What is the diagnosis and treatment of coccidioidomycosis?

Diagnosis of Coccidioidomycosis

Serological testing is the primary diagnostic method for coccidioidomycosis, with most patients diagnosed via EIA, immunodiffusion, or complement fixation (CF) testing, though culture and histopathology provide definitive proof of infection. 1

Diagnostic Approach Algorithm

Initial Serological Testing

• Order serological testing in all patients with suspected coccidioidomycosis, looking for IgM antibodies (appear 1-3 weeks after symptom onset) followed by IgG antibodies (appear 4-8 weeks later) 1
• EIA, immunodiffusion, and CF testing are commercially available with varying sensitivity and specificity 1
• Important caveat: Serologic tests may be negative early in infection or persistently negative despite active disease, particularly in immunocompromised patients 1
• In HIV-infected patients with CD4+ counts <250 cells/µL, serologic tests are less frequently positive than in immunocompetent persons 1

Definitive Diagnostic Methods

• Culture from any clinical site proves the diagnosis - Coccidioides grows on routine blood agar and Sabouraud dextrose agar at 25-30°C, with mycelial growth visible as early as 4-5 days (hold cultures up to 6 weeks) 1
• Histopathology showing spherules or endospores is considered proven disease, even without positive culture 1
• Standard fungal stains (GMS, CFW, H&E, PAS) should be used on clinical specimens 1, 2
• In patients ill enough for hospitalization or with negative serology, culture of sputum or bronchoscopic specimens may provide more rapid diagnosis 1

Specialized Testing

• Coccidioidal antigen testing via EIA is available and particularly helpful in highly immunocompromised patients 1
• Recent studies suggest CSF antigen may be very sensitive in coccidioidal meningitis 1
• Nucleic acid amplification tests exist but are not yet commercially available 2

Essential Workup for All Diagnosed Patients

Baseline Assessment

• Obtain chest radiograph in all patients - look for dense infiltrates (often upper lobe), hilar or mediastinal adenopathy 1
• Quantitative CF testing should be performed and repeated approximately every 12 weeks during care to evaluate treatment response 1
• Document specific risk factors: immunosuppression status, pregnancy status (especially third trimester), African or Filipino ancestry, diabetes, cardiopulmonary comorbidities 1

Evaluation for Disseminated Disease

• Obtain CSF sample from all patients with sustained headache, altered mental status, unexplained nausea/vomiting, or focal neurologic deficits 1, 3
• CSF in meningitis shows low glucose, elevated protein, lymphocytic pleocytosis; CF antibody frequently detected in CSF (culture positive in <33% of cases) 1
• For suspected extrapulmonary lesions, tissue diagnosis via biopsy or needle aspiration is usually required - direct sampling is justified given management implications 1
• Blood cultures may be positive in patients with diffuse pulmonary disease but are positive in only a minority overall 1

Key Clinical Indicators Requiring Attention

Severity Markers Warranting Treatment

• Weight loss >10% 1, 4
• Night sweats >3 weeks duration 1, 4
• Infiltrates exceeding 50% of one lung or bilateral disease 1, 4
• CF titers ≥1:16 (equivalent to 1/32 or higher) 1, 4
• Symptoms persisting >2 months or ≥12 months 4, 3
• Prominent or persistent hilar adenopathy 4

Warning Signs of Dissemination

• Progressive headache or mental status changes 4
• New skin lesions (cutaneous involvement occurs in 15-67% of disseminated cases) 4, 5
• Joint pain/swelling or bone pain 4
• Critical point: 90% of persons with disseminated skin infection have other extrapulmonary sites, necessitating thorough investigation 5

Common Diagnostic Pitfalls

• Do not rely solely on CF antibody titers to diagnose disseminated disease - while higher titers correlate with dissemination in groups, individual variability is substantial and tissue diagnosis is usually required 1, 3
• Do not rule out coccidioidomycosis based on negative serology alone - antibody tests may remain negative despite active infection, especially early or in immunosuppressed patients 1
• Do not assume positive serology equals disseminated disease - any positive antibody test usually indicates recent or active infection, but tissue-destructive lesions require direct evidence 1
• In immunosuppressed patients (high-dose corticosteroids ≥20 mg/day for ≥2 weeks, TNF inhibitors, organ transplant recipients, HIV), maintain higher clinical suspicion as serologic responses may be blunted 1

Monitoring Strategy Post-Diagnosis

• Serial clinical assessments for 1-2 years are necessary to document resolution or identify complications early 3
• Follow pulmonary infiltrates to resolution with repeat imaging after initial infection 1
• Repeat quantitative CF testing every 12 weeks during active management 1