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

Background: Increasing cases of vaccine-related severe cutaneous adverse reactions (SCARs) are reported in the literature.

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

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

Results: A total of 255 cases of SCARs following vaccination were identified. 231 (91%) of the reported cases of vaccine-associated SCARs were identified as SJS/TEN. The pooled incidence of SCARs following vaccination was 1.676 per million (95% confidence interval=0.136-20.668; I = 97%). The H1N1 vaccine (n=52), coronavirus disease 2019 (COVID-19) vaccines (n=38; 23 [61%] from mRNA vaccines), and influenza vaccine (n=33) contributed to most of these cases. AGEP and DRESS were frequently reported with COVID-19 vaccines, particularly the mRNA vaccines (57.1% [4/7] and 83.3% [5/6], respectively) and viral vector vaccines (28.6% [2/7] and 16.7% [1/6]). No SCAR was reported for protein-based COVID-19 vaccines. Six cases of fatal SJS/TEN were reported, with two cases associated with the COVID-19 vaccine.

Conclusions: SCARs following vaccination were extremely rare, with a high proportion of these cases SJS/TEN. Most suspected culprits included the H1N1 vaccine, the influenza vaccine, the varicella vaccines, and COVID-19 vaccines especially mRNA vaccines. However, concurrent medication use may confound underlying attribution of SCARs to vaccines.