Coccidioidomycosis

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]
  • 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