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We describe an unusual presentation of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome in a 15-year-old male, recalcitrant to low-dose anti-histamines, which subsequently responded to high-dose fexofenadine., (© 2024 Wiley Periodicals LLC.)

Background: Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment., Objective: Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU., Methods: Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17., Results: Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency ( n  = 2649, RR = 1.36, 95%CI:1.30-1.43, p  < 0.00001), cure ( n  = 2649, RR = 1.54, 95%CI:1.42-1.66, p  < 0.00001) and recurrence ( n  = 446, RR = 0.34, 95%CI:0.20-0.58, p  < 0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate ( n  = 2317, RR = 0.76, 95% CI:0.59-0.97, p  = 0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported., Conclusions: CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results.

Background: A fexofenadine/pseudoephedrine combination tablet (F/P) is an optimal product for nasal obstruction. It contains fexofenadine hydrochloride, a histamine H1-receptor antagonist for sneezing and rhinorrhea and pseudoephedrine hydrochloride, an α-adrenergic agonist. The effect of an antihistamine-decongestant on nasal obstruction has been demonstrated in previous studies, but onset of action and efficacy data on nasal obstruction are limited., Objective: We estimated the efficacy of F/P on nasal obstruction in patients with house dust mite-induced allergic rhinitis (AR) versus fexofenadine (F) using objective methods., Methods: In this single-center, single-dose, prospective, randomized, parallel-group study, 24 adult patients with a history of at least 2 years of AR and nasal obstruction were randomized to receive F/P or F. The effect on nasal obstruction was evaluated using nasal airflow and visual analog scale (VAS) score measured at 30-minute intervals before and for 8 hours after dosing. The primary end point was onset of action, based on a comparison of absolute change from baseline in nasal airflow between F/P and F. The protocol was registered in a clinical trial registry as UMIN 000041845., Results: The onset of action for F/P was 30 minutes based on nasal airflow and 60 minutes based on VAS. F/P maintained a significant beneficial effect after onset of effect, while F showed no significant change during the test period., Conclusions: We found F/P had a clear effect on nasal obstruction associated with perennial AR when compared with F. There was a time lag in nasal airflow improvement and nasal obstruction relief.

To gain a comprehensive overview of the landscape of clinical trials for the H 1 -receptor antagonists (H 1 R antagonists) cetirizine, levocetirizine, loratadine, desloratadine, and fexofenadine and their potential use cases in drug repurposing (the use of well-known drugs outside the scope of the original medical indication), we analyzed trials from clincialtrials.gov using novel custom-coded software, which itself is also a key emphasis of this paper. To automate data acquisition from clincialtrials.gov via its API, data processing, and storage, we created custom software by leveraging a variety of open-source tools. Data were stored in a relational database and annotated facilitating a specially adapted web application. Through the data analysis, we identified use cases for repurposing and reviewed backgrounds and results in the scientific literature. Even though we found very few trials with published results for repurpose indications, extended literature research revealed some prominent use cases: Cetirizine seems promising in mitigating infusion-associated reactions and is also more effective than placebo in the treatment of androgenetic alopecia. Loratadine may be beneficial in the prophylaxis of G-CSF-related bone pain. In COVID-19, H 1 R antagonists may be helpful, but placebo-controlled scientific evidence is needed. For asthma, the effect of H 1 R antagonists only seems to be secondary by alleviating allergy symptoms. Our novel method to find potential use cases for repurposing of H 1 R antagonists allows for high automation, reduces human error, and was successful in revealing potential areas of interest. The software could be used for similar research questions and analyses in the future., (© 2023. The Author(s).)

