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Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS), with an estimated 2.3 million people being affected globally, and is a major cause of permanent disability. About 90 % of the affected patients with MS have relapsing-remitting type. Fingolimod became the first FDA approved oral drug in 2010 with an i...
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Context 1
... tomography (CT) of the head revealed periventricular hypodensities unchanged from previous imaging studies. Magnetic resonance imaging (MRI) of the brain revealed multiple non-enhancing lesions in cerebral white matter consistent with MS and unchanged from previous MRI obtained 3 months before this presentation ( Figs. 1 and 2). ...
Citations
... We obtained the data of 25 individuals (from a total of 24 case reports) with herpes viral and cryptococcal infections associated with fingolimod and siponimod treatment (Table 3) (Patil et al., 2020;Carpenter et al., 2017;Gross et al., 2012;Dahshan et al., 2021;Harirchian et al., 2020;Muccilli et al., 2019;Hagiya et al., 2016;Kaur et al., 2020;Wienemann et al., 2020;Cuascut et al., 2019;Ma et al., 2020;Chong et al., 2019;Pham et al., 2017;Anene-Maidoh et al., 2017;Seto et al., 2016;Ward et al., 2016;Forrestel et al., 2016;Achtnichts et al., 2015;Huang, 2015;Issa and Hentati, 2015;Pfender et al., 2015;Uccelli et al., 2011; Key Safety Topics -Infections -Cryptococcal Meningitis 2021; Ratchford et al., 2012). Patients were mostly female (M: F: 11:14). ...
Sphingosine-1-phosphate (S1P) receptor modulators are a new class of oral disease-modifying therapies used for Multiple Sclerosis (MS). These are immunomodulatory drugs and can thus increase the risk of certain infections in these patients. This paper summarizes the existing data on the most common opportunistic infections associated with the drugs in this class: Varicella Zoster Virus (VZV), Herpes Simplex Virus (HSV), and Cryptococcus neoformans. A literature review and descriptive analysis of reported cases and clinical phase III study findings on the incidences of these infections were conducted using PubMed and Google Scholar. Results regarding fingolimod, siponimod, ozanimod, and ponesimod were obtained. Overall, the incidence of these infections was found to be extremely low in MS patients treated with S1P receptor modulators. Among the four drugs in this class, the incidence rates of VZV, HSV, and cryptococcal infections were either similar or slightly higher than placebo, with some infections not reported in cases of ozanimod and ponesimod. Most of these resulted in favorable outcomes, with very few disabilities or fatalities. However, this paper highlights the increasing relevance of assessing infectious risk factors to promote the early identification of serious complications related to these drugs. Opportunistic infections should be considered in the differential diagnosis of an MS relapse in the setting of disease-modifying treatment.
A 21-year-old woman with multiple sclerosis (taking regular fingolimod) developed sudden-onset severe headache with nausea and malaise. Neurological examination was normal and she was afebrile. Blood results showed lymphocytes 0.53 x 109/L and C reactive protein 19 mg/L. CT scan of head and venogram were normal. CSF showed an opening pressure of 33 cm H2O and an incidental light growth of Cryptococcus neoformans, confirmed with positive India Ink stain and a positive cryptococcal antigen (1:100). She was treated for cryptococcal meningoencephalitis with amphotericin and flucytosine. Her presenting symptoms had closely mimicked subarachnoid haemorrhage. This atypical presentation of cryptococcal CNS infection highlights the need for vigilance in immunosuppressed patients.
Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.
Being introduced in 2010, fingolimod was among the first oral therapies for relapsing multiple sclerosis (MS). Since that time, postmarketing surveillance has noted several case reports of various cryptococcal infections associated with fingolimod use. To date, approximately 15 such case reports have been published. We present the first and unique case of cryptococcal chest wall mass and rib osteomyelitis associated with fingolimod use. The patient presented with left-side chest pain and was found to have a lower left chest wall mass. Computerized tomography (CT) showed chest wall mass with the destruction of left 7th rib. Aspirate from the mass grew Cryptococcus neoformans. The isolate was serotype A. Fingolimod was stopped. The patient received liposomal amphotericin B for 2 weeks and started on fluconazole with a plan to continue for 6–12 months. The follow-up CT in 6 weeks showed a marked decrease in the size of the chest wall mass. In conclusion, our case highlights the atypical and aggressive form of cryptococcal infection possibly related to immunosuppression from fingolimod use.
Introduction
The important development that the multiple sclerosis (MS) treatment field has experienced in the last years comes along with the need of dealing with new adverse event such as the increase risk of infections. In the shared therapeutic decision-making process, the MS expert neurologist should also balance the risks of specific infections under each particular treatment and be familiar with new mitigation strategies.
Areas covered
In this review, the authors provide an up-to-date review of the infection risk associated with MS treatments with a specific focus on risk mitigating strategies. The search was conducted using Pubmed® database (2000 – present) to identify publications that reported infection rates and infection complications for each treatment (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, cladribine, natalizumab, alemtuzumab, rituximab, and ocrelizumab).
Expert opinion
Since the emergence of the first natalizumab-related PML case, the arrival of new MS therapies has come hand in hand with new infectious complications. MS-specialist neurologist has to face new challenges regarding the management of immunosuppression-related infectious complications. The implementation of patient-centered management focus on preventive and mitigating strategies with a multidisciplinary approach should be seen in the future as a marker of excellence of MS management.
