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Background Methods Results Conclusions Acute urticaria is a prevalent inflammatory dermatosis characterized by fulminant wheals, often accompanied by severe pruritis. It may also cause nausea, vomiting, and abdominal pain. Numerous studies have substantiated the pivotal involvement of double‐stranded DNA (dsDNA) in autoimmunity. However, the role of dsDNA in the pathogenesis of acute urticaria is unclear.We measured serum dsDNA levels in patients and controls. The relationship between dsDNA levels and environmental exposures (temperature, ultraviolet [UV] index, and season) was investigated by correlating disease onset dates with archived meteorological data. Finally, we used quantitative PCR to determine the expressions of genes encoding dsDNA receptors, single‐stranded RNA (ssRNA) receptors, exosome formation, and type I interferon in the peripheral blood of patients and controls.Serum dsDNA levels were significantly higher in patients with acute urticaria compared with controls (mean values 1.38 and 0.94 ng/ml, respectively, P < 0.001). dsDNA levels were higher in patients exposed to higher environmental temperatures and UV indices and were higher during the summer months. We also found that the expressions of genes encoding dsDNA receptors, ssRNA receptors, absent in melanoma factor 2 (AIM2)‐related inflammatory factors, and interferon alpha were up‐regulated in patients.We demonstrated that serum dsDNA levels are elevated in acute urticaria and are influenced by climatic factors such as temperature, ultraviolet index, and season. We also found that elevated dsDNA promotes the expression of AIM2‐related factors and type I interferons. This study generates new hypotheses regarding the pathogenesis of acute urticaria and suggests novel therapeutic targets. [ABSTRACT FROM AUTHOR]