Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria Martin Metz, MD*; Elisabeth Scholz, Cand Med*; Marta Ferrán, MD†; Iñaki Izquierdo, MD, PhD‡; Ana Giménez-Arnau, MD, PhD†; and Marcus Maurer, MD* Background: Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a dual antagonist of both histamine and platelet-activating factor. Objective: To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU. Methods: A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge. Results: After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P  .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment. Conclusion: Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms. Ann Allergy Asthma Immunol. 2010;104:86 –92. INTRODUCTION Acquired cold urticaria (ACU) is characterized by the imme- diate appearance of itchy wheals and angioedema in response to cold exposure or cooling of the skin. 1–4 Patients with ACU are at risk of systemic symptoms and even life-threatening complications 2,3,5,6 and, therefore, must be advised against exposing large skin areas to cold (eg, by swimming in cold water). 1,4,6 Acquired cold urticaria also has important occu- pational and employment implications. 7 Acquired cold urti- caria is rather evenly distributed by sex (55% women) and age (mean [SD] age, 41  16 years), at least in the Berlin, Germany, population, according to the only scientific epide- miologic study available. 8 Diagnosis is made on the basis of the history and cold challenge test results. 1– 4,9 Acquired cold urticaria often lasts for several years 1,3,8 and can have a substantial impact on patients’ quality of life, necessitating effective treatment. 3 As with all physical urticarias, avoid- ance of the triggering factor (cooling of the skin) is a basic part of managing ACU. 2,3 In most patients, ACU is idiopath- ic. 1,2,10 Its pathogenesis remains mostly unclear, but it is known that mast cell degranulation releases histamine and other mediators, thus causing the wheal-and-flare reac- tion. 2,3,6,10 Platelet-activating factor (PAF) 11 is a mediator implicated in many inflammatory conditions, including ACU. The intra- dermal injection of PAF leads to a dose-dependent, biphasic, wheal-and-flare response. 12 Platelet-activating factor triggers the binding of neutrophils to endothelial cells, which may be part of an inflammatory response. 13 A classic experimental study 14 showed an association between PAF and edema in patients with ACU. Affiliations: * Department of Dermatology and Allergy, Allergie-Centrum- Charité, Charité-Universitätsmedizin, Berlin, Germany; † Department of Der- matology, Hospital del Mar, Universitat Autònoma, Barcelona, Spain; ‡ Depart- ment of Clinical Development, J. Uriach & Co, SA, Barcelona, Spain. Disclosures: Dr Metz is or recently was an investigator and/or speaker for Essex Pharma, JADO Technologies, Merckle Recordati, and Schering- Plough; Dr Izquierdo is head of the Clinical Development and Advice Department, J. Uriach & Co, SA; Dr Giménez-Arnau is or recently was an investigator, speaker, and/or advisor for Bayer Schering Pharma, Basilea, and J. Uriach & Co, SA; and Dr Maurer is or recently was an investigator, speaker, and/or advisor for Almirall Hermal, Bayer Schering Pharma, Bio- frontera, Essex Pharma, Genentech, JADO Technologies, Jerini, Merckle Recordati, Novartis, Schering-Plough, Shire, Symbiopharm, UCB, and J. Uriach & Co, SA. Funding Sources: This study was supported by J. Uriach & Co, Barce- lona, Spain; and partially supported by the National Scientific Research Program of the Spanish Minister of Science and Technology. Received for publication July 7, 2009; Received in revised form August 28, 2009; Accepted for publication September 16, 2009. © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.anai.2009.11.013 86 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY