Immunological events in chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a highly debilitating skin disease associated with systemic features. We have made significant progress in several aspects relating to this condition. However, the exact physiopathology remains unknown. There is mounting evidence for an autoimmune basis, demonstrated by the CSU serum ability to activate healthy donors skin mast cells and blood basophils. However, it is only seen among 35-40% of patients. Mast cells and basophils play an important role in this skin condition. Both cells in CSU patients have unique features that differentiate them from basophils and mast cells from healthy donors. In the case of basophils, basopenia is typically found in CSU patients. Basophils from CSU patients also tend to be hyporesponsive to stimuli that act through the IgE receptor, responsive to other stimuli as MCP-1 or C5a, and hyperesponsive when incubated with sera. Eosinophils are also present in CSU skin biopsies, yet their exact role has not yet been defined. Likewise, endothelial cells also play a function, as indirectly demonstrated by an increase of vasoactive peptides in skin and plasma of CSU patients' samples. All these facts orchestrate a systemic inflammation response producing a significant increase of several inflammatory markers. Unfortunately, we lack a unitary model that could explain the exact role of each of these players. In this review, we will describe the history and discover the pathway to the present knowledge on the immunological facts of this disease.