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Peltier effect–based temperature challenge: An improved method for diagnosing cold urticaria

2004; Elsevier BV; Volume: 114; Issue: 5 Linguagem: Inglês

10.1016/j.jaci.2004.07.018

1097-6825

Frank Siebenhaar, Petra Staubach, Martin Metz, Markus Magerl, Jürgen Jung, Marcus Maurer,

Allergic Rhinitis and Sensitization

To the Editor: Acquired cold urticaria (ACU), a frequent form of physical urticaria, is characterized by weal and flare–type skin reactions and/or angioedema after cold exposure.1.Lee C.W. Sheffer A.L. Primary acquired cold urticaria.Allergy Asthma Proc. 2003; 24: 9-12PubMed Google Scholar, 2.Wanderer A.A. Hoffman H.M. The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromes.Immunol Allergy Clin North Am. 2004; 24: 259-286Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar ACU is diagnosed by a history of such symptoms and a positive immediate cold-contact stimulation test (CST), ie, the development of urticarial skin lesions at sites of cold challenge3.Wanderer A.A. Grandel K.E. Wasserman S.I. Farr R.S. 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: 417-423Abstract Full Text PDF PubMed Scopus (107) Google Scholar. Various CSTs have been described, the most common of which involves the application of an ice cube to the skin.3.Wanderer A.A. Grandel K.E. Wasserman S.I. Farr R.S. 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: 417-423Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4.Koeppel M.C. Bertrand S. Abitan R. Signoret R. Sayag J. Cold urticaria: clinical findings in 104 patients.Ann Dermatol Venereol. 1996; 123: 627-632PubMed Google Scholar, 5.Mathelier-Fusade P. Aissaoui M. Bakhos D. Chabane M.H. Leynadier F. Clinical predictive factors of severity in cold urticaria.Arch Dermatol. 1998; 134: 106-107Crossref PubMed Scopus (43) Google Scholar However, ice cube challenge tests (1) reportedly fail to confirm ACU in 1 of 5 affected patients,6.Neittaanmaki H. Cold urticaria: clinical findings in 220 patients.J Am Acad Dermatol. 1985; 13: 636-644Abstract Full Text PDF PubMed Scopus (123) Google Scholar (2) are not suited or standardized to assess threshold temperatures of urticaria induction, and (3) occasionally result in cold damage at test sites. To develop a safer, more sensitive, and standardized CST procedure and to determine and monitor threshold temperatures of patients with ACU,7.Sibbald R.G. Physical urticaria.Dermatol Clin. 1985; 3: 57-69PubMed Google Scholar we have generated and tested an electronic device (TempTest) that allows testing of as many as 4 different temperatures using the Peltier effect.8.Toth-Kasa I. Abraham T. Obal Jr., F. Husz S. Electronic device producing various temperatures for testing cold and heat urticaria.Arch Dermatol Res. 1981; 271: 447-449Crossref PubMed Scopus (6) Google Scholar Low-voltage Peltier thermoelectric elements operate as heat/cool bodies, ie, depending on the direction and intensity of current passing through 2 dissimilar semiconductors, 1 side of the thermal element is cooled, whereas the other is heated. TempTest is equipped with 4 thermal elements embedded in plastic bodies so that as many as 4 different temperatures can be simultaneously applied to skin areas of 7 cm2 each (Fig 1). Thermal element settings range from 0°C to 45°C (±0.1°C) and are regulated via a central microprocessor control unit, which constantly monitors, adjusts, and displays the actual temperature at the skin challenge site. To assess how CSTs using TempTest or traditional methods compare in terms of sensitivity, specificity, and safety, we performed a prospective clinical trial testing 30 patients with ACU and 30 patients with chronic urticaria who had never experienced cold induced urticaria with both TempTest (left arm) and ice cube challenge (right arm). The study was approved by the Ethics Committee of the University of Mainz and performed in accordance with national and international guidelines. Patients who (1) did not provide informed consent, (2) had been subjected to skin testing within the past 10 days, or (3) had received glucocorticoids within the past 10 days or antihistamines within the past 3 days were excluded from the study. The ice cube was placed on the patient's right volar forearm for 5 minutes, and at the same time, a 4°C TempTest thermal element was applied to the left forearm for 5 minutes. Test sites were inspected for erythema and weals as well as thermal skin damage after 15 minutes and 48 hours, respectively, and patients were asked to quantify and document pruritus at both skin test sites. Ice cube challenge test results confirmed ACU in 25 of 30 patients (83%) who had experienced cold-induced urticaria in the past (Table I). All of these 25 patients, and 3 additional patients who had not reacted to the ice cube challenge, exhibited positive skin reactions (erythema, weal, and itch) at cold-exposed test sites after TempTest challenge (total, 28 of 30; 92%; Table I). This indicates that TempTest is not significantly different from the traditional method in detecting ACU (Fisher exact test, P = .4). None of the 30 patients with chronic urticaria, who had never experienced cold-induced urticaria, showed positive skin reactions following ice cube or TempTest challenge (Table I). TempTest and ice cube challenge did not result in thermal skin damage in any of the 60 patients tested (Table I).Table IComparison of skin cold challenges performed with TempTest or traditional skin testing procedures∗Traditional skin testing procedures: CST, ice cube challenge; CTTT, water bath challenge. Sensitivity: positive test results in patients with history of cold-induced symptoms. Specificity: positive test results in patients without history of cold-induced symptoms. Safety: occurrence of thermal skin damage in patients.Traditional methodsTempTestCSTSensitivity25/30 (83%)28/30 (93%)Specificity0/30 (100%)0/30 (100%)Safety0/60 (100%)0/60 (100%)CTTTOperabilityPreprocessing15 minNoPostprocessing10 minNoAssistance requiredYesNoAccuracy±2° to 4°C±1°CReproducibilityDifficultExcellent∗ Traditional skin testing procedures: CST, ice cube challenge; CTTT, water bath challenge. Sensitivity: positive test results in patients with history of cold-induced symptoms. Specificity: positive test results in patients without history of cold-induced symptoms. Safety: occurrence of thermal skin damage in patients. Open table in a new tab Taken together, these findings indicate that TempTest CSTs provide highly sensitive and specific results as well as safe, fast, and practical test settings. Thus, we tested the operability of TempTest challenges in assessing critical temperature thresholds (CTTs) of patients with ACU in a series of pilot experiments. Thresholds for temperature or stimulation time are useful markers for ACU severity and can also be used to monitor the effects of therapeutic interventions in patients with ACU.3.Wanderer A.A. Grandel K.E. Wasserman S.I. Farr R.S. 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: 417-423Abstract Full Text PDF PubMed Scopus (107) Google Scholar We chose to determine CTTs rather than cold stimulation time thresholds (CSTT) because TempTest is ideally suited to expose skin to defined temperatures that differ by only 1°C. Moreover, traditional CTT tests (CTTTs) using water bath challenges are potentially dangerous because they can trigger systemic reactions.2.Wanderer A.A. Hoffman H.M. The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromes.Immunol Allergy Clin North Am. 2004; 24: 259-286Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 3.Wanderer A.A. Grandel K.E. Wasserman S.I. Farr R.S. 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: 417-423Abstract Full Text PDF PubMed Scopus (107) Google Scholar CSTTs, on the other hand, can readily be assessed by safe and standardized ice cube challenges.3.Wanderer A.A. Grandel K.E. Wasserman S.I. Farr R.S. 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: 417-423Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4.Koeppel M.C. Bertrand S. Abitan R. Signoret R. Sayag J. Cold urticaria: clinical findings in 104 patients.Ann Dermatol Venereol. 1996; 123: 627-632PubMed Google Scholar Traditional CTTTs in 10 patients with ACU using water bath challenges were found to be time and labor consuming (as long as 40 minutes; assistance required), unprecise (±4°C), and overall cumbersome to both patients and investigators (Table I). In contrast, TempTest-based CTTTs in these patients provided quick and accurate results (within 10 minutes; no assistance required; ±1°C), suggesting that TempTest is superior to traditional test methods in assessing CTTs. Patients with ACU are in danger of experiencing severe and sometimes lethal systemic reactions including hypotension and shock after extended cold challenge, eg, swimming in cold water.2.Wanderer A.A. Hoffman H.M. The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromes.Immunol Allergy Clin North Am. 2004; 24: 259-286Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Currently used CST methods vary widely between different centers (eg, challenges with ice cubes, ice packs, water baths, or ice water–filled cups placed on the patient's skin) and can result in skin damage (eg, after ice cube challenge) and/or dangerous systemic reactions (eg, after cold water bath challenge). Thus, standardized, reliable, exact, and safe test methods that allow comparison of results obtained at different centers need to be developed to diagnose ACU (so that patients can be advised to avoid cold exposure). Because the underlying causes of ACU remain unidentified in most patients, therapeutic measures are usually aimed at reducing ACU symptoms, eg, by antihistamines. It is therefore necessary to control treatment effects objectively and accurately in patients with ACU on the basis of monitoring CTTs or CSTTs. This can be achieved only by using standardized and practicable test methods that yield precise and reproducible results, which until now were unavailable for assessing CTTs. Our findings suggest that Peltier effect–based testing provides a sensitive and specific method to diagnose ACU and to determine CTTs in patients with ACU. In addition, TempTest cold challenges did not result in thermal damage, a known side effect of traditional CSTs and CTTTs, in any of the 60 patients tested in the study reported here or in more than 200 additional patients tested so far. In fact, virtually all patients tested favored TempTest CSTs and CTTTs over traditional testing in terms of comfort and convenience.