Coccidioidomycosis (Valley Fever)

Risk factors

• Residence in or travel to endemic areas
• Occupational dust exposure: construction, archaeology, agriculture, military training
• Pregnancy (third trimester and postpartum, especially for dissemination)
• African American or Filipino ethnicity (higher risk of dissemination)
• HIV/AIDS with CD4 <250 cells/microL
• Solid organ transplantation, TNF-alpha inhibitor therapy
• Diabetes mellitus (associated with chronic pulmonary disease)

Pathophysiology

Arthroconidia released from soil are inhaled and convert to large spherules containing endospores within tissue. Endospores rupture, releasing new endospores that propagate locally and may disseminate via lymphohematogenous spread. Cell-mediated immunity is critical for control. Defective Th1 response permits dissemination to skin, bones, joints, and central nervous system.

Clinical presentation

Differential diagnosis

• Community-acquired bacterial pneumonia — Acute onset, lobar consolidation, leukocytosis without eosinophilia; geography and exposure should prompt fungal serology in endemic areas
• Tuberculosis — Chronic cough, weight sweats, upper-lobe cavitation; AFB testing and Coccidioides serology may both be required
• Histoplasmosis — Different geography (Ohio/Mississippi valleys), bird/bat exposure, intracellular yeast on histopathology
• Sarcoidosis — Bilateral hilar adenopathy, non-caseating granulomas, elevated ACE; coccidioidomycosis can mimic on imaging
• Lung malignancy — Solitary pulmonary nodule; coccidioidomas mimic; biopsy or growth on imaging required to distinguish
• Eosinophilic pneumonia — Peripheral eosinophilia, infiltrates; rule out parasitic and drug causes; Coccidioides serology in endemic regions
• Erythema nodosum from sarcoid, IBD, or strep — Coccidioidomycosis is a classic infectious cause; serology in endemic exposure

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Inhaled arthroconidia<br/>SW US, dust exposure] --> B[Spherules in tissue]
  B --> C{Host response}
  C -->|Most| D[Asymptomatic /<br/>mild flu-like illness]
  C -->|Symptomatic 40%| E[Acute pulmonary<br/>fever, EN, arthralgias, eosinophilia]
  C -->|Immunocompromised,<br/>Filipino/AA, pregnancy| F[Dissemination]
  F --> G[Skin / bone /<br/>joint]
  F --> H[Meningitis<br/>basilar enhancement]
  E --> I[Observe or fluconazole<br/>3-6 mo]
  G --> J[Fluconazole >=12 mo]
  H --> K[Fluconazole 800-1200 mg<br/>LIFELONG]

Treatment

Complications

• Progressive pulmonary disease with cavitation, hemoptysis, or pyopneumothorax from cavity rupture
• Disseminated infection to skin, bones, joints, soft tissue
• Coccidioidal meningitis with hydrocephalus, stroke, and high mortality if untreated
• Reactivation in immunocompromised hosts
• Drug toxicity from prolonged azole therapy (hepatotoxicity, QT prolongation, alopecia)

PANCE pearls

• Peripheral eosinophilia in a patient with pneumonia and recent southwestern US travel is coccidioidomycosis until proven otherwise.
• Filipino and African American patients have a markedly higher risk of dissemination and CNS disease.
• Pregnancy in the third trimester is one of the strongest risk factors for dissemination.
• Coccidioidal meningitis requires LIFELONG fluconazole — relapse rate is approximately 80% if therapy is stopped.
• Solitary pulmonary nodules (coccidioidomas) often do not require treatment but must be distinguished from malignancy.

References

• IDSA 2016 — 2016 Infectious Diseases Society of America Clinical Practice Guideline for the Treatment of Coccidioidomycosis (Galgiani et al., Clin Infect Dis 2016)
• CDC — CDC — Valley Fever (Coccidioidomycosis): epidemiology, surveillance, clinical features