ANSWER
Coccidioidomycosis: Cultures of the biopsy samples grew Coccidioides immitis. In addition, a coccidioidomycosis immunoassay revealed a complement fixation (CF) titer of 1:128, with positive immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies.
Coccidioidomycosis (commonly referred to as “valley fever ”) is a fungal infection caused by inhalation of the spores of C immitis, a fungus endemic to the semi-arid areas of the southwest United States, particularly central California, Arizona, parts of Texas, and Mexico. Epidemiologic studies show that approximately 50-60% of patients experience no symptoms, whereas approximately 40% develop cold- or flu-like symptoms; these symptoms often resolve without treatment. About 10% develop pulmonary disease. A small percentage of patients develop disseminated disease, usually with involvement of the skin, the bones, and the central nervous system (CNS), though case reports have described involvement of almost every organ system. Less than 1% of patients experience CNS involvement, which is associated with the greatest morbidity and mortality and is generally fatal without treatment; these patients frequently require lifelong treatment. The risk factors for complication include the extremes of ages, any immunocompromised state (HIV, immunosuppressant use, cancer), and the third trimester of pregnancy. African Americans and Filipinos have the greatest risk of developing dissemination, whereas whites have the lowest risk.
The clinical manifestations of coccidioidomycosis depend on the organs involved. On clinical examination, patients who live in endemic regions or who have traveled to endemic regions may present with insidious symptoms of cough, fever, chills, night sweats, weight loss, myalgia, and fatigue. Patients may also present with a rash, bone pain, and/or meningeal symptoms. Erythema nodosum, seen in about 25% of patients, is considered a good prognostic marker.
The diagnosis is often made by performing a serologic test (a coccidioidomycosis panel, which is an enzymatic immunoassay). The CF titer indicates the severity of infection. Titers of 1:32 or greater should be followed by bone scanning and lumbar puncture to evaluate for dissemination. Chest radiographs may show a simple lobar pneumonia, multilobar involvement, cavitary lesions, empyema, or effusion. Bone involvement should be evaluated with bone scanning or magnetic resonance imaging (MRI). Meningeal symptoms can be evaluated by performing a lumbar puncture and examining the cerebrospinal fluid (CSF). If imaging of the brain is considered, MRI is more sensitive than computed tomography (CT) for detecting lesions. Biopsy samples of associated lesions can grow in almost any culture medium, and any sample suspected of being positive should be appropriately labeled as a biohazard.
In general, a mild infection does not require treatment. A moderate infection may be treated with either fluconazole or itraconazole. Moderate-to-severe infection may warrant treatment with amphotericin. Itraconazole is thought to have better bone penetration, whereas fluconazole has better CNS penetration. Surgical intervention is required in certain cases, such as those with bony involvement or progressive pericardial effusion. Newer pharmacologic agents, including voriconazole and posaconazole, are also being investigated for patients who have progressive disease resistant to standard therapy.
The prognosis for uncomplicated disease is good. After the infection resolves, the individual has lifelong immunity to repeat infection. In cases of complicated and/or disseminated disease, patients may have substantial morbidity, depending on the areas of involvement. Although no practical methods of prevention are available, there are vaccines currently undergoing clinical investigation.
The patient in this case was initially placed on fluconazole at 800 mg/day. Because of the presence of high titers, as well as systemic symptoms, further workup was performed to evaluate for systemic involvement. The findings from chest radiographs and a lumbar puncture were unremarkable. A bone scan, however, showed multiple areas of increased uptake in the facial bones and the right clavicle, in several vertebral bodies, and in both hips. The diagnosis of disseminated coccidioidomycosis was made. With input from an Infectious Disease specialist, the dosage of fluconazole was increased to 1200 mg/day and the patient was kept in the hospital for several days. Eventually, the systemic symptoms resolved and the patient was discharged to home on continuing oral fluconazole therapy and close followup.
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