ClinicSpeak: chickenpox and shingles in MSers treated with fingolimod

The problem of chickenpox and shingles on fingolimod and other DMTs. #ClinicSpeak #MSBlog #MSResearch

“The article below on  Varicella-zoster virus (VZV) infection in MSers on fingolimod is timely and very relevant to field. VZV is a herpes virus  that causes chicken pox and once infected is responsible for recurrent localised infections called shingles. This study is important as there have been two deaths on fingolimod due disseminated chicken pox infection. One MSer had not had chicken pox as a child and the other had very low level of antibodies. This is why we pre-screen all our patients prior to starting fingolimod to make sure they have got antibodies against the virus; if they don’t we vaccinate them and delay starting fingolimod for 4-6 weeks. However, even if you have previously had chicken pox, and have antibodies, you are at risk of getting shingles on fingolimod. So you need to be vigilant of symptoms that might suggest reactivation of the virus.”

“Early symptoms of shingles may include headache, photophobia (sensitivity to light) and non-specific flu-like symptoms. You may feel itching, tingling, or pain in a band, strip, or small area of skin, where the shingles rash will appear several days or weeks later. The rash quickly turns into small blisters, that burst and then scab over, and finally clear up over a few weeks. The rash is often very painful and may be itchy. The rash occurs in a typical dermatomal distribution; a big word to describe the area of skin supplied by a single nerve root from the brain or spinal cord. This occurs because the virus lives inside the neurons and when it reactivates it travels down the nerve to the area of skin supplied by those specific nerve. This is why the rash wrap around either the left or right side of your body or appear on your face around one eye. It is possible to have more than one area of rash on your body, but this is quite rare.”

“Shingles develops in stages: the prodromal stage (before the rash appears) is characterised by pain, burning, tickling, tingling, and/or numbness in the area supplied by the affected nerve. This phase typically last several days before the rash appears. Flu-like symptoms usually develop just before the rash appears. Depending where the shingles is located you may experience swelling and tenderness of the local lymph nodes draining that area. The active stage is when the rash and blisters appear on teh skin; typically in a band, strip, or small area. The rash can appear anywhere on the body; it is usually located to only one side of the body. Soon after the rash appears small blisters will form with clear fluid inside  them. The fluid may become cloudy after a few days; the cloudiness is due to white blood cells attacking the virus. Rarely, some people won’t get a rash, or the rash will be very small or mild and missed. It is often missed when it occurs in the hair, ear or between the cheeks of you buttocks. When the rash occur on the forehead, cheek, nose, and around one eye (so called herpes zoster ophthalmicus), it may spread to infect the cornea of the eye and threaten your sight. This is really a medical emergency and need urgent treatment. The pain of shingles can be excruciating and is often described as if someone is piercing your skin with needles. Once the blisters break open, they tend to ooze, and crust over in about 5 days. The rash heals in about 2 to 4 weeks and often leaves some scaring or loss of pigment. The area of the scarring is typically anaesthetic; i.e. when you prick it with a needle you can’t feel pain. The latter is clinical sign we use to diagnose post-herpetic scarring. In a significant number of affected people they are left with post-herpetic neuralgia; chronic pain in the distribution of the nerve affected by the shingles. Post-herpetic neuralgia is the most common complication and typically last months or years. Symptoms of post-herpetic neuralgia are aching, burning and stabbing pain in the area of the earlier shingles rash. Persistent neuralgia may last years and the affected area could be sensitive to touch. In some cases post-herpetic neuralgia can be so severe that affects activities of daily living such as eating, sleep and physical functioning; when it is this bad it is usually associated with depression.”

“If you are on fingolimod, or any othe DMT, and develop shingles you need to contact you doctor so that you can be started on anti-viral drugs. We use acyclovir/aciclovir, valacyclovir/valaciclovir or famcyclovir/famciclovir to treat shingles; Professor Julian Gold who works with us and has extensive eperience with shingles as an HIV infectious disease expert favours famcyclovir due it long half-life inside cells. All these drugs are now off patent so are relatively cheap.”

Epub: Arvin et al. Varicella-Zoster Virus Infections in Patients Treated With Fingolimod: Risk Assessment and Consensus Recommendations for Management. JAMA Neurol. 2014. doi: 10.1001/jamaneurol.2014.3065.

IMPORTANCEVaricella-zoster virus (VZV) infections increasingly are reported in MSers 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 MSers 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 MSers 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, MSers received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all MSers received fingolimod, 0.5 mg/d (total exposure of 54 000 patient-years at the time of analysis).

RESULTS: Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 MSer-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 MSer-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for MSers 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 MSer’s VZV immune status before initiating fingolimod therapy and immunization for MSers 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.

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • I got chicken pox when I was 17, two days after finishing my A-levels. I developed he first signs of PPMS 10 years later. Must have been the pox.

  • It's recognizable (thankfully in a much more mildly form). Another symptom that needs mentioning next Neuro-appointment. (on Fingolimod). Thanks

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