Disseminated coccidioidomycosis

A 79-year-old man with type 2 diabetes and neuropathy presented to a Minneapolis hospital with 3 months of headaches and right ankle redness, swelling and pain. MRI of the ankle showed bony erosions (figure 1). Ankle synovial fluid had 30 000 white blood cells/mm (93% neutrophils); synovial fluid culture was positive for Coccidioides spp., confirmed by DNA probe. Serum complement-fixing anti-Coccidioides antibodies were positive at a titre of 1:128. Brain MRI was unremarkable. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and an elevated CSF protein supporting a diagnosis of meningitis; CSF Coccidioides antigen, anti-Coccidioides antibody testing and fungal cultures were negative. Additional history revealed that the patient had spent winters in Arizona for a decade. We diagnosed the patient with ankle coccidioidomycosis and probable coccidioidal meningitis. He underwent a belowknee amputation for pain and loss of function. Histopathology of the talus bone showed granulomatous inflammation with endospore-filled spherules consistent with Coccidioides spp. (figure 2). Coccidioides spp. (C. immitis and C. posadasii) are dimorphic fungi endemic to the Southwest United States. Most coccidioidal infections are subclinical, and most clinical presentations are limited to pneumonia. Dissemination occurs in 0.5%–1.0% of cases and most commonly involves the skin, skeletal system and meninges. 2 Presumptive diagnosis of coccidioidomycosis can be made by detecting anti-Coccidioides antibodies; definitive diagnosis is confirmed by isolation of the organism or visualisation of endospore-filled spherules. 4 Our patient’s clinical and MRI findings led to an initial, inaccurate diagnosis of neuropathic arthropathy (Charcot). The isolation of Coccidioides spp. from synovial fluid culture and the visualisation of spherules in the talus bone established a definite diagnosis of coccidioidal arthritis with osteomyelitis. CSF testing for anti-Coccidioides antibodies and fungal culture lacks sensitivity. In contrast, a recent study suggests that Coccidioides antigen testing of the CSF has higher sensitivity. In our patient with definite ankle coccidioidomycosis, the new-onset headaches, laboratory evidence of meningitis with lack of an alternative diagnosis and the resolution of headaches with fluconazole 800 mg/day (past 2 years) support a diagnosis of probable coccidioidal meningitis despite his negative Coccidiodes-specific CSF studies. We plan to treat the patient with lifelong azole therapy as recommended for coccidioidal meningitis.