Etiopathogenesis of Chronic Spontaneous Urticaria: Immunological Overview and Differential Diagnosis

Abstract

Urticaria is an inflammatory skin disorder that affects up to 20% of the world population at some point during their life. It presents with wheals, angioedema or both due to activation and degranulation of skin mast cells and the release of histamine and other mediators.       Mast cells have a key pathogenetic role in the The pathophysiology of urticaria and can be activated by different mechanisms. The most wellknown activation mechanism is the contact with an agent that induces a hypersensitivity reaction of the I type with production of IgE that binds to FcεRI receptors. A new exposure to the trigger factor induces the receptor cross-linking and the activation of the intracellular signaling resulting in mediator’s production.     The first indication that urticaria could have an autoimmune basis, with an intrinsic immune imbalance, excluding extrinsic factors as the cause, comes from the so‑called "autologous serum skin test"(ASST), in which by intradermal injection of the serum of the CU patient, an erythematous papule is produced at the injection site.It is generally believed now that two types of autoimmunity (type I and type II) contribute to the pathogenesis of CSU, which are mediated by IgE autoantibodies and IgG autoantibodies, respectively. Autoantibodies against IgE or FcɛR1 are the most often present circulating antibodies in CSU patients who are ASST positive, accounting for about 40% of all CSU patients. Of the two, anti-FcɛRI antibodies are likely to be more prevalent. Dermal MCs and basophils both have the FcɛRI receptor on their surface, and autoantibodies to this receptor can cause persistent activation and degranulation of both cells in a way that is IgE-independent. on the other hand, IgG-anti IgE antibodies may bind to and crosslink receptor-bound IgE on the surface of MCs and basophils, resulting in the activation and degranulation of these cells.