Coccidioidal meningitis after liver transplantation in a nonendemic region: a case report.

Coccidioidomycosis is a fairly common diagnosis in immunocompromised individuals in endemic regions but may be underdiagnosed elsewhere. We report a case of coccidioidal meningitis diagnosed after liver transplantation in a nonendemic region (Northeastern United States) based on delayed seroconversion in the cerebrospinal fluid. Diagnosis was initially suggested by travel history and retinal lesions. The patient was treated successfully with fluconazole. This is a rare report of nonfatal coccidioidal meningitis after liver transplantation in a nonendemic region. A 42-year-old white man with a history of cirrhosis related to hepatitis C virus (genotype 2B), hemachromatosis (C282Y heterozygous), and alcoholism as well as diabetes mellitus underwent orthotopic liver transplantation (OLT). Computed tomography (CT) of the chest performed on day 9 after OLT for fevers revealed multiple bilateral small pulmonary nodules; a chest roentgenogram at the time of OLT was normal. Bronchoscopy with bronchoalveolar lavage was performed with negative bacterial, fungal, and viral studies; he was given 8 days of empiric treatment with fluconazole 100 mg po qD, and the fevers resolved. Nine weeks after OLT he returned with headache, nuchal rigidity, altered mental status, and temperature of 100.6°F. At the time of presentation, he was taking cyclosporine A (Neoral), atovaquone, famciclovir, interferon alpha, ribavirin, insulin, esomeprazole, thiamine, and folate. He had been on itraconazole 100 mg daily for 6 weeks after OLT to maintain his serum cyclosporine level; this had been discontinued 3 weeks prior to admission due to an elevated cyclosporine A level (622 ng/ml). Further historical data was not available due to the patient’s altered mental status. (Table 1) shows the abnormal cerebrospinal fluid (CSF) results. An MRI scan revealed multiple nonenhancing T2 hyperintense foci within the subcortical and periventricular white matter (Fig. 1A) and nonspecific T2 hyperintense signal within the central pons in triangular configuration. Chest CT showed significant reduction in the size of the pulmonary nodules. The patient was treated empirically for bacterial meningitis with ceftriaxone, ampicillin, and vancomycin. The lumbar puncture was repeated 3 days later, which showed an increased white blood cell (WBC) count and lymphocytic predominance (Table 1). On day 8, he had a grand mal seizure. Repeat lumbar puncture showed doubling of the WBC count with a markedly low glucose ( 20 mg/dl) and increased total protein; serum was sent for fungal serologic testing (including the coccidioidomycosis complement fixation test and coccidioidomycosis immunodiffusion test) to the Centers for Disease Control and Prevention. With worsening clinical and CSF parameters by day 12, he was begun on fluconazole (800 mg IV, then 400 mg IV per day) and antituberculosis therapy. His cyclosporine dose was reduced; interferon alpha and ribavirin were stopped. Subsequent CSF samples showed a reduction in the WBC count with negative Gram stains, fungal smears, acid fast smears, VDRL test, and PCR assays for herpes simplex virus, Bartonella, Mycobacteria, Varicella, Toxoplasma, and cytomegalovirus. Bacterial, fungal, and mycobacterial cultures as well as cryptococcal antigen assays of the blood and CSF were also negative. On day 13, a brain MRI revealed new irregular nodular enhancement along the superior surface of the posterior fossa contents, as well as nonspecific leptomeningeal enhancement filling the fissures of the superior vermis (Fig. 1B), suggesting granulomatous disease. A retinal exam showed multiple lesions suggestive of fungal disease (Fig. 1C). Antibacterial and antituberculosis treatments were stopped and fluconazole was continued. Subsequent information from his family confirmed that he had resided in Arizona for 16 years and