Prevalence of Metabolic Syndrome in Chronic Urticaria: A Systematic Review and Meta‐Analysis

Chronic urticaria (CU) is characterised by recurrent wheals and/or angioedema for at least 6 weeks [1]. Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, defined by at least three of abdominal obesity, elevated triglycerides, reduced HDL cholesterol, hypertension and elevated fasting glucose [2]. Recent literature suggests a potential link between CU and MetS, although the strength of this association remains unclear [3, 4]. Early intervention in patients with MetS is crucial to prevent progression to chronic disease [5]. We aimed to quantify the prevalence of MetS in patients with CU and evaluate the association between MetS and CU. We searched MEDLINE, Embase, and CINAHL from inception to January 28, 2025, supplemented by hand-searching reference lists of included studies. We screened studies independently and in duplicate in two phases to identify observational studies evaluating MetS in patients with CU. We extracted data on study designs, participant characteristics, and prevalence estimates or measures of association for MetS. We conducted restricted maximum likelihood random effects meta-analyses of logit-transformed prevalences and odds ratios (OR). We evaluated study risk of bias using Hoy et al.'s tool for studies of prevalence and the Quality in Prognostic Studies tool [6, 7]. We quantified heterogeneity using Cochran's Q and I2 statistics and assessed publication bias using Egger's tests and funnel plots. We conducted a priori subgroup analyses based on geographical region (using World Health Organization regions), urticaria type (spontaneous vs. inducible), and risk of bias (high vs. moderate vs. low), performed meta-regressions for age, gender, angioedema, urticaria duration, and urticaria severity, and undertook sensitivity analyses for study design. We evaluated the certainty of the evidence using the GRADE approach. From 227 unique citations, we included 10 studies reporting on 81,679 patients from six countries (median mean age: 41.6 years; median 66% women). Five (71%) studies found a positive association between CU and MetS, one (14%) found a negative association, and one (14%) showed no significant association. Eight (80%) studies were cross-sectional, one (10%) was a case–control, and one (10%) was a retrospective cohort. With low certainty in the evidence due to serious risk of bias and serious inconsistency, the pooled prevalence of MetS in patients with CU was 25.2% (95% CI 19.5–31.8, I2 = 92.9%, p < 0.001, 10 studies, 12,640 patients) (Figure 1A). With low certainty due to serious risk of bias and serious inconsistency, patients with CU had greater odds of MetS than healthy controls (OR 1.59, 95% CI 1.01–2.50, I2 = 95.3%, p < 0.001, 7 studies, 81,250 patients) (Figure 1B). Subgroup analyses found that MetS was less common in patients with CU from the Americas (9.8%, 95% CI 6.2–15.2; 1 study; 173 patients; subgroup p value < 0.001) and the prevalence of MetS was lower in studies with a low risk of bias (13.1%, 95% CI 8.4–19.7; 2 studies; 11,434 patients) compared to those with a moderate risk (29.0%, 95% CI 24.7–33.8; 8 studies; 1206 patients; subgroup p value < 0.001). Meta-regressions for age and gender did not show significant associations. Sensitivity analyses showed no significant differences between study designs for prevalence (cross-sectional 23.8%, 95% CI 17.5–31.5; case–control 30.6%, 95% CI 21.8–41.0; retrospective cohort 33.3%, 95% CI 22.9–45.6; p = 0.300) or association (cross-sectional OR 1.46, 95% CI 0.89–2.39; case–control OR 2.68, 95% CI 1.81–3.96; p = 0.058) outcomes. We did not identify sufficient data to perform any other prespecified subgroup analyses or meta-regressions. We did not detect any signal for publication bias. Additional information about methods and findings are available in the following repository: https://osf.io/t8bcq. Our review is limited by the availability and quality of evidence. The included studies were conducted in Turkey, Israel, India, Italy, South Korea and Brazil, with a notable absence of studies from North American countries. Although we identified a lower prevalence of MetS in patients from the Americas compared to patients from European and South-East Asian regions, this finding was informed by one small study. Second, 8 of 10 (80%) studies evaluating the prevalence of MetS had a moderate risk of bias due to poor external validity, with most studies recruiting non-consecutively from single-centre populations. Meanwhile, six of seven (86%) studies reporting data for the association between CU and MetS had a high risk of bias due to insufficient consideration of potential confounding variables. The lack of statistical adjustment for important confounders, including age, sex, comorbid autoimmune conditions and lifestyle factors, potentially contributed to the substantial heterogeneity observed in our meta-analysis, which considerably limits the clinical applicability of our pooled estimates. Owing to the lack of temporal information in the included studies, residual confounding, and high heterogeneity, a causal relationship between CU and MetS cannot be established. Future prospective studies with larger samples, robust methodology and increased representation of patient populations are needed. We identified low certainty evidence suggesting a substantial prevalence of MetS in patients with CU and increased odds of MetS. While allergists and immunologists should actively consider the presence of MetS in tandem with other common comorbidities in patients with CU, including anxiety, depression, and autoimmune thyroiditis, the evidence should be considered preliminary and requires validation through well-designed prospective studies with diverse populations [8, 9]. Physicians should interpret findings cautiously and consider MetS screening in CU patients as part of comprehensive care, while recognising that the magnitude of association remains uncertain. Daniel G. Rayner: conceptualisation, methodology, formal analysis, investigation, writing – original draft, visualisation, supervision, project administration. David Gou: validation, investigation, writing – original draft, visualisation. Wayne Sun: investigation, writing – review and editing. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this review are publicly available in OSF at https://osf.io/t8bcq.

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