Varicella-zoster virus acute myelitis in a patient with MS treated with natalizumab

Bourre, Bertrand; Lefaucheur, Romain; Ahtoy, Patrick; Travers, Floriane; Fetter, Damien

doi:10.1212/01.wnl.0000439052.05262.1d

Cited by 13 publications

(9 citation statements)

References 4 publications

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“…Although there are a number of case reports suggesting overrepresentation of symptomatic HSV and VZV infections in natalizumab-treated MS patients, [15][16][17][18][19][20][21] valid data on the incidence of symptomatic HSV or VZV reactivation in MS patients with and without natalizumab treatment are not available; therefore, it is presently not possible to link the increased incidence of significant rises of anti-VZV IgG levels with an increased risk of symptomatic VZV reactivation or reinfection. At least for four of the six patients, the rise of anti-VZV IgG levels was not accompanied by herpes zoster nor other clinical symptoms of VZV disease, indicating subclinical reactivation or reinfection in these cases.…”

Section: Discussionmentioning

confidence: 99%

“…13 Furthermore, a growing number of case reports are suggestive of an increase in the risk of HSV and VZV infections in MS patients undergoing treatment with fingolimod 14 and natalizumab. [15][16][17][18][19][20][21] A study on functional T-cell analyses in patients treated with fingolimod also shows a slightly reduced antiviral T-cell response with respect to herpes viruses, occasionally accompanied by subclinical reactivation of VZV or Epstein-Barr virus (EBV) in the saliva. 22 Nevertheless, larger studies defining susceptibility to neurotropic herpesvirus infections in differently treated MS patients, in comparison to healthy people, are missing.…”

Section: Introductionmentioning

confidence: 99%

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Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

et al. 2015

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Background: Serious adverse drug reactions of disease-modifying drugs in multiple sclerosis (MS) therapy may include enhanced susceptibility to reactivation of neurotropic herpes viruses like varicella-zoster virus (VZV) and the John Cunningham (JC) polyomavirus. Objective: Because symptomatic reactivation of these viruses are rare events, we determined the incidence of rises in anti-VZV IgG antibody levels as a potential marker for enhanced susceptibility to subclinical and symptomatic reactivation of neurotropic viruses. Methods: Anti-VZV IgG levels were measured in paired serum samples taken 6-8 months apart from natalizumab-treated MS patients, healthy blood donors and human immunodeficiency virus (HIV) infected patients. Results: The incidence of significant rises in anti-VZV IgG levels in natalizumab-treated MS patients was 4.26 per 100 person-years, which was significantly higher than in healthy blood donors. Retrospective evaluation of the available medical records of patients with rises of anti-VZV IgG levels did not reveal herpes zoster (i.e. shingles) manifestations. Conclusions:The increased incidence of significant rises of anti-VZV IgG levels in natalizumab-treated MS patients might indicate an association of natalizumab treatment of MS with an elevated risk of a subclinical VZV reactivation and/or reinfection events. Whether this is predictive of an increased risk of herpes zoster or even symptomatic reactivation of other neurotropic viruses remains to be determined in larger prospective studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

et al. 2015

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“…Natalizumab, an anti-α4β1-integrin antibody inhibiting leukocyte migration across the blood brain barrier into the CNS utilized in the treatment of multiple sclerosis (MS), has been reported to be associated with progressive multifocal leukoencephalopathy (PML) caused by JC virus, and also increases the risk of VZV encephalitis and myelitis (Bourre et al 2013 ; Fine et al 2013 ; Yeung et al 2013 ). The anti-CD52 antibody alemtuzumab approved for the treatment of MS and leukemia, which depletes circulating T and B cells, was also reported to cause severe VZV infection, although not involving the CNS (Williamson and Berger 2015 ).…”

Section: Host Factors That Determine Susceptibility To Vzv-associatedmentioning

confidence: 99%

Determinants of neurological syndromes caused by varicella zoster virus (VZV)

Kennedy

Mogensen

2020

J. Neurovirol.

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Varicella zoster virus (VZV) is a pathogenic human herpes virus which causes varicella as a primary infection, following which it becomes latent in peripheral autonomic, sensory, and cranial nerve ganglionic neurons from where it may reactivate after decades to cause herpes zoster. VZV reactivation may also cause a wide spectrum of neurological syndromes, in particular, acute encephalitis and vasculopathy. While there is potentially a large number of coding viral mutations that might predispose certain individuals to VZV infections, in practice, a variety of host factors are the main determinants of VZV infection, both disseminated and specifically affecting the nervous system. Host factors include increasing age with diminished cell-mediated immunity to VZV, several primary immunodeficiency syndromes, secondary immunodeficiency syndromes, and drug-induced immunosuppression. In some cases, the molecular immunological basis underlying the increased risk of VZV infections has been defined, in particular, the role of POL III mutations, but in other cases, the mechanisms have yet to be determined. The role of immunization in immunosuppressed individuals as well as its possible efficacy in preventing both generalized and CNS-specific infections will require further investigation to clarify in such patients.

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“…A review of some 20 cases of such herpes and/or varicella cases associated with natalizumab use was published in 2013 [84]. The authors searched the US FDA Adverse Event Reporting System (FAERS) and MEDLINE to identify infections that were laboratory confirmed by PCR of the CSF for herpes simplex virus or varicella zoster virus, noting reports of varicella zoster virus myelitis [85][86][87], herpes simplex encephalitis [88], herpes simplex virus meningitis [89], and zoster [90]. Of the 20 patients, seven received prior immunosuppressives, seven did not receive immunosuppressives, and data were missing for the remaining six patients.…”

Section: Natalizumabmentioning

confidence: 99%

Infection Risk in Patients on Multiple Sclerosis Therapeutics

Williamson

Berger

2015

CNS Drugs

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The interface of multiple sclerosis (MS) and infection occurs on several levels. First, infectious disease has been postulated as a potential trigger, if not cause, of MS. Second, exacerbation of MS has been well-documented as a consequence of infection, and, lastly, infectious diseases have been recognized as a complication of the therapies currently employed in the treatment of MS. MS is a disease in which immune dysregulation is a key component. Examination of central nervous system (CNS) tissue of people affected by MS demonstrates immune cell infiltration, activation and inflammation. Therapies that alter the immune response have demonstrated efficacy in reducing relapse rates and evidence of brain inflammation on magnetic resonance imaging (MRI). Despite the altered immune response in MS, there is a lack of evidence that these patients are at increased risk of infectious disease in the absence of treatment or debility. Links between infections and disease-modifying therapies (DMTs) used in MS will be discussed in this review, as well as estimates of occurrence and ways to potentially minimize these risks. We address infection in MS in a comprehensive fashion, including (1) the impact of infections on relapse rates in patients with MS; (2) a review of available infection data from pivotal trials and postmarketing studies for the approved and experimental DMTs, including frequency, types and severity of infections; and (3) relevant risk minimization strategies, particularly as they pertain to progressive multifocal leukoencephalopathy (PML).

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Varicella-zoster virus acute myelitis in a patient with MS treated with natalizumab

Cited by 13 publications

References 4 publications

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

Determinants of neurological syndromes caused by varicella zoster virus (VZV)

Infection Risk in Patients on Multiple Sclerosis Therapeutics

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