Primary Cutaneous Cryptococcus in a Patient With Multiple Sclerosis Treated With Fingolimod

Forrestel, Amy; Modi, Badri; Longworth, Sarah; Wilck, Marissa B.; Micheletti, Robert G.

doi:10.1001/jamaneurol.2015.4259

Cited by 41 publications

(22 citation statements)

References 6 publications

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“…76 Cryptococcal central nervous system and skin infections have also been reported. [78][79][80] Three cases of PML associated with fingolimod monotherapy have been confirmed 81 ; routine assessment of JCV antibody status and maintenance of vigilance for PML symptoms or MRI changes is reasonable.…”

Section: Self Injectable Therapiesmentioning

confidence: 96%

Disease modifying therapies for relapsing multiple sclerosis

Wingerchuk

Weinshenker

2016

BMJ

141

116

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Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.

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Section: Self Injectable Therapiesmentioning

confidence: 96%

Disease modifying therapies for relapsing multiple sclerosis

Wingerchuk

Weinshenker

2016

BMJ

141

116

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“…Monogenic disorders such as X-linked CD40L deficiency, chronic granulomatous disease, and Job syndrome are also associated with susceptibility to CM ( 98 – 100 ). T-cell suppressing biological therapy such as natalizumab or fingolimod is also a risk factor ( 101 , 102 ).…”

Section: Non-hiv Factors Of Susceptibilitymentioning

confidence: 99%

Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy

2018

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Cryptococcal meningoencephalitis is responsible for upwards of 15% of HIV-related deaths worldwide and is currently the most common cause of non-viral meningitis in the US, affecting both previously healthy and people with immune suppression caused by cancer chemotherapy, transplantation, and biologic therapies. Despite a continued 30–50% attributable mortality, recommended therapeutic strategies have remained largely unchanged since the 1950s. Recent murine models and human studies examining the role of the immune system in both susceptibility to the infection as well as host damage have begun to influence patient care decisions. The Damage Framework Response, originally proposed in 1999, was recently used to discuss dichotomous etiologies of host damage in cryptococcal disease. These include patients suffering microbiological damage with low host immunity (especially those immunosuppressed with HIV) and those having low (live) microbiological burden but high immune-mediated damage (HIV-related immune reconstitution syndrome and non-HIV-related postinfectious inflammatory response syndrome). Cryptococcal disease in previously healthy hosts, albeit rare, has been known for a long time. Immunophenotyping and dendritic cell-T cell signaling studies on cerebral spinal fluid of these rare patients reveal immune capacity for recognition and T-cell activation pathways including increased levels of HLA-DR and CD56. However, despite effective T-cell signals, brain biopsy and autopsy specimens demonstrated an M2 alternative macrophage polarization and poor phagocytosis of fungal cells. These studies expand the paradigm for cryptococcal disease susceptibility to include a prominent role for immune-mediated damage and suggest a need for careful individual consideration of immune activation during therapy of cryptococcal disease in diverse hosts.

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“…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%

Case Report: Fingolimod and Cryptococcosis

Samudralwar

Spec

Cross

2019

International Journal of MS Care

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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.

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Primary Cutaneous Cryptococcus in a Patient With Multiple Sclerosis Treated With Fingolimod

Cited by 41 publications

References 6 publications

Disease modifying therapies for relapsing multiple sclerosis

Disease modifying therapies for relapsing multiple sclerosis

Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy

Case Report: Fingolimod and Cryptococcosis

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