Skip to main content

Advertisement

Log in

Modern Approaches to the Diagnosis and Treatment of Cold Contact Urticaria

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Cold contact urticaria (CCU) is a common subtype of physical urticaria characterized by itchy wheals and/or angioedema due to skin mast cell activation and the release of proinflammatory mediators after cold exposure. The underlying causes are largely unknown. When CCU is suspected, cold stimulation tests and threshold testing should be done to confirm the diagnosis and to determine the severity and course of CCU, respectively. Avoidance of critical cold exposure should be recommended but is often impossible, especially for severely affected patients with high temperature and low exposure time thresholds. Symptomatic treatment of choice is the use of modern, nonsedating antihistamines. Patients should be informed that complete protection from CCU symptom development may require increased doses of antihistamines. Standardizing cold provocation tests and further characterization of the natural course of CCU and its variants may lead to a better understanding of the disease-driving mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interests, published recently, have been highlighted as:• Of importance •• Of major importance

  1. Siebenhaar F, Weller K, Mlynek A, et al.: Acquired cold urticaria: clinical picture and update on diagnosis and treatment. Clin Exp Dermatol 2007, 32:241–245.

    Article  CAS  PubMed  Google Scholar 

  2. Magerl M, Borzova E, Gimenez-Arnau A, et al.: The definition and diagnostic testing of physical and cholinergic urticarias—EAACI/GALEN/EDF/UNEV consensus panel recommendations. Allergy 2009, 64:1715–1721.

    Article  CAS  PubMed  Google Scholar 

  3. Zuberbier T, Asero R, Bindslev-Jensen C, et al.: EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009, 64:1417–1426.

    Article  CAS  PubMed  Google Scholar 

  4. Wanderer AA, Grandel KE, Wasserman SI, Farr RS: Clinical characteristics of cold-induced systemic reactions in acquired cold urticaria syndromes: recommendations for prevention of this complication and a proposal for a diagnostic classification of cold urticaria. J Allergy Clin Immunol 1986, 78:417–423.

    Article  CAS  PubMed  Google Scholar 

  5. Neittaanmaki H: Cold urticaria. Clinical findings in 220 patients. J Am Acad Dermatol 1985, 13:636–644.

    Article  CAS  PubMed  Google Scholar 

  6. Alangari AA, Twarog FJ, Shih MC, Schneider LC: Clinical features and anaphylaxis in children with cold urticaria. Pediatrics 2004, 113:e313–e317.

    Article  PubMed  Google Scholar 

  7. Katsarou-Katsari A, Makris M, Lagogianni E, et al.: Clinical features and natural history of acquired cold urticaria in a tertiary referral hospital: a 10-year prospective study. J Eur Acad Dermatol Venereol 2008, 22:1405–1411.

    Article  CAS  PubMed  Google Scholar 

  8. Mathelier-Fusade P, Aissaoui M, Bakhos D, et al.: Clinical predictive factors of severity in cold urticaria. Arch Dermatol 1998, 134:106–107.

    Article  CAS  PubMed  Google Scholar 

  9. Moller A, Henning M, Zuberbier T, Czarnetzki-Henz BM: [Epidemiology and clinical aspects of cold urticaria]. Hautarzt 1996, 47:510–514.

    Article  CAS  PubMed  Google Scholar 

  10. Murphy GF, Austen KF, Fonferko E, Sheffer AL: Morphologically distinctive forms of cutaneous mast cell degranulation induced by cold and mechanical stimuli: an ultrastructural study. J Allergy Clin Immunol 1987, 80:603–611.

    Article  CAS  PubMed  Google Scholar 

  11. Kaplan AP, Beaven MA: In vivo studies of the pathogenesis of cold urticaria, cholinergic urticaria, and vibration-induced swelling. J Invest Dermatol 1976, 67:327–332.

    Article  CAS  PubMed  Google Scholar 

  12. Wasserman SI, Soter NA, Center DM, Austen KF: Cold urticaria. Recognition and characterization of a neutrophil chemotactic factor which appears in serum during experimental cold challenge. J Clin Invest 1977, 60:189–196.

    Article  CAS  PubMed  Google Scholar 

  13. Grandel KE, Farr RS, Wanderer AA, et al.: Association of platelet-activating factor with primary acquired cold urticaria. N Engl J Med 1985, 313:405–409.

    CAS  PubMed  Google Scholar 

  14. Ormerod AD, Kobza Black A, Dawes J, et al.: Prostaglandin D2 and histamine release in cold urticaria unaccompanied by evidence of platelet activation. J Allergy Clin Immunol 1988, 82:586–589.

    Article  CAS  PubMed  Google Scholar 

  15. Tillie-Leblond I, Gosset P, Janin A, et al.: Tumor necrosis factor-alpha release during systemic reaction in cold urticaria. J Allergy Clin Immunol 1994, 93:501–509.

    Article  CAS  PubMed  Google Scholar 

  16. Kaplan AP, Garofalo J, Sigler R, Hauber T: Idiopathic cold urticaria: in vitro demonstration of histamine release upon challenge of skin biopsies. N Engl J Med 1981, 305:1074–1077.

    Article  CAS  PubMed  Google Scholar 

  17. Koda H, Kanaide A, Asahi M, Urabe H: Essential IgG cryoglobulinemia with purpura and cold urticaria. Arch Dermatol 1978, 114:784–786.

    Article  CAS  PubMed  Google Scholar 

  18. Doeglas HM, Rijnten WJ, Schroder FP, Schirm J: Cold urticaria and virus infections: a clinical and serological study in 39 patients. Br J Dermatol 1986, 114:311–318.

    Article  CAS  PubMed  Google Scholar 

  19. Miralles Lopez JC, Lopez Andreu FR, Sanchez-Gascon F, et al.: Cold urticaria associated with acute serologic toxoplasmosis. Allergol Immunopathol (Madr) 2005, 33:172–174.

    Article  CAS  Google Scholar 

  20. Kranke B, Mayr-Kanhauser S, Aberer W: Helicobacter pylori in acquired cold urticaria. Contact Dermatitis 2001, 44:57–58.

    Article  CAS  PubMed  Google Scholar 

  21. Kalogeromitros D, Gregoriou S, Papaioannou D, et al.: Acquired primary cold contact urticaria after Hymenoptera sting. Clin Exp Dermatol 2004, 29:93–95.

    Article  CAS  PubMed  Google Scholar 

  22. Mathelier-Fusade P, Leynadier F: Acquired cold urticaria after jellyfish sting. Contact Dermatitis 1993, 29:273.

    Article  CAS  PubMed  Google Scholar 

  23. Kranke B, Mayr-Kanhauser S: Cold urticaria and angiotensin converting enzyme inhibitor. Acta Derm Venereol 2002, 82:149–150.

    Article  PubMed  Google Scholar 

  24. Wanderer AA, Hoffman HM: The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromes. Immunol Allergy Clin North Am 2004, 24:259–286, vii.

    Article  PubMed  Google Scholar 

  25. Siebenhaar F, Staubach P, Metz M, et al.: Peltier effect-based temperature challenge: an improved method for diagnosing cold urticaria. J Allergy Clin Immunol 2004, 114:1224–1225.

    Article  PubMed  Google Scholar 

  26. • Mlynek A, Magerl M, Siebenhaar F, et al.: Results and relevance of critical temperature threshold testing in patients with acquired cold urticaria. Br J Dermatol 2009 Sep 28 (Epub ahead of print). This articles discusses the relevance of determining temperature thresholds in CCU patients in order to assess disease severity.

  27. Kivity S, Schwartz Y, Wolf R, Topilsky M: Systemic cold-induced urticaria—clinical and laboratory characterization. J Allergy Clin Immunol 1990, 85:52–54.

    Article  CAS  PubMed  Google Scholar 

  28. Kaplan AP: Unusual cold-induced disorders: cold-dependent dermatographism and systemic cold urticaria. J Allergy Clin Immunol 1984, 73:453–456.

    Article  CAS  PubMed  Google Scholar 

  29. Kaplan AP, Garofalo J: Identification of a new physically induced urticaria: cold-induced cholinergic urticaria. J Allergy Clin Immunol 1981, 68:438–441.

    Article  CAS  PubMed  Google Scholar 

  30. Matthews CN, Warin RP: Delayed cold urticaria. Br J Dermatol 1977, 97(Suppl 15):32.

    Article  PubMed  Google Scholar 

  31. Czarnetzki BM, Frosch PJ, Sprekeler R: Localized cold reflex urticaria. Br J Dermatol 1981, 104:83–87.

    Article  CAS  PubMed  Google Scholar 

  32. Wanderer AA: Systemic cold urticaria (atypical acquired cold urticaria). J Allergy Clin Immunol 1991, 87:137–138.

    Article  CAS  PubMed  Google Scholar 

  33. Hoffman HM, Mueller JL, Broide DH, et al.: Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 2001, 29:301–305.

    Article  CAS  PubMed  Google Scholar 

  34. Hoffman HM, Wanderer AA, Broide DH: Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol 2001, 108:615–620.

    Article  CAS  PubMed  Google Scholar 

  35. Soter NA, Joshi NP, Twarog FJ, et al.: Delayed cold-induced urticaria: a dominantly inherited disorder. J Allergy Clin Immunol 1977, 59:294–297.

    Article  CAS  PubMed  Google Scholar 

  36. Gandhi C, Healy C, Wanderer AA, Hoffman HM: Familial atypical cold urticaria: description of a new hereditary disease. J Allergy Clin Immunol 2009, 124:1245–1250.

    Article  PubMed  Google Scholar 

  37. Zuberbier T, Asero R, Bindslev-Jensen C, et al.: EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy 2009, 64:1427–1443.

    Article  CAS  PubMed  Google Scholar 

  38. Wanderer AA, Ellis EF: Treatment of cold urticaria with cyproheptadine. J Allergy Clin Immunol 1971, 48:366–371.

    Article  CAS  PubMed  Google Scholar 

  39. Neittaanmaki H, Myohanen T, Fraki JE: Comparison of cinnarizine, cyproheptadine, doxepin, and hydroxyzine in treatment of idiopathic cold urticaria: usefulness of doxepin. J Am Acad Dermatol 1984, 11:483–489.

