Specialty dermatology ICD-9-CM 708.2 DiseasesDB 4688 | ICD-10 L50.2 (ILDS L50.210) OMIM 120100 | |
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Cold urticaria (essentially meaning "cold hives") is a disorder where hives (urticaria) or large red welts form on the skin after exposure to a cold stimulus. The welts are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about 7mm in diameter to as big as about 27mm diameter or larger. The disease is classified as chronic when hives appear for longer than 6 weeks; they can last for life, though their course is often unpredictable. This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to occur between ages 18–25, although it can occur as early as 5 years old in some cases.
Contents
Types
Cold urticaria may be divided into the following types:
Primary cold contact urticaria
Primary cold contact urticaria is a cutaneous condition characterized by weals, and occurs in rainy, windy weather, and after swimming in cold water and after contact with cold objects, including ice cubes.
Secondary cold contact urticaria
Secondary cold contact urticaria is a cutaneous condition characterized by weals, due to serum abnormalities such as cryoglobulinemia or cryofibrinogenemia are extremely rare, and are then associated with other manifestations such as Raynaud's phenomenon or purpura.
Reflex cold urticaria
Reflex cold urticaria is a cutaneous condition in which generalized cooling of the body induces widespread wealing.
Familial cold urticaria
Familial cold urticaria (also properly known as familial cold autoinflammatory syndrome, FCAS) is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22 °C (72 °F).
It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells syndrome and NOMID. It is rare and is estimated as having a prevalence of 1 per million people and mainly affects Americans and Europeans.
FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (aka NLRP3) gene at location 1q44. The disease was described in The Lancet Volume 364 by Hoffman H.M. et al.
The effect of FCAS on the quality of life of patients is far reaching. A survey of patients in the United States in 2008 found, "To cope with their underlying disease and to try to avoid symptomatic, painful, flares patients reported limiting their work, school, family, and social activities. Seventy-eight percent of survey participants described an impact of the disease on their work, including absenteeism and impaired job advancement; frequently, they quit their job as a consequence of their disease".
Treatment using anakinra (Kineret) has been shown effective for FCAS, although this does mean daily injections of the immunosuppressant into an area such as the lower abdomen. The monoclonal antibody canakinumab (Ilaris) is also used.
Symptoms
When the body is exposed to the cold in individuals afflicted by the condition, hives appear and the skin in the affected area typically becomes itchy. Hives result from dilation of capillaries which allow fluid to flow out into the surrounding tissue which is the epidermis.They resolve when the body absorbs this fluid. The border of a hive is described as polycyclic, or made up of many circles, and changes as fluid leaks out and then is absorbed. Pressing on a hive causes the skin to blanch distinguishing it from a bruise or papule. Hives can last for a few minutes or a few days, and vary from person to person. Also, a burning sensation occurs. During a severe reaction, low blood pressure, which can be life-threatening, can occur. A serious reaction is most likely to occur if the hives occur with less than 3 minutes of exposure (during a cold test).
Cause
The hives are a histamine reaction in response to cold stimuli, including a drastic drop in temperature, cold air, and cold water. There are many causes for cold hives, most are idiopathic (meaning they have no known cause). Some rare conditions can cause cold hives, and it can be useful to test for these conditions if the cold hives are in any way unusual.
Scientists from the USA National Institutes of Health have identified a genetic mutation in three unrelated families that causes a rare immune disorder characterized by excessive and impaired immune function: immune deficiency, autoimmunity, inflammatory skin disorders and cold-induced hives (cold urticaria).
"The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID."
Diagnosis
Diagnosis is typically obtained by an allergist or other licensed practitioner performing a cold test. During the cold test, a piece of ice is held against the forearm, typically for 3–4 minutes. A positive result is a specific looking mark of raised red hives. The hives may be the shape of the ice, or it may radiate from the contact area of the ice.
" However, while these techniques assist in diagnosis, they do not provide information about temperature and stimulation time thresholds at which patients will start to develop symptoms."
which is essential because it can establish disease severity and monitor the effectiveness of treatment.
Treatment
The first-line therapy in ColdU, as recommended by EAACI/GA2 LEN/EDF/WAO guidelines, is symptomatic relief with second-generation H1- antihistamines. if standard doses are ineffective increasing up to 4-fold is recommended to control symptoms.
The second-generation H1-antihistamine, rupatadine, was found to significantly reduced the development of chronic cold urticaria symptom without an increase in adverse effects using 20 and 40 mg.
Allergy medications containing antihistamines such as diphenhydramine (Benadryl), cetirizine (Zyrtec), loratidine (Claritin), cyproheptadine (Periactin), and fexofenadine (Allegra) may be taken orally to prevent and relieve some of the hives (depending on the severity of the allergy). For those who have severe anaphylactic reactions, a prescribed medicine such as doxepin, which is taken daily, should help to prevent and/or lessen the likelihood of a reaction and thus, anaphylaxis. There are also topical antihistamine creams which are used to help relieve hives in other conditions, but there is not any documentation stating it will relieve hives induced by cold temperature.
Cold hives can result in a potentially serious, or even fatal, systemic reaction (anaphylactic shock). People with cold hives may have to carry an injectable form of epinephrine (like Epi-pen or Twinject) for use in the event of a serious reaction. The best treatment for this allergy is avoiding exposure to cold temperature.
Ebastine has been proposed as an approach to prevent acquired cold urticaria.