Severe Cutaneous Adverse Reactions Following Vaccination: A Systematic Review and Meta-Analysis

Abstract

Background: An increasing number of vaccine-related severe cutaneous adverse reactions (SCARs) have been reported in the literature.

Objectives: To provide comprehensive information on the clinical spectrum of vaccine-associated SCARs.

Methods: This was a systematic review and meta-analysis of case reports, case series, cohort studies, case-control studies, and post-market surveillance data on SCARs following vaccination. Data were extracted on demographic information, vaccine types, past medical history, medication use, and SCAR types, manifestations, management, and prognosis. The SCARs examined included acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and generalized bullous fixed drug eruptions.

Results: A total of 255 cases of SCARs following vaccination were identified. Of these, 231 (91%) were classified as SJS/TEN. The pooled incidence of SCARs following vaccination was 1.676 per million (95% confidence interval = 0.136-20.668; I² = 97%). The most frequently implicated vaccines were H1N1 vaccines (n = 52), coronavirus disease 2019 (COVID-19) vaccines (n = 38, of which 23 [61%] were mRNA vaccines), and influenza vaccines (n = 33). Acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms were most frequently reported with COVID-19 vaccines, particularly mRNA vaccines (57.1% [4 of 7] and 83.3% [5 of 6], respectively) and viral vector vaccines (28.6% [2 of 7] and 16.7% [1 of 6], respectively). No SCARs were reported for protein-based COVID-19 vaccines. Six cases of fatal SJS/TEN were identified, including 2 cases associated with the COVID-19 vaccine.

Conclusions: SCARs following vaccination are extremely rare, with SJS/TEN comprising the majority of reported cases. The most frequently suspected vaccine culprits include H1N1, influenza, varicella, and COVID-19 vaccines, particularly mRNA vaccines. However, concurrent medication use may confound the attribution of SCARs to vaccines.

Keywords: Acute generalized exanthematous pustulosis; Drug reaction with eosinophilia and systemic symptoms; Severe cutaneous adverse reactions; Stevens-Johnson syndrome/toxic epidermal necrolysis; Vaccines.