Cold urticaria#Primary cold contact urticaria

Cold urticaria may be divided into the following types:{{cite book |author1=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages=267–8 |isbn=978-1-4160-2999-1 }}

Primary cold contact urticaria is a cutaneous condition characterized by wheals, 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 is a cutaneous condition characterized by wheals, 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 is a cutaneous condition in which generalized cooling of the body induces widespread welting.

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{{cite journal |last1=Tunca |first1=Mehmet |last2=Ozdogan |first2=Huri |title=Molecular and Genetic Characteristics of Hereditary Autoinflammatory Diseases |journal=Current Drug Targets. Inflammation and Allergy |date=2005 |volume=4 |issue=1 |pages=77–80 |doi=10.2174/1568010053622957 |pmid=15720239 |doi-access=free |publisher=Bentham Science Publishers }} elicited by exposure to cold – sometimes temperatures below {{convert|22|C|F}}.{{cite book |last1=James |first1=William D. |last2=Berger |first2=Timothy G. |last3=Elston |first3=Dirk M. |last4=Grekin |first4=Roy C. |last5=Neuhaus |first5=Isaac M. |last6=Wei |first6=Maria L. |title=Andrews' Diseases of the Skin: Clinical Dermatology |date=2006 |publisher=Saunders, Elsevier |location=Philadelphia, PA |isbn=0-7216-2921-0 |pages=165–166 |edition=10th |chapter=Erythema and Urticaria}}

It has been mapped to CIAS1{{cite journal |vauthors=Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD |title=Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome |journal=Nat. Genet. |volume=29 |issue=3 |pages=301–5 |date=November 2001 |pmid=11687797 |doi=10.1038/ng756 |pmc=4322000}} 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.{{cite web |title=Familial cold autoinflammatory syndrome |url=https://medlineplus.gov/genetics/condition/familial-cold-autoinflammatory-syndrome |website=MedlinePlus |publisher=U.S. National Library of Medicine, National Institutes of Health |access-date=27 July 2021}}

FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (aka NLRP3) gene at location 1q44.{{cite web| last = CAPS| first = Community| title = Familial Cold Auto-inflammatory Syndrome (FCAS): Fact Sheet| publisher = Regeneron Pharmaceuticals| date = 2008-01-01| url = http://www.capscommunity.com/caps_fact_fcas_md.html| access-date = 2010-02-01| archive-url = https://web.archive.org/web/20160304031454/http://www.capscommunity.com/caps_fact_fcas_md.html| archive-date = 2016-03-04| url-status = dead}}{{cite web |last1=Tweedie |first1=Susan |last2=Braschi |first2=Bryony |last3=Gray |first3=Kristian |last4=Jones |first4=Tamsin E. M. |last5=Seal |first5=Ruth L. |last6=Yates |first6=Bethan |last7=Bruford |first7=Elspeth A. |title=Symbol report for NLRP3 |website=HGNC |publisher=Human Genome Organisation |access-date=27 July 2021 |id=16400 |url=https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16400}}{{cite journal |last1=Smith |first1=David W. |last2=Johnson |first2=Kenneth A. |last3=Bingman |first3=Craig A. |last4=Aceti |first4=David J. |last5=Blommel |first5=Paul G. |last6=Wrobel |first6=Russell L. |last7=Frederick |first7=Ronnie O. |last8=Zhao |first8=Qin |last9=Sreenath |first9=Hassan |last10=Fox |first10=Brian G. |last11=Volkman |first11=Brian F. |last12=Jeon |first12=Won Bae |last13=Newman |first13=Craig S. |last14=Ulrich |first14=Eldon L. |last15=Hegeman |first15=Adrian D. |last16=Kimball |first16=Todd |last17=Thao |first17=Sandy |last18=Sussman |first18=Michael R. |last19=Markley |first19=John L. |author19-link=John Markley |last20=Phillips |first20=George N. Jr.|title=1Q44 |url=https://www.rcsb.org/structure/1Q44 |website=PDB |publisher=Research Collaboratory for Structural Bioinformatics |access-date=27 July 2021 |doi=10.2210/pdb1Q44/pdb |date=2003}}{{cite journal |last1=Hoffman |first1=Hal M. |last2=Rosengren |first2=Sanna |last3=Boyle |first3=David L. |last4=Cho |first4=Jae Y. |last5=Nayar |first5=Jyothi |last6=Mueller |first6=James L. |last7=Anderson |first7=Justin P. |last8=Wanderer |first8=Alan A. |last9=Firestein |first9=Gary S. |author9-link=Gary Firestein |title=Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist |journal=The Lancet |date=November 2004 |volume=364 |issue=9447 |pages=1779–1785 |doi=10.1016/S0140-6736(04)17401-1 |pmid=15541451 |publisher=Elsevier |pmc=4321997}}

