BI26 Primary cutaneous cryptococcosis in the context of fingolimod-induced lymphopenia: a case report and scoping review to inform preventive monitoring strategies

Abstract

Fingolimod is an oral therapy for relapsing–remitting multiple sclerosis (MS). It suppresses focal inflammatory activity by binding to sphingosine-1-phosphate receptors, causing lymphocyte sequestration within lymphoid tissues. This results in relative peripheral lymphopenia and increases the risk of opportunistic infections such as cryptococcosis. To our knowledge, we present the first reported case of cutaneous cryptococcosis associated with fingolimod use in the UK. We also review the published literature on fingolimod-associated cryptococcosis. We report the case of a 34-year-old man with relapsing–remitting MS who had remained clinically stable on fingolimod monotherapy for 5 years and presented with a nonhealing, indurated erythematous lesion with a warty surface on the left forehead. Diagnostic evaluation included skin biopsy, fungal culture and immunological investigations. A scoping review was undertaken using a systematic search of PubMed, ScienceDirect and Google Scholar to identify published cases of fingolimod-associated cryptococcosis from 2020 onwards to capture recent cases. Following screening and eligibility assessment, 21 unique case reports were included for analysis. Investigations confirmed Cryptococcus neoformans infection with marked CD4 lymphopenia. Fingolimod was discontinued due to severe lymphopenia and opportunistic infection, and the lesion resolved following oral fluconazole therapy with co-trimoxazole prophylaxis over 2 months. Across the identified cases in the literature, C. neoformans infection occurred after variable durations of fingolimod exposure, ranging from 3.75 to 12 years (median 6). While our case involved isolated cutaneous disease, central nervous system involvement with meningoencephalitis was the most commonly reported manifestation. Most cases demonstrated profound CD4 lymphopenia, frequently below 0.1 × 109 cells L−1. Fingolimod-associated cryptococcosis, including rare cutaneous manifestations, represents a serious complication of long-term therapy and is strongly associated with profound CD4 lymphopenia. These findings emphasize the critical need for vigilance and routine monitoring of CD4 lymphocyte subset counts to facilitate early diagnosis and timely intervention.