Population Characteristics, Symptoms, and Risk Factors of Idiopathic Chilblains: A Systematic Review, Meta-Analysis, and Meta-Regression

Abstract

Background: Chilblains/perniosis is a non-freezing cold injury causing painful inflammatory skin lesions. Its pathogenesis remains poorly understood because it is often studied as secondary to other underlying conditions. Methods: We systematically investigated the population characteristics, symptoms, and predisposing factors of chilblains in healthy adults exposed to cool/cold environments. We screened PubMed, Embase, and Cochrane Library, and we adopted PRISMA reporting guidelines (PROSPERO: CRD42021245307). The risk of bias was assessed by two independent reviewers (RTI item bank). Random-effects model meta-analyses were performed to calculate the pooled prevalence of histopathological features. Mixed-effects meta-regressions were used to assess other sources of between-study heterogeneity. Results: Thirteen studies (477 patients) were included. Chilblains affect more women than men, up to 12% of the body skin surface, and most frequently, the hands and fingers. Meta-analyses of nine studies (303 patients) showed a frequent presence of perivascular lymphocytic infiltrate (81%), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%). Meta-regressions (p ≤ 0.05) showed that smoking and frequent occupational exposure to water increase the likelihood of histopathological features. Conclusions: The population characteristics, symptoms, and predisposing factors of chilblains revealed in this analysis should be incorporated in medical care to improve the condition’s diagnosis and management.