Vaccine-associated lupus and related organ involvements: A pharmacovigilance analysis of VAERS database 1990-2025

The relationships between vaccines and the development of systemic lupus erythematosus (SLE) and related organ involvements remain unclear.

We analyzed data from the Vaccine Adverse Event Reporting System (VAERS) during the period of 1990 to 2025 to determine the incidence of vaccine-associated SLE over time. The relationships between vaccines and the development of SLE and organ involvements were assessed by disproportionality and case-control analyses.

1976 (0.017%) cases of vaccine-associated lupus were identified amongst 11,301,263 adverse events (AEs) reported in VAERS (1990-2025). Median time from vaccination to symptom onset was 8 (0-8,070) days. The most common manifestations are musculoskeletal and connective tissue disorders (82.94%) followed by skin and subcutaneous tissue lesions (10.83%), while kidney and nervous system involvements are rare. 702 (40.48%) patients had serious outcomes, and 22 (3.13%) died. Human papilloma virus (HPV) vaccine is associated with lupus AEs, especially musculoskeletal/connective tissue disorders, kidney and nervous system involvements. Hepatitis B virus (HBV) vaccine also shows correlations with lupus AEs, particularly musculoskeletal/connective tissue disorders. COVID-19, influenza and zoster vaccines show no relationship with lupus AEs and specific organ involvements. Recombinant protein vaccines show significant links with lupus AEs.

Vaccine-associated lupus is uncommon and manifestations are generally mild. HPV and HBV vaccines show strong associations with lupus AEs with distinct organ involvements.