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

SIMPLE SUMMARY: Chilblains/perniosis is a non-freezing cold injury, most commonly idiopathic, and it affects the dorsal feet or hands, fingers, feet, and toes, causing painful inflammatory skin lesions. The disorder occurs in both sexes and is (often) studied as secondary to other underlying conditions (Raynaud disease, lupus), as well as blood or connective tissue diseases. Patient-related and environmental factors appear to contribute to developing chilblains, but their pathogenesis remains poorly understood. Therefore, this study aimed to uncover important aspects of the idiopathic chilblains and to objectively conclude the socio-demographics and the frequency of the various features of the disorder. The present systematic review investigated the population characteristics, symptoms, and predisposing factors of chilblains in otherwise healthy adults who are exposed to cool/cold environments. Using the pooled prevalence and standard errors of histopathological features, we estimated the likelihood of the histopathology presence, based on patients’ smoking habits, work characteristics, and percent of their body surface area affected. We also shed light on the impact of patients’ outdoor and strenuous occupations, especially when involving exposure to water. The result of this systematic review meta-analysis and meta-regression should be incorporated in medical care to improve the condition’s diagnosis and management and support the formulation of prevention guidelines. 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.