Urticaria, commonly known as hives, is a prevalent skin condition characterized by the sudden appearance of raised, itchy welts. The chronic form of this condition, where hives persist for six weeks or more, is classified as Chronic Spontaneous Urticaria (CSU). In CSU, the welts appear without any identifiable external trigger, distinguishing it from an acute allergic reaction. Autoimmune hives represent a specific subset of CSU where the body mistakenly attacks its own tissues, driving the persistent symptoms.
How Autoimmune Hives Develop
Autoimmune hives arise from a malfunction in the body’s immune system, specifically involving mast cells and basophils, which are immune cells containing histamine. In a typical allergic reaction, an external substance binds to an antibody on these cells, signaling them to release histamine. However, in autoimmune CSU, the body produces autoantibodies, primarily of the Immunoglobulin G (IgG) type, that act as the trigger instead of an outside allergen.
These IgG autoantibodies frequently target the high-affinity IgE receptor, known as FcεRI, which is found on the surface of mast cells and basophils. When the autoantibodies bind to this receptor, they mimic the action of an allergen, causing the receptor to become activated. The resulting activation forces the mast cells to degranulate, releasing histamine, leukotrienes, and other inflammatory mediators.
A second, less common mechanism involves IgG autoantibodies targeting the IgE antibodies themselves, which are already bound to the mast cell receptors. By binding and cross-linking these surface-bound IgE molecules, the autoantibodies cause inappropriate mast cell activation. Studies suggest that an autoimmune mechanism may be present in up to 50% of patients diagnosed with chronic spontaneous urticaria.
Identifying the Clinical Signs
The physical manifestations of autoimmune hives are consistent with those of other forms of chronic spontaneous urticaria. The characteristic lesions are intensely itchy, raised wheals that are well-defined with surrounding redness. Individual lesions typically disappear in one area of the skin within 24 hours, only to reappear in a different location.
The disease is defined by its chronicity, requiring the presence of these spontaneous wheals for at least six continuous weeks. Up to 40% of patients with CSU also experience angioedema, a deeper swelling of the tissue layers below the skin. Angioedema most commonly affects the face, particularly the lips and eyelids, but it can also involve the tongue or throat, sometimes causing difficulty breathing.
Testing for Autoimmunity
The diagnostic process for autoimmune hives begins with a thorough evaluation to exclude other underlying conditions, such as infections, allergic triggers, or drug reactions. Once other causes are ruled out, specific testing can be employed to determine if the hives have an autoimmune driver.
The Autologous Serum Skin Test (ASST) is one method used to detect the presence of circulating factors in the blood that can activate mast cells. In the ASST, a small amount of the patient’s own blood serum is injected intradermally into a normal area of their skin. A positive result, indicated by the formation of a wheal and flare reaction, demonstrates that the patient’s serum contains factors capable of causing mast cell degranulation. While the ASST suggests a form of “autoreactivity,” it is not solely specific for the IgG autoantibodies.
More specific laboratory tests, such as basophil activation tests or immunoassays, can confirm the presence of IgG autoantibodies directed against IgE or the FcεRI receptor. These tests help classify the condition into different endotypes. Type IIb autoimmune CSU is specifically mediated by these activating IgG autoantibodies. Patients confirmed to have Type IIb autoimmune CSU often exhibit higher disease severity and may be more likely to have concomitant autoimmune diseases, such as thyroid conditions.
Treatment and Long-Term Care
The management of autoimmune hives follows a tiered approach established by international guidelines, focusing on suppressing the mast cell activation that drives the symptoms. The first line of treatment involves the regular use of non-sedating, second-generation H1 antihistamines. For many patients with CSU, standard doses are often insufficient, necessitating an increase to up to four times the standard daily dose to achieve symptom control.
If symptoms remain poorly controlled despite the increased H1 antihistamine dose, a second-line approach may involve adding other medication classes, such as H2 blockers or leukotriene receptor antagonists. When symptoms are refractory to the maximum tolerated dose of antihistamines, treatment escalates to a third line, often involving targeted biological therapies.
The biologic agent Omalizumab is commonly used for this purpose, as it targets the IgE pathway to reduce mast cell activation. For a small subset of patients whose hives do not respond to Omalizumab, strong immunosuppressants like Cyclosporine may be used to dampen the overall immune response. Patients are also educated on avoiding non-specific factors, such as stress, hot temperatures, or non-steroidal anti-inflammatory drugs, which can exacerbate the underlying condition. Patients with a history of severe angioedema are advised to carry an epinephrine auto-injector in case of a rapidly progressing episode.