History of Urticaria

Abstract

The beginning of the twentieth century ushered in the era of molecular medicine, eventually leading to unravelling of the molecular and immunological basis of urticaria. The mast cell and its histamine content remain central to the pathophysiology of the pruritic wheal in most forms of urticaria, and the synthesis, storage,regulation of release of histamine as well as molecular characterisation of its receptors are becoming well understood. The challenge of the past 50 years has been to understand the causation of the promiscuous activation of dermal and mucosal mast cells in idiopathic chronic urticaria and angioedema. The discovery in the 1980s of autoreactivity in the serum of some patients with chronic urticaria (the autologous serum skin test) was a major step forward and prompted attempts to identify and characterise this activity. The subsequent finding in chronic urticaria of specific complement-dependent autoantibodies, which release histamine and other mediators from mast cells and basophils via dimerisation of their high affinity IgE receptors, has stimulated intense interest in the multifactorial modes of activation of mast cells and basophils in this disorder. Antihistamines, discovered in the 1940s, remain the cornerstone of treatment of most types of urticaria. Although recent derivative (“second-generation”) compounds manifest greatly refined properties, they are often only moderately effective. New therapeutic approaches “round the corner” include bradykinin B2 antagonists (for angioedema) and the anti-IgE immunobiologic omalizumab