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