Fingolimod and Cryptococcus: A Reminder of the Intersection between Immunomodulation and Infectious Disease

Background: The use of immunomodulatory and immunosuppressive therapies in multiple sclerosis (MS) has allowed practitioners to regulate disease activity. The use of these potent medications also comes with an understanding that patients may become susceptible to otherwise uncommon infections. The approval of fingolimod in 2010 presented the first oral option for relapsing MS. Since 2015, post-marketing safety data have reported five cases of cryptococcal meningitis and disseminated cryptococcosis developing in patients on fingolimod. We present another case of cryptococcal infection with the use of fingolimod in a 45-year-old man who was on the medication for approximately two years.

Objectives: Report a case of cryptococcal infection associated with fingolimod use and the therapeutic hurdles that follow.

Methods: We describe a recent case of pulmonary cryptococcosis with the use of fingolimod, the details of the clinical course, and therapeutic challenge to balance active multiple sclerosis and ongoing opportunistic infection. We use this to discuss the mechanism of action of fingolimod and its potential relationship to cryptococcosis susceptibility.

Results: A 45-year-old male with relapsing remitting MS, managed with interferon beta-1b before transitioning to fingolimod 2 years prior to presentation. He presented with progressively worsening dysphagia. Computed tomography (CT) of the chest revealed multiple pulmonary nodules. Serum cryptococcus antigen was 1:80 titer, and bronchoalveolar lavage fungal culture revealed rare Cryptococcus neoformans organisms. Cerebrospinal stains and cultures did not indicate cryptococcal neurological involvement. Fingolimod was discontinued, and a 12-month course of fluconazole was initiated. Despite no new clinical symptoms or signs, interim brain MRI revealed gadolinium enhancing lesions compatible with active demyelinating disease. Subsequently glatiramer acetate was initiated, with close clinical monitoring, including plans for frequent repeat neuroimaging.

Conclusions: This case adds to the literature documenting cryptococcal infections in patients using fingolimod and highlights the need to use efficacious disease-modifying therapies to treat demyelinating disease in patients with MS, while balancing risks associated with therapy. Prescribers and patients with MS need to be aware of the risks of opportunistic infections associated with disease-modifying MS therapies.