Advancements in Novel Therapeutics for Chronic Spontaneous Urticaria

Abstract

Chronic urticaria (CU) is defined by pruritic wheals with or without angioedema, associated with severe itch, which persist for greater than 6 weeks. Lesions move from one part of the body to another and generally are evanescent, lasting less than 24 hours. The global prevalence of the disease ranges from 0.5% to 5% and is correlated with an annual economic burden of over $200 million in the United States. Chronic urticaria can be further divided into chronic spontaneous urticaria and chronic inducible urticaria. Whereas chronic spontaneous urticaria has no identifiable trigger, chronic inducible urticaria can be provoked by both physical and nonphysical stimuli. As many as 7% to 30% of patients with CU can have both types. Mast cells are the major effector cells in the pathogenesis of CU. When activated, mast cells characteristically release bioactive mediators including histamine that bind to specific receptors causing vasodilation and extravasation of fluid from the blood vasculature. This causes the characteristic wheals and itch. However, the pathophysiology of CU is much more complex, involving many mast cell surface receptors, cytokines, and cell activation pathways that are targets for many of the currently available and investigational therapies. Studies have demonstrated that CU causes a significant amount of distress and disruption to patients’ daily lives that can be evaluated using validated patient-reported outcomes measures. In this review, we review CU epidemiology, pathophysiology, subtypes, and diagnosis and discuss current and novel therapies.