Coccidioidomycosis

Essentials of Diagnosis

• Acute infection: influenza-like illness, fever, backache, headache, fatigue and cough; erythema nodosum common

• Dissemination may result in meningitis, bony lesions, or skin and soft tissue abscesses

• Common opportunistic infection in patients with AIDS

• Chest radiograph findings vary from pneumonitis to cavitation

• Serologic tests useful; large spherules containing endospores demonstrable in sputum or tissues

General Considerations

• Consider this diagnosis in any obscure illness in a patient who has been in an endemic area

• Infection results from inhalation of Coccidioides immitis or Coccidioides posadasii; both are molds that grow in soil of southwestern United States, Mexico, and Central and South America

• Dissemination occurs in < 1% of immunocompetent persons, but mortality of disseminated disease is high

Demographics

• Disseminated coccidioidomycosis occurs in about 0.1% of white and 1% of nonwhite patients. Filipinos and blacks and pregnant women of all races are especially susceptible

• In endemic areas, coccidioidomycosis is a common opportunistic infection with risk for dissemination in individuals with AIDS

Symptoms and Signs

Primary coccidioidomycosis

• Incubation period is 10–30 days

• Symptoms, usually respiratory, occur in 40%

• Nasopharyngitis with fever and chills

• A common, though frequently unrecognized, cause of community-acquired pneumonia in endemic areas

• Arthralgias with periarticular swelling of knees and ankles

• Erythema nodosum can develop 2–20 days after symptom onset

• Persistent pulmonary lesions develop in 5%

Disseminated coccidioidomycosis

• Can involve any organ

• Productive cough

• Enlarged mediastinal lymph nodes

• Lung abscesses, empyema

• Complicated skin and bone infections

• Untreated in immunocompromised patients, fungemia with diffuse miliary infiltrates on chest radiograph and early death

• Meningitis in 30–50% and may result in chronic basilar meningitis

• Subcutaneous abscesses and verrucous skin lesions

• Lymphadenitis may progress to suppuration

• Higher incidence of miliary infiltrates, lymphadenopathy, and meningitis in patients with AIDS, but skin lesions are uncommon

Differential Diagnosis

• Histoplasmosis, cryptococcosis, nocardiosis, blastomycosis

• Sarcoidosis

• Pneumoconiosis, eg, silicosis

• Tuberculosis

• Upper respiratory tract infection

• Atypical pneumonia

• Lymphoma (including lymphocytic interstitial pneumonitis)

Laboratory Tests

• In primary coccidioidomycosis, moderate leukocytosis and eosinophilia

• IgM antibodies are positive in early disease

• In disseminated coccidioidomycosis, rising serum complement fixation titer (≥ 1:16); titers can be used to assess treatment adequacy

  • Complement fixation titer may be low in meningitis without other disseminated disease

  • In HIV-infected patients, complement fixation false-negative rate is as high as 30%

• Coccidioides antigen testing may augment CSF antibody testing

• In coccidioidal meningitis, cerebrospinal fluid (CSF) complement fixation antibodies are positive in > 90%. CSF shows increased cell count, lymphocytosis, and reduced glucose, and positive cultures are found in 30%

• Blood cultures are rarely positive

Imaging Studies

• Chest radiographic findings vary

  • Nodular and lobar upper lobe pulmonary infiltrates are most common

  • Hilar lymphadenopathy suggests localized disease

  • Mediastinal lymphadenopathy suggests dissemination

  • Pleural effusions

  • Lytic bone lesions

Medications

• For disease limited to the chest with no evidence of progression, symptomatic therapy

• For disease in the chest, bones, and soft tissues

  • Itraconazole, 400 mg orally daily divided into two doses or

  • Fluconazole, 200–400 mg, or higher, orally once or twice daily

  • Therapy must be continued for 6 months or longer after the disease is inactive to prevent relapse

  • Posaconazole may be beneficial in some patients with disease refractory to intraconazole, fluconazole, voriconazole

• For progressive pulmonary or extrapulmonary disease,

  • Intravenous liposomal amphotericin B until favorable clinical response and declining complement fixation titer

  • Oral azoles may be used for mild cases

• For meningitis,

  • High-dose oral fluconazole (400–800 mg/day or higher) is first choice

  • In cases refractory to fluconazole, some clinicians prescribe lumbar or cisternal intrathecal amphotericin B daily in increasing doses up to 1–1.5 mg/day

  • Systemic therapy with liposomal amphotericin B, 3–5 mg/kg/day intravenously, is generally given concurrently with intrathecal therapy but is not sufficient alone for the treatment of meningeal disease

  • Voriconazole or posaconazole may be alternatives to intrathecal amphotericin B in patients who do not respond to fluconazole

  • Once the patient is clinically stable, oral therapy with an azole, usually with fluconazole (400 mg/day) and given lifelong, is the recommended alternative to intrathecal amphotericin B therapy

  • Short-term systemic corticosteroids following cerebrovascular events associated with coccidioides meningitis may be beneficial

Surgery

• Surgical drainage is necessary for soft-tissue abscesses, necrotic bone disease, and complicated pulmonary disease (eg, rupture of a coccidioidal cavity)

Follow-Up

• Follow serum complement fixation titers, observe for a decrease during therapy

• Perform serial complement fixation titers after therapy; rising titers indicate relapse and warrant reinstitution of therapy

Complications

• Lung abscesses may rupture into the pleural space, producing empyema, and may extend to bones, skin, and occasionally pericardium and myocardium

• Cerebral vasculitis with stroke and hydrocephalus may complicate chronic meningitis necessitating CSF shunting

Prognosis

• Good for patients with limited disease

• Nodules, cavities, and fibrotic residuals may rarely progress after long periods of stability or regression

• Disseminated and meningeal forms have mortality rates exceeding 50% in the absence of therapy