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 that "[t]o 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".{{cite journal|doi=10.1185/03007990802081543|pmid=18423104|year=2008|last1=Stych|first1=B|last2=Dobrovolny|first2=D|title=Familial cold auto-inflammatory syndrome (FCAS): characterization of symptomatology and impact on patients' lives.|volume=24|issue=6|pages=1577–82|journal=Curr Med Res Opin|s2cid=23371016}}

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.{{cite journal| last1 = Ross JB | title = Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-up| date = 2010-02-01| pmid = 18258152| last2 = Finlayson| first2 = LA| last3 = Klotz| first3 = PJ| last4 = Langley| first4 = RG| last5 = Gaudet| first5 = R| last6 = Thompson| first6 = K| last7 = Churchman| first7 = SM| last8 = McDermott| first8 = MF| last9 = Hawkins| first9 = PN| volume = 12| issue = 1| pages = 8–16| journal = Journal of Cutaneous Medicine and Surgery|display-authors=etal| doi = 10.2310/7750.2008.07050| s2cid = 34516905}}{{cite journal| last = Samy K Metyas | first = Hal M Hoffman| title = Anakinra prevents symptoms of familial cold autoinflammatory syndrome and Raynaud's disease.| journal = The Journal of Rheumatology| volume = 33| issue = 10| pages = 2085–2087| publisher = Journal of Rheumatology| date = 2008-02-01| url = http://www.jrheum.org/content/33/10/2085.abstract| access-date =2010-02-01| pmid = 16981288}} The monoclonal antibody canakinumab (Ilaris) is also used.{{cite journal|doi=10.1358/dot.2009.45.10.1436882|pmid=20069137|year=2009|last1=Walsh|first1=GM|title=Canakinumab for the treatment of cryopyrin-associated periodic syndromes|volume=45|issue=10|pages=731–5|journal=Drugs of Today}}

File:Cold allergy symptoms.jpg

When the body is exposed to the cold in individuals affected 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.{{citation needed|date=April 2020}} 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.{{cite journal | author = Bailey Evan, Shaker Marcus | year = 2008 | title = An Update on Childhood Urticaria and Angioedema | journal = Current Opinion in Pediatrics | volume = 20 | issue = 4| pages = 425–30 | doi=10.1097/mop.0b013e328305e262| pmid = 18622198 | s2cid = 27406621 }} Pressing on a hive causes the skin to blanch (turn pale as blood flow is interrupted), distinguishing it from a bruise or papule.

Hives may appear immediately or after a delay.{{Cite book |last=Yasmeen |first=Jabeen Bhat |chapter-url=https://books.google.com/books?id=oPkWEAAAQBAJ&pg=SA4-PA15 |title=Concise Dermatology |date=2021-03-04 |publisher=CRC Press |isbn=978-1-000-33966-6 |editor-last=Sarkar |editor-first=Rashmi |language=en |chapter=Immunologically mediated skin disorders |quote=Idiopathic cold urticaria may be immediate, delayed, localized, familial, or acquired.}} Hives can last for a few minutes or a few days, and vary from person to person. Also, a burning sensation occurs. A serious reaction is most likely to occur for patients where the hives occur with less than three minutes of exposure (during a cold test).{{cite journal |author1=Soter Nicholas A. |author2=Wasserman Stephen I. |author3=Austen K. Frank | year = 1976 | title = Cold Urticaria: Release into the Circulation of Histamine and Eosinophil Chemotactic Factor of Anaphylaxis during Cold Challenge | journal = New England Journal of Medicine| volume = 294 | issue = 13| pages = 687–90 | doi=10.1056/nejm197603252941302|pmid=55969 }}

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{{specify|date=July 2014}} 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).

