Chronic Urticaria - Pathophysiology

Pathophysiology

See also: List of human leukocyte antigen alleles associated with cutaneous conditions

The skin lesions of urticarial disease are caused by an inflammatory reaction in the skin, causing leakage of capillaries in the dermis, and resulting in an edema which persists until the interstitial fluid is absorbed into the surrounding cells.

Urticaria is caused by the release of histamine and other mediators of inflammation (cytokines) from cells in the skin. This process can be the result of an allergic or nonallergic reaction, differing in the eliciting mechanism of histamine release.

Allergic urticaria
Histamine and other proinflammatory substances are released from mast cells in the skin and tissues in response to the binding of allergen-bound IgE antibodies to high-affinity cell surface receptors. Basophils and other inflammatory cells are also seen to release histamine and other mediators, and are thought to play an important role, especially in chronic urticarial diseases.
Autoimmune urticaria
In the past decade, many cases of chronic idiopathic urticaria have been noted to be the result of an autoimmune trigger. For example, roughly one-third of patients with chronic urticaria spontaneously develop autoantibodies directed at the receptor FcεRI located on skin mast cells. Chronic stimulation of this receptor leads to chronic hives. Patients often have other autoimmune conditions, such as autoimmune thyroiditis.
Infections
Hive-like rashes commonly accompany viral illnesses, such as the common cold. They usually appear three to five days after the cold has started, and may even appear a few days after the cold has resolved.
Nonallergic urticaria
Mechanisms other than allergen-antibody interactions are known to cause histamine release from mast cells. Many drugs, for example morphine, can induce direct histamine release not involving any immunoglobulin molecule. Also, a diverse group of signaling substances, called neuropeptides, have been found to be involved in emotionally induced urticaria. Dominantly inherited cutaneous and neurocutaneous porphyrias (porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been associated with solar urticaria. The occurrence of drug-induced solar urticaria may be associated with porphyrias. This may be caused by IgG binding, not IgE.
Dietary histamine poisoning
This is termed scombroid food poisoning. Ingestion of free histamine released by bacterial decay in fish flesh may result in a rapid-onset, allergic-type symptom complex which includes urticaria. However, the urticaria produced by scombroid is reported not to include wheals.
Stress and chronic idiopathic urticaria
Chronic idiopathic urticaria has been anecdotally linked to stress since the 1940s. A large body of evidence demonstrates an association between this condition and both poor emotional well-being and reduced health-related quality of life. A link between stress and this condition has also been shown. A recent study has demonstrated an association between stressful life events (e.g. bereavement, divorce, etc.) and chronic idiopathic urticaria and also an association between post-traumatic stress and chronic idiopathic urticaria.

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