Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 36-04: Coccidioidomycosis + Key Features Download Section PDF Listen +++ +++ 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 + Clinical Findings Download Section PDF Listen +++ +++ 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) + Diagnosis Download Section PDF Listen +++ +++ 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 + Treatment Download Section PDF Listen +++ +++ 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) + Outcome Download Section PDF Listen +++ +++ 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 + References Download Section PDF Listen +++ + +Choi K et al. The utility of screening for coccidioidomycosis in recipients of inhibitors of tumor necrosis factor α. Clin Infect Dis. 2019 Mar 5;68(6):1024–30. [PubMed: 30084971] + +Gabe LM et al. Diagnosis and management of coccidioidomycosis. Clin Chest Med. 2017 Sep;38(3):417–33. [PubMed: 28797486] + +Galgiani JN et al. Executive summary: 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis. 2016 Sep 15;63(6):717–22. [PubMed: 27559032] + +Galgiani JN et al. Treatment for early, uncomplicated coccidioidomycosis: what is success? Clin Infect Dis. 2020 Apr 15;70(9):2008–12. [PubMed: 31544210] + +Jackson NR et al. Central nervous system infections due to coccidioidomycosis. J Fungi (Basel). 2019 Jun 28;5(3):E54. [PubMed: 31261704] + +Thompson GR 3rd et al. Current concepts and future directions in the pharmacology and treatment of coccidioidomycosis. Med Mycol. 2019 Feb 1;57(Suppl 1):S76–84. [PubMed: 30690601]