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Cold Induced Urticaria

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Other Names

  • Cold Induced Urticaria
  • Cold urticaria (ColdU)

Background

  • This page refers to cold-induced urticaria

History

  • First described by Frank in 1792[1]
  • In 1866, Bourdon reported a patient with cold Urticaria with systemic symptoms[2]

Epidemiology

  • Overall, the epidemiology is poorly defined
  • Prevalence
    • One European study estimated the prevalence at 0.05% of the population[3]
    • Prevalence is higher in Northern climates

Pathophysiology

    • Presents as pruritic wheals with or without angioedema
    • Occurs due to the release of leukotrienes, histamine and pro-inflammatory mast cell mediators after cold exposure
    • Characterized by cold-induced wheals that usually occur on rewarming and resolve within an hour
    • It is self-limited, lasting 4–5 years on average
  • Definition
    • Defined as chronic when it persists for 6 weeks or longer
    • Very little is known or understood about 'acute' cold urticaria, lasting less than 6 weeks

Etiology

Potential causes and clinical associations of cold urticaria (click to enlarge).[4]
  • Primary (no clear cause)
    • Defined when a secondary, or triggering, etiology cannot be determined
  • Secondary (associated with)
    • Bacterial and viral infections
    • Medications
    • Hymenoptera stings
    • Hematological malignancies and immunotherapy
    • Autoimmune
    • Lymphoproliferative
  • Cold Exposure
    • Critical temperature thresholds (CTT) range from below 4°C to higher than 27°C.[5]
    • Cold triggers include:
      • Contact with cold objects or surfaces
      • Cold water (eg swimming or taking cold showers)
      • Low ambient temperature (cold seasons, air conditioning)
      • Wind
      • Consumption of cold foods (ice cream, etc) and beverages
    • Often worse in winter, however no seasonal variation was noted in a study by Siebenhaar et al[6]
    • Patients typically develop symptoms within 1 to 5 minutes of exposure

Pathogenesisis

  • General
    • The cause of cold urticaria is not well understood
    • Proposed etiologies include some component of autoallergy, autoimmunity, neurogenic pathways and aberrant temperature sensing
  • Allergy
    • Cold exposure may generate auto-antigens, IgE response, mast cell degranulation and wheal formation
    • Direct evidence supporting this supporting this theory is lacking
  • Autoimmune
    • Type IIb autoimmunity with mast cell-targeting and activating autoantibodies may be involved
    • IgG auto antibodies are implicated
  • Neurogenic
  • Aberrant Temperature Sensing

Associated Conditions

  • Anaphylaxis (cold-induced anaphylaxis)
    • In one study, up to 20% of life threatening conditions presented with life threatening reactions[7]
  • Angioedema

Risk Factors

  • Demographics
    • Young adults
    • Females > Males[8]
    • Ages 20-40s

Differential Diagnosis

Clinical Features

Cold induced urticaria following ice application[9]
  • History
    • Important to clarify history, onset, trigger, etc
    • Symptoms are typically local, occur minutes after exposure
    • Systemic symptoms, anaphylaxis can develop if exposed to large surface area (i.e. swimming in cold water)
      • Constitutional: fever, fatigue
      • Skin: itchy wheals1 with or without angioedema affecting lips, tongue, pharynx
      • Respiratory: dyspnea, hoarseness, laryngeal angioedema, nasal congestion
      • Gastrointestinal: nausea, abdominal pain, diarrhoea
      • Cardiovascular: tachycardia, hypotension, shock
      • Reproductive: uterine contractions
      • CNS: headache, disorientation, fainting, vertigo
    • Sensation can be described as burning, redness, severe itching, swelling
  • Physical Exam
  • Special Tests

Evaluation

Demonstration of the Ice Cube Test and the TempTest[4]

Special Tests

  • Ice Cube Test
    • Sometimes referred to as cold stimulation testing
    • Apply melting ice cube in a thin plastic bag or non-latex medical glove to the forearm for 5 minutes
    • Test reading occurs 10 minutes after the end of cold stimulation
    • Positive test: whealing with or without itching in the contact area
    • Sensitivity is 53-83%, specificity 97-100%[10]
  • TempTest
    • Standardized testing technique which provides objective, validated and reproducible results
    • Identifies critical skin threshold and critical temperature threshold
    • Progressively lower temperatures exist along a proprietary ice pack (see images)

Laboratory

  • The provider should consider:
    • Complete Blood Count (CBC)
    • Erythrocyte Sedimentation Rate (ESR)
    • C-reactive Protein (CRP)
  • Tests to avoid
    • Cryoglobulins (present in less than 1% of cold induced urticaria)

Classification

Classification of Cold Induced Urticaria (click to enlarge)[4]
  • Cold urticaria (ColdU) is a subtype of chronic inducible urticaria
    • Can be broken down into typical vs atypical
    • See table

Management

  • Trigger avoidance
    • Cold avoidance
    • Important to measure trigger thresholds before and during any treatments to measure efficacy
    • Effectiveness of cold avoidance is limited, effect on quality of life needs to be studied
  • Lifestyle modifications
    • Recognize places with lower ambient temp (supermarket, warehouse, air conditioned rooms, ice rink, etc)
    • Precaution when traveling to caves, mountains, rivers and lakes
    • Household activities such as defrosting the freezer, cleanings windows
    • Avoid cryotherapy or cryorejuvinating procedures
    • Avoid ice cream, ice, cold fruits and vegetables, cold drinks
    • Avoid water (swimming, water polo, diving) and winter sports (hockey, figure skating, skiing, snowboarding, curling
    • Occupations (diving, butcher, sailor, fishing, polar explorer, climber, pathologist, surgeon)
  • Cold desensitization
    • Not routinely used because of the risk of Cold Agglutination, patient noncompliance, rapid and marked loss of effect in the absence of regular cold exposure.