{{blockquote|"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."{{cite news |url=https://www.nih.gov/news-events/news-releases/nih-scientists-find-cause-rare-immune-disease |publisher=National Institute of Allergy and Infectious Diseases, National Institutes of Health |date=11 January 2012 |title=NIH scientists find cause of rare immune disease: Genetic mutation leads to cold allergy, immune deficiency and autoimmunity}}}}

Diagnosis is typically obtained by an allergist or other licensed practitioner performing a cold test. During the cold test, a piece of ice is placed inside a thin plastic bag and held against the forearm, typically for 3–4 minutes.{{Cite book |last1=Traidl-Hoffmann |first1=Claudia |url=https://books.google.com/books?id=dStQEAAAQBAJ&pg=PA127 |title=Allergic Diseases – From Basic Mechanisms to Comprehensive Management and Prevention |last2=Zuberbier |first2=Torsten |last3=Werfel |first3=Thomas |date=2021-11-21 |publisher=Springer Nature |isbn=978-3-030-84048-8 |pages=127 |language=en}} 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.{{cite journal |author1=Abajian M. |author2=Curto-Barredo L. |author3=Krause K. |author4=Santamaria E. |author5=Izquierdo I. |author6=Church M. |author7=Maurer M. |author8=Giménez-Arnau A. | year = 2016 | title = Rupatadine 20 Mg and 40 Mg Are Effective in Reducing the Symptoms of Chronic Cold Urticaria | url = http://edocs.fu-berlin.de/docs/servlets/MCRFileNodeServlet/FUDOCS_derivate_000000006072/4446.pdf| journal = Acta Dermato Venereologica Acta Derm Venerol | volume = 96 | issue = 1| pages = 56–59 | doi=10.2340/00015555-2150|pmid=26038847 |doi-access=free }} 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.

Management largely consists of avoiding exposures that could trigger a reaction and taking medicine to manage the reaction. The best treatment for this allergy is avoiding exposure to cold temperatures.{{Cite web |title=Cold urticaria |url=https://www.mayoclinic.org/diseases-conditions/cold-urticaria/symptoms-causes/syc-20371046 |access-date=27 July 2021 |website=Mayo Clinic}}

Anything that lowers the skin temperature (not body's core temperature) can trigger a reaction in affected people. Avoiding exposures limits the risk of a reaction. The reaction usually affects the body parts that are exposed, so cold air could trigger a reaction to exposed skin or in the breathing passages if cold air is inhaled. Risky exposures include:

• Situations:
• Cold weather, including snow: Exposure to cold or cool air can quickly trigger a reaction; for example walking by the open freezer cases in a supermarket.
• Air conditioning: Entering a cool building during a summer day can result in a reaction.
• Cool/cold surfaces: Sitting on sidewalks which are cool, leaning on or grabbing a cold pole can result in hives forming on the area which had contact with the cool surfaces.
• Cold IV lines: Sometimes IV lines are cold, which can result in a reaction. A line of hives may appear within {{Convert|6 to 8|in|cm|abbr=on}} from the IV site in the pattern of a line going up the limb.
• Activities:
• File:Ice water.jpgCold foods and drinks: Eating or drinking cold or cool substances such as ice cream or iced tea may result in a reaction inside the mouth and throat.
• Swimming: Swimming can be especially dangerous, as the rapid heart rate combined with the onset of hives can lead to hypotension, shock, and drowning.
• Sweat: A reaction may even occur on a warm day or coming out of a sauna when there is sweat on the skin, since the reaction is triggered by skin temperature, not core temperature. If there is a breeze, it will rapidly cool the skin and create hives.
• Restriction of blood flow: Activities which cause tense muscles and reduce blood flow can cool the body parts enough to trigger itching and hives.

