Cold urticaria is a skin condition characterized by the sudden appearance of hives and other symptoms upon exposure to cold temperatures. This physical reaction can range from mild skin irritation to severe whole-body responses. While its triggers are clearly linked to cold, the underlying causes are not always straightforward, leading to questions about its classification as an autoimmune disease.
What is Cold Urticaria
Cold urticaria (CU) is a type of physical urticaria, where hives are triggered by a physical stimulus like cold. Upon exposure to cold air, water, or objects, individuals develop itchy welts on the affected skin. These red, swollen, and often burning rashes typically appear within minutes after cold exposure and can last for one to two hours. Symptoms might worsen as the skin rewarms.
Beyond skin reactions, severe cases can lead to systemic symptoms, particularly with extensive cold exposure like swimming in cold water. These reactions can include generalized swelling, a racing heart, fainting, and even anaphylaxis. Swelling of the lips, tongue, and throat can also occur, posing a risk to breathing.
Cold urticaria can be acquired or familial. Acquired forms are more common, with the primary type often having an unknown cause. Familial cold urticaria, now called familial cold autoinflammatory syndrome (FCAS), is a rare genetic form with symptoms that can appear later, last longer, and may include flu-like symptoms.
Defining Autoimmune Disease
An autoimmune disease occurs when the body’s immune system, which normally defends against foreign invaders, mistakenly attacks its own healthy cells and tissues. This misdirected response stems from a breakdown in immune tolerance, where the immune system fails to distinguish between “self” and “non-self” components.
The immune system’s attack can involve various mechanisms, including the production of autoantibodies, which are specialized proteins that target the body’s own substances. Additionally, autoreactive T-cells can directly attack and damage healthy tissues. This internal assault leads to inflammation and damage in the affected organs or systems.
There are over 100 different types of autoimmune diseases, each potentially affecting various parts of the body. Common examples include rheumatoid arthritis, where the immune system attacks the joints, and lupus, which can affect multiple organ systems. Other well-known autoimmune conditions are type 1 diabetes and Hashimoto’s thyroiditis.
Exploring the Autoimmune Connection
Whether cold urticaria is an autoimmune disease is complex, as it encompasses a spectrum of conditions. While many cases of acquired cold urticaria have an unknown cause, a subset is considered to have an autoimmune basis.
In certain individuals, the immune system mistakenly produces autoantibodies. These autoantibodies often target components on the surface of mast cells, which are immune cells in the skin responsible for releasing histamine and other inflammatory mediators that cause hives. Specifically, autoantibodies can bind to the high-affinity IgE receptor (FcεRI) on mast cells and basophils, or less commonly, to IgE itself.
When these autoantibodies bind to mast cells, they trigger the release of histamine and other chemicals, even without a typical allergen. This process mimics an allergic reaction, leading to the characteristic hives, swelling, and itching. The presence of these functional autoantibodies classifies these cases as autoimmune cold urticaria.
Not all instances of cold urticaria involve these specific autoantibodies. Familial cold autoinflammatory syndrome (FCAS), for example, is a genetic autoinflammatory condition with cold-induced symptoms. However, it involves different genetic mutations and inflammatory pathways, distinct from autoantibody-mediated autoimmune cold urticaria.
Cold urticaria can also occur as a secondary condition alongside other diagnosed autoimmune diseases, suggesting broader immune dysregulation. Conditions like Hashimoto’s thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, and celiac disease have been observed in patients with chronic urticaria, including cold-induced forms.
Diagnosing and Managing Cold Urticaria
Diagnosis typically begins with a detailed medical history and physical examination. The primary diagnostic tool is the cold stimulation test, also known as the ice cube test. An ice cube is placed on the forearm for a few minutes. A positive result is the development of a distinct hive or welt on the exposed skin area within minutes after removal, often as the skin rewarms.
While the ice cube test is central, additional blood tests may be performed for chronic or atypical cases, or if an underlying condition is suspected. These tests can help rule out secondary causes, such as infections or blood disorders. If an autoimmune connection is suspected, specific autoantibody testing, like for anti-IgE or anti-FcεRI antibodies, and inflammatory markers might be considered.
Management focuses on symptom control and trigger avoidance. Non-drowsy antihistamines are generally the first-line treatment, often taken before anticipated cold exposure. For individuals not controlled with antihistamines, particularly those with a suspected autoimmune component or severe symptoms, advanced therapies like omalizumab may be considered. Omalizumab is a monoclonal antibody that targets IgE, helping to reduce mast cell activation. In severe or resistant cases, immunosuppressants might also be explored.
Alongside medication, lifestyle modifications are important. Individuals should avoid sudden temperature changes, dress warmly in cold weather, and take precautions during activities involving cold water, such as swimming. Carrying an epinephrine auto-injector is recommended for those with a history of severe systemic reactions or anaphylaxis.