Abstract
Opportunistic fungal infections are a rare complication of immunomodulatory therapy for multiple sclerosis1,2. We report the first case of cryptococcal meningitis with siponimod therapy. A 61 year old man presented with a deterioration in gait over one month, with a new non-enhancing lesion in the left dentate nucleus on MRI, mimicking disease progression. Lumbar puncture revealed a normal opening pressure despite CSF pleiocytosis with 18 mononuclear cells per mL and a raised protein of 0.74 g/L. Microscopy showed 2+ yeast cells consistent with a Cryptococcus species, with the titre of cryptococcal antigen in CSF and serum greater 1 in 1024. Induction anti-fungal therapy was commenced with intravenous amphotericin followed by oral fluconazole. Siponimod therapy was stopped and his peripheral lymphocyte returned to greater than 1.0 per mL within 14 days. Despite high fungal load and rapid normalisation of the lymphocyte count, throughout his treatment course he remained afebrile with no symptoms of raised intracranial pressure to suggest immune reconstitution inflammatory syndrome (IRIS). He remains well at follow-up 9 months after diagnosis. This case highlights the need to maintain a high index of suspicion for alternative aetiologies when evaluating a patient with MS who presents with progressive neurological symptoms, especially with the breadth of treatment options and rising numbers of older patients at risk of immunosenescence.
