Autoimmune urticaria
Autoimmune urticaria, also known as chronic autoimmune urticaria, is a type of chronic urticaria characterized by the presence of autoantibodies in the patient's immune system that target the body's own mast cells, leading to episodes of hives. This immunologically distinct type of urticaria is considered autoimmune because the immune system, which normally protects the body from foreign organisms, mistakenly attacks the body's own cells, causing inflammation and other symptoms.
The condition is chronic, meaning it persists for more than six weeks, and can last for many years. Symptoms include recurrent episodes of hives, which are red, itchy, and swollen areas on the skin. These episodes can be triggered by various factors, including heat, stress, or for no identifiable reason.
Autoimmune urticaria is a relatively rare condition, affecting a small percentage of the population. However, it can significantly impact the quality of life of those affected due to the unpredictability and discomfort of the symptoms. The exact cause of autoimmune urticaria is not fully understood, but it is believed to involve a complex interplay of genetic and environmental factors.
Diagnosis is typically based on the clinical history and physical examination, and confirmed by laboratory tests. Treatment primarily involves managing symptoms and includes the use of antihistamines, corticosteroids, monoclonal antibodies, and in some cases, immunosuppressive drugs.
Despite ongoing research, many aspects of autoimmune urticaria remain poorly understood, and it continues to be a challenging condition to manage. The economic burden is significant, with costs as high as $2050 per year per patient in the United States.
History
Urticaria, commonly known as hives, has been recognized as a medical condition for centuries, with descriptions of the characteristic skin lesions appearing in ancient medical texts. However, the understanding of urticaria as an autoimmune condition is a relatively recent development in medical history.The term autoimmune urticaria refers to a subset of chronic spontaneous urticaria cases where the immune system appears to play a significant role. This understanding began to evolve in the mid to late 20th century as advances in immunology revealed the complex interactions between the immune system and various diseases.
The concept of autoimmunity, where the body's immune system attacks its own cells, was not widely accepted until the 1950s. As the understanding of the immune system and its role in disease evolved, researchers began to explore the possibility that some cases of chronic urticaria could be driven by autoimmune processes. The first article that discussed urticaria as a type I hypersensitivity was in 1962.
In the 1980s and 1990s, researchers discovered that a significant proportion of patients with CSU had circulating autoantibodies, particularly against the high-affinity IgE receptor and IgE itself. These autoantibodies were found to be capable of activating mast cells and basophils, the key effector cells in urticaria, leading to the release of histamine and other inflammatory mediators that cause the characteristic hives and itching.
One of the key studies that shaped the current understanding of autoimmune urticaria was published by Hide et al. in 1993. This study demonstrated that sera from patients with CSU could induce histamine release from basophils and cutaneous mast cells, and this effect was mediated by IgG autoantibodies against the alpha subunit of the high-affinity IgE receptor.
Subsequent research has further refined understanding of autoimmune urticaria. For example, a study by Sabroe et al. in 1999 showed that intradermal injection of autologous serum caused a wheal and flare reaction in a majority of patients with CSU, providing further evidence of the role of autoantibodies in this condition.
Pathogenesis
Autoimmune urticaria is characterized by the presence of autoantibodies, which are antibodies that the immune system mistakenly produces against the body's own cells. In the case of autoimmune urticaria, these autoantibodies primarily target the high-affinity IgE receptor on mast cells and basophils, or less commonly, IgE itself.In a healthy immune system, antibodies are produced to identify and neutralize foreign bodies such as bacteria and viruses. However, in autoimmune conditions like autoimmune urticaria, the immune system mistakenly identifies its own cells as foreign and produces antibodies against them. This leads to an immune response where the body attacks its own tissues, causing inflammation and damage.
Immune response
In autoimmune urticaria, autoantibodies bind to the FcεRI receptors or IgE on the surface of mast cells and basophils. These autoantibodies cross-link and dimerise FcεRI, leading to mast cell basophil activation which triggers a cascade of events that lead to the degranulation of these cells and the release of histamine and other inflammatory mediators into the surrounding tissues. These mediators include preformed substances like histamine, proteases, interleukin-1, and tumor necrosis factor-α, as well as newly synthesized mediators such as leukotrienes, prostaglandins, cytokines, and chemokines. These substances cause increased expression of cell adhesion molecules by the endothelium of the post capillary venules, leading to leukocyte recruitment, including eosinophils, which characterize the late phase reaction.Mast cells also have the ability to behave as antigen presenting cells, activating T cells and maintaining the duration of the wheals through an MHC class II-dependent signaling pathway.
Comorbidities
Autoimmune urticaria is often associated with a range of comorbidities. These include other autoimmune diseases and atopic diseases like atopic dermatitis, asthma, and rhino-conjunctivitis. Anti-thyroid and anti-nuclear antibodies are often found as well. As such, thyroid diseases are particularly prevalent, as well as vitiligo. One study found an increased prevalence of gastroesophageal reflux disease in autoimmune urticaria patients.Psychiatric disorders, including anxiety, depression, and somatoform disorders, are also common among patients, with an overall prevalence of any psychiatric comorbidity estimated at 31.6%. Sleep–wake disorders, mood disorders, and trauma and stressor-related disorders are among the most prevalent psychiatric conditions. As autoimmune urticaria persists, the prevalence of comorbidities such as rheumatic diseases, inflammatory diseases, and psychiatric disorders tends to increase.
Diagnosis and testing
Diagnosing autoimmune urticaria involves a combination of clinical evaluation, diagnostic criteria, and various testing methods. The process aims to confirm the presence of the disease, identify potential triggers, and rule out other conditions that may present with similar symptoms.Diagnostic criteria
The diagnosis of autoimmune urticaria is primarily based on the clinical presentation and the duration of symptoms. The condition is considered chronic if the hives persist for six weeks or longer. In addition to the clinical presentation, the presence of autoantibodies against the high-affinity IgE receptor or IgE itself can support the diagnosis of autoimmune urticaria.Testing methods
Several testing methods can be used to support the diagnosis and identify potential triggers. Skin tests, such as the autologous serum skin test, can be used to detect the presence of functional autoantibodies. In this test, a small amount of the patient's serum is injected into the skin. A positive reaction, which is the formation of a wheal and flare, indicates the presence of functional autoantibodies.Blood tests can also be used to detect the presence of autoantibodies. The Enzyme-Linked Immunosorbent Assay is a common method used to detect autoantibodies against FcεRI or IgE in the serum. This test involves adding the patient's serum to a plate coated with the antigen of interest. If the autoantibodies are present, they will bind to the antigen. An enzyme-linked antibody is then added, which binds to the autoantibodies. A substrate is added, which the enzyme converts to produce a color change, indicating the presence of autoantibodies.