1 INTRODUCTION
Cutaneous leukocytoclastic angiitis (CLA) is characterized by inflammation of the superficial skin microvessels, typified by neutrophil inflammation and nuclear fragmentation (1). Clinically, CLA predominantly presents as symmetric palpable purpura on the lower extremities and other dependent areas of the body(2). Extensive research has identified various factors associated with CLA, including idiopathic causes, infection, inflammatory disease, drug intake, and malignancies(3). Although many CLA cases resolve spontaneously within a few weeks, severe, intractable, chronic or recurrent cases may necessitate systemic treatment(2).
We studied some of the viruses implicated in CLA in theherpesvirales, herpesviridae : subfamilyAlphaherpesvirinae , genus Simplexvirus , speciesSimplexvirus humanalpha1 (HSV-1), subfamilyAlphaherpesvirinae , genus Simplexvirus , speciesSimplexvirus humanalpha2 (HSV-2), subfamilyBetaherpesvirinae , genus Roseolovirus , species Human herpesvirus 6 (HHV-6), subfamily Alphaherpesvirinae , genusVaricellovirus , species Varicellovirus humanalpha3 (CMV), subfamily Gammaherpesvirinae , genus Lymphocryptovirus , species Lymphocryptovirus humangamma4 (EBV) and subfamilyAlphaherpesvirinae , genus Varicellovirus (VZV). Studies have indicated that HSV, including both HSV-1 and HSV-2, can incite angiitis through the reactivation of latent HSV infections, leading to perivascular inflammation, with a notable emphasis on HSV-2 infections(4). VZV, a neurotropic alphaherpesvirus, can induce a sustained inflammatory response and pathological remodeling of blood vessels (5). Instances have demonstrated cutaneous angiitis following CMV infection (6). EBV, a widespread herpesvirus, has also been associated with angiitis(7). HHV-6, encompassing HHV-6A and HHV-6B species, has shown links to angiitis based on biopsy specimens and molecular research (8, 9).
Nevertheless, it remains uncertain whether these associations between herpes viruses and CLA are causal. This study seeks to explore the potential causal relationship between herpes viruses and CLA. Mendelian randomization(MR), an epidemiological approach, is employed to assess causality, utilizing genetic variation as instrumental variables (IVs) to mitigate potential confounding and reverse causality issues(10). This method proves particularly valuable when randomized controlled trials and observational studies are unfeasible(10). In this investigation, we employ a two-sample MR (TSMR) analysis using summary-level data from comprehensive genome-wide association studies (GWASs) on herpes viruses and angiitis to examine these causal associations.