Medications

  • Second Generation Antihistamines
    • Considered first (normal dose) and second line (high dose) treatment
    • Increasing dose above recommended appears to help control symptoms[11]
    • Take before known or expected exposure
    • About 20% of patients do not show any response, even with high doses
  • Omalizumab
    • Targets circulating IgE and affects mast cell and basophil function
    • Considered a second line agent
    • Efficacy was demonstrated in a large meta-analysis[12]
  • Epinephrine autoinjector
    • Recommended to prescribe to patients at high risk of severe symptoms[13]
  • Additional drugs that are not well studied
    • Cyclosporin
    • Tricyclic antidepressants (doxepin)
    • Immunosuppressive drugs (azathioprine, mycophenolate mofetil)
    • Cinnarizine
    • Antibiotics
    • Biological therapeutics licensed for other conditions (anakinra, etanercept, reslizumab and dupilumab) appear to have efficacy based on case reports
    • Topical Syk inhibitor and rilonacept (an interleukin 1 blocker) are in development

Rehab and Return to Play

Rehabilitation

  • Not applicable

Return to Play/ Work

  • Symptoms are usually transient
  • Can return to play once cleared by a physician
    • Important to take preventative medications before exercise or other suspected triggers
  • Return to play or sport in the event of anaphylaxis or angioedema will require careful discussion

Complications and Prognosis

Prognosis

  • Duration
    • Self limited condition which lasts 6 years on average[14]
    • Studies have suggested that only one quarter of patients will develop resolution of their symptoms within 10 years[15]
    • The disease may persist for up to 20 years
    • Predictors of longer duration include early onset, severe disease, higher temperature threshold[16]

Complications

See Also

References

  1. ↑ Frank JP. De curandis hominum morbis epitome. Mannheim, Schwan, Goetz. 1792; 3:104.
  2. ↑ Bourdon H. Note sur l’urticaire intermittente. Bull Mem Soc Hop. 1866;3:259–62.
  3. ↑ Moller A, Henning M, Zuberbier T, Czarnetzki-Henz BM. Epidemiology and clinical aspects of cold urticaria. Hautarzt. 1996;47:150.
  4. ↑ 4.0 4.1 4.2 Maltseva, Natalya, et al. "Cold urticaria–What we know and what we do not know." Allergy 76.4 (2021): 1077-1094.
  5. ↑ 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. 2010;162:198-200.
  6. ↑ Siebenhaar F, Degener F, Zuberbier T, Martus P, Maurer M. 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.
  7. ↑ Deza G, Brasileiro A, Bertolin-Colilla M, Curto-Barredo L, Pujol RM, Gimenez-Arnau AM. Acquired cold urticaria: clinical features, particular phenotypes, and disease course in a tertiary care center cohort. J Am Acad Dermatol. 2016;75(5):918–924.e912.
  8. ↑ 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;2008(22):1405.
  9. ↑ Huissoon, Aarnoud, and Mamidipudi Thirumala Krishna. "Cold-induced urticaria." New England Journal of Medicine 358.8 (2008): e9.
  10. ↑ Holm JG, Agner T, Thomsen SF. Diagnostic properties of provocation tests for cold, heat, and delayed-pressure urticaria. Eur J Dermatol. 2017;27:406-408.
  11. ↑ Kulthanan K, Hunnangkul S, Tuchinda P, et al. Treatments of cold urticaria: a systematic review. J Allergy Clin Immunol. 2019;143:1311-1331.
  12. ↑ Maurer M, Metz M, Brehler R, et al. Omalizumab treatment in patients with chronic inducible urticaria: a systematic review of published evidence. J Allergy Clin Immunol. 2018;141:638-649.
  13. ↑ Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133:1270-1277.
  14. ↑ Neittaanmäki H, Fraki JE, Gibson JR. Comparison of the new antihistamine acrivastine (BW 825C) versus cyproheptadine in the treatment of idiopathic cold urticaria. Dermatologica. 1988;177:98-103.
  15. ↑ Jain SV, Mullins RJ. Cold urticaria: a 20-year follow-up study. J Eur Acad Dermatol Venereol. 2016;30(12):2066–71.
  16. ↑ Deza G, Brasileiro A, Bertolin-Colilla M, Curto-Barredo L, Pujol RM, Giménez-Arnau AM. Acquired cold urticaria: clinical features, particular phenotypes, and disease course in a tertiary care center cohort. J Am Acad Dermatol 2016;75:918-924.
Created by:
John Kiel on 30 June 2019 22:56:17
Authors:
Last edited:
16 April 2022 12:01:39

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