Epidemiology
Endemic Areas
- San Joaquin Valley
- Arizona
- Northern Mexico
- Limited Areas of Central and South America
Risk Factors
- Travel to Endemic Areas
- Increasing incidence (and severity) of coccidioidomycosis in older adults that travel to endemic desert areas during the winter months (“snowbirds”)
[Leake et al. J Infect Dis 2000; 181: 1435-1440]
- Increasing incidence (and severity) of coccidioidomycosis in older adults that travel to endemic desert areas during the winter months (“snowbirds”)
- Anti-TNF-alpha Therapy: 29 reported cases
- Incidence: infliximab (93% of reported cases) > etanercept (7% of of reported cases)
- There have been no reported cases of coccidioidomycosis with adalimumab
- All of the cases had concomitant use of immunosuppressives (corticosteroids or methotrexate)
- Almost all of the cases had a history of residence in an endemic area and presented with pneumonia-like presentation
- Only two of the published cases resulted in death
[Tsiodras S, Samonis G, Boumpas DT, et al. Fungal infections complicating tumor necrosis factor-alpha blockade therapy. Mayo Clin Proc 2008; 83:181-194]
[Bergstrom L, Yocum DE, Ampel NM, et al. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor-alpha antagonists. Arthritis Rheum 2004; 50:1959-1966]
(diabetes mellitus and rheumatalogic disease are not defined risk factors for coccidioidomycosis)
Risk Factors for Dissemination
- Filipino Race:
- Hispanic Race:
- Diabetes Mellitus: [Santelli, et al; Am J Med, 2006; 119:964-969]
Physiology
- Nearly all infections are acquired through inhalation of airborne arthroconidia (spores)
Diagnosis
CBC
- Peripheral eosinophilia (50% of cases)
Sputum GS/Cult+Sens:
- xxx
Pleural Fluid: exudate (see [[Pleural Effusion-Exudate]])
- pH:
- Glucose: usually >60 mg/dL
- Cell Count/Diff: lymphocyte-predominant
- Cultures: positive for C. Immitis in 20% of cases
- Cholesterol: elevated >55-60 mg/dL (seen in all exudates)
- Pleural: serum cholesterol ratio: elevated (seen in all exudates)
Pleural Biopsy
- Cultures are almost always positive
CXR/Chest CT Patterns:
- Pleural Effusion: 50% of cases with effusion have coexistent parenchymal disease/ effusion usually unilateral and >50% of hemithorax
- Alveolar Infiltrates:
- Lung Nodule: 0.5-3.0 cm round/ oval, sharply circumscribed solitary nodule/ upper-lobe predilection (may occur in anterior segment of upper lobes, unlike TB)/occasional calcification/ cavitation is common (thick or thin-walled cavities)
- Hydropneumothorax: occurs in cases where Cocci cavity ruptures into pleural space
- Diffuse Small Nodules: typical in disseminated Cocci in immunocompromised host
FOB-BAL
- Papanicolaou stain of sample could provide rapid diagnosis (Pap stain is superior to 10% KOH and Calcofluor White stain)
Coccidoidomycosis Skin Test
- xxx
Coccidoidomycosis Immunodiffusion (ID)
- Qualitative
- May be negative in HIV
Coccidoidomycosis Complement Fixation (CF) Test
- Confirmatory for Immunodiffusion
- Usually elevated in primary Cocci with effusion
- May be negative in HIV
PCR
- Not commercially available
LP:
- CSF Cultures: rarely positive, even in florid cases of Cocci meningitis
Blood c/s:
- Rarely positive, require several days for growth, and cultures are potentially hazardous for lab personnel
Bone Marrow c/s:
- Rarely positive, require several days for growth, and cultures are potentially hazardous for lab personnel
Clinical
Primary Coccidioidomycosis
- Interstitial Pneumonia (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])
- Alveolar Pneumonia-Like Syndrome (see Pneumonia, [[Pneumonia]])
- Fever
- Pleuritic chest pain
- Pleural Effusion (occurs in only 7% of cases) (see xxxx, [[Pleural Effusion-Exudate]])
- Upper Airway Involvement (see xxxx, [[Obstructive Lung Disease]])
- Unlikely to produce significant UA obstruction
- Erythema Nodosum or Erythema Multiforme (see Erythema Nodosum and Erythema Multiforme): these skin findings seen in 50% of cases
Chronic Cavitary Coccidioidomycosis (2% of cases)
- Multiple Cavities
- Hydropneumothorax (occurs in 1-5% of cases): due to rupture into pleural space
- Usually preceded by acute illness with systemic toxicity
Disseminated Coccidioidomycosis
- Arthritis (“Desert Rheumatism”) (see Arthritis, [[Arthritis]])
- Bone Lesions
- Coccioidal Meningitis (see Meningitis, [[Meningitis]]): confusion, delirium (meningeal findings are rare)
- Skin Ulcers
Treatment
Mild-Moderate Coccidioidomycosis (Pulmonary or Disseminated)
- Itraconazole 400 mg/day or Fluconazole 400 mg/day x 6-24 mo
- IV Itraconazole (limit use to 2 wks to avoid cyclodextrin nephrotoxicity/avoid with CrCl <30 ml/min)
- Alternative: Ketoconazole 400 mg/day x 6-24 mo
- Alternative: Amphotericin 0.7-1 mg/kg/day (to total dose 1-2 g)
Severe Coccidioidomycosis (Pulmonary, Disseminated, or Immunosuppressed Host)
- Amphotericin 0.7-1 mg/kg/day followed by Itraconazole 400 mg/day or Fluconazole 400 mg/day x 6-24 mo
- IV itra is available (limit use to 2 wks to avoid cyclodextrin nephrtoxicity/avoid with CrCl <30 ml/min)
- Alternative: Amphotericin 0.7-1 mg/kg/day (to total dose 2 g)
CNS Coccidioidomycosis
- Flucon 400-800 mg/day for life
- Alternative: Itraconazole 400 mg/day for life
- Alternative: intrathecal Amphotericin
Treatment of Primary Coccidioidomycosis (with or without pleural effusion)
- No treatment required (unless evidence of dissemination exists: negative Cocci skin test, etc.)
- High Cocci-CF titer alone does not mandate treatment
Treatment of Cavitary Coccidioidomycosis
- Chest Tube Drainage: indicated for hydropneumothorax (most cases will require thoracotomy with repair, lobectomy, and decortication)
- Antifungal Therapy: not required in these cases
Prevention
- Vaccine: in development
References
- Sarosi GA, Lawrence JP, Smith DK, et al. Rapid diagnostic evaluation of bronchial washings in suspected coccidioidomycosis. Semin Respir Infect 2001; 16:238-241
- Ampel NM. Coccidioidomycosis among persons with human immunodeficiency virus infection in the era of highly active antiretroviral therapy (HAART). Semin Respir Infect 2001; 16: 257-262
- Singh VR, Smith DK, Lawrence J, et al. Coccidioidomycosis in patients infected with human immunodeficiency virus: Review of 91 cases at a single institution. Clin Infect Dis1996; 23:563-568
- Tsiodras S, Samonis G, Boumpas DT, et al. Fungal infections complicating tumor necrosis factor-alpha blockade therapy. Mayo Clin Proc 2008; 83:181-194
- Bergstrom L, Yocum DE, Ampel NM, et al. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor-alpha antagonists. Arthritis Rheum 2004; 50:1959-1966