Cold urticaria, often referred to as cold hives, is a skin condition characterized by the formation of large, red welts on the skin following exposure to a cold stimulus. These hives are typically itchy, and affected areas, such as the hands and feet, may also become swollen. The size of these welts can vary significantly, ranging from approximately 7 mm to 27 mm or even larger. This disorder can manifest in two primary forms: an inherited type known
as familial cold urticaria, or an acquired type called primary acquired cold urticaria. The acquired form commonly begins between the ages of 18 and 25, though it can appear as early as five years old in some individuals. Understanding the triggers and manifestations of this condition is crucial for managing its impact on daily life.
Symptoms and Risks Associated with Cold Exposure
When individuals with cold urticaria are exposed to cold, hives appear, and the skin in the affected area typically becomes itchy. These hives are a result of the dilation of capillaries, which allows fluid to leak into the surrounding epidermal tissue. The welts resolve as the body reabsorbs this fluid. The border of a hive is often described as polycyclic, meaning it is made up of many circles, and its appearance changes as fluid leaks out and is then absorbed. Pressing on a hive causes the skin to blanch, turning pale as blood flow is interrupted, which helps distinguish it from a bruise or papule. Hives can appear immediately or after a delay, and their duration varies from a few minutes to several days, differing from person to person. A burning sensation may also accompany the hives.
Severe reactions are more likely in patients whose hives appear within less than three minutes of cold exposure during a cold test. Life-threatening risks associated with cold urticaria include suffocation due to swollen tissue in the throat (pharyngeal angioedema) if cold foods or beverages are consumed. Drowning can occur after shock from swimming in cold water, and anaphylactic shock is another serious potential complication. The common form of cold urticaria often presents with a rapid onset of hives on the face, neck, or hands after cold exposure. This form is common and typically lasts for an average of five to six years, primarily affecting young adults between 18 and 25 years old. Many individuals with this condition also experience dermatographism and cholinergic hives.
Causes and Genetic Factors
Cold urticaria hives are essentially a histamine reaction in response to cold stimuli, which can include a drastic drop in temperature, cold air, or cold water. While many cases are spontaneous and idiopathic, meaning they have no known mechanism of origin, some rare conditions can cause cold hives. It can be beneficial to test for these conditions if the cold hives present in an unusual manner. Scientists from the USA National Institutes of Health have identified a genetic mutation in three unrelated families that leads to a rare immune disorder. This disorder is characterized by both excessive and impaired immune function, including immune deficiency, autoimmunity, inflammatory skin disorders, and cold-induced hives.
This identified mutation occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. Researchers have named this condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID. Familial cold urticaria, also known as familial cold autoinflammatory syndrome (FCAS), is an autosomal dominant condition. It is characterized by a rash, conjunctivitis, fever/chills, and joint pain, all triggered by exposure to cold, sometimes even temperatures below 22 °C (72 °F). FCAS has been mapped to CIAS1 and is considered a slightly milder member of a disease family that includes Muckle-Wells syndrome and NOMID. It is a rare condition, estimated to affect about 1 per million people, primarily impacting Americans and Europeans. FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (also known as NLRP3) gene at location 1q44.
Diagnosis and Management Strategies
Diagnosis of cold urticaria is typically performed by an allergist or another licensed practitioner through a cold test. During this test, a piece of ice, placed inside a thin plastic bag, is held against the forearm, usually for three to four minutes. A positive result is indicated by a specific mark of raised red hives. These hives may take the shape of the ice or radiate from the contact area. While these techniques aid in diagnosis, they do not provide information about the temperature and stimulation time thresholds at which patients will begin to develop symptoms. This information is essential for establishing disease severity and monitoring the effectiveness of treatment.
For individuals with cold urticaria, it is crucial to learn how to protect themselves from a rapid drop in body temperature. Regular antihistamines are generally not effective for this condition. However, one particular antihistamine, cyproheptadine (Periactin), has been found to be useful. The tricyclic antidepressant doxepin has also been identified as an effective blocking agent of histamine. Additionally, a medication called ketotifen, which prevents mast cells from releasing histamine, has been successfully employed. Severe reactions can occur with exposure to cold water, with swimming in cold water being the most common cause of such reactions. This can lead to a massive discharge of histamine, potentially resulting in low blood pressure, fainting, shock, and even loss of life.
