Cryptococcal meningoencephalitis in an IgG(2)-deficient patient with multiple sclerosis on fingolimod therapy for more than five years – case report

BACKGROUND: Fingolimod (Gilenya®), a first-in-class sphingosine-1-phosphate receptor modulator is approved for the treatment of relapsing-remitting multiple sclerosis. Fingolimod-induced selective immunosuppression leads to an increased risk of opportunistic infections such as cryptococcosis. So far, a total of 8 cases of fingolimod-related cryptococcal meningoencephalitis have been published. CASE PRESENTATION: A 49-year-old female with relapsing-remitting multiple sclerosis presented with cephalgia, fever, confusion and generalized weakness. She had been on fingolimod therapy for the past 5.5 years. Clinical examination suggested meningoencephalitis and laboratory findings showed an IgG(2) deficiency. Initially no pathogen could be detected, but after 4 days Cryptococcus neoformans was found in the patient’s blood cultures leading to the diagnosis of cryptococcal meningoencephalitis. After antimycotic therapy, her symptoms improved and the patient was discharged. CONCLUSION: MS patients on immunomodulatory therapy are at constant risk for opportunistic infections. Cephalgia, fever and generalized weakness in combination with fingolimod-induced lymphopenia should be considered a red flag for cryptococcosis.