Vitamin D and Chronic Urticaria: A Review of Potential Mechanisms, Clinical Evidence, and Future Directions.

Vitamin D has long been recognized for its essential role in calcium and phosphorus homeostasis and skeletal maintenance. Over the past few decades, however, accumulating evidence has uncovered its pivotal nonskeletal function in orchestrating immune responses, sparking considerable interest in its association with various autoimmune disorders and inflammatory skin diseases. Chronic urticaria (CU) is a common skin disease with a complex etiology, and immune dysfunction is closely implicated in its pathogenesis. This narrative review systematically summarizes the epidemiological evidence, potential mechanisms of action, and clinical intervention studies regarding the relationship between vitamin D and CU. The available evidence, however, remains heterogeneous, and causality has not been firmly established owing to the predominance of cross-sectional designs and the presence of multiple confounding factors. Although most interventional studies report positive effects of vitamin D supplementation as an adjunct to standard therapy, findings are conflicting because of considerable heterogeneity in dosing regimens, treatment duration, and baseline vitamin D status. Based on the reviewed evidence, we propose a "threshold model," which posits that vitamin D modulates the immune activation threshold rather than directly triggering disease. The deficiency of vitamin D lowers this threshold and increases CU susceptibility, whereas the clinical onset of CU requires additional triggering factors such as infections or autoantibodies. This model remains a theoretical framework requiring further clinical and mechanistic validation. This narrative review aims to provide an integrated perspective for understanding the complex relationship between vitamin D and CU and to offer a theoretical basis for the development of comprehensive treatment strategies.