Disseminated cryptococcosis in a patient with multiple sclerosis treated with fingolimod

Multiple sclerosis (MS), a leading nontraumatic cause of neurologic disability,¹ is an inflammatory disorder involving autoreactive T cells attacking myelin sheaths in the CNS, resulting in demyelination and axonal loss. The development of disease-modifying therapies (DMTs) for MS has been remarkable in recent years. Many approved DMTs for MS are parenteral. Oral fingolimod^2,3 (Gilenya, Novartis, Basel, Switzerland) was approved by the US Food and Drug Administration (FDA) in 2010. Immunomodulation including sequestration of lymphocytes in the secondary lymphoid organs is the main proposed mechanism of action. In a phase 3 trial, rare but fatal viral infections were observed.² One patient with MS developed disseminated primary varicella-zoster virus infection. Another patient had herpes simplex encephalitis. Both patients received fingolimod 1.25 mg once daily, a dose that is higher than the currently FDA-approved dose. Although fingolimod at 0.5 mg once daily did not show increased infection incidence in individual trials that led to FDA approval, a recent analysis of pooled trial data demonstrated a relatively higher rate of varicella-zoster virus infections in patients treated with fingolimod 0.5 mg daily than in placebo recipients.⁴ Disseminated cryptococcosis is a rare opportunistic infection reported in immunocompromised individuals such as patients with AIDS.⁵ In this report, we describe a patient with MS who received fingolimod therapy and subsequently developed disseminated cryptococcal infection.