International guidelines for the treatment of chronic spontaneous urticaria support the updosing of second-generation antihistamines to four times of the approved dose when adequate symptom control cannot be achieved with the standard dosage. However, this recommendation is primarily based on expert opinions, and there is a lack of large, well-designed, double-blind clinical trials. Most the existing trials provide insufficient data, and due to the heterogeneity of the conducted trials on antihistamine effects (definition of control, design, quality, lack of an active comparator, no placebo arm, small sample size, outcomes) and their short duration, comparative analysis is challenging. However, it can be concluded that the use of modern second-generation antihistamines is both effective and safe based on the available data and our own long-term experiences in the specialized outpatient clinic of a university dermatology department, even though increased dosages (up to fourfold as per the current international guidelines) may be necessary for symptom control. Another therapeutic option for refractory symptoms in chronic spontaneous urticaria is subcutaneous administration of omalizumab at a dosage of 300 mg at 4‑week intervals as a very safe and effective treatment., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of patients with AR develop symptoms before age 6 years. Although a diagnosis of AR is associated with higher socioeconomic status, underserved and urban populations have more indoor aeroallergen sensitizations and are likely underdiagnosed with AR, further exacerbating health-care disparities. AR negatively impacts quality of life, school performance, and overall health outcomes. Untreated AR in children increases the risk for poor asthma control, increased asthma severity, and exacerbations. Many patients believe that they have seasonal allergies only but in reality have both perennial and seasonal AR, which may change the approach to allergen avoidance measures and treatment recommendations. Pharmacotherapy of AR has expanded, with many intranasal corticosteroids, intranasal antihistamines, and second-generation oral antihistamines approved for pediatric use. Allergen immunotherapy, including both subcutaneous and sublingual forms, are approved for children and are disease modifying, potentially reducing further allergen sensitization and progression to asthma. Many of the currently available biological therapies indicated for pediatric asthma and/or atopic diseases reduce AR symptoms as well. Children with moderate to severe or refractory AR or those with comorbidities should be referred to allergists for diagnostic testing and expanded management options, including immunotherapy and potential biological treatment., (© American Academy of Pediatrics, 2023. All rights reserved.)

Background: Allergic rhinoconjunctivitis and chronic urticaria are common histamine-driven diseases, exerting detrimental effects on cognitive functions, sleep, daily activities, and quality of life. Non-sedating second-generation H 1 -antihistamines are the first-line treatment of choice. Aim of the study was to define the role of bilastine among second-generation H 1 -antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria in patients of different ages., Methods: An international Delphi study was carried out to assess consensus among experts from 17 European and extra-European countries on three main topics: 1) Burden of disease; 2) Current treatment options; 3) Specific characteristics of bilastine among second-generation antihistamines., Results: Here, we present the results obtained for a selection of 15 out of 27 consensus statements, focused on disease burden, role of second-generation antihistamines and bilastine profile. The rate of concordance was ≥98% for 4 statements, ≥ 96% for 6, ≥ 94% for 3, and ≥90% for 2., Conclusions: The high degree of agreement obtained suggests a wide awareness of the burden of allergic rhinoconjunctivitis and chronic urticaria among experts from all over the world and reflects a broad consensus on the role of second-generation antihistamines in general and of bilastine in particular for their management.

This publication is the second part of the German-language S3 guideline on urticaria. It covers the management of urticaria and should be used together with Part 1 of the guideline on classification and diagnosis. This publication was prepared according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system conditions in German-speaking countries. Chronic urticaria has a high impact on the quality of life and daily activities of patients. Therefore, if causal factors cannot be eliminated, effective symptomatic treatment is necessary. The recommended first-line treatment is to administer new generation, non-sedating H1 antihistamines. If the standard dose is not sufficiently effective, the dose should be increased up to fourfold. For patients who do not respond to this treatment, the second-line treatment in addition to antihistamines in the treatment algorithm is omalizumab and, if this treatment fails, ciclosporin. Other low-evidence therapeutic agents should only be used if all treatments in the treatment algorithm agreed upon by the guideline group fail. Both the benefit-risk profile and cost should be considered. Corticosteroids are not recommended for long-term treatment due to their inevitable severe side effects., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Summary: Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions . Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.

Background: Chronic urticaria (CU), characterized by ≥6 weeks of intense pruritus, remains a debilitating condition for patients. New and safe treatments are needed to manage CU recalcitrant to standard therapy. Objective: A review of the current literature of standard and novel therapeutics in the management of CU was conducted. Methods: A literature search via a medical literature data base and clinical trial data base was conducted to identify treatment options for CU and current clinical trials. Results: Second-generation antihistamines, omalizumab, and cyclosporine remain the most proven therapeutic options for CU. Dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 are all undergoing clinical trials for CU. Although ligelizumab demonstrated initial promising results, a phase III study was discontinued due to a nonsuperior clinical impact compared with omalizumab. Conclusion: Novel therapies are needed for the treatment of recalcitrant CU. With a deeper understanding of the pathophysiology of CU, promising therapeutics are in clinical trials for CU.

Background: Guidelines recommend standard doses of antihistamines as first-line, and updosing of antihistamines as second-line treatment for the management of chronic urticaria (CU). However, remission rates with different types of first- and second-line treatments and indicators of antihistamine response are largely lacking in the literature., Objectives: To examine response rates to first- and second-line treatments in CU, and to identify patient characteristics that can predict antihistamine treatment outcomes., Methods: We retrospectively analyzed treatment outcomes of 657 CU (556 chronic spontaneous urticaria (CSU), 101 chronic inducible urticaria (CIndU)) patients who had at least 3-months of follow-up data., Results: A standard dose of second generation antihistamines (sgAH) was effective in 43.1 % of the patients. An additional 28.8 % of patients were in remission with second-line treatments. Among patients whose disease was in remission with a standard dose of sgAHs, 14.8 % benefited from switching from their current sgAH to another sgAH. Updosing sgAHs, combination of two different sgAHs, sgAH and first generation H 1 -antihistamine combination, and sgAH and leukotriene receptor antagonist combination provided remission in 38.3 %, 35.8 %, 37.5 % and 25 % of patients who were given these treatments, respectively. Baseline UCT score ≤ 4, emergency referral and family history of CSU were found to be risk factors for antihistamine refractoriness in patients with CSU., Conclusions: A step-wise approach to the management of CU is practical as more patients respond to treatment at each step. The presence of baseline UCT score ≤ 4, emergency referral and family history of CSU might be helpful to determine patients who require third-line treatments in advance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent., Objectives: We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria., Methods: We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software., Results: We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo., Conclusions: Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.

Background: Allergic rhinitis (AR) is associated with disturbed sleep and subsequent functioning, and an impaired quality of life (QoL). The symptoms of AR exhibit prominent circadian variations, with symptoms being more common at the night-time or early morning. Addressing these allergy-related sleep issues, impaired QoL, and circadian variation in symptoms is important from the patient perspective and should be considered in the management of AR., Objective: To review the efficacy of cetirizine, a second-generation antihistamine and selective H1-receptor antagonist, in relation to improvement in the QoL of the patients, addressing the sleep disturbances and circadian variations in the symptoms of AR in clinical practice, and establishing its role as a contemporary antihistamine for the management of AR compared to newer antihistamines., Methods: Systematic literature review of the databases such as PubMed/MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials from 1990 to 2020., Results: The symptoms of AR exhibited a circadian variation, with symptoms being worse during the night and early morning. The patients with AR encountered several sleep-related symptoms, including poor sleep quality, daytime somnolence, fatigue, and impaired productivity and QoL. Impaired QoL in AR was related to the disease severity. Administration of cetirizine at bedtime provides effective control of sleep impairment and symptoms of AR, besides improving the QoL. The efficacy of cetirizine has been demonstrated to be superior or comparable to the newer second-generation antihistamines. Cetirizine exhibits a tolerability profile comparable to the newer antihistamines., Conclusion: With long years of clinical experience and a good tolerability profile, cetirizine represents a valuable therapeutic option for the management of AR, even 30 years after its introduction. Cetirizine is included in the National List of Essential Medicines of India for the management of allergic disorders in view of its established efficacy and safety profile as well as being a cost-effective option., (© Journal of the Association of Physicians of India 2011.)

Background: A standard dose of second-generation H1 -antihistamines is recommended as the first-line treatment of chronic spontaneous urticaria (CSU), previous studies have found that approximately 20-50% of CSU children fail to control their symptoms and required step-up treatments., Objective: To evaluate the predictors of uncontrolled symptoms with first-line medication and describe the treatment outcomes of CSU children in the southern region of Thailand., Methods: This retrospective chart review of CSU patients, aged 2-18 years, who were initially treated with the standard dose of second-generation H1 -antihistamine at the Pediatric Allergy Clinic, Songkhlanagarind Hospital, from January 2008 to July 2018. The data were collected at the initial visit (demographic data, onset of rash, frequency of urticaria, presence of angioedema, previous resolved CU, laboratory investigation results) and follow-up visits (treatment outcome, time to controlled urticaria)., Results: The medical records of 192 CSU children were reviewed; their median age were 8.5 years and the mean frequency of rash was 4 days/week. Forty-seven children (24.4%) fail to controlled symptoms with a standard dose of second -generation H1 -antihistamines and a factor significantly associated was frequency of rash for more than 4 days per week (OR = 4.36, P < 0.001). The median time to controlled urticaria was 1.28 months., Conclusions: Most of CSU children in the southern region of Thailand experienced controlled symptoms with a standard dose of second-generation H1 -antihistamines, and the frequency of urticaria for more than 4 days per week was a factor associated with uncontrolled symptoms that regimen.

Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March - November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2-<12 years) followed EMA-authorized processes. Pharmacokinetic/pharmacodynamic simulation and modeling and a pharmacokinetic study were conducted to identify and confirm the pediatric dose (10 mg/day). A Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group study was performed to confirm the safety of bilastine 10 mg/day in children. In this article, evidence is reviewed for use of bilastine in children with allergic rhinoconjunctivitis or urticaria. Several cases are presented which demonstrate its role in routine clinical practice.

Purpose of Review: To explore our current understanding of receptor profiles acted upon by medications used to treat dry eye disease (DED)., Recent Findings: Research into histaminic and muscarinic receptor affinities for drugs targeting the ocular surface has not kept up with bench research pertaining to the receptor profile of the ocular surface. These insights are necessary for better evaluation of medications used in DED and other allergic disorders., Summary: At the H1 receptor, Ketotifen (pKa = 9.2), pyrilamine (pKa = 9.0), and epinastine (pKa = 8.0) had the highest affinities, whereas ranitidine (pKa = 4.2) and cimetidine (pKa = 4.9) had the lowest. Ketotifen, a second-generation antihistamine, was found to have a pKa of 6.7 at muscarinic receptors which was higher than that of diphenhydramine (pKa = 6.4), a first-generation antihistamine. Additionally, second-generation antihistamines have higher affinity for H3 receptors, which have been linked to urticaria, compared to first-generation. Azelastine, a second-generation, demonstrated significant affinity (pKa = 7.1) at the H3 receptor compared to all other drugs. Antazoline (pKa = 4.4) and diphenhydramine (pKa = 4.6), both first-generation antihistamines, had the lowest affinities for the H3 receptor. These findings raise questions about the use of antihistamines in the treatment of DED and allergic disorders., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The absence of blisters, the presence of mild systemic symptoms, and the patient's age guided the diagnosis.

The hypereosinophilic syndrome (HES) is a rare disorder characterized by hypereosinophilia and infiltration of various organs with eosinophils. Eosinophilic cystitis (EC), mimicking bladder cancer clinically but also in ultrasound and in radiographic imaging, is one potential manifestation of the HES occurring in adults as well as in children. This case report describes the course of disease in a 57-year-old male presenting with severe gait disorders and symptoms of a low compliance bladder caused by a large retropubic tumor. After extensive urine and serologic examination and histologic confirmation of EC the patient was subjected to medical treatment with cetirizine and prednisolone for 5 weeks. While gait disorders rapidly resolved, micturition normalized only 10 months after initiation of therapy. Based upon this course the authors recommend patience and reluctance concerning radical surgical intervention in EC. Key Points • Eosinophilic cystitis is a rare condition with app. 200 cases reported, so far. • Etiology of eosinophilic cystitis is obscure, but allergies and parasitic infections may trigger the disease. • Genetic alterations (e.g., BRAF mutations) may predispose for the disease • Corticosteroids and antihistamines are the backbone of therapy and may be complemented by antibiotics and non-steroidal anti-inflammatory drugs in case of concomitant (underlying) infections. • As recovery can occur even after a long time, radical surgery should be restricted to highly selected cases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Evidence from pain research shows that the effectiveness of active pharmacological treatments can be enhanced by placebo effects. The "open drug administration" is superior to "hidden drug administration.​" In a randomized controlled trial, we aimed to show that the targeted use of placebo effects increases the efficacy of an antihistamine (dimetindene) infusion in participants with atopic dermatitis. We openly infused dimetindene (drug) in full sight with information (intervention group 1: OPEN-DRUG+INST), openly infused drug with an additional classical conditioning learning experience (intervention group 2: OPEN-DRUG+INST+COND) or infused drug without any information or sight (i.e., hidden administration (control group 1: HIDDEN-DRUG)). Control group 2 received a placebo infusion (saline) declared as dimetindene and also experienced the conditioning experience (PLAC+INST+COND). Itch was experimentally induced with histamine via a skin prick test. Outcome was assessed at the subjective (primary end point: experimental itch intensity, numeric rating scale), and objective level (secondary end point: wheal size, mm 2 ). Experimental-induced itch intensity decreased in all groups but at different rates (P < 0.001). The groups with the open administration, whether it was dimetindene or placebo, had significantly stronger reductions in itch compared to the HIDDEN-DRUG group (OPEN-DRUG+INST+COND: P < 0.001; OPEN-DRUG+INST: P = 0.009; and PLAC+INST+COND: P < 0.001). Additional drug conditioning mediated via expectation led to a stronger reduction of itching (P = 0.001). Results on wheal size were similar (P = 0.048), however, no significant difference between the HIDDEN-DRUG group and the PLAC+INST+COND group (P = 0.967) was found. We conclude that specifically generated targeted placebo effects can significantly increase the action of a drug (dimetindene) and should be used in clinical practice., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background and Objectives: According to current guidelines, oral antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU). Up-dosing antihistamines to 4-fold the licensed dose is recommended if control is not achieved. Such indications are based mainly on expert opinion. Objectives: To critically review and analyze clinical evidence on the efficacy and safety of higher-than-licensed dosage of second-generation oral antihistamines in the treatment of CSU., Material and Methods: A systematic literature review was performed following a sensitive search strategy. All articles published in PubMed, EMBASE, and the Cochrane Library between 1961 and October 2018 were examined. Publications with CSU patients prescribed secondgeneration antihistamines in monotherapy compared with placebo, licensed dosages, and/or higher dosages were included. Articles were evaluated by peer reviewers. Quality was evaluated using the Jadad and Oxford scores., Results: We identified 337 articles, of which 14 were included in the final evaluation (fexofenadine, 6; cetirizine, 2; levocetirizine and desloratadine, 1; levocetirizine, 1; rupatadine, 2; ebastine, 1; and bilastine, 1). Only 5 studies were placebo-controlled. The number of patients included ranged from 20 to 439. The observation lapse was ≤16 weeks. High fexofenadine doses produced a significant dosedependent response and controlled urticaria in most patients. Cetirizine, levocetirizine, rupatadine, and bilastine were more effective in up-dosing. The most frequent adverse events were headache and drowsiness., Conclusion: The low quality and heterogeneity of the articles reviewed made it impossible to reach robust conclusions and reveal the need for large-scale randomized clinical trials.

Alzheimer's disease (AD) is a progressively neurodegenerative disease characterized by cognitive deficits and alteration of personality and behavior. As yet, there is no efficient treatment for AD. 5HT 2A receptor (5HT 2A R) is a subtype of 5HT 2 receptor belonging to the serotonin receptor family, and its antagonists have been clinically used as antipsychotics to relieve psychopathy. Here, we discovered that clinically first-line antiallergic drug desloratadine (DLT) functioned as a selective antagonist of 5HT 2A R and efficiently ameliorated pathology of APP/PS1 mice. The underlying mechanism has been intensively investigated by assay against APP/PS1 mice with selective 5HT 2A R knockdown in the brain treated by adeno-associated virus (AAV)-ePHP-si-5HT 2A R. DLT reduced amyloid plaque deposition by promoting microglial Aβ phagocytosis and degradation, and ameliorated innate immune response by polarizing microglia to an anti-inflammatory phenotype. It stimulated autophagy process and repressed neuroinflammation through 5HT 2A R/cAMP/PKA/CREB/Sirt1 pathway, and activated glucocorticoid receptor (GR) nuclear translocation to upregulate the transcriptions of phagocytic receptors TLR2 and TLR4 in response to microglial phagocytosis stimulation. Together, our work has highly supported that 5HT 2A R antagonism might be a promising therapeutic strategy for AD and highlighted the potential of DLT in the treatment of this disease., (© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Current drug therapies for cutaneous leishmaniasis are often difficult to administer and treatment failure is an increasingly common occurrence. The efficacy of anti-leishmanial therapy relies on a combination of anti-parasite activity of drugs and the patient's immune response. Previous studies have reported in vitro antimicrobial activity of histamine 1-receptor antagonists (H1RAs) against different pathogens. We used an ex vivo explant culture of lymph nodes from mice infected with Leishmania major to screen H1RAs compounds. Azelastine (AZ) and Fexofenadine (FX) showed remarkable ex vivo efficacy (EC50 = 0.05 and 1.50 μM respectively) and low in vitro cytotoxicity yielding a high therapeutic index. AZ significantly decreased the expression of H1R and the proinflammatory cytokine IL-1ẞ in the ex vivo system, which were shown to be augmented by histamine addition. The anti-leishmanial efficacy of AZ was enhanced in the presence of T cells from infected mice suggesting an immune-modulatory mechanism of parasite suppression. L. major infected BALB/c mice treated per os with FX or intralesionally with AZ showed a significant reduction of lesion size (FX = 69%; AZ = 52%). Furthermore, there was significant parasite suppression in the lesion (FX = 82%; AZ = 87%) and lymph nodes (FX = 81%; AZ = 36%) with no observable side effects. AZ and FX and potentially other H1RAs are good candidates for assessing efficacy in larger studies as monotherapies or in combination with current anti-leishmanial drugs to treat cutaneous leishmaniasis., Competing Interests: The authors have declared that no competing interests exist.

Background: Although previous studies have reported that levocetirizine is utilized for the treatment of children with allergic rhinitis (AR), its conclusions remain inconsistent. This study aims to evaluate the efficacy and harms of levocetirizine for children with AR., Methods: Electronic database sources will be undertaken from the beginning to the present: MEDLINE, EMBASE, The Cochrane Library, CINAHL, ACMD, PsycINFO, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will not apply any restrictions to language and publication status. We will only consider randomized controlled trials of levocetirizine for children with AR. Two authors will independently scan literature, select studies, and collect data. Study quality for each included trial will be assessed using Cochrane risk of bias tool, and statistical analysis will be conducted using RevMan 5.3 software., Results: This study will summarize the present evidence to systematically assess the efficacy and harms of levocetirizine for children with AR., Conclusion: The findings of this study intent to adequately inform stakeholders or clinicians, as well as to help develop treatment guidelines., Study Registration Number: INPLASY202040111.

Background: A number of guidelines for management of CU were established based on evidences in adults. In children, the response to CU treatment was not widely studied., Objective: To investigate the medications used to control symptoms of CU in children and to identify factors associated with time to control CU., Methods: Medical records of children with controlled CU visiting Allergy clinic, Siriraj hospital were examined. Controlled CU was defined as no urticarial lesion while the patients used the same daily medications over 8-12 weeks. Demographic data, clinical progression of CU and medications used in each visit were recorded. The steps of CU management were categorized into groups according to the Joint Task Force Practice Parameter (JTFPP) in CU 2014 guideline., Results: One hundred children (48 males) with 'controlled CU' were recruited. The median age at first visit was 8 (5.4010.60) years. Thirty-two percent of the patients had associated angioedema. The median time to control CU was 9 (6.9011.10) months. Forty-four percent of the patients control CU with standard dose of second generation antihistamine (step 1) and the rest of the patients used the medications in step 2 to control CU. None of the patients needed systemic corticosteroid or immunomodulatory agent. The steps of treatment, angioedema and associated conditions related to CU did not affect time to control., Conclusions: Only up to a half of pediatric patients with CU had a favorable response to standard dose of second generation antihistamine. The rest required step 2 treatment of JTFPP to control their symptoms.

