Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Case Report

A Case of Fingolimod-associated Cryptococcal Meningitis

Author(s): Ilad Alavi Darazam*, Mohammad Mahdi Rabiei, Omid Moradi, Farid Javandoust Gharehbagh, Mehrdad Roozbeh, Ramin Nourinia, Firouze Hatami, Maziar Shojaei and Legha Lotfollahi

Volume 20, Issue 4, 2022

Published on: 03 September, 2022

Page: [337 - 342] Pages: 6

DOI: 10.2174/1570162X20666220629124225

Price: $65

conference banner
Abstract

Background: Leukopenia, a rare adverse effect of Fingolimod therapy, paves the way for opportunistic infections. In this study, we reported rare fingolimod associated cryptococcal meningitis.

Case Presentation: A 39-year-old woman with RRMS was referred to the emergency department. The patient's major complaints were headache, fever, weakness, and progressive loss of consciousness within the last two days prior to the referral. The patient had a history of hospitalization due to RRMS [two times]. In the second hospitalization, interferon Beta-1a was replaced with Fingolimod. Using polymerase chain reaction, Cryptococcus neoformans was detected in CSF. Liposomal amphotericin B and fluconazole [800 mg per day] were started. Six weeks later, the patient was discharged without any major complaints.

Conclusion: Albeit fingolimod associated cryptococcal meningitis is a rare event, Fingolimod therapy in patients with MS should be performed cautiously. Regular follow-ups may give rise to a timely diagnosis of probable fingolimod associated cryptococcal meningitis. Fingolimod therapy can lead to lymphocytopenia and various infections. We, therefore, suggest that intermittent blood lymphocyte counts as well as monitoring of clinical manifestations among MS patients treated with Fingolimod to avoid additional neurological and physical disabilities in these patients.

Keywords: Multiple sclerosis, relapsing-remitting multiple sclerosis, fingolimod, cryptococcal meningitis, central nervous system, DMAMS.

