Cu develops following exposure to cold stimulus and present as diffuse or localized urticaria, angioedema or systemically as anaphylactic reaction. The symptoms develop 2-5 minutes following exposure and may last for 1-2 hours. The skin reacts abnormally to the cold in CU. It may occur following swimming in cold water or exposure to cold conditions. The skin turns red and becomes itchy. Fever, headache, anxiety, tiredness or fainting is also reported in CU. Cold water swimming is most common cause of severe cold urticarial reaction. 

The essential or acquired cold urticaria has various sub-categories. It includes localized cold urticaria, delayed cold urticaria, reflex cold urticaria or secondary cold urticaria and primary acquired cold urticaria. From all, the primary acquired CU is the most frequently encountered form of CU. It develops 5 to 30 min after exposure to cold stimuli. The reaction most commonly occurs during the rewarming phase, though it may occur in cold also. It starts with itching and reddening of the skin, followed by a burning sensation. Hives may appear which usually last for 30 minutes. Palpitations, headache, fainting, or wheezing attacks may also occur in the affected person.

Secondary CU is a less common type of urticaria and develops in response to underlying medical conditions like autoimmune diseases or systemic infections. The major symptoms of secondary CU are similar to that of primary CU. Hives develop on exposure to cold and secondary CU patients gives positive CST, almost immediately after cold exposure. Major infections and systemic diseases that trigger CU include cryoglobulinemia (with or without malignancies), viral infections like HIV and hepatitis, bacterial infection like syphilis and some parasitic infections.
Other types of essential CU include -
Delayed cold urticaria: The symptoms develop many hours after the exposure to cold.
Localized cold urticaria: As the name implies, it occurs locally at the sites of previously taken ladybug bites or ragweed injections for allergies.
Reflex cold urticaria: It occurs as extensive development of welts following local exposure to cold, which results in a sudden drop of body temperature e.g. following application of ice packs.
Familial or hereditary form of cold urticaria is a rare type which develops as early as 30 min following exposure to cold stimuli and may persist up to 48 hours. Leucocytosis or arthralgia, fever, tiredness and headache may also develop along with itchy and red skin.

• Fever

  He denied fever, purpura, hemoglobinuria, Raynaud's disease, or arthralgias. Family history was negative for cold urticaria. Immunologic studies revealed elevated IgM (186 mg/dL) as well as decreased CH100 and C4 (8.0 mg/dL). [ncbi.nlm.nih.gov]

  A candidate gene for familial Mediterranean fever. Nature Genet. 17, 25–31 (1997). 22 Centola, M. et al. [doi.org]

  In addition to the skin rash, episodes are characterized by fever, chills, and joint pain, most often affecting the hands, knees, and ankles. [ghr.nlm.nih.gov]

  They are characterized by intermittent episodes of fever, urticarial rash, arthralgias, and abdominal pain. In FCAS, the symptoms are precipitated by exposure to cold. [genedx.com]

• Urticaria

  Acquired cold urticaria with a negative cold stimulation test has been described in seven patients in whom the standard ice cube test did not induce localized urticaria. Subsequent total body cold exposure induced a generalized urticaria. [ncbi.nlm.nih.gov]

  The essential or acquired cold urticaria has various sub-categories. It includes localized cold urticaria, delayed cold urticaria, reflex cold urticaria or secondary cold urticaria and primary acquired cold urticaria. [symptoma.com]

• Pruritus

  Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge. [ncbi.nlm.nih.gov]

  Caroline Gaudy-Marqueste, Antihistamines, Pruritus, 10.1007/978-3-319-33142-3_48, (363-377), (2016). [doi.org]

• Skin Rash

  In addition to the skin rash, episodes are characterized by fever, chills, and joint pain, most often affecting the hands, knees, and ankles. [ghr.nlm.nih.gov]

  When the skin reddens and forms bumps or a welt the test is positive. Often the rewarming of the skin after the cold contact leads to the skin rash. [healthcentral.com]

  People who have intense physical reactions to low temperatures — including skin rashes and hives, swelling, fatigue, anxiety, headaches, and wheezing or trouble breathing — may suffer from " cold urticaria" or "cold-induced urticaria ," which is the formal [bustle.com]

  Medical review by: Khanh-Van Le-Bucklin, Rebecca Hicks Last medical review: January 01, 2015 Updated: February 20, 2017 Allergies Allergy Treatment Cold Skin & Rashes Top Allergies Dr. [drgreene.com]

  rash, hepatotoxicity, GI disturbances. [e-ijd.org]

