Understanding the Course of Urticaria: From Acute to Chronic and to Remission

Abstract Purpose of Review This review aims to provide an overview and update on the current knowledge of acute (spontaneous) urticaria (AU) and chronic spontaneous urticaria (CSU), the underlying mechanisms that drive AU progression to CSU and remission, and characterize the existing knowledge gap. A summary of current and prospective treatment options serves to guide treatment decisions. Recent Findings Cutaneous mast cells (MC) are known as central effector cells in AU and CSU pathogenesis. In CSU, the two established endotypes, type I “autoallergy”, defined by the production of IgE antibodies against autoantigens, and type IIb “autoimmunity”, characterized by the production of functional IgG autoantibodies targeting IgE or FcεRI on MCs, have contributed crucially to pathophysiological understanding. Currently, total IgE and IgG anti-TPO antibodies are the only biomarkers available, which are used in clinical practice to guide treatment decisions. With the characterization of Bruton’s tyrosine kinase, an intracellular signaling molecule, and Mas-related G protein-coupled receptor member X2, an IgE-independent activating receptor that represents a link between MCs and sensory nerve endings, novel insights in pathophysiology and promising potential treatment targets have been gained. Summary The upstream mechanisms leading to MC activation in AU, the processes mediating either progression from AU to CSU or early resolution of AU, as well as the question of what drives remission in CSU remain largely unresolved. Ongoing research aims at identifying predictors of disease courses, characterizing mechanisms in non-autoallergic/autoimmune CSU, and establishing biomarkers for early risk stratification and personalized therapy.