“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.”
IMPORTANCE: Varicella-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.