• Eczema

  The case report is of a 22-year old male who had previously been diagnosed as suffering from eczema. [ncbi.nlm.nih.gov]

  Cancer, Sunscreen Warnings, Acne, Aesthetic Mishaps, Eczema View Issue [practicaldermatology.com]

  Urticaria differs from eczema (atopic dermatitis) in that eczema is characterized by dryness, crusting, blistering, cracking, oozing, or bleeding. Hives are not typically described in these ways. [verywell.com]

  On the other hand, only 4 of the 30 patients had eczema. There was a high rate of atopy in the patients’ families. Of 28 patients who had their family history available, 25 (89.3%) had a family history of atopy. [pediatrics.aappublications.org]

  Urticaria may be confused with a variety of other dermatologic diseases that are similar in appearance and are pruritic including atopic dermatitis (eczema), maculopapular drug eruptions, contact dermatitis, insect bites, erythema multiforme, pityriasis [emedicine.medscape.com]

The cold stimulation test (CST) also called as ice cube test is the main diagnostic test used for the evaluation and diagnosis of CU. The test comprises of application of a cold stimulus (0–4°C).
Test procedure: In a patient suspected of CU, ice cube in a plastic bag is placed on the volar surface of the forearm for about five minutes allowing 5- 10 min time for rewarming. This increase in skin temperature is required for the formation of hives. Appearance of a coalescent wheal or hive is considered as positive test result for CU. Once diagnosed is established, the degree of sensitivity can be determined by repeating the cold stimulation for shorter durations. It also establishes the minimum time required for the development of wheal, called as cold stimulation time test. In case the test is negative result with five minute application time, it can be repeated with longer application time i.e. for 10 minutes [6] [11].
The test is considered negative when no wheal appears after the application of cold stimulus. It may occur in the atypical forms of CU [11]. Also, a familial CU is not ruled out by a negative response to CST. Sometimes, exposure of 20 -30 min is required to develop the response to CST.

CU has usually a benign course and patients need to be advised regarding the importance of proper protection to avoid development of CU when exposure to cold is unavoidable. Also, exposure to rapid cold development should be avoided. Physicians generally urge the CU patients to keep a CU activity score daily diary [12] to identify the potential triggers for CU episode. The therapy for cold urticaria may be difficult. It involves avoidance of triggering factors, education, use of antihistamines and use of epinephrine autoinjector in severe cases.
In case of severe CU attack and anaphylaxis, proper action and prompt use of epinephrine autoinjector is needed. In most cases, second generation anithistamines are the drug of choice in managing CU induced itchiness and hives [13] [14]. An example for H2 receptor blocker is Tegamet which is found to be very effective in managing CU.
In case of secondary CU, the underlying systemic infections and diseases should be treated to improve the skin symptoms. Despite use, the response to H1 antihistamines is highly variable. Low concentration corticosteroids used for short duration helps only in temporary and partial suppression of the symptoms. In patients who fail to give a positive response to conventional prescription medications, induction of cold tolerance is may be tried. The major drawback of this method is that it is very difficult to perform daily for an extended period of time and is generally not practical. Conventional antihistamines are usually ineffective and higher doses of antihistamines which are non-sedating in nature can be helpful under such circumstances. Some other related drugs which can be used to manage CU include epinephrine, diphenhydramine, cyproheptadine, hydrochloride, cetirizine, ketotifen and doxepin.
Preventive measures to avoid CU attack include the using warm clothes when exposed to cold weather. Avoiding swimming in cold water is especially important as in some cases the consciousness of the patient may be lost during a CU attack leading to drowning and death.

CU is a chronic disease lasting for many years. The prognosis is fairly good and about 30% of the diagnosed individuals experience spontaneous remission of symptoms within a period 5 to 10 years.

CU is a common condition affecting about 2 or 3 per 100 population. It is present in around 6 to 34% of all the diagnosed cases of physical utricaria [1] [2]. Regions with the colder environment show a high frequency of CU [2]. Triggering factors can vary greatly from patient to patient. The major triggering factors that may lead to a reaction include - consumption of cold food, cold drinks, swimming in cold water and exposure to cold weather.

Cold urticaria can either be primary (idiopathic with no known cause) or secondary in response to an underlying haematologic condition or infectious diseases. Most reported cases are idiopathic in nature. Patients having cold-dependent antibodies, e.g. cryoglobulins or cold agglutinins can also develop CU [3]. A very rare form of familial CU is also reported which has a dominant pattern of inheritance [4]. CU is a very unique inflammatory condition that is characterized by degranulation of mast-cell upon exposure to cold stimuli. In some cases, CU may also lead to anaphylaxis – a life threatening reaction [5] [6].

