Fungus

Coccidioidomycosis

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Coccidioidomycosis, Coccidiomycosis, Coccidioides immitis, Coccidioides posadasii, Primary Pulmonary Coccidiomycosis, Valley Fever

  • See Also
  1. Fungal Lung Infection
  • Epidemiology
  1. Important opportunistic infection in southwestern US
    1. Most U.S. cases occur in Arizona (two thirds) and California (one third)
    2. International regions include Mexico, Central America and South America
  2. Incidence: 42.6 cases per 100,000 in endemic U.S. regions (2011)
    1. Incidence increased 7 fold in the prior 13 years (associated with expanding territory, warming climate)
  • Pathophysiology
  1. Fungal organism: Coccidioides immitis or Coccidioides posadasii
    1. Organisms are found growing normally in soil in endemic regions
  2. Transmission: Inhalation of airborne spores (when soil is disturbed)
    1. No known person-to-person or zoonotic spread
    2. No known transplacental transmission
    3. Rarely, Solid Organ Transplant has transmitted Coccidioidomycosis
  3. Incubation: Symptom onset 3 weeks after inhalation of spores
  4. Course
    1. Subclinical and spontaneous resolution in 50% of patients
    2. Lifelong immunity after first infection typically prevents recurrent infection with re-exposure
  5. Affected Organs
    1. Lung most commonly affected (similar to Pneumocystis)
    2. Presents as Community Acquired Pneumonia in endemic regions
  • Risk Factors
  1. Endemic region exposure within last 2 months (all cases)
  2. Dusty outdoor activities
    1. Agriculture
    2. Construction
    3. Archaeology
    4. Outdoor recreational activities (e.g. hiking)
    5. Correctional facilities
  3. Cellular Immune Deficiency
  4. Diabetes Mellitus
  5. Older adults
  6. Black or Filipino patients
  7. Pregnancy and postpartum (disseminated disease or complicated disease)
  • Symptoms
  1. General Symptoms (onset 1-3 weeks after exposure)
    1. Prolonged Fever
    2. Prolonged Fatigue
    3. Headache
    4. Night Sweats
    5. Weight loss
    6. Arthralgias
  2. Chest symptoms
    1. Productive cough
    2. Dyspnea
    3. Hemoptysis
    4. Pleuritic Chest Pain
  3. Rash
    1. Erythema Nodosum
    2. Erythema Multiforme
  • Signs
  1. Fever
  2. Cervical adenopathy
  3. Skin lesions
    1. Resemble Erythema Nodosum
  4. Lung
    1. Pleural Effusion
    2. Friction rub
    3. Pulmonary rales
  • Lab
  1. Sputum KOH
    1. Positive for fungal elements
  2. Complete Blood Count
    1. Eosinophilia >5%
  3. Blood complement-fixing antibodies
    1. Positive
  • Imaging
  1. Chest XRay (often normal)
    1. Pulmonary Infiltrates
    2. Hilar Adenopathy
    3. Pleural Effusion
    4. Empyema
  • Diagnosis
  1. Coccidioidomycosis Enzyme Immunoassay (EIA for IgG, IgM)
    1. Initial screening positive within 1-3 weeks of exposure
      1. IgM positive by the third week in 90% of patients
      2. Consider retesting if initially negative (esp. if immunosuppression or early test)
      3. IgM negative after 3 months of infection
    2. High Test Sensitivity but lower Test Specificity (False Positive risk)
  2. Coccidioidomycosis Immunodiffusion
    1. Confirms positive EIA test
    2. Immunodiffusion has greater Test Specificity for Coccidioidomycosis
  3. Other tests
    1. Coccidioidomycosis PCR is not typically used
  • Differential Diagnosis
  1. See Community Acquired Pneumonia
    1. Most patients are misdiagnosed as Bacterial Pneumonia on initial presentation
  2. Fungal Lung Infection
    1. Aspergillosis
    2. Blastomycosis
    3. Histoplasmosis
    4. Paracoccidioidomycosis
    5. Sporotrichosis
  3. Pneumonia
    1. Community Acquired Pneumonia
    2. Mycoplasma pneumonia
    3. Influenza Pneumonia
  4. Lung Abscess
  5. HIV Related infections