« Previous
Graphical Abstract
[1]
Smith KJ, McDonald WI. The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R Soc Lond B Biol Sci 1999; 354(1390): 1649-73.
[http://dx.doi.org/10.1098/rstb.1999.0510] [PMID: 10603618]
[2]
Miller DH, Barkhof F, Berry I, Kappos L, Scotti G, Thompson AJ. Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: Concerted action guidelines. J Neurol Neurosurg Psychiatry 1991; 54(8): 683-8.
[http://dx.doi.org/10.1136/jnnp.54.8.683] [PMID: 1940938]
[3]
Samudralwar RD, Spec A, Cross AH. Fingolimod and cryptococcosis: collision of immunomodulation with infectious disease. Int J MS Care 2019; 21(6): 275-80.
[http://dx.doi.org/10.7224/1537-2073.2018-080] [PMID: 31889932]
[4]
Wang Z, Kawabori M, Houkin K. FTY720 (Fingolimod) ameliorates brain injury through multiple mechanisms and is a strong candidate for stroke treatment. Curr Med Chem 2020; 27(18): 2979-93.
[PMID: 31785606]
[5]
Huang D. Disseminated cryptococcosis in a patient with multiple sclerosis treated with fingolimod. Neurology 2015; 85(11): 1001-3.
[http://dx.doi.org/10.1212/WNL.0000000000001929] [PMID: 26291283]
[6]
Nakhaei-Nejad M, Barilla D, Lee C-H, Blevins G, Giuliani F. Characterization of lymphopenia in patients with MS treated with dimethyl fumarate and fingolimod. Neurol Neuroimmunol Neuroinflamm 2017; 5(2): e432.
[http://dx.doi.org/10.1212/NXI.0000000000000432] [PMID: 29296636]
[7]
Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis. Lancet Infect Dis 2017; 17(8): 873-81.
[http://dx.doi.org/10.1016/S1473-3099(17)30243-8] [PMID: 28483415]
[8]
Spec A, Powderly WG. Cryptococcal meningitis in AIDS. Handb Clin Neurol 2018; 152: 139-50.
[http://dx.doi.org/10.1016/B978-0-444-63849-6.00011-6] [PMID: 29604972]
[9]
Grebenciucova E, Reder AT, Bernard JT. Immunologic mechanisms of fingolimod and the role of immunosenescence in the risk of cryptococcal infection: A case report and review of literature. Mult Scler Relat Disord 2016; 9: 158-62.
[http://dx.doi.org/10.1016/j.msard.2016.07.015] [PMID: 27645366]
[10]
Shih CC, Chen YC, Chang SC, Luh KT, Hsieh WC. Cryptococcal meningitis in non-HIV-infected patients. QJM 2000; 93(4): 245-51.
[http://dx.doi.org/10.1093/qjmed/93.4.245] [PMID: 10787453]
[11]
Grebenciucova E. Cryptococcal meningitis: Case report. Reactions 2016; 1621: 115.
[12]
Ward MD, Jones DE, Goldman MD. Cryptococcal meningitis after fingolimod discontinuation in a patient with multiple sclerosis. Mult Scler Relat Disord 2016; 9: 47-9.
[http://dx.doi.org/10.1016/j.msard.2016.06.007] [PMID: 27645342]
[13]
Zivadinov R, Reder AT, Filippi M, et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology 2008; 71(2): 136-44.
[http://dx.doi.org/10.1212/01.wnl.0000316810.01120.05] [PMID: 18606968]
[14]
Subei AM, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis. CNS Drugs 2015; 29(7): 565-75.
[http://dx.doi.org/10.1007/s40263-015-0261-z] [PMID: 26239599]
[15]
Chun J, Hartung H-P. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 2010; 33(2): 91-101.
[http://dx.doi.org/10.1097/WNF.0b013e3181cbf825] [PMID: 20061941]
[16]
Kowarik MC, Pellkofer HL, Cepok S, et al. Differential effects of fingolimod (FTY720) on immune cells in the CSF and blood of patients with MS. Neurology 2011; 76(14): 1214-21.
[http://dx.doi.org/10.1212/WNL.0b013e3182143564] [PMID: 21464424]
[17]
Levin SN, Kaplan TB. Infectious complications of novel multiple sclerosis therapies. Curr Infect Dis Rep 2017; 19(2): 7.
[http://dx.doi.org/10.1007/s11908-017-0562-0] [PMID: 28233190]
[18]
Zhao Z, Ma C-L, Gu Z-C, Dong Y, Lv Y, Zhong M-K. Incidence and risk of infection associated with fingolimod in patients with multiple sclerosis: A systematic review and meta-analysis of 8,448 patients from 12 randomized controlled trials. Front Immunol 2021; 12: 611711.
[19]
Erratum: Oral fingolimod in primary progressive multiple sclerosis (INFORMS): A phase 3, randomised, double-blind, placebo-controlled trial (The Lancet (2016) 387(10023) (1075–1084) (S0140673615013148) (10.1016/S0140-6736(15)01314-8)). The Lancet 2017; 389(10066): 254.
[http://dx.doi.org/10.1016/S0140-6736(15)01314-8]
[20]
Saida T, Itoyama Y, Kikuchi S, et al. Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study. BMC Neurol 2017; 17(1): 17.
[http://dx.doi.org/10.1186/s12883-017-0794-5] [PMID: 28129749]
[21]
Achtnichts L, Obreja O, Conen A, Fux CA, Nedeltchev K. Cryptococcal meningoencephalitis in a patient with multiple sclerosis treated with fingolimod. JAMA Neurol 2015; 72(10): 1203-5.
[http://dx.doi.org/10.1001/jamaneurol.2015.1746] [PMID: 26457631]
[22]
Anene-Maidoh TI, Paschall RM, Scott Graham R. Refractory cryptococcal meningoencephalitis in a patient with multiple sclerosis treated with fingolimod: A case report. Interdiscip Neurosurg 2018; 12: 8-9.
[http://dx.doi.org/10.1016/j.inat.2017.10.005]
[23]
Abassi M, Boulware DR, Rhein J. Cryptococcal meningitis: Diagnosis and management update. Curr Trop Med Rep 2015; 2(2): 90-9.
[http://dx.doi.org/10.1007/s40475-015-0046-y] [PMID: 26279970]
[24]
Chong I, Wang KY, Lincoln CM. Cryptococcal meningitis in a multiple sclerosis patient treated with Fingolimod: A case report and review of imaging findings. Clin Imaging 2019; 54: 53-6.
[http://dx.doi.org/10.1016/j.clinimag.2018.11.005] [PMID: 30544079]
[25]
Pham C. Obstructive hydrocephalus (first report) secondary to cryptococcal meningitis: Case report. Reactions 2017; 1664: 131-2.
[26]
Ma SB, Griffin D, Boyd SC, Chang CC, Wong J, Guy SD. Cryptococcus neoformans var grubii meningoencephalitis in a patient on fingolimod for relapsing-remitting multiple sclerosis: Case report and review of published cases. Mult Scler Relat Disord 2020; 39: 101923.
[http://dx.doi.org/10.1016/j.msard.2019.101923] [PMID: 31986367]
[27]
Huang D. Disseminated cryptococcosis in a patient with multiple sclerosis treated with fingolimod. Neurology 2015; 85(11): 1001.
[28]
Seto H, Nishimura M, Minamiji K, et al. Disseminated Cryptococcosis in a 63-year-old Patient with Multiple Sclerosis Treated with Fingolimod. Intern Med 2016; 55(22): 3383-6.
[http://dx.doi.org/10.2169/internalmedicine.55.7255] [PMID: 27853088]
[29]
Ward MD, Jones DE, Goldman MD. Cryptococcal meningitis after fingolimod discontinuation in a patient with multiple sclerosis. Mult Scler Relat Disord 2016; 9: 47-9.
[http://dx.doi.org/10.1016/j.msard.2016.06.007] [PMID: 27645342]
[30]
Pham C, Bennett I, Jithoo R. Cryptococcal meningitis causing obstructive hydrocephalus in a patient on fingolimod. BMJ Case Rep 2017; 2017: bcr2017220026.
[http://dx.doi.org/10.1136/bcr-2017-220026] [PMID: 28687690]
[31]
Chong I, Wang KY, Lincoln CM. Cryptococcal meningitis in a multiple sclerosis patient treated with Fingolimod: a case report and review of imaging findings. Clin Imaging 2019; 54: 53-6.
[http://dx.doi.org/10.1016/j.clinimag.2018.11.005] [PMID: 30544079]
[32]
Wienemann T, Müller A, MacKenzie C, et al. Cryptococcal meningoencephalitis in an IgG(2)-deficient patient with multiple sclerosis on fingolimod therapy for more than five years - case report. BMC Neurol 2020; 20(1): 158.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy