltrates and cavitary lesions. In one small series, bronchoscopy established a diagnosis of coccidioidal infection in almost 70% of these cases.5
- Bronchoscopy is especially useful in patients with tracheal or endobronchial coccidioidal infection, in whom the appearance of lesions can range from erythematous plaques to submucosal nodules to endobronchial masses and diagnosis is established histologically or from culture.
- Bronchoscopy has a very low yield in solitary pulmonary nodules secondary to coccidioidomycosis and is not recommended in these patients.
- Transthoracic needle biopsy
- Peripheral solitary pulmonary nodules secondary to coccidiomycosis are especially amenable to diagnosis by percutaneous transthoracic needle biopsy.
- Most percutaneous transthoracic needle biopsies are CT guided, which allows direct visualization of the needle into the lesion.
- Specimen fungal stains demonstrating spherules or culture growing C immitis are diagnostic.
- Cytology of the specimen should be obtained to rule out malignancy.
- Thoracentesis
- The typical effusion is exudative and lymphocytic with modest eosinophilia.
- Pleural fluid cultures have a low yield, with isolation of C immitis in less than 20% of patients.
- Pleural biopsy
- Closed pleural biopsy may be diagnostic in patients with coccidioidal pleural effusions.
- Identification of spherules infiltrating the pleural is diagnostic.
- Culture of pleural biopsy specimens has the highest yield, with isolation of C immitis of in all cases in one small series.
- Lumbar puncture
- Typical findings in coccidioidal meningitis are an elevated white blood cell count, high protein, and low glucose.
- Measurement of cerebrospinal fluid (CSF) CF titers establish the diagnosis of coccidioidal meningitis.
- Elevated CSF CF titers can also be seen with isolated epidural coccidioidal involvement, but only the CSF total protein value is elevated in that situation.
- False-positive CSF CF titers are rare, but they can occur in patients with very high serum CF titers and no meningeal involvement.
- Rarely, the CSF CF titer can be positive with negative serum CF titers in patients with meningitis as their only site of coccidioidal infection.
- Surgical biopsy
- This may be required if the diagnosis cannot be established using the aforementioned approaches.
- Surgical biopsy is best suited for sampling lymph nodes or parenchymal lung disease.
- Cervical mediastinoscopy can access most mediastinal lymph nodes and video-assisted thoracoscopy can be used to obtain parenchymal lung tissue.
Histologic Findings
Spherules can be seen in tissue specimens using standard stains such as hematoxylin and eosin or Papanicolaou stains. Other useful stains include periodic acid-Schiff stain (PAS) or Gomori methenamine silver stain.
Staging
Staging is not applicable to coccidioidal infections.
More on Coccidioidomycosis |
| Overview: Coccidioidomycosis |
 Differential Diagnoses & Workup: Coccidioidomycosis |
| Treatment & Medication: Coccidioidomycosis |
| Follow-up: Coccidioidomycosis |
| Multimedia: Coccidioidomycosis |
| References |
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Further Reading
Keywords
coccidioidomycosis, coccidioides infection, coccidioidal infection, cocci infection, coccidioidal pneumonia, coccidioidal lung infection, San Joaquin Valley fever, valley fever,
