Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria

Background Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. Objectives To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. Methods Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg(-1) dairy of cyclosporin (Sa ndimmun(R), n = 20) or placebo (n = 10) for 4 weeks. Nonresponders were off ered open-label cyclosporin for 4 weeks. All were followed for up to 20 wee ks or until clinical relapse; all took cetirizine 20 mg daily throughout th e study. The primary measure of efficacy was a daily urticaria activity sco re (UAS) of weal numbers and itch (maximum score 42 per week). A positive r esponse was defined as a reduction to < 25% of baseline weekly UAS and rela pse as a return to > 75%. The effect of cyclosporin on serum HRA was assess ed by in vitro basophil histamine release assays and ASSTs before and after treatment. Results Twenty-nine patients (19 active, 10 controls) completed the randomi zed trial medication. Eight of 19 on active treatment but none on placebo h ad responded at 4 weeks (P < 0.05). Three others on active drug met the cri terion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS be tween weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for act ive and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-respo nders (seven randomized to active and 10 to placebo) chose open-label cyclo sporin and 11 responded after 4 weeks. Six of the eight randomized active d rug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study endpoi nt. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8 %) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to p ost-treatment serum was also reduced (P < 0.05). Conclusions This study shows that cyclosporin is effective for chronic urti caria and provides further evidence for a role of histamine-releasing autoa ntibodies in the pathogenesis of this chronic 'idiopathic' disease.