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.