CU can also occur as an idiopathic condition or may be transmitted as an autosomal dominant trait i.e. when an individual acquires a single gene copy either from father or mother. The dominant gene overshadows the normal gene hindering it from expressing itself. In such cases there is 50% risk of transmitting this disorder to the offspring in each pregnancy irrespective of the sex of the child. The chance of acquiring disease remains the same in subsequent pregnancies.

Familial CU is relatively rare and is presented differently in different patients. The defective gene in familial CU is located on the long arm of chromosome 1 (Iq40).

In some cases, CU may occur as a manifestation of underlying autoimmune condition of the patient during which body’s natural protective defense mechanism start attacking own healthy tissue.

Cu is found over a broad age group ranging from 3 months to 74 years, though, is found more frequently in young adults (20-30 years). Both men and women are affected equally with this disease.
Acquired or essential CU accounts for approximately 1 to 3% of all the reported cases of urticaria. It frequently affects middle-aged and young adults but is also seen in children and elderly. The disease duration spans from 4.8 to 9.3 years with 50% of the affected people showing improvement in around 5 years [1] [2] [7]. It is seen commonly associated various physical and cholinergic urticaria. Familial form of CU is rare in occurrence.

The pathophysiology of cold urticaria is not clearly understood. However, the role of IgE antibodies has been suggested. Upon exposure to cold temperature, IgE antibodies react with specific skin antigens, resulting in the release of various inflammatory mediators including histamine [8] [9] [10]. Despite the clear implication of mast cells in the development of cold urticaria [9], the exact mechanism leading to their degranulation is yet to be elucidated.

Avoidance of cold temperature is the single best and most effective way of preventing an episode of CU. More severe cases of CU are reported in individuals after surfing and swimming in cold water. It is therefore advisable to instruct patients to refrain themselves from engaging in such activities.
Some of the other preventive measures include-
1. Administration of over the counter antihistamine medication before the cold exposure.
2. Shielding the body from exposure to cold water by wearing a wet suit while swimming. However it should be noted that the success of this method is not scientifically proven.
3. Refraining from consumption of cold food and drinks to avoid CU induced swelling of throat.
4. Carrying a physician prescribed epinephrine autoinjector e.g. Epipen, Auvi-Q and using it in case of an anaphylactic attack.
5. Before undergoing a scheduled surgery, inform the concerned surgeon about the condition so that the operating team can take necessary actions to prevent an episode of CU induced complication during and after surgery.

Cold urticaria (CU) is a form of chronic physical urticaria which is difficult to diagnose and manage. Symptoms may range from mild, localized urticaria to anaphylaxis. Exposure to cold is the major triggering factor in most of the reported cases.
CU is generally of two types:
Acquired also called as essential CU: The symptoms develop within 2 to 5 minutes following exposure to cold. The symptoms last for about 1 to 2 hours.
Hereditary or familial CU: The symptoms develop at least 24 to 48, hours, post exposure and last for about 24 to 48 hours.
The best method preventive method is to avoid exposure to cold environments. It does not have any cure and generally resolves itself within a span of 5 to 10 years following the first incidence. Milder symptoms are treated using antihistamines and in case of anaphylactic attacks, epinephrine auto injectors are used to manage the situation.

Cold urticaria (CU) is a condition in which the body reacts to cold temperature in the form of red itchy skin. Fever, anxiety, headache, tiredness, and fainting are also experienced by some individuals. Some may experience palpitation (sensation of abnormal heart beat) and wheezing (whistling sound heard during breathing) also. There are essentially two types of CU.
1. Acquired (essential) CU - The symptoms of acquired CU develop relatively faster, often within a few minutes after exposure and the whole episode will subdue in one to two hours post exposure.
2. Familial (heriditary) CU - The symptoms of familial CU usually develop 30 minutes after the exposure to cold and can last up to 48 hours post exposure.
CU can be clinically confirmed via cold stimulation test (CST) and medical history. Cetirizine is the drug of choice and is found to be more effective with less side effects when compared to that of other antihistamines available in the market. Cold urticaria can also affect children and sometimes anaphylaxis is also reported among this group. History of CU with anaphylaxis in children deserves special attention and epinephrine autoinjector should always be carried along with them. Parents should be trained to use the injector in case of an anaphylactic attack.
CU is a preventable disease and patients can reduce the number of episodes by simply preventing themselves from exposure to cold temperature. Swimming and surfing in cold water is the most frequent triggering factor and therefore the utmost care should be exercised.

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