title: Up-dosing with bilastine results in improved effectiveness in cold contact urticaria.
abstract: BACKGROUND
  Cold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge.
  
  
  METHODS
  Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds (CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine.
  
  
  RESULTS
  Bilastine 20 mg was highly effective (P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly (P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1-3 h after cold challenge were significantly (P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treatment was well tolerated without evidence of increased sedation with dose escalation.
  
  
  CONCLUSIONS
  Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines.
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Krause
authors.forename: A
authors.initials: A
authors.lastname: Spohr
authors.forename: T
authors.initials: T
authors.lastname: Zuberbier
authors.forename: M K
authors.initials: MK
authors.lastname: Church
authors.forename: M
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D003080:Cold Temperature / Q000009:adverse effects*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011446:Prospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014581:Urticaria / Q000188:drug therapy* / Q000209:etiology; D055815:Young Adult
chemical_list: D001562:Benzimidazoles; D010880:Piperidines; C445659:bilastine
keywords: H1-antihistamine; bilastine; cold contact urticaria; cytokines; histamine