Urticaria, commonly known as hives, is a skin condition characterized by the sudden appearance of raised, intensely itchy welts called wheals. Most people experience acute hives triggered by a clear external factor like a food allergy or an infection. However, a substantial group suffers from a chronic form, defined by the persistence of hives for six weeks or longer, often recurring daily without any apparent outside cause. When no external trigger is found, the condition is termed Chronic Spontaneous Urticaria (CSU). Between 30% and 50% of these chronic cases are believed to have an underlying autoimmune cause, meaning the body’s own immune system is mistakenly driving the reaction.
How Autoimmunity Causes Hives
Autoimmune hives result from a malfunction where the immune system generates autoantibodies that target components involved in the allergic response. The immune system produces Immunoglobulin G (IgG) antibodies that specifically attack the high-affinity IgE receptor (FcεRI) found on the surface of mast cells. Mast cells store and release histamine, the chemical responsible for the itching and swelling associated with hives. The binding of the IgG autoantibodies to the mast cell receptors mimics the action of an external allergen.
This binding causes the mast cells to spontaneously degranulate, releasing histamine and other inflammatory mediators into the surrounding skin tissue. This self-directed activation is why the hives are “spontaneous” and occur without an outside trigger. Some patients also exhibit a different autoimmune mechanism where IgE autoantibodies are directed against self-proteins, such as thyroid peroxidase, leading to continuous mast cell activation. The presence of these autoantibodies creates a constant state of internal alert, perpetually triggering the release of inflammatory chemicals and sustaining the chronic hive outbreaks.
Recognizing the Symptoms and Duration
Autoimmune hives are characterized by wheals, which appear as well-circumscribed areas of swelling that are typically pale in the center with a surrounding red flare. These individual lesions are transient, usually fading completely within 24 hours without leaving a bruise or scar. The defining feature is the relentless recurrence, as new wheals continuously emerge to replace the fading ones, maintaining the chronic state.
In addition to the surface welts, about 40% to 50% of patients also experience angioedema, a deeper, more diffuse swelling. Angioedema often affects the eyelids, lips, tongue, hands, or feet. While it is less itchy than surface hives, it can be painful or cause a tight sensation. These spontaneous outbreaks must persist for at least six weeks for diagnosis.
Diagnosing Autoimmune Hives
The diagnostic process for autoimmune hives begins by confirming the diagnosis of Chronic Spontaneous Urticaria and ruling out other potential causes, such as physical triggers, infections, or allergic reactions. Once other causes are eliminated, specific tests can be performed to support the autoimmune nature of the condition. One specialized procedure is the Autologous Serum Skin Test (ASST), which detects the presence of circulating histamine-releasing autoantibodies.
The ASST involves drawing a small sample of the patient’s blood, allowing it to clot, and then spinning it down to separate the serum. This serum is then injected intradermally into the patient’s forearm, typically alongside a histamine control and a saline control. A reaction at the serum injection site, resulting in a wheal that is at least 1.5 millimeters larger than the saline control after 30 minutes, indicates a positive test. This positive result suggests the presence of activating autoantibodies in the patient’s circulation.
Blood work is also used to check for an association with other autoimmune conditions. A strong link exists between CSU and autoimmune thyroid disease, so physicians routinely test for thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg) antibodies. Elevated levels of these thyroid antibodies are found in a significant percentage of patients with autoimmune CSU, suggesting a common underlying immune vulnerability.
Treatment and Long-Term Management
The initial therapeutic approach for managing autoimmune hives typically involves high-dose, non-sedating H1 antihistamines, often prescribed at doses up to four times the standard amount. This higher dosing regimen aims to block the effects of the excessive histamine released by the activated mast cells. However, for a substantial number of patients, this first-line treatment fails to provide sufficient symptom control.
For those who remain symptomatic, second-line treatment involves biologic medications, such as Omalizumab. Omalizumab is a monoclonal antibody that targets Immunoglobulin E (IgE). By binding to free IgE in the circulation, the drug effectively lowers the overall IgE levels and causes the high-affinity IgE receptors on the mast cell surface to decrease in number.
This action dampens the overall reactivity of the mast cells, making them less susceptible to activation by the circulating autoantibodies. Patients who do not respond adequately to Omalizumab may be considered for third-line treatments, which can include immunosuppressants like Cyclosporine. Long-term management focuses on finding the right combination of medications to achieve complete symptom control and maintain a high quality of life.