    Article  CAS  PubMed  Google Scholar 

  40. Church MK, Maurer M, Simons FER, et al.: Should first-generation H1-antihistamines still be available as over-the-counter medications? A GA2LEN task force report. Allergy 2010 (in press).

  41. Juhlin L, de Vos C, Rihoux JP: Inhibiting effect of cetirizine on histamine-induced and 48/80-induced wheals and flares, experimental dermographism, and cold-induced urticaria. J Allergy Clin Immunol 1987, 80:599–602.

    Article  CAS  PubMed  Google Scholar 

  42. Dubertret L, Pecquet C, Murrieta-Aguttes M, Leynadier F: Mizolastine in primary acquired cold urticaria. J Am Acad Dermatol 2003, 48:578–583.

    Article  PubMed  Google Scholar 

  43. Magerl M, Schmolke J, Siebenhaar F, et al.: Acquired cold urticaria symptoms can be safely prevented by ebastine. Allergy 2007, 62:1465–1468.

    Article  CAS  PubMed  Google Scholar 

  44. •• Siebenhaar F, Degener F, Zuberbier T, et al.: High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol 2009, 123:672–679. The efficacy and safety of high-dose, nonsedating antihistamines in the reduction of clinical symptoms in CCU is shown in a placebo-controlled, randomized trial.

    Article  CAS  PubMed  Google Scholar 

  45. Di Leo E, Nettis E, Cassano N, et al.: Treatment of acquired cold urticaria with rupatadine. Allergy 2009, 64:1387–1388.

    Article  PubMed  Google Scholar 

  46. Metz M, Scholz E, Ferran M, et al.: Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in acquired cold urticaria. Ann Allergy Asthma Immunol 2010, 104:86–92.

    Article  CAS  PubMed  Google Scholar 

  47. Bonadonna P, Lombardi C, Senna G, et al.: Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination. J Am Acad Dermatol 2003, 49:714–716.

    Article  PubMed  Google Scholar 

  48. Marsland AM, Beck MH: Cold urticaria responding to systemic ciclosporin. Br J Dermatol 2003, 149:214–215.

    Article  CAS  PubMed  Google Scholar 

  49. Boyce JA: Successful treatment of cold-induced urticaria/anaphylaxis with anti-IgE. J Allergy Clin Immunol 2006, 117:1415–1418.

    Article  CAS  PubMed  Google Scholar 

  50. •• Bodar EJ, Simon A, de Visser M, van der Meer JW: Complete remission of severe idiopathic cold urticaria on interleukin-1 receptor antagonist (anakinra). Neth J Med 2009, 67:302–305. The good response to anti-interleukin-1 in a case of severe CCU suggests a possible role for interleukin-1 not only in the pathogenesis of cryopyrin-associated periodic syndromes but also in CCU.

    CAS  PubMed  Google Scholar 

  51. Bird JA, Burks W: Peanut allergy saves a patient with cold-induced hypotension and urticaria. J Pediatr 2010, 156:687.

    Article  PubMed  Google Scholar 

  52. Toth-Kasa I, Jancso G, Obal F Jr, et al.: Involvement of sensory nerve endings in cold and heat urticaria. J Invest Dermatol 1983, 80:34–36.

    Article  CAS  PubMed  Google Scholar 

  53. Keahey TM, Indrisano J, Kaliner MA: A case study on the induction of clinical tolerance in cold urticaria. J Allergy Clin Immunol 1988, 82:256–261.

    Article  CAS  PubMed  Google Scholar 

  54. von Mackensen YA, Sticherling M: Cold urticaria: tolerance induction with cold baths. Br J Dermatol 2007, 157:835–836.

    Article  Google Scholar 

  55. Hoffman HM, Throne ML, Amar NJ, et al.: Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum 2008, 58:2443–2452.

    Article  CAS  PubMed  Google Scholar 

  56. Goldbach-Mansky R, Kastner DL: Autoinflammation: the prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. J Allergy Clin Immunol 2009, 124:1141–1149; quiz 1150–1151.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

Dr. Zuberbier has served as a consultant for Schering-Plough, Novartis, Laboratorios Leti, Stallergenes, Bayer Schering Pharma, Ansell, Kryolan, UCB, MSD Pharmaceuticals, DST, Sanofi-Aventis, and Procter & Gamble.

Dr. Maurer has served as a speaker and/or advisor for Almirall Hermal, Bayer Schering Pharma, Biofrontera AG, Essex Pharma, Genentech, JADO Technologies, Jerini AG, Merckle Recordati, Novartis, Sanofi-Aventis, Schering-Plough, LEO Pharma A/S, MSD Pharmaceuticals, Merck & Co., Shire, SymbioPharm, UCB, and the Uriach Group. No other potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marcus Maurer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krause, K., Zuberbier, T. & Maurer, M. Modern Approaches to the Diagnosis and Treatment of Cold Contact Urticaria. Curr Allergy Asthma Rep 10, 243–249 (2010). https://doi.org/10.1007/s11882-010-0121-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-010-0121-3

Keywords

Navigation