Severe Autoimmune Adverse Events Post Herpes Zoster Vaccine: A Case-Control Study of Adverse Events in a National Database

July 2015 | Volume 14 | Issue 7 | Original Article | 681 | Copyright © July 2015

Yi Chun Lai BSa and Yik Weng Yew MBBS MPHa,b

aHarvard T.H. Chan School of Public Health, Boston, MA
bNational Skin Centre, Singapore

Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases.

J Drugs Dermatol. 2015;14(7):681-684.


Zoster vaccine (Zostavax®) is a live attenuated vaccine recommended for healthy adults 60 years or older to reduce the incidence of herpes zoster.1 Patients with autoimmune diseases, such as rheumatoid arthritis (RA), are found to have a 1.5 to 2 fold increased risk for herpes zoster, compared to the general population.2 As a result, in 2012, the American College of Rheumatology (ACR) recommended zoster vaccine for older RA patients receiving non-biologic disease-modifying antirheumatic drugs (DMARD) therapies or before starting DMARD or biologic treatment.2 However, cases of autoimmune adverse effects such as arthritis, vasculitis, systemic lupus erythematosus (SLE), thrombocytopenia, alopecia, Guillain-Barre syndrome (GBS), optic neuritis, and multiple sclerosis after zoster vaccinations have been reported in the Vaccine Adverse Event Reporting System (VAERS), a national vaccine monitoring system in the United States. There have also been published case reports of bullous pemphigoid following vaccination.3,4
Hepatitis B virus (HBV) and Human Papillomavirus (HPV) vaccines have also been reported to be associated with an increased risk of serious autoimmune adverse events (SAAEs). There were several published case reports of SAAEs following HBV5,6 and HPV7,8 vaccination. Case series and case-control studies had also demonstrated increased risks of SAAEs post HBV and HPV vaccinations,9-12 though there were other studies that showed conflicting results.13-15 Therefore, it is important to evaluate whether zoster vaccine also results in an increased risk of autoimmunity. In this study of adverse events reported in the VAERS monitoring database, we aim to investigate if zoster vaccination is associated with an increased risk of autoimmune adverse effects using a previously established matched case-control study methodology.16


The VAERS is a national vaccine safety surveillance database maintained jointly by the U.S. Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) to analyze adverse events following immunization. They periodically followed up on specific serious adverse events and deaths recorded in the VAERS.
The VAERS was analyzed using a matched case-control study design previously described by Geier et al.16 in 2005. Information regarding SAAEs following zoster vaccination was retrieved from the VAERS database using the CDC Wonder online interface ( Since the zoster vaccine was approved and licensed by the FDA in May 2006, all SAAEs associated with vaccines administered from May 2006 through November 2014 were identified as cases. The SAAEs were specified as arthritis (VAERS codes: 10003246 or 10039073), vasculitis (VAERS code: 10047115), SLE (VAERS code: 10042945), thrombocytopenia (VAERS code: 10050245, 10021245, 10043554, or 10043561), alopecia (VAERS code: 10001760 or 10073736), GBS (VAERS code: 10018767), as well as optic neuritis and multiple sclerosis (VAERS code: 10030942 and 10028245). Patients who received zoster vaccine were considered exposed, while those