An Analysis of Spontaneously Reported Data of Vesicular and Bullous Cutaneous Eruptions Occurring Following Vaccination with the Adjuvanted Recombinant Zoster Vaccine.

ABSTRACT

INTRODUCTION: With the approval of the adjuvanted recombinant zoster vaccine (RZV; Shingrix, GSK) in October 2017, GSK established enhanced safety surveillance measures to allow prompt identification of potential safety signals not observed during clinical development. In Germany, cases of vesicular and bullous cutaneous eruptions following RZV vaccination were reported. OBJECTIVE: Our objective was to search and analyse 2.5 years of worldwide spontaneously reported post-marketing data for vesicular and bullous cutaneous eruptions, represented by adverse events suggestive of (1) herpes zoster (HZ) and (2) non-HZ vesicular and bullous cutaneous eruptions, that occurred following RZV vaccination. METHODS: We conducted a descriptive analysis of all identified reports of HZ and non-HZ vesicular and bullous cutaneous eruptions following RZV vaccination and an observed versus expected (O/E) analysis of reports of HZ that met criteria of varicella zoster virus (VZV) reactivations following RZV vaccination (i.e., time to onset [TTO] of the event < 30 days or missing after any dose). RESULTS: Until the data lock point, 32,597,779 RZV doses had been distributed globally. There were 2423 reports of HZ (including complications) identified, of which 645 met the criteria of possible vaccination failure (i.e., TTO of the event ≥ 30 days or missing following a complete RZV vaccination schedule). The O/E analysis of 1928 reports assessed as possible VZV reactivations indicated that the observed number of cases was lower than that expected in the general population. Additionally, 810 reports of non-HZ vesicular and bullous cutaneous eruptions were identified, including injection site rashes attributed to the vaccine's reactogenicity. CONCLUSION: This review of spontaneously reported post-marketing data did not raise safety concerns regarding the occurrence of vesicular and bullous cutaneous eruptions following vaccination with RZV.

Shingles is a disease caused by reactivation of the chickenpox virus. It mostly affects adults aged 50 years and older and patients of all ages who have an impaired immune system. Diagnosis of shingles is often based only on the presence of symptoms such as a typical rash and pain. However, rashes can have various other causes (e.g., allergies, autoimmune diseases, and infections). Consequently, rashes with other causes may be misdiagnosed as shingles. Adults at increased risk of shingles and/or aged 50 years and older may be vaccinated with Shingrix (GSK, Belgium) to protect them from shingles and its complications. Since Shingrix became available in Germany, blister-like skin rashes have been reported that occurred shortly after vaccination. We searched the GSK safety database for reports of blister-like skin rashes that occurred following vaccination with Shingrix and that were spontaneously reported from countries where Shingrix was first marketed. To analyse these reports of rashes, we described the reports that we retrieved, we performed a statistical analysis to quantify whether the number of events assessed as reactivations of the chickenpox virus following Shingrix vaccination was higher than the number of reactivations that would be expected in the general population, and we described possible explanations for the observed rashes and underlying disease mechanisms. Our analyses did not raise safety concerns related to the onset of these rashes after vaccination with Shingrix. This paper raises awareness about the varying causes of rashes since a shingles-like rash that onsets shortly after vaccination with Shingrix is not necessarily caused by vaccination. In conclusion, this analysis shows that caution is needed when evaluating rashes in older adults and that all potential contributing factors (e.g., pre-existing diseases, medication, vaccination) should be considered.