Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study.

BACKGROUND: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. METHODS: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). RESULTS: Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. CONCLUSIONS: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.

Role of Substance P and Its Receptor Neurokinin 1 in Chronic Prurigo: A Randomized, Proof-of-Concept, Controlled Trial with Topical Aprepitant.

Substance P (SP) and its receptor neurokinin 1 (NK1R) are thought to be involved in the pathogenesis of chronic prurigo. Here, we assessed SP serum levels, cutaneous NK1R expression, and the effects of topical aprepitant, an NK1R antagonist, in patients with chronic prurigo. SP and NK1R were increased, compared with controls, in the serum and in lesional vs. non-lesional skin of the patients, respectively. Aprepitant, in a randomized, placebo-controlled, split-sided, doubleblind trial, reduced the intensity of pruritus as assessed by visual analogue scale by >50% from baseline to day 28 (-35.2), but so did placebo vehicle (-38.1, p= 0.76). Overall clinical scores improved significantly by day 28 in both treatment groups, with no significant difference between the 2 groups (p=0.32). Our findings imply that both SP and NK1R are involved in the pathogenesis of chronic prurigo. Parallel groupdesigned trials are needed to assess the efficacy of topical aprepitant treatment in this condition.

The Urticaria Activity Score-Validity, Reliability, and Responsiveness.

BACKGROUND: Chronic spontaneous urticaria is characterized by fluctuating symptoms. Its activity is assessed with the urticaria activity score (UAS). Two versions of the urticaria activity score used for 7 consecutive days (UAS7) are available: (1) The guideline-recommended UAS7, with once-daily documentation, and (2) the UAS7TD, with twice-daily documentation. OBJECTIVE: To better characterize both UAS7 versions with regard to their validity, reliability, sensitivity to change, minimal important difference (MID), and smallest detectable change (SDC). METHODS: One hundred thirty adult patients with chronic spontaneous urticaria completed both UAS7 versions, the Patients Global Assessment (PatGA) of disease activity, the Urticaria Control Test (UCT), the Chronic Urticaria Quality of Life Questionnaire, and the Dermatology Life Quality Index before and after the initiation of omalizumab therapy. Physicians completed a Physician Global Assessment of disease activity. RESULTS: The UAS7 and the UAS7TD showed high correlation with the activity anchor PatGA (r = 0.568, P < .001 and r = 0.605, P < .001) and the UCT (r = -0.580, P < .001 and r = -0.585, P < .001). The wheal and pruritus scores of the UAS7 and the UAS7TD exhibited respectable internal consistency and, in each UAS7 version, correlated well with each other (Cronbach α = 0.78, r = 0.640, P < .001, and Cronbach α = 0.77, r = 0.626, P < .001). Changes in the UAS7 and UAS7TD correlated well with PatGA changes (r = 639, P < .001, and r = .763, P < .001) and with UCT changes (r = -0.642, P < .001, and r = -0.703, P < .001). The MID was 11 for the UAS7 (SDC = 12) and 12 for the UAS7TD (SDC = 11). CONCLUSIONS: The UAS7 and UAS7TD show good and comparable clinimetric properties, including good sensitivity to change, and similar MIDs.

Clinical Measures of Chronic Urticaria.

The use of standardized, valid, and reliable clinical measures is an important element in modern patient management, particularly in diseases that are not objectively assessable and are associated with a high disease burden. Chronic urticaria is such a disorder for which several new and well-developed clinical measures became available. These measures comprise tools to assess disease activity, disease control, and health-related quality-of-life impairment. This review provides an overview of the currently available clinical measures for chronic urticaria. In addition, it provides information on their strengths and limitations and how to best use them and evaluate their results.

Anti-pruritic Effect of Sertaconazole 2% Cream in Atopic Dermatitis Subjects: A Prospective, Randomized, Double-blind, Vehicle-controlled, Multi-centre Clinical Trial of Efficacy, Safety and Local Tolerability.

