Sporotrichosis in the Central Nervous System Caused bySporothrix brasiliensis

TO THE EDITOR—The metropolitan region of Rio de Janeiro is hyperendemic for catassociated sporotrichosis, and Sporothrix brasiliensis has been implicated in the majority of cases in this region. A unique clinical profile has been characterized by disseminated cases in nonimmunosuppressed patients, hypersensitivity reactions, and an increase in the number of patients with human immunodeficiency virus (HIV), with a higher incidence of severe disseminated cases, hospitalizations, and deaths [1, 2]. From January 1999 through March 2013, 3618 adult patients were diagnosed with sporotrichosis at the Instituto Nacional de Infectologia Evandro Chagas/ Fundação Oswaldo Cruz, the main referral center for the treatment of this mycosis in Rio de Janeiro State. Among these patients, 48 were coinfected with HIV, and the disseminated or disseminated cutaneous forms were present in the majority of these patients (58.3%), in contrast with the localized forms (lymphocutaneous or fixed cutaneous [41.7%]) [2]. The first patient with sporotrichosis and HIV coinfection had meningitis; since that first diagnosis, all patients with disseminated sporotrichosis have undergone a lumbar puncture to exclude central nervous system (CNS) invasion. Furthermore, the remaining 3 patients had fungus present in the cerebrospinal fluid (CSF). All but 1 patient was male, and the median CD4 cell count was 104/μL. Sporothrix brasiliensis was identified using T3B polymerase chain reaction fingerprinting [3]. Patients had skin lesions and developed subacute meningoencephalitis during the infection. Two patients died due to hydrocephalus complications. One patient presented with Cryptococcus neoformans coinfection of the CNS and died of complications that were not related to sporotrichosis. The first diagnosed patient is still alive 16 years after the onset of sporotrichosis. Three of these cases have been previously reported [4, 5]. CNS involvement in sporotrichosis, although rare, has been previously described in immunosuppressed patients, particularly within recent decades due to the HIV pandemic. When we analyzed this cohort of HIV-infected sporotrichosis patients, we found a considerable number of patients with disseminated forms of the disease, in whom S. brasiliensis was found in the CSF (14.3%). In a murine model, S. brasiliensis was the most virulent member of the Sporothrix schenckii complex, with dissemination to different organs including the CNS [6]. Sporothrix brasiliensis produces large amounts of urease and melanin, which are virulence factors that can promote penetration into tissues and evasion from the immune system [7]. We propose that S. brasiliensis, similar to what has been observed in C. neoformans infection, is neurotropic in humans, although the mechanisms implicated in CNS invasion and persistence are not yet completely understood [8, 9]. These findings highlight the potential aggressiveness of S. brasiliensis in immunosuppressed patients, particularly patients with HIV and advanced disease. CNS involvement is challenging to treat and is associated with a worse prognosis because its sterilization is difficult. In areas where HIV and sporotrichosis overlap, physicians should be aware of this potentially disastrous association and should perform an early lumbar puncture to aggressively treat CNS disease. Close follow-up of patients is necessary in order to document CSF sterilization, and alternative treatment strategies, such as novel azoles and combination therapy, may be considered.