Abstract Details

Title Fingolimod related cryptococcal meningitis and immune reconstitution inflammatory syndrome in two patients with multiple sclerosis

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-011

Objective We report two cases of fingolimod associated cryptococcal meningitis while on fingolimod and subsequent central nervous system immune reconstitution inflammatory syndrome (CNS IRIS) after drug discontinuation.

Background Fingolimod is an immune suppressing medication for multiple sclerosis (MS) that sequesters lymphocytes in lymph nodes, and thereby reduces peripheral blood lymphocytes. Fingolimod associated lymphopenia occurs in 7% of patients. Fingolimod is associated with opportunistic infections, including an increasing number of cryptococcal meningitis cases. Few of these cases of been published, and risk factors have not been identified.

Design/Methods We reviewed records for multiple sclerosis patients managed on fingolimod at a university clinic who later developed cryptococcal meningitis.

Results Two women with fingolimod associated cryptococcal meningitis were identified, ages 40 and 48, with a mean duration of fingolimod treatment of 4.5 years. Both patients were lymphopenic at presentation (mean nadir of 207/µL). They presented with headache, fever, and altered mental status. Their MRIs had leptomeningeal enhancement. Spinal fluid analysis was notable for marked neutrophilic pleocytosis and elevated protein. Cryptococcus neoformans was identified on culture. Fingolimod was discontinued after the diagnosis. Both patients required a ventriculoperitoneal shunt for persistent elevation of intracranial pressure. They had clinical and radiological deterioration at mean 101 +/- 25 days after discontinuation of fingolimod despite continuing on antifungal therapy. They were diagnosed with CNS IRIS and had some improvement with steroids.

Conclusions Cryptococcal meningitis with fingolimod is rare but underreported. Risk may be higher with longer durations of therapy or lymphopenia. Prognosis is poor, and clinical deterioration should be closely monitored for hydrocephalus, relapsing infection, or CNS IRIS. The risk for recurrence with other immunotherapies is unknown. Prompt lumbar punctures for atypical symptoms, serum cryptococcal antigen screening, and CD4 monitoring may be needed for earlier identification.

Authors/Disclosures
Fernando X. Cuascut Lassus, MD PRESENTER	Dr. Cuascut Lassus has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Cuascut Lassus has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Cuascut Lassus has received personal compensation in the range of $500-$4,999 for serving as a Speaker with MSAA.
Steven R. Dunham, Jr., MD	Dr. Dunham has nothing to disclose.
George J. Hutton, MD, FAAN (Baylor College of Medicine)	Dr. Hutton has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Autoimmunity Biologic Solutions, Inc.. The institution of Dr. Hutton has received research support from Biogen. The institution of Dr. Hutton has received research support from Genentech. The institution of Dr. Hutton has received research support from Genzyme.

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