Jump to content

Cold urticaria

From Wikipedia, the free encyclopedia
Cold Urticaria
Other namesCold hives
Allergic urticaria on arm in the form of hives induced by cold.
CausesExposure to cold stimulus

Cold urticaria (essentially meaning cold hives) is a disorder in which large red welts called hives (urticaria) form on the skin after exposure to a cold stimulus.[1] The hives are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about mm in diameter to as big as about 27 mm or larger.

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 begin between ages 18 and 25, although it can occur as early as 5 years old in some cases. Life-threatening risks include suffocation resulting from swollen tissue (pharyngeal angioedema) induced by cold foods or beverages, drowning after shock from swimming in cold water, and anaphylactic shock.[2]



Cold urticaria may be divided into the following types:[3]

Primary cold contact urticaria


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.[3]

Secondary cold contact urticaria


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.[3]

Reflex cold urticaria


Reflex cold urticaria is a cutaneous condition in which generalized cooling of the body induces widespread welting.[3]

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[4] elicited by exposure to cold - sometimes temperatures below 22 °C (72 °F).[3][5]

It has been mapped to CIAS1[6] 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.[7]

FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (aka NLRP3) gene at location 1q44.[8][9][10][11]

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".[12]

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.[13][14] The monoclonal antibody canakinumab (Ilaris) is also used.[15]

Signs and symptoms

Hives on the back from exposure to cold air on an individual with cold allergy. The hives were induced by riding a stationary bike shirtless for an hour next to a door cracked open on a cool day. The temperature of the air flowing in was around 10 °C (50 °F). The lighter band at chest height was covered by a heart rate monitor strap.

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] 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.[16] 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.[17] 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).[18]



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] 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."[19]



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.[20] 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.[21] 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,[21] which is essential because it can establish disease severity and monitor the effectiveness of treatment.[21]



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.[22]

Avoiding triggers


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 6 to 8 in (15 to 20 cm) from the IV site in the pattern of a line going up the limb.
  • Activities:
    • glass of ice water
      Drinking cold beverages can trigger hives in people with cold urticaria.
      Cold 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.[23] If standard dosing is ineffective, increasing dosages up to fourfold is recommended to control symptoms.[24]

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 20 mg and 40 mg.[21]

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.[25] 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]

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.[26]

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.[27]

Ebastine has been proposed as an approach to prevent acquired cold urticaria.[28]

