Chronic Spontaneous Urticaria: the Emerging Role of Coagulation

Abstract

Chronic urticaria (CU) is a cutaneous disease characterized by the recurrent eruption of short-lived wheals for at least six weeks. The wheals, which are surface swelling of the dermis accompanied by itching, may be elicited by different stimuli, or occur spontaneously. The pathogenesis of spontaneous CU has long remained a mystery, with food allergy, intolerance to food additives and chronic infections having been indicated as the main causes of the disease. The demonstration of histamine releasing autoantibodies in the serum of CU patients led to consider it of autoimmune origin in about 45 % of cases, this condition being “idiopathic” in the remaining 55 %. We recently evaluated the possible involvement of blood coagulation in its pathophysiology by measuring in CU patients the plasma levels of prothrombin fragment F1 + 2, a polypeptide released into the circulation during the activation of prothrombin to thrombin, and D-dimer, a marker of fibrin lysis. Interestingly, both F1 + 2 and D-dimer plasma levels were extremely high during the acute phase of disease, but were completely normal after remission, paralleling urticaria severity. It is noteworthy that thrombin causes an increase in vascular permeability, thus amplifying the CU inflammatory network. Moreover, immunohistochemical studies showed expression of tissue factor, the main initiator of coagulation, in CU skin lesions, and co-localization experiments demonstrated that tissue factor is expressed by eosinophils in the inflammatory infiltrate. All these findings support that coagulation activation contributes in the pathophysiology of spontaneous CU, and provide the rationale for using also anticoagulant and antifibrinolytic agents to treat it.