Pathophysiology of urticaria

Pathophysiology

Histamine

Histamine is the most important mediator of urticaria. Histamine is produced and stored in mast cells. There are several mechanisms for histamine release via mast cell surface receptors. A variety of immunologic, nonimmunologic, physical, and chemical stimuli may be responsible for the degranulation of mast cell granules and the release of histamine into the surrounding tissue and circulation. About one third of patients with chronic urticaria have circulating functional histamine-releasing IgG autoantibodies that bind to the high-affinity IgE receptor (Fc epsilon RI). Release of mast cell mediators can cause inflammation and accumulation and activation of other cells, including eosinophils, neutrophils, and possibly basophils. Histamine causes endothelial cell contraction, which allows vascular fluid to leak between the cells through the vessel wall, contributing to tissue edema and wheal formation.

When injected into skin, histamine produces the “triple response” of Lewis, the features of which are local erythema (vasodilation), the flare characterized by erythema beyond the border of the local erythema, and a wheal produced from leakage of fluid from the postcapillary venule. Histamine induces vascular changes by a number of mechanisms ( Figure 6-8 ). Blood vessels contain two (and possibly more) receptors for histamine. The two most studied are designated H1 and H2.

H1 RECEPTORS.

H1 receptors, when stimulated by histamine, cause an axon reflex, vasodilation, and pruritus. Acting through H1 receptors, histamine causes smooth-muscle contraction in the respiratory and gastrointestinal tracts and pruritus and sneezing by sensory-nerve stimulation. They are blocked by the vast majority of clinically available antihistamines called H1 antagonists (e.g., chlorpheniramine), which occupy the receptor site and prevent attachment of histamine.

H2 RECEPTORS.

When H2 receptors are stimulated, vasodilation occurs. H2 receptors are also present on the mast cell membrane surface and, when stimulated, further inhibit the production of histamine. Activation of H2 receptors alone increases gastric acid secretion. Cimetidine (Tagamet), ranitidine (Zantac), and famotidine (Pepcid) are H2 blocking agents (antihistamines). H2 receptors are present at other sites. Activation of both H1 and H2 receptors causes hypotension, tachycardia, flushing, and headache. The H2 blocking agents are used most often to suppress gastric acid secretion. They are used occasionally, usually in combination with an H1 blocking agent, to treat urticaria.