This study was a prospective, parallel-group, randomized, double-blind, vehicle-controlled, multi-centre clinical trial to compare the efficacy of topical sertaconazole 2% cream with vehicle in reducing chronic pruritus in subjects with atopic dermatitis, and to assess its safety and local tolerability. A total of 70 subjects applied either of the 2 treatments twice daily for a period of 4 weeks on affected, itchy skin areas. Treatment efficacy was evaluated primarily considering the item itch intensity on a 5-point verbal rating scale. Insomnia, state of atopic dermatitis (Scoring Atopic Dermatitis; SCORAD), quality of life and therapy benefit were also assessed. No significant difference between active treatment and vehicle was found at any of the time-points for any of the investigated parameters. Under the experimental conditions of the study, sertaconazole 2% cream did not exert anti-pruritic effects that were better than vehicle in subjects with atopic dermatitis who had chronic pruritus. Trial registration ClinicalTrials.gov #NCT01792713.

Physical urticarias and cholinergic urticaria.

Physical urticarias are a unique subgroup of chronic urticaria in which urticarial responses can be reproducibly induced by different specific physical stimuli acting on the skin. These conditions include urticaria factitia/symptomatic dermographism, delayed pressure urticaria, cold contact urticaria, heat contact urticaria, solar urticaria, and vibratory urticaria/angioedema. Physical urticarias and cholinergic urticarias are diagnosed based on the patients' history and provocation tests including trigger threshold testing where possible. Treatment is mainly symptomatic. Many patients benefit from avoiding eliciting triggers, and desensitization to these triggers can be helpful in some physical urticarias and in cholinergic urticaria.

Diagnosis of urticaria.

Acute urticaria do not need extensive diagnostic procedures. Urticaria activity score is a useful tool for evaluation of urticaria. Complete blood count, Erythrocyte sedimentation rate and C reactive protein are important investigations for diagnosis of infections in urticaria. Autologous serum skin test is a simple office procedure for diagnosis of auto reactive urticaria. Closed ball point pen tip is a simple test to diagnose dermographism.

The inhibition by levocetirizine and fexofenadine of the histamine-induced wheal and flare response in healthy Caucasian and Japanese volunteers.

This randomized, double-blind, placebo-controlled crossover study compared inhibition by one 5 mg dose of levocetirizine with two 60 mg doses of fexofenadine separated by 12 h of histamine-induced wheal and flare responses in 9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more inhibitory than fexofenadine on wheal, flare and pruritus (p < 0.005). Variability, evaluated from the standard deviation of inhibition, ranged from 14% to 23.2% for levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine had a faster onset of action (30-90 min versus 2 h), shorter time to maximum effect (3-4 versus 3-6 h) and longer duration of action (at least 24 h versus ~12 h) than fexofenadine. The plasma levels of levocetirizine rose more quickly, reached higher levels, were more consistent and decreased slower than those of fexofenadine. There were no clinically significant ethnic differences in responsiveness to the drugs.

Effects of a Novel GA(2)LEN Training Program on Urticaria on the Knowledge of General Practitioners in Saudi-Arabia.

Continued education in allergology of both general practitioners and specialists can be achieved by various measures including publications, online tools, and lectures. GA(2)LEN, the Global Allergy and Asthma European Network, has developed 1-day training programs on a number of allergic diseases including asthma, allergic rhinitis, pruritus, angioedema, and urticaria. Here, we assessed the impact of one of these training programs (on urticaria) on the knowledge of 100 participating physicians in Saudi-Arabia by repeated multiple choice examinations. We found that only 5.7% of 70 participants, who took both the pretraining and posttraining examination, passed the pretraining test, that is, answered 70% of the questions correctly. Notably, 68.6% of these participants passed the examination after participating in the 1-day training program (P < 0.001). Participation in the training program also resulted in a significant increase of questions answered correctly (P < 0.001). Taken together, the GA(2)LEN 1-day training programs on selected allergic diseases are an effective means to improve levels of knowledge on these diseases in physicians including general practitioners and the use of these training programs should be promoted and increased.