EBV, Epstein-Barr virus; IVIG, intravenous immunoglobulin.
Idiopathic 75%–90% of cases 25%–50% of adult patients have IgG, anti-IgE, and anti-FcεR1 (high-affinity IgE receptor alpha chain) autoantibodies
Angioedema Hereditary angioedema (autosomal dominant inherited deficiency of Cl-esterase inhibitor)
From Lasley MV, Kennedy MS, Altman LC: Urticaria and angioedema. In Altman LC, Becker JW, Williams PV, editors: Allergy in Primary Care, Philadelphia, 2000, Saunders, p 234.
factors; 35% to 40% of chronic urticaria cases have an autoimmune process due to IgG autoantibodies binding directly toIgE or to the IgE receptor. Physical urticaria and angioedemaare characterized by known eliciting external factors that mayinclude pressure, cold, heat, exercise, or exposure to sun or water.
The most common physical urticaria is dermatographism, affecting 2% to 5% of persons. Dermatographism means “writing on the skin” and is easily diagnosed by firmly scratching the skin with a blunt point, such as the wooden tip of a cotton swab or tongue depressor. It is characterized by an urticarial reaction localized to the site of skin trauma. It has been suggested that trauma induces an IgE-mediated reaction causing histamine to be released from the mast cells.
Cholinergic urticaria, characterized by the appearance of 1to 3-mm wheals surrounded by large erythematous flares after an increase in core body temperature, occurs commonly in young adults. Lesions may develop during strenuous exercise, after a hot bath, or emotional stress. The lack of airway symptoms differentiates it from exercise-induced anaphylaxis.
Cold urticaria occurs with exposure to cold and may develop within minutes on areas directly exposed to cold or on rewarming of the affected parts. Ingestion of cold drinks may result in lip swelling. Cold urticaria syndromes can be categorized into acquired and familial disorders. Severe reactions resulting in death can occur with swimming or diving into cold water. Patients must never swim alone, avoid total body exposure to cold, and have injectable epinephrine available.
Hereditary angioedema (HAE) is an autosomal dominant disease due to a deficiency of Cl inhibitor. The genetic defect may be caused by spontaneous mutation; approximately 25% of cases occur in patients without any family history. The disease is estimated to affect approximately 10,000 persons in the United States. It is characterized by unpredictable, recurrent attacks of episodic swelling that involves the face, peripheral extremities, genitalia, abdomen, oropharynx, and pharynx. Episodes are often triggered by trauma. Asphyxiation from laryngeal attacks is a significant cause of mortality. Patients with HAE rarely have urticaria associated with angioedema. The majority of patients (85%) have type I disease, which is due to decreased production of Cl-esterase inhibitor. A minority of patients (15%) have type II disease, which is due to production of dysfunctional Cl-esterase inhibitor. A low C4 level serves as an initial screening test. Patients with reduced C4 should have quantitative and functional levels of Cl-esterase inhibitor measured. C2 levels are low during an acute attack. Type III HAE patients have normal laboratory evaluation. These patients are more typically females, but some males have been reported in the literature. Three products are approved to treat HAE attacks: Berinert (for acute facial or abdominal attacks in children ≥13 years old), Kalbitor (for acute attacks in children ≥16 years of age), and Cinryze (for prophylaxis in adolescents and adults).