See also



  1. ^ Feinberg, Jeff H.; Toner, Charles B. (2008). "Successful Treatment of Disabling Cholinergic Urticaria". Military Medicine. 173 (2): 217–20. doi:10.7205/MILMED.173.2.217. PMID 18333501.
  2. ^ Siebenhaar F, Weller K, : clinical picture and update on diagnosis and treatment (May 2007). "Acquired cold urticaria: Clinical picture and update on diagnosis and treatment". Clin. Exp. Dermatol. 32 (3): 241–5. doi:10.1111/j.1365-2230.2007.02376.x. PMID 17355280. S2CID 32159216.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ a b c d e Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 267–8. ISBN 978-1-4160-2999-1.
  4. ^ Tunca, Mehmet; Ozdogan, Huri (2005). "Molecular and Genetic Characteristics of Hereditary Autoinflammatory Diseases". Current Drug Targets. Inflammation and Allergy. 4 (1). Bentham Science Publishers: 77–80. doi:10.2174/1568010053622957. PMID 15720239.
  5. ^ James, William D.; Berger, Timothy G.; Elston, Dirk M.; Grekin, Roy C.; Neuhaus, Isaac M.; Wei, Maria L. (2006). "Erythema and Urticaria". Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Philadelphia, PA: Saunders, Elsevier. pp. 165–166. ISBN 0-7216-2921-0.
  6. ^ Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (November 2001). "Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome". Nat. Genet. 29 (3): 301–5. doi:10.1038/ng756. PMC 4322000. PMID 11687797.
  7. ^ "Familial cold autoinflammatory syndrome". MedlinePlus. U.S. National Library of Medicine, National Institutes of Health. Retrieved 27 July 2021.
  8. ^ CAPS, Community (2008-01-01). "Familial Cold Auto-inflammatory Syndrome (FCAS): Fact Sheet". Regeneron Pharmaceuticals. Archived from the original on 2016-03-04. Retrieved 2010-02-01.
  9. ^ Tweedie, Susan; Braschi, Bryony; Gray, Kristian; Jones, Tamsin E. M.; Seal, Ruth L.; Yates, Bethan; Bruford, Elspeth A. "Symbol report for NLRP3". HGNC. Human Genome Organisation. 16400. Retrieved 27 July 2021.
  10. ^ Smith, David W.; Johnson, Kenneth A.; Bingman, Craig A.; Aceti, David J.; Blommel, Paul G.; Wrobel, Russell L.; Frederick, Ronnie O.; Zhao, Qin; Sreenath, Hassan; Fox, Brian G.; Volkman, Brian F.; Jeon, Won Bae; Newman, Craig S.; Ulrich, Eldon L.; Hegeman, Adrian D.; Kimball, Todd; Thao, Sandy; Sussman, Michael R.; Markley, John L.; Phillips, George N. Jr. (2003). "1Q44". PDB. Research Collaboratory for Structural Bioinformatics. doi:10.2210/pdb1Q44/pdb. Retrieved 27 July 2021.
  11. ^ Hoffman, Hal M.; Rosengren, Sanna; Boyle, David L.; Cho, Jae Y.; Nayar, Jyothi; Mueller, James L.; Anderson, Justin P.; Wanderer, Alan A.; Firestein, Gary S. (November 2004). "Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist". The Lancet. 364 (9447). Elsevier: 1779–1785. doi:10.1016/S0140-6736(04)17401-1. PMC 4321997. PMID 15541451.
  12. ^ Stych, B; Dobrovolny, D (2008). "Familial cold auto-inflammatory syndrome (FCAS): characterization of symptomatology and impact on patients' lives". Curr Med Res Opin. 24 (6): 1577–82. doi:10.1185/03007990802081543. PMID 18423104. S2CID 23371016.
  13. ^ Ross JB; Finlayson, LA; Klotz, PJ; Langley, RG; Gaudet, R; Thompson, K; Churchman, SM; McDermott, MF; Hawkins, PN; et al. (2010-02-01). "Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-up". Journal of Cutaneous Medicine and Surgery. 12 (1): 8–16. doi:10.2310/7750.2008.07050. PMID 18258152. S2CID 34516905.
  14. ^ Samy K Metyas, Hal M Hoffman (2008-02-01). "Anakinra prevents symptoms of familial cold autoinflammatory syndrome and Raynaud's disease". The Journal of Rheumatology. 33 (10). Journal of Rheumatology: 2085–2087. PMID 16981288. Retrieved 2010-02-01.
  15. ^ Walsh, GM (2009). "Canakinumab for the treatment of cryopyrin-associated periodic syndromes". Drugs of Today. 45 (10): 731–5. doi:10.1358/dot.2009.45.10.1436882. PMID 20069137.
  16. ^ Bailey Evan, Shaker Marcus (2008). "An Update on Childhood Urticaria and Angioedema". Current Opinion in Pediatrics. 20 (4): 425–30. doi:10.1097/mop.0b013e328305e262. PMID 18622198. S2CID 27406621.
  17. ^ Yasmeen, Jabeen Bhat (2021-03-04). "Immunologically mediated skin disorders". In Sarkar, Rashmi (ed.). Concise Dermatology. CRC Press. ISBN 978-1-000-33966-6. Idiopathic cold urticaria may be immediate, delayed, localized, familial, or acquired.
  18. ^ Soter Nicholas A.; Wasserman Stephen I.; Austen K. Frank (1976). "Cold Urticaria: Release into the Circulation of Histamine and Eosinophil Chemotactic Factor of Anaphylaxis during Cold Challenge". New England Journal of Medicine. 294 (13): 687–90. doi:10.1056/nejm197603252941302. PMID 55969.
  19. ^ "NIH scientists find cause of rare immune disease: Genetic mutation leads to cold allergy, immune deficiency and autoimmunity". National Institute of Allergy and Infectious Diseases, National Institutes of Health. 11 January 2012.
  20. ^ Traidl-Hoffmann, Claudia; Zuberbier, Torsten; Werfel, Thomas (2021-11-21). Allergic Diseases – From Basic Mechanisms to Comprehensive Management and Prevention. Springer Nature. p. 127. ISBN 978-3-030-84048-8.
  21. ^ a b c d Abajian M.; Curto-Barredo L.; Krause K.; Santamaria E.; Izquierdo I.; Church M.; Maurer M.; Giménez-Arnau A. (2016). "Rupatadine 20 Mg and 40 Mg Are Effective in Reducing the Symptoms of Chronic Cold Urticaria" (PDF). Acta Dermato Venereologica Acta Derm Venerol. 96 (1): 56–59. doi:10.2340/00015555-2150. PMID 26038847.
  22. ^ "Cold urticaria". Mayo Clinic. Retrieved 27 July 2021.
  23. ^ Abajian, Marina; Curto Barredo, Laia; Krause, Karoline; Santamaria, Eva; Izquierdo, Iñaki; Church, Martin K.; Maurer, Marcus; Giménez Arnau, Ana (2016). "Rupatadine 20 mg and 40 mg are Effective in Reducing the Symptoms of Chronic Cold Urticaria". Acta Dermato Venereologica. 96 (1). Medical Journals Sweden: 56–59. doi:10.2340/00015555-2150. ISSN 0001-5555. PMID 26038847.
  24. ^ Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. (2014). "The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update". Allergy. 69 (7): 868–887. doi:10.1111/all.12313. PMID 24785199.
  25. ^ Mahmoudi, Massoud (May 2001). "Cold-induced urticaria". The Journal of the American Osteopathic Association. 101 (s5). American Osteopathic Association, De Gruyter: S1-4. doi:10.7556/jaoa.2001.20027 (inactive 31 January 2024). PMID 11409259.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  26. ^ Sánchez-Borges, Mario; González-Aveledo, Luis; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo (August 2017). "Review of Physical Urticarias and Testing Methods". Current Allergy and Asthma Reports. 17 (8): 51. doi:10.1007/s11882-017-0722-1. ISSN 1529-7322. PMID 28634900.
  27. ^ Brodská P, Schmid-Grendelmeier P (2012). "Treatment of severe cold contact urticaria with omalizumab: case reports". Case Rep Dermatol. 4 (3): 275–80. doi:10.1159/000346284. PMC 3551415. PMID 23341807.
  28. ^ Magerl M, Schmolke J, Siebenhaar F, Zuberbier T, Metz M, Maurer M (December 2007). "Acquired cold urticaria symptoms can be safely prevented by ebastine". Allergy. 62 (12): 1465–8. doi:10.1111/j.1398-9995.2007.01500.x. PMID 17900265. S2CID 12051897.