Immunologic mechanisms of fingolimod and the role of immunosenescence in the risk of cryptococcal infection: A case report and review of literature

Grebenciucova, Elena; Reder, Anthony T.; Bernard, Jacqueline

doi:10.1016/j.msard.2016.07.015

Cited by 69 publications

(52 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently in the post marketing setting, treatment with fingolimod has been linked to several cases of infection with the opportunistic fungal pathogen C. neoformans, which causes a severe fungal meningitis if left untreated (Achtnichts, Obreja, Conen, Fux, & Nedeltchev, 2015;Commissioner, O, n.d.;Grebenciucova, Reder, & Bernard, 2016;Huang, 2015;Ward, Jones, & Goldman, 2016). Previous research showed that S1P is important for maintaining C. neoformans in granulomas in the lung and in neutrophil killing (Farnoud, Bryan, Kechichian, Luberto, & Del Poeta, 2015;McQuiston, Luberto, & Del Poeta, 2010).…”

Section: Conclusion and Final Thoughtsmentioning

confidence: 99%

Sphingosine-1-phosphate receptors and innate immunity

Bryan

Poeta

2018

Cellular Microbiology

118

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P) is a signalling lipid that regulates many cellular processes in mammals. One well-studied role of S1P signalling is to modulate T-cell trafficking, which has a major impact on adaptive immunity. Compounds that target S1P signalling pathways are of interest for immune system modulation. Recent studies suggest that S1P signalling regulates many more cell types and processes than previously appreciated. This review will summarise current understanding of S1P signalling, focusing on recent novel findings in the roles of S1P receptors in innate immunity.

show abstract

Section: Conclusion and Final Thoughtsmentioning

confidence: 99%

Sphingosine-1-phosphate receptors and innate immunity

Bryan

Poeta

2018

Cellular Microbiology

118

View full text Add to dashboard Cite

show abstract

“…To date, several cases of cryptococcal infection have been reported in patients using fingolimod (Table 1). 1,6,[14][15][16][17][18][19] These cases included CNS cryptococcosis as well as other sites of dissemination, but none described isolated pulmonary involvement. Due to the emergence of these earlier cases, the prescribing information for fingolimod was changed (May 2018) to include its association with cryptococcal infection, with higher risk after 2 years of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 The incidence of these pathogens could call into question the effectiveness of cellular immunity after fingolimod exposure, although earlier studies suggested that only T-cell trafficking was affected. 6 Cryptococcus can be acquired through inhalation of spores and requires intact cellular immunity to prevent infection and dissemination. T-cell-mediated immunity in particular is critical in granuloma formation and containment of this pathogen.…”

mentioning

confidence: 99%

Case Report: Fingolimod and Cryptococcosis

Samudralwar

Spec

Cross

2019

International Journal of MS Care

View full text Add to dashboard Cite

The use of immunomodulatory and immunosuppressive therapies in multiple sclerosis (MS) has allowed practitioners to regulate MS disease activity, with the caveat that these potent medications may render patients susceptible to opportunistic infections. The approval of fingolimod presented the first oral option for relapsing MS. Since 2015, postmarketing safety data have documented several published cases of cryptococcal meningitis and disseminated cryptococcosis associated with fingolimod use. However, surveillance mechanisms for opportunistic infections and management of active demyelinating disease with ongoing infection have not been adequately addressed. We present a case of isolated pulmonary cryptococcosis with the use of fingolimod to highlight the hurdles in balancing efficacious disease-modifying therapies for MS while treating an opportunistic infection associated with that therapy.

show abstract

“…OIs typically associated with HIV infection other than those already discussed have been only rarely reported in association with MS therapies—mostly medications that affect lymphocyte trafficking, such as natalizumab and fingolimod, or those resulting in depletion of T lymphocytes, such as alemtuzumab. CNS, cutaneous, and disseminated cryptococcosis have been rarely reported with fingolimod use, and to a lesser extent natalizumab use [ 23 ]. Individual cases of Kaposi sarcoma, cutaneous histoplasmosis, and CNS toxoplasmosis have also been reported in non-HIV-infected patients with MS receiving fingolimod [ 22 , 49 , 50 ].…”

Section: Other Infections Of Concernmentioning

confidence: 99%

Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management

Epstein

Dunn

Deresinski

2018

Open Forum Infectious Diseases

117

115

View full text Add to dashboard Cite

Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.

show abstract

Immunologic mechanisms of fingolimod and the role of immunosenescence in the risk of cryptococcal infection: A case report and review of literature

Cited by 69 publications

References 47 publications

Sphingosine-1-phosphate receptors and innate immunity

Sphingosine-1-phosphate receptors and innate immunity

Case Report: Fingolimod and Cryptococcosis

Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management

Contact Info

Product

Resources

About