    1. Pneumocystis jiroveci (PCP Pneumonia)
    2. Cryptococcosis
  6. Tuberculosis
  7. Parasitic Infections
    1. Loeffler Syndrome
    2. Paragonimiasis
  8. Malignancy
    1. Lung Cancer
    2. Lymphoma
  9. Autoimmune Conditions
    1. Collagen Vascular Disease
    2. Eosinophilic Pneumonia
    3. Granulomatosis with Polyangiitis (formerly Wegener's Granulomatosis)
    4. Sarcoidosis
  • Management
  • General
  1. Uncomplicated cases (>50%) resolve spontaneously without Antifungal management
  2. Patient Education related to potential complications
    1. Return for persistent respiratory symptoms (Chronic Pulmonary Sequelae)
    2. Return for signs of disseminated disease findings (skin lesions, Joint Pain, atypical Headache)
  1. Indications
    1. Risk Factors for disseminated disease (see below)
    2. Clinically Significant disease
      1. Anti-coccidioides complement fixation Antibody titer >1:16
      2. Bilateral Pulmonary Infiltrates
      3. Pulmonary Infiltrates involving >1/2 of one lung
      4. Overall symptoms >2 months
      5. Fever >1 month
      6. Night Sweats >3 weeks
      7. Weight loss >10%
      8. Hospitalization
      9. Inability to work
  2. Approach
    1. Obtain initial Anti-coccidioides complement fixation Antibody titer
      1. Obtain repeat complement fixation every 1 to 3 months and continue for 2 years (from same lab)
      2. Titer >1:32 is associated with worse prognosis (including disseminated disease)
      3. Expect decreasing titer over time in response to Antifungal
    2. Obtain Chest XRay every 1 to 3 months
    3. Observe for disseminated disease and Meningitis
    4. Treatment course: 3 to 6 months up to 12 months or until complement fixation Antibody titers stabilize
  3. Children
    1. Fluconazole 6 to 12 mg/kg/day
  4. Non-Pregnant Adults
    1. Fluconazole 400-800 mg/day
    2. Itraconazole 200 mg twice daily
  5. Pregnancy
    1. Amphotericin B IV (esp. First Trimester)
    2. May consider Fluconazole instead of Amphotericin B in second and third trimesters
    3. Monitor complement fixation every 6-12 weeks
    4. Consider testing at initial Prenatal Visit in endemic regions
  6. Lactation
    1. Fluconazole 400-800 mg/day
  • Complications
  1. Pulmonary Granuloma
    1. May form with initial infection in immunocompetent hosts
    2. Granulomas may contain dormant, noncontagious endospores
      1. May later activate and disseminate if patient becomes immunosuppressed
  2. Chronic Pulmonary Sequelae (5-10%)
    1. Lung Nodules including cavitary Nodules
    2. Chronic fibrocavitary Pneumonia
  3. Meningitis
    1. Fatal without aggressive management
    2. Findings
      1. Frequent or atypical Headaches
      2. Altered Mental Status
      3. Meningismus
      4. Nausea or Vomiting
      5. Vision changes
    3. Management
      1. Life-long Antifungal therapy
  4. Extra-pulmonary Dissemination (1% within 2 years of initial infection)
    1. Bone, joint or soft tissue infection
    2. Risk Factors for dissemination
      1. Advanced Age
      2. Black or Filipino patient
      3. Diabetes Mellitus
      4. Pregnancy or peripartum
      5. Inflammatory rheumatic disease
      6. Immune deficiency
        1. Certain genetic mutations
        2. Hematologic Malignancy
        3. High dose Corticosteroids
        4. TNF Inhibitor
        5. Chemotherapy
        6. Lymphoma
        7. Status-post thymectomy
        8. Uncontrolled HIV Infection
  • Prevention
  1. Consider respirator use on construction sites in endemic regions
  • Resources
  1. Valley Fever (CDC)
    1. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/health-professionals.html
  • References
  1. Galgiani (2016) Clin Infect Dis 63(6): e112-46 +PMID:27470238 [PubMed]
  2. Herrick (2020) Am Fam Physician 101(4): 221-8 [PubMed]