Cold Induced Urticaria
- 1 Other Names
- 2 Background
- 3 Pathophysiology
- 4 Risk Factors
- 5 Differential Diagnosis
- 6 Clinical Features
- 7 Evaluation
- 8 Classification
- 9 Management
- 10 Rehab and Return to Play
- 11 Complications and Prognosis
- 12 See Also
- 13 References
- Cold Induced Urticaria
- Cold urticaria (ColdU)
- This page refers to cold-induced urticaria
- First described by Frank in 1792
- In 1866, Bourdon reported a patient with cold Urticaria with systemic symptoms
- Overall, the epidemiology is poorly defined
- One European study estimated the prevalence at 0.05% of the population
- Prevalence is higher in Northern climates
- 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
- 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
- Primary (no clear cause)
- Defined when a secondary, or triggering, etiology cannot be determined
- Secondary (associated with)
- Bacterial and viral infections
- Hymenoptera stings
- Hematological malignancies and immunotherapy
- Cold Exposure
- Critical temperature thresholds (CTT) range from below 4°C to higher than 27°C.
- Cold triggers include:
- Contact with cold objects or surfaces
- Cold water (eg swimming or taking cold showers)
- Low ambient temperature (cold seasons, air conditioning)
- 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
- Patients typically develop symptoms within 1 to 5 minutes of exposure
- The cause of cold urticaria is not well understood
- Proposed etiologies include some component of autoallergy, autoimmunity, neurogenic pathways and aberrant temperature sensing
- Cold exposure may generate auto-antigens, IgE response, mast cell degranulation and wheal formation
- Direct evidence supporting this supporting this theory is lacking
- Type IIb autoimmunity with mast cell-targeting and activating autoantibodies may be involved
- IgG auto antibodies are implicated
- Aberrant Temperature Sensing
- Anaphylaxis (cold-induced anaphylaxis)
- In one study, up to 20% of life threatening conditions presented with life threatening reactions
- Young adults
- Females > Males
- Ages 20-40s
- Cold Injury Mimics
- Familial cold autoinflammatory syndrome (FCAS)
- Cryoglobulinemic vasculitis (CryoVas)
- 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
- 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%
- 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)
- 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)
- Cold urticaria (ColdU) is a subtype of chronic inducible urticaria
- Can be broken down into typical vs atypical
- See table
- 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.
- Second Generation Antihistamines
- Considered first (normal dose) and second line (high dose) treatment
- Increasing dose above recommended appears to help control symptoms
- Take before known or expected exposure
- About 20% of patients do not show any response, even with high doses
- Targets circulating IgE and affects mast cell and basophil function
- Considered a second line agent
- Efficacy was demonstrated in a large meta-analysis
- Epinephrine autoinjector
- Recommended to prescribe to patients at high risk of severe symptoms
- Additional drugs that are not well studied
- Tricyclic antidepressants (doxepin)
- Immunosuppressive drugs (azathioprine, mycophenolate mofetil)
- 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
- 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
- Self limited condition which lasts 6 years on average
- Studies have suggested that only one quarter of patients will develop resolution of their symptoms within 10 years
- The disease may persist for up to 20 years
- Predictors of longer duration include early onset, severe disease, higher temperature threshold
- Frank JP. De curandis hominum morbis epitome. Mannheim, Schwan, Goetz. 1792; 3:104.
- Bourdon H. Note sur l’urticaire intermittente. Bull Mem Soc Hop. 1866;3:259–62.
- Moller A, Henning M, Zuberbier T, Czarnetzki-Henz BM. Epidemiology and clinical aspects of cold urticaria. Hautarzt. 1996;47:150.
- Maltseva, Natalya, et al. "Cold urticaria–What we know and what we do not know." Allergy 76.4 (2021): 1077-1094.
- 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.
- 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.
- 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.
- 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.
- Huissoon, Aarnoud, and Mamidipudi Thirumala Krishna. "Cold-induced urticaria." New England Journal of Medicine 358.8 (2008): e9.
- 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.
- Kulthanan K, Hunnangkul S, Tuchinda P, et al. Treatments of cold urticaria: a systematic review. J Allergy Clin Immunol. 2019;143:1311-1331.
- 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.
- 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.
- 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.
- Jain SV, Mullins RJ. Cold urticaria: a 20-year follow-up study. J Eur Acad Dermatol Venereol. 2016;30(12):2066–71.
- 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.