cold urticaria

Last reviewed 01/2018

Cold urticaria

• acquired cold urticaria (ACU) is a subtype of physical urticaria that is caused by the release of proinflammatory mast cell mediators after cold exposure
• ACU
  • characterized by the development of weal-and-flare type skin reactions and/or angiooedema caused by release of histamine, leukotrienes and other proinflammatory mast-cell mediators after exposure of the skin to cold (1)
  • symptoms typically occur minutes after the skin is exposed to cold air, liquids or objects - usually limited to cold-exposed skin areas
    • note though that extensive cold contact may result in generalized urticarial symptoms and/or in systemic reactions including headache, dyspnoea, hypotension and loss of consciousness - most frequently results from extensive cold contact during water exposure
      • patients with a history of oropharyngeal oedema seem to be at particularly high risk for developing shock-like reactions after aquatic activity
  • most frequently affects young adults - affects women more than men (2:1)
    • mean duration of the disease is 4-5 years (1)
      • remission or at least improvement of symptoms in 50% of patients within 5 years
      • incidence of ACU has been estimated to be 0.05%
        • higher incidences are found in regions with a cold climate
• differential diagnosis
  • subdivided into primary and secondary ACU - are different designations in accordance with an unknown (primary) or suspected (secondary) underlying cause or disease for ACU
    • ACU can be the secondary manifestation of underlying hematologic or infectious diseases (eg, cryoglobulinemia or mononucleosis)
    • there are also some very rare atypical subtypes of cold urticaria
      • includes two hereditary familial cold syndromes: delayed cold urticaria and familial cold auto-inflammatory syndrome (FCAS)
• aetiology
  • causes and mechanisms involved in the aetiology and pathogenesis largely unknown
    • reported associations with viral or bacterial infections including borreliosis, hepatitis, infectious mononucleosis, and human immunodeficiency virus infection
      • other associations include with Helicobacter pylori colonization, acute toxoplasmosis and other parasitic infections
      • infections of the upper respiratory tract, teeth or urogenital tract may also be associated with ACU
      • infrequent immunological findings in patients with ACU include cryoglobulinaemia, composed of monoclonal IgG and mixed types of IgG/IgM and IgG/IgA/cryoglobulins
      • prevalence of functional anti-IgE antibodies (IgG and IgM) has been described
      • an association with haematological, lymphatic or neoplastic diseases has been reported
• diagnosis/investigation
  • requires specialist review
    • cold-provocation testing -a positive immediate cold-stimulation test (CST), i.e. the development of urticarial skin lesions at sites of cold challenge, verifies the presence of ACU
• management
  • seek specialist advice
  • avoidance of cold - avoidance of cold exposure is desirable (but not always achievable)
  • symptomatic therapy
    • antihistamine treatment is the most common and the most effective symptomatic therapeutic option to prevent and reduce patients reactions after cold exposure - however, sufficient reduction of urticarial symptoms in many patients with ACU requires high dosing with antihistamines, up to four times the daily recommended dose
    • other treatment options for the therapy of severe ACU with high risk of life-threatening reactions and/or an insufficient response to antihistamines, include the concomitant use of leucotriene antagonists, ciclosporin, corticosteroids
    • there is study evidence that combination therapy with antihistamines and leukotriene receptor antagonists is more effective than each drug given alone (2)
  • curative therapy
    • antibiotic therapy should be considered in some patients (1)
      • occasionally, patients with ACU have been shown to benefit from such treatment even if no underlying infection can be detected
  • further treatment options
    • induction of cold tolerance (hardening) is an effective method of treating patients with ACU
    • treatment with topical capsaicin has been reported to prevent ACU symptoms

Reference:

• (1) Siebenhaar F et al. Acquired cold urticaria: clinical picture and update on diagnosis and treatment.Clin Exp Dermatol. 2007 May;32(3):241-5.
• (2) Bonadonna P et al. Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination.J Am Acad Dermatol. 2003 Oct;49(4):714-6.