Chronic spontaneous urticaria (CSU) is characterized by the occurrence of hives, angio-oedema or both for a period of at least 6 weeks. Many patients remain symptomatic despite treatment with H1 antihistamines, even at higher doses. This systematic review assessed the quality of the evidence for the effects of omalizumab as treatment in patients with CSU. We searched PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials up to 7 August 2014. Three review authors independently carried out study selection, risk of bias assessment and data extraction. Two review authors analysed the data. Five randomized controlled trials (RCTs), which included 1116 participants, were evaluated. All the RCTs were judged as having a low risk of bias. There was a statistically significant improvement in measures of disease activity and quality of life following treatment with omalizumab when compared with placebo [mean difference (MD) -11·58, 95% confidence interval (CI) -13·39 to -9·77 and MD -13·12, 95% CI -16·30 to -9·95, respectively]. Complete response and partial response were more frequent after treatment with omalizumab [risk ratio (RR) 6·44, 95% CI 3·95-10·49 and RR 4·08, 95% CI 2·98-5·60, respectively]. There was no difference in the proportion of participants reporting adverse events between the omalizumab and placebo treatment groups (RR 1·05, 95% CI 0·96-1·16). There was high-quality evidence to support the effectiveness and safety of omalizumab 300 mg per month for the treatment of CSU for up to 6 months.

BackgroundNon-hereditary angioedema (non-HAE) is characterized by local swelling due to self-limiting, subcutaneous or submucosal extravasation of fluid, and can be divided into three subtypes. These subtypes are believed to have different pathophysiological backgrounds and are referred to in recent guidelines as bradykinin-mediated (e.g. caused by angiotensin-converting-enzyme-inhibitors), mast cell-mediated (e.g. angioedema with wheals) or idiopathic (cause unknown). Bradykinin-mediated subtypes are more closely related to hereditary angioedema than the other forms. Because clinical features of these non-HAE subtypes have not been studied in detail, we have looked at the clinical characteristics of symptoms and potential differences in clinical presentation of bradykinin-mediated and mast cell-mediated angioedema (AE) subtypes.MethodsA questionnaire was sent to patients presenting with AE at our tertiary outpatient clinic to document clinical characteristics, potential triggers and location of AE. The severity of AE attacks was analysed using visual analogue scales (VAS).ResultsThe questionnaire was returned by 106 patients, of which 104 were included in the analysis. AE with wheals, idiopathic AE, and drug-associated AE occurred in 64 (62%), 25 (24%) and 15 patients (14%) respectively. Most patients (62%) reported prodromal symptoms while 63% reported multiple locations for an attack. Face and oropharynx were the main locations of AE attacks of any subtype while swelling was the symptom most frequently reported as severe. Overall severity of the last attack was indicated as severe by 68% of the patients. There were no differences between the subgroups.ConclusionThis similarity in clinical presentation raises the possibility that ACEi-induced, mast cell-mediated and idiopathic AE share common pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s13601-015-0049-8) contains supplementary material, which is available to authorized users.

BackgroundTreatment with second-generation antihistamines is recommended in patients with chronic spontaneous urticaria (CSU). Some patients remain unresponsive even after up-dosing up to fourfold. Many third line treatment options have limited availability and/or give rise to significant side effects. We investigated effectiveness and safety of antihistamine treatment with dosages up to fourfold and higher.MethodsThis retrospective analysis of patients’ records was performed in adult CSU patients suffering wheals and/or angioedema (AE). Demographic, clinical, and therapeutic data was extracted from their medical records. We recorded the type, maximum prescribed dosage, effectiveness, and reported side effects of antihistamine treatment.ResultsOf 200 screened patients, 178 were included. Treatment was commenced with a once daily dose of antihistamines. Persisting symptoms meant that up-dosing up to fourfold occurred in 138 (78%) of patients, yielding sufficient response in 41 (23%). Up-dosing antihistamines was necessary in 110 (80%) patient with weals alone or weals with angioedema and 28 (64%) with AE only (p = 0.039). Of the remaining 97 patients with insufficient response, 59 were treated with dosages higher than fourfold (median dosage 8, range 5–12). This was sufficient in 29 patients (49%). Side effects were reported in 36 patients (20%), whereof 30 (17%) experienced somnolence. Side effects after up-dosing higher than fourfold were reported in six out of 59 patients (10%).ConclusionUp-dosing antihistamines higher than fourfold dosage seems a feasible therapeutic option with regards to effectiveness and safety. The need for third line therapies could be decreased by 49%, with a very limited increase of reported side effects.

Background Chronic spontaneous urticaria (CSU) is characterized by recurrent itchy weals and/or angioedema and is believed to be driven by mast cell activation. It was shown that excessive mast cell activation during anaphylaxis initiates contact activation, resulting in bradykinin release. Evidence for bradykinin release was never demonstrated in CSU. Objective To study biomarkers of bradykinin release in CSU. Methods Plasma samples of CSU patients were collected during routine visits at the outpatient clinic. Cleaved high molecular weight kininogen (cHK) was used as a biomarker for bradykinin release. cHK, factor XIIa‐C1‐inhibitor (FXIIa‐C1‐INH), kallikrein‐C1‐INH, plasmin‐antiplasmin (PAP) complexes and soluble urokinase‐type plasminogen activator receptor (suPAR) levels were determined by ELISA. Clinical data and data on tryptase levels were collected from medical records. cHK levels were compared to previously determined levels in hereditary angioedema (HAE). Results One hundred seventeen samples from 88 CSU patients and 28 samples from healthy controls were analysed. Median cHK level in CSU was 9.1% (range: 1.4%‐21.5%), significantly increased compared to healthy controls (median 6.0% range: 0%‐19.9%; P = .0005) and comparable to HAE (n = 46, median 10.3%, range 0%‐44.3%, P > .9999). cHK levels normalized in patients during disease remission (median 6.5% range 1.5%‐20.8%) but were not dependent on the presence of angioedema, acute angioedema attacks or response to antihistamines. Surprisingly, cHK levels were inversely correlated to serum tryptase (r = −0.65 P = .0137). C1‐INH complexes and suPAR levels were not elevated in patients compared to healthy controls. PAP‐complex levels in patients were elevated compared to healthy controls but there was no correlation between PAP‐complex and cHK levels. Conclusions cHK levels are elevated in symptomatic CSU patients compared to healthy controls, indicating increased bradykinin production. Increased cHK levels are not limited to patients with angioedema. Clinical relevance If elevated bradykinin generation has clinical implications in the pathology of CSU is open to debate.