The first-line therapy is symptomatic relief with second-generation H₁-antihistamines.{{cite journal |last1=Abajian |first1=Marina |last2=Curto Barredo |first2=Laia |last3=Krause |first3=Karoline |last4=Santamaria |first4=Eva |last5=Izquierdo |first5=Iñaki |last6=Church |first6=Martin K. |last7=Maurer |first7=Marcus |last8=Giménez Arnau |first8=Ana |title=Rupatadine 20 mg and 40 mg are Effective in Reducing the Symptoms of Chronic Cold Urticaria |journal=Acta Dermato Venereologica |date=2016 |volume=96 |issue=1 |pages=56–59 |doi=10.2340/00015555-2150 |issn=0001-5555 |doi-access=free |publisher=Medical Journals Sweden|pmid=26038847 }} If standard dosing is ineffective, increasing dosages up to fourfold is recommended to control symptoms.{{cite journal |vauthors=Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, etal | year = 2014 | title = The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update | pmid = 24785199 | journal = Allergy | volume = 69 | issue = 7| pages = 868–887 | doi=10.1111/all.12313}}

The second-generation H₁-antihistamine rupatadine was found to significantly reduce the development of chronic cold urticaria symptom without an increase in adverse effects at doses of {{val|20|ul=mg}} and {{val|40|u=mg}}.

Allergy medications containing antihistamines such as diphenhydramine (Benadryl), cetirizine (Zyrtec), loratadine (Claritin), cyproheptadine (Periactin), and fexofenadine (Allegra) may be taken orally to prevent and relieve some of the hives.{{cite journal |last1=Mahmoudi |first1=Massoud |title=Cold-induced urticaria. |journal=The Journal of the American Osteopathic Association |date=May 2001 |volume=101 |issue=s5 |pages=S1-4 |doi=10.7556/jaoa.2001.20027 |pmid=11409259 |publisher=American Osteopathic Association, De Gruyter |doi-broken-date=1 November 2024 |doi-access=free}} For those who have severe anaphylactic reactions, a prescribed medicine such as doxepin, taken daily, should help to prevent and/or lessen the likelihood of a reaction and thus, anaphylaxis. The effectiveness of topical antihistamine creams against hives induced by cold temperature has not been evaluated.{{citation needed|date=January 2021}}

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.{{Cite journal |last1=Sánchez-Borges |first1=Mario |last2=González-Aveledo |first2=Luis |last3=Caballero-Fonseca |first3=Fernan |last4=Capriles-Hulett |first4=Arnaldo |date=August 2017 |title=Review of Physical Urticarias and Testing Methods |url=http://link.springer.com/10.1007/s11882-017-0722-1 |journal=Current Allergy and Asthma Reports |volume=17 |issue=8 |page=51 |doi=10.1007/s11882-017-0722-1 |pmid=28634900 |issn=1529-7322}}

Studies have found that omalizumab (Xolair) may be an effective and safe treatment for cold urticaria in patients who do not sufficiently respond to standard treatments.{{cite journal| pmc=3551415 | pmid=23341807 | doi=10.1159/000346284 | volume=4 | issue=3 | title=Treatment of severe cold contact urticaria with omalizumab: case reports |vauthors=Brodská P, Schmid-Grendelmeier P| journal=Case Rep Dermatol | pages=275–80| year=2012 }}

Ebastine has been proposed as an approach to prevent acquired cold urticaria.{{cite journal |vauthors=Magerl M, Schmolke J, Siebenhaar F, Zuberbier T, Metz M, Maurer M |title=Acquired cold urticaria symptoms can be safely prevented by ebastine |journal=Allergy |volume=62 |issue=12 |pages=1465–8 |date=December 2007 |pmid=17900265 |doi=10.1111/j.1398-9995.2007.01500.x |s2cid=12051897 }}

• Amyloidosis
• Cholinergic urticaria, a similar hives reaction in response to heat
• Aquagenic urticaria
• Diascopy
• Erythema
• Goose bumps, an unrelated, normal response to cold temperatures
• List of cutaneous conditions
• Skin lesion
• PLAID syndrome

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{{Medical resources

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeshID = D056587

| DiseasesDB = 4688

| ICD10 = {{ICD10|L|50|2|l|50}} (ILDS L50.210)

| ICD9 = {{ICD9|708.2}}

| ICDO =

| OMIM = 120100

}}

{{Urticaria and erythema}}

Category:Thermal medicine

Category:Urticaria and angioedema