Herpes Zoster and Multiple Sclerosis

Lenman, J. A. R.; Peters, T. J.

doi:10.1136/bmj.2.5651.218

Cited by 26 publications

(18 citation statements)

References 9 publications

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“…However, most initial evidence has been negative in confirmatory studies. The peculiar ability of some herpes viruses to produce in humans recurrent exacerbations and remain latent for long periods [7] have provided a fair theoretical framework for research since the 1960s [19]; along the years, many herpes viruses have been postulated, particularly EBV, HSV1, 2, HHV6 and VZV [2,30,38,47]; however, most laboratory or subsequent studies have been either inconclusive or negative [19,23,24,37]. In the case of VZV some epidemiological inferences have been made [30,41], however, the ubiquitous presence of the virus in humans, either in the latent stage within neural cells from sensory ganglia or in common diseases such as varicella, which is almost universal in countries endemic for MS, provide confusing evidence and the associations remain controversial.…”

Section: Discussionmentioning

confidence: 99%

Varicella-zoster virus at relapses of multiple sclerosis

2007

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The possible participation of different herpes viruses was studied during exacerbations of multiple sclerosis (MS). We searched for the presence of DNA from the following herpes viruses: varicella zoster virus (VZV), herpes-simplex viruses 1 and 2; Epstein-Barr virus (EBV) and human herpes-virus-6 (HHV6) in mononuclear cells from patients with MS during relapse (n = 40), MS during remission (n = 131) and controls (n = 125). Additionally, immune cells containing viral antigens were quantified by flow cytometry, and VZV load was determined by real time PCR in 2 MS patients at various times during relapse and remission. DNA from VZV was found in 95% of MS patients during relapse and in 17% during remission; all controls were negative; by contrast, DNA from HHV6 was found in 24% of MS patients during relapse and in 2% during remission; DNA from herpes simplex viruses was not found in any subject; and DNA from EBV was found in a similar percentage of subjects from all groups. Sequential quantification of VZV-load showed a curve that increased during relapse and disappeared at remission. Also, VZV antigens were found inside a large number of immune cells from MS patients during relapse as compared with MS patients on remission and controls. In the typical forms of VZV infection, varicella and herpes-zoster, DNA from VZV is found in mononuclear cells exclusively during brief periods at the beginning of the active infection, but not during latency; thus, the conspicuous presence of VZV during relapses of MS may indicate a period of active infection and suggests the participation of VZV in the pathogenesis of MS.

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Section: Discussionmentioning

confidence: 99%

Varicella-zoster virus at relapses of multiple sclerosis

2007

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“…The unexpected finding of high frequency of varicella during childhood did change our initial hypothesis of dietary or ambiental differences that could participate in the recent rise of MS in Mexico and brought again the old hypothesis of childhood viral disorders mentioned in several epidemiological studies [7]. Although varicella was first mentioned in the early 1960's [8] over the years it lost hypothetical ground as compared with other viral agents, favoring particularly Epstein-Barr virus and human herpes virus 6 [9,10], however, even these agents have been challenged in recent reports [11][12][13]. Nonetheless, in our study the antecedent of varicella infection was highly significant as compared with other infectious diseases of childhood.…”

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confidence: 94%

On the viral hypothesis of multiple sclerosis: Participation of varicella-zoster virus

Sotelo

2007

Journal of the Neurological Sciences

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“…20–23 In an age-adjusted retrospective analysis of claims databases, HZ incidence was approximately twice as high in patients with MS as in the general population (6 per 1000 patient-years) (Novartis Pharma AG; annual Periodic Safety Update Report to US Food and Drug Administration; submitted on October 18, 2013 [data not available in the public domain]). The observed rate of HZ was higher in patients receiving fingolimod compared with those receiving placebo in the clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Varicella-Zoster Virus Infections in Patients Treated With Fingolimod

et al. 2015

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IMPORTANCE Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity.OBJECTIVE To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management.DESIGN, SETTING, AND PARTICIPANTS Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated.INTERVENTIONS In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54 000 patient-years at the time of analysis).MAIN OUTCOMES AND MEASURES Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting.RESULTS Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation.CONCLUSIONS AND RELEVANCE Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient's VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.

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Herpes Zoster and Multiple Sclerosis

Cited by 26 publications

References 9 publications

Varicella-zoster virus at relapses of multiple sclerosis

Varicella-zoster virus at relapses of multiple sclerosis

On the viral hypothesis of multiple sclerosis: Participation of varicella-zoster virus

Varicella-Zoster Virus Infections in Patients Treated With Fingolimod

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