URTICARIA AND ANGIOEDEMA

Urticaria and angioedema are usually the clinical consequence of vasoactive mediators derived from mast cells in the skin or mucosal tissues. Efforts to classify mast cell-mediated causes of urticaria and angioedema have generally been frustrated by their diverse pathogenesis and clinical course. The term acute is typically used to describe fleeting lesions whose recurrence does not extend beyond 6 weeks. Chronic is the term used to describe lesions that persist for more than a few hours but usually less than a day, and recurrences extend for more than 6 weeks. These definitions do not take histology into account. Skin biopsies of fleeting lesions demonstrate a paucity of inflammatory cells, whereas more persistent lesions display a spectrum of perivascular cuffing by predominantly T cells and monocytes. The presence of leukocytoclastic vasculitis in persistent lesions indicates an underlying immune complex disease. Many of the physical urticarias have fleeting lesions that can be induced with the appropriate stimulus for years. This review article has emphasized the clinical course and histology of urticaria and angioedema lesions in an effort to provide a more complete understanding of the pathogenesis and appropriate treatment. Clearly, avoidance of an identifiable inciting stimulus is optimum management, although most patients have no etiology defined or the cause is not realistically avoidable. At present, treatment options for these patients rely on antihistamines to control the immediate consequence of mast cell degranulation. Corticosteroids are reserved for the treatment of patients whose urticaria or angioedema lesions persist, reflecting the increasing involvement of mononuclear cells in the disease process. For leukocytoclastic vasculitis, corticosteroids are indicated, and cytotoxic drugs may be required for adequate treatment. Future treatments of urticaria and angioedema will evolve based on elucidation of the relevant cells and soluble mediators and will include counterregulatory or antagonistic peptides and drugs. C1 esterase inhibitor deficiency is a relatively uncommon cause of angioedema but is important to understand because of its ability to clinically mimic mast cell-mediated angioedemas and its unique pathogenesis and treatment. HAE can be divided into two serologic subtypes that simply reflect the location of the defect in one of the codominantly expressed C1- INH genes on chromosome 11. AAE can be divided into two serologic subtypes. AAE type I is due to massive consumption of C1-INH, presumably by tumor- related immune complexes. AAE type II is due to an anti-C1-INH autoantibody. Acute management of angioedema in any patient with C1-INH deficiency is directed toward maintenance of a patent airway, hemodynamic stability, relief of pain, and identification of causes precipitating the attack. Patients with HAE can be treated prophylactically with attenuated androgens, antifibrinolytic agents, or C1-INH infusions. Although these same agents may be of some benefit in patients with AAE, therapy for these patients is directed toward the underlying disease with AAE type I and immunosuppression with AAE type II. Future approaches to the treatment of C1-INH deficiency will include recombinant C1-INH for passive replacement as well as exploration of the potential for gene therapy.