MD University of Iowa hospital and clinics, United States
Introduction: Fingolimod is an immunomodulatory agent used for treatment of relapsing forms of Multiple sclerosis (MS). A recent PubMed literature review revealed only 10 cases of Crypococcus neoformans (CN) infection in patients on fingolimod. We present a case of CN meningitis in a patient with MS on Fingolimod.
Description: 25 y/o female with history of MS, on fingolimod, was admitted with a month of progressive headache and altered mental status. MRI brain revealed stable MS. Lumbar puncture (LP) revealed pleocytosis and hypoglycorrhachia. Meningitis panel revealed PCR positive for CN. CSF CN PCR antigen titer was 1:160. CSF culture revealed CN. HIV test was negative. Fingolimod was stopped and Liposomal amphotericin B and Flucytosine were started. Multiple therapeutic LPs were performed, to monitor for treatment efficacy, to check the opening pressures and to help with headaches. An episode of loss of consciousness with tonic posturing and eye roll was observed but EEG did not reveal any evidence of seizure activity. Reimaging revealed extensive meningeal enhancement in supra and infratentorial brain parenchyma, flattening of bilateral optic discs, and multiple foci of nodular enhancement throughout cervical and thoracic cord, suspected due to Immune reconstitution inflammatory syndrome (IRIS). In the setting of recurrent headaches, need for LPs, and worsening intracranial hypertension (ICH), 3% saline was started with a goal Na 145-155. An external ventricular drain (EVD) was placed by neurosurgery. Steroids were started for suspected IRIS. Patient's symptoms improved. EVD was clamped and later removed. Patient was discharged on Ocrelizumab for MS management and consolidation therapy with fluconazole and flucytosine.
Discussion: Fingolimod can increase the risk of Cryptococcus (CN) infection. CN primarily presents with fever, malaise, headaches, neck stiffness, photophobia, and lethargy. Severe cases may lead to coma or death. Diagnosis requires cryptococcal serum antigen, neuroimaging prior to LP to rule out ICH or CNS mass lesions. Lumbar punctures with India ink, culture, and PCR on CSF are essential. Treatment involves liposomal amphotericin B with flucytosine for 2 weeks, followed by fluconazole. Monitor for complications like IRIS, especially if immunosuppressant medication is stopped.
