DIAGNOSIS: Coccidioidal granulomatous meningitis and abscesses
Coccidioides immitis is a diphasic and multimorphic fungus with a hyphal/arthroconidial "saprobic" phase in nature and in routine culture, and a spherule/endospore "parasitic" phase in human tissues (1). It grows in soil, which is often sandy and alkaline, and is endemic to the southwestern United States- principally, California, Arizona, and Texas- and also to Mexico and Central and South America, where the climate is defined as arid to semi-arid with hot summers, few winter freezes and low rainfall (1-4). Cases have recently been discovered outside the traditional areas, suggesting the endemic area may be wider than originally described (2). Coccidioidomycosis is characterized by four different types of clinical forms: pulmonary (asymptomatic or symptomatic), disseminated, residual pulmonary and primary cutaneous (i.e. direct skin inoculation). Primary infection with C. immitis is almost always inhalational, and accidental inhalation of airborne arthroconidia causes an estimated 100,000 infections annually, however up to two-thirds of infected persons have no symptoms or have a self-limited respiratory illness (2,4). An estimated 5% of patients with clinically apparent primary pulmonary coccidioidomycosis develop hematogenous dissemination beyond the lungs (1), which represents a serious public health threat. The most common sites of extrapulmonary disease include skin, lymph nodes, bones/joints, and central nervous system (CNS) (especially meninges) (1,2,4). The risk is higher among male, pregnant women, those with cellular immunodeficiencies and specific racial groups (particularly African American and Filipino) (1,2,4). In this case, the patient had been immunocompromised due to immunosuppression for the liver transplant and previously for her primary liver disease (autoimmune hepatitis), and diabetes mellitus. Interestingly, many patients, including our patient, with disseminated disease have normal chest radiographs, since dissemination occurs weeks to months after the initial infection, during which time the initial pulmonary disease has resolved (2).
CNS lesions in extrapulmonary disseminated coccidioidomycosis are universally fatal if untreated and are found principally in two forms; meningitis and pseudotumor (5). Of these, meningitis is much more frequent and is seen in 30% to 50% of all patients with dissemination (6,7). CNS involvement usually occurs shortly after exposure, although its recognition may be delayed (2). Meningitis usually involves the basilar portions of the brain (basilar meningitis) with prominent exudation, and a thick opaque membrane is formed, which frequently obstructs cerebrospinal fluid (CSF) flow or blocks CSF resorption, resulting in often hydrocephalus (8,9). This is known to be one of the major complications of coccidioidal CNS disease, which may require VP shunt placement, as seen in our patient.
Although approximately 40 cases of coccidioidal intracranial abscesses have been described in the literature (8), spinal coccidioidal abscesses are extremely rare and only a few cases have been reported. Most cases occurred as a result of an extension of a contiguous (vertebral) bone infection, causing spinal cord compression (7,10-12). There have been four cases of intradural spinal abscesses reported, including the current case, with no evidence of coccidioidal infection in the surrounding bones or any other extrameningeal tissue (8,13). All of the four cases had accompanying meningitis detected by MRI, and the two cases of them, including ours, had tissue biopsy confirmation and were extramedullary in localization (8). Intramedullary examples with tissue biopsy confirmation have not been described.
Microscopically, thick-walled spherules, ranging in size from 20 ¦Ìm to 150 ¦Ìm, are diagnostic of coccidioidomycosis and are best observed with GMS and PAS stains. The spherules are often filled with 3- to 5-¦Ìm endospores, which are released on rupture of the spherules. Histopathologically, there is a predominantly suppurative reaction to recently released endospores and a granulomatous reaction to maturing spherules. As seen in our case, the typical active lesions tend to have central suppuration and a surrounding granulomatous reaction (1). The hyphal forms, with or without formation of mature arthroconidia, are extremely rarely produced in a leptomeningeal granuloma of coccidioidomycosis (14). Hagman et al. reported 5 cases of CNS coccidioidomycosis with identifiable hyphal forms in the brain tissue or CSF and suggested that plastic foreign bodies, such as a VP shunt, may enhance hyphal growth in CSF, which may increase the risk of shunt malfunction (13), although no hyphal forms were identified in our patient with a VP shunt.
In conclusion, we present a 31-year-old, post liver transplant woman who presented with spinal (intradural extramedullary) coccidioidal granulomata and abscesses. Clinical suspicion was possible in this case based on the history of previous coccidioidal meningitis. Even without such history, coccidioidomycosis should be considered in the differential diagnosis of any mass lesion associated with leptomeningeal abnormalities in the spinal cord in a patient who is immunocompromised and lives in an endemic area, although it is relatively rare. In addition, not only communicating hydrocephalus but also mass (granuloma, abscess) formation should be included among the major complications of coccidioidal meningitis.
Contributed by Hidehiro Takei, M.D., J. Clay Goodman, M.D., Suzanne Z. Powell, M.D.