Environmental determinants of large vessel vasculitis onset: a scoping review with complementary narrative synthesis of genetic susceptibility

Large vessel vasculitis (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK), are rare immune-mediated disorders characterized by inflammation of large arteries. Epidemiological patterns, marked geographic gradients, age and sex differences, and temporal clustering, suggest that environmental factors contribute to disease onset in genetically susceptible individuals, yet no systematic mapping of this evidence exists. The study sought to systematically map current evidence on environmental exposures investigated in relation to LVV onset, identify methodological gaps, and characterize research priorities. Genetic susceptibility data were additionally synthesized to contextualize gene-environment interactions.

We conducted a scoping review following PRISMA-ScR guidelines. PubMed and Embase were searched from inception to August 2026. Studies were eligible if they assessed environmental exposures in relation to GCA or TAK onset using an epidemiological design with a comparator group, Mendelian randomization, or mechanistic approach with direct relevance to human susceptibility. Genetic susceptibility was synthesized through a complementary narrative review.

Of 3,596 records identified, 2,137 were screened after deduplication, and 44 studies were included in the narrative synthesis, of which 34 with established temporality and epidemiological design were summarized in a structured evidence table. Air pollution, infections, antibiotic use, hormonal exposures, and cardiometabolic factors emerge as candidate environmental modulators of LVV onset, although causal links remain uncertain. Genetic susceptibility implicates antigen presentation, immune regulation, innate immune activation, and vascular remodeling pathways, which likely modulate individual responsiveness to environmental triggers.

This review identifies multiple candidate environmental exposures in LVV and highlights critical methodological gaps regarding exposure timing and genomic integration. Integrative exposomic-genomic approaches represent the critical next step toward identifying modifiable risk factors and preventive strategies.