Last updated: October 30, 2014
ICD9 Code: idiopathic urticaria 708.1; Angioedema 995.1; Hereditary angioedema 277.6
ICD10 Code: idiopathic urticaria L50.1; Angioedema T78.3; Hereditary angioedema (C1 esterase inhibitor deficiency) D84.1
Definition: Urticaria are well-demarcated, evanescent skin reactions characterized by erythematous or blanched elevations of the upper layers of the dermis, usually associated with intense pruritus.
A common distinction relevant to the etiology and treatment of this condition is duration: Acute urticaria is defined by symptom duration of <6 weeks, whereas chronic urticaria is present for >6 weeks. Angioedema, which often occurs along with urticaria, represents a similar process that primarily affects deeper subcutaneous tissue and is not usually associated with pruritus. Some conditions, such as the various types of hereditary and acquired angioedema, are associated with angioedema without concomitant urticaria.
Etiology: There are numerous potential inciting stimuli for urticaria. However, even after thorough investigation, a substantial number of patients will have no cause found. A major advance in the understanding of chronic urticaria has been the demonstration of circulating IgG autoantibodies with reactivity to the a subunit of the high-affinity IgE receptor (Fc-epsiol-RI) or to IgE itself, which have been demonstrated in about 40% of patients with idiopathic urticaria. In addition to this autoimmune urticaria, physical causes of urticaria are also common, accounting for ~15% of cases of chronic urticaria. Sub-types of physical urticaria include pressure urticaria, delayed pressure urticaria, exercise-induced urticaria, cold-induced urticaria (including familial forms), solar-induced urticaria, aquagenic urticaria, and cholinergic urticaria (typically brought on by heat). Additional causes of urticaria include drugs, biological products, animal stings and bites, and systemic diseases (including diseases characterized by abundant complement protein consumption, such as SLE). Mechanistically, some of these represent true type I hypersensitivity, mediated by IgE antibodies (e.g., reactions to foreign proteins such as insect venom). Others are caused by mast cell degranulation unrelated to IgE antibodies (e.g., reaction to radiocontrast dye). Mechanisms are not known for many stimuli. Among rheumatologic drugs, NSAIDs are probably the most common cause of urticaria and angioedema. Because they also inhibit the degradation of kinins, angiotensin-converting enzyme inhibitors may be associated with angioedema. Although similar in gross appearance to common urticaria, the lesions of urticarial vasculitis are distinct both clinically (individual lesions persist for hours to days, as opposed to minutes to hours) and pathologically (with true vasculitis). Hereditary angioedema and acquired angioedema are a group of conditions characterized by angioedema without associated urticarial; some forms relate to absent or dysfunctional C1 esterase inhibitor.
Pathology: Histopathologic examination of urticarial lesions reveals dilatation and engorgement of capillaries in the skin and a minimal perivascular infiltrate often composed of lymphocytes and eosinophils. Different than what is see with vasculitis, there is neither destruction of the vessel walls nor obliteration of the vascular lumen.
Demographics: Urticaria is common, and ~10% to 20% of the population will experience urticaria at some time.
Diagnosis: Urticaria is a clinical diagnosis. Investigation into causes should be focused. Many inciting stimuli will be evident from a thorough history and physical examination supplemented by focused laboratory testing as appropriate. At present, tests for autoantibodies to Fc(RI) or IgE are not widely available. In the appropriate clinical setting, measurement of complement components may be of value (see Complement).
Treatment: For acute urticaria, removal of any offending agent and use of H1 antihistamines (older agents: diphenhydramine, hydroxyzine, cyproheptadine, brompheniramine, chlorpheniramine; newer nonsedating agents: fexofenadine, loratadine, cetirizine, desloratadine) are the mainstay of therapy. For chronic urticaria, H1 anti-histamines are still an important part of the therapeutic regimen because pruritus is often the primary complaint, and excessive scratching can exacerbate the problem. In severe refractory cases, full doses of H1 antihistamines with the addition of H2 antihistamines have been recommended. Inhibitors of leukotrienes, such as montelukast, have also been reported to be useful. In autoimmune urticaria, corticosteroids have been used in short courses for patients with severe disease. Inhibitors of calcineurin such as cyclosporine have also been used, as has intravenous immunoglobulin. The anti-IgE monoclonal antibody omalizumab has been effective in some cases. For patients with hereditary angioedema, attenuated androgens and plasma-derived C1 esterase inhibitor concentrates are used.
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