Angioedema and Urticaria

Definition

Angioedema and urticaria result from diverse causes, both immune mediated and non–immune mediated. They often occur together, along a spectrum ranging from benign and self-limited to life threatening.

Urticaria is defined by erythematous, pruritic wheals of cutaneous edema. Angioedema is a similar process, occurring in the deep dermis, subcutaneous, and submucosal tissues, with more diffuse edema. As a result of dermal sparing, angioedema tends to be nonpruritic.

Sites of angioedema involvement include the face, tongue, larynx, extremities, genitalia, and gastrointestinal tract. The latter may present with symptoms suggesting an acute intraabdominal process. Life-threatening airway obstruction may result from laryngeal involvement.

Urticaria and angioedema can be acute or chronic. Often the cause remains unknown. Inherited conditions such as hereditary angioedema (HAE) and C1 esterase inhibitor (C1-INH) deficiency may be suggested by family history. Angioedema due to deficient C1-INH may also be acquired, often in the context of an underlying autoimmune or malignant condition. A deficiency of C1-INH allows activation of the complement cascade due to cleavage of C1 by its esterase, with resultant vasodilation and angioedema.

Acute urticaria or angioedema result from activation and degranulation or degradation of mast cells and basophils, which can be mediated by immunoglobulin E (IgE) or other triggers (e.g., complement-mediated or direct mast cell–releasing agents). These cells release or generate various mediators causing vasodilation and increased vascular permeability. The extensive list of agents includes histamine, histamine-releasing factors, prostaglandin D, leukotrienes C4 and D4, platelet-activating factor, anaphylatoxins (C3a, C4a, C5a), bradykinin, kallikrein, cytokines such as interleukin (IL)–4 and IL-5, and interferon-γ. The clinical features of mast cell degradation are similar, regardless of the classification and underlying cause ( Box 130.1 ).