Autoimmune urticaria

History

Descriptions of urticaria appear in ancient medical texts, but its recognition as an autoimmune condition is recent. The concept of autoimmunity gained acceptance in the 1950s, and the first article discussing urticaria as a type I hypersensitivity appeared in 1962. In the 1980s and 1990s, researchers found that many patients with chronic spontaneous urticaria had circulating autoantibodies against the high-affinity IgE receptor (FcεRI) and IgE itself, capable of activating mast cells and basophils.

A key study in 1993 by Hide et al. showed that sera from these patients induced histamine release from basophils and cutaneous mast cells via IgG autoantibodies against the alpha subunit of FcεRI. Further work by Sabroe et al. in 1999 demonstrated that intradermal injection of autologous serum produced a wheal and flare reaction in most patients with chronic spontaneous urticaria, reinforcing the role of autoantibodies.

Pathogenesis

Autoimmune urticaria involves autoantibodies that mistakenly target the high-affinity IgE receptor (FcεRI) on mast cells and basophils, or less commonly IgE itself. These autoantibodies cross-link and dimerise FcεRI, triggering degranulation and release of histamine and other inflammatory mediators, including preformed substances like histamine, proteases, interleukin-1, and tumor necrosis factor-α, as well as newly synthesized leukotrienes, prostaglandins, cytokines, and chemokines. These mediators increase expression of cell adhesion molecules on post-capillary venule endothelium, recruiting leukocytes such as eosinophils that characterize the late phase reaction. Mast cells can also act as antigen-presenting cells, activating T cells via MHC class II-dependent signaling to prolong wheal duration.

Diagnosis and testing

Diagnosis relies on clinical presentation and symptom duration of six weeks or longer, supported by detection of autoantibodies against FcεRI or IgE. The autologous serum skin test (ASST) injects a small amount of the patient's serum into the skin; a wheal and flare reaction indicates functional autoantibodies. Blood tests such as enzyme-linked immunosorbent assay (ELISA) detect autoantibodies by adding patient serum to an antigen-coated plate, followed by an enzyme-linked antibody and a substrate that produces a color change.

Differential diagnosis includes allergic reactions, physical urticaria (triggered by pressure, cold, or heat), mastocytosis, mast cell activation syndrome, and systemic diseases like urticarial vasculitis, Schnitzler's syndrome, Gleich's syndrome, or thyroid disease. Specific symptoms, triggers, and test results help distinguish autoimmune urticaria from these conditions.

Treatment

Treatment aims to control symptoms and prevent exacerbations through a stepwise approach. First-line therapy uses antihistamines, including first-generation types like diphenhydramine (which may cause drowsiness) and second-generation types such as cetirizine and loratadine; doxepin is also sometimes used. If antihistamines are ineffective or symptoms are severe, second-line options include immunosuppressants like corticosteroids (used short-term due to side effects) and biologics such as omalizumab, an anti-IgE antibody for cases unresponsive to other treatments. Lifestyle modifications involve avoiding known triggers like certain foods, alcohol, stress, and extreme temperatures, while regular exercise, a healthy diet, and good sleep hygiene may help manage symptoms.

Did You Know?

• Anti-thyroid and anti-nuclear antibodies are often found in autoimmune urticaria patients.
• One study found an increased prevalence of gastroesophageal reflux disease in autoimmune urticaria patients.
• As autoimmune urticaria persists, the prevalence of comorbidities such as rheumatic diseases, inflammatory diseases, and psychiatric disorders tends to increase.