Background: Allergic rhinitis (AR) is a non-infectious immune disease and incidents of the disease has continuously increased in Thailand. Ginger, a Thai herb, is used in food and Thai traditional medicine. This study was designed to assess efficacy and safety of ginger extract in comparison with loratadine for AR treatment., Methods: AR patients were treated with ginger extract 500 mg (n = 40) against those treated with loratadine 10 mg (n = 40) in a randomized, double-blind, controlled trial for 3 and 6 weeks. The efficacy was evaluated from clinical examinations i.e. total nasal symptom scores (TNSS), cross-sectional area of the nasal cavity with acoustic rhinometry (ARM) and rhinoconjunctivitis quality of life questionnaire (RQLQ). The safety of treatment was measured by blood pressure, blood analysis and history-taking for side effects., Results: The results showed both ginger extract and loratadine treated groups significantly decreased TNSS scores but there was no significant difference between the two groups. In acoustic rhinometry measurement, the ginger treated group significantly gradually increased the estimated volume of the nasal cavity and decreased distances from the nostril, but the loratadine treated group did not cause a change. Both groups gave significantly improvement in every aspect of the RQLQ at third weeks. The treatment with ginger extract was as safe as loratadine as shown by renal and liver function results obtained from blood analysis. Both treatments had no effect on blood pressure of the patients., Conclusions: The ginger extract is as good as loratadine in improving nasal symptoms and quality of life in AR patients. However, ginger extract caused less side effects especially, drowsiness, fatigue, dizziness and constipation. Therefore, the ginger extract could be used as alternative treatment for patients with AR., Trial Registration: Registered with ClinicalTrials.gov (Registration number: NCT02576808) on 15 October 2015.

Background: To conduct an in vitro investigation into the effect of different concentrations of levocetirizine hydrochloride on the growth of human dermal papilla cells (hDPCs) the underlying mechanisms involved., Methods: hDPCs were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing different concentrations of levocetirizine hydrochloride for 48 h. The growth of hDPCs was observed by immunofluorescence staining, and the cell proliferation was detected by MTT assay. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, and 10,000 ng/mL levocetirizine hydrochloride for 48 h, the mRNA expressions of cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), G protein-coupled receptor 44 (GPR44), protein kinase B (AKT), and glycogen synthase kinase 3β (GSK3β) were determined by real-time fluorescence-based quantitative polymerase chain reaction (PCR), and the protein expressions of PTGDS, phosphorylated protein kinase B (pAKT), and phosphorylated glycogen synthase kinase 3β (pGSK3β) were detected by Western blotting. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, 10,000 ng/mL levocetirizine hydrochloride for 24 h, the secretion levels of prostaglandin D2 (PGD2) and PGD2 receptor (PGD2R) in the culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) was performed using SPSS 17.0 software, and the LSD-t test was used for pairwise comparisons., Results: Immunofluorescence staining showed that hDPCs in the 100 ng/mL group grew well, with over 90% confluency. Methyl thiazolyl tetrazolium (MTT) method showed that the proliferation rate of hDPCs significantly differed between different levocetirizine hydrochloride groups and the blank control group (F=42.22, P<0.05), while the proliferation rate was significantly higher in the 100 ng/mL group (115.80%±5.10%) than in the blank control group (100%) (t=28.26, P<0.05). The relative mRNA expressions of COX-2, PGF2a, PTGDS, GPR44, and AKT showed significant differences in different levocetirizine hydrochloride groups (the F values were 1.97, 3.66, 2.17, 2.66, and 7.32, respectively; all P<0.05), whereas the mRNA expressions of PGE2 and GSK3β showed no significant difference (F=0.87, F=1.19, respectively; both P>0.05). The mRNA expressions of COX-2, PTGDS, and GPR44 in the 100 ng/mL group (0.840.08, 0.810.10, and 0.85±0.09, respectively) were significantly lower than those in the blank control group (t=1.97, t=2.17, and t=2.65, respectively; all P<0.05), whereas the mRNA expressions of PGF2α and AKT in the 100 ng/mL group (1.96±0.25 and 1.74±0.32, respectively) were significantly higher than those in the blank control group (t=3.662 and t=7.325, respectively; both P<0.05). There were significant differences in the levels of PTGDS, pAKT, pGSK3β, PGD2, and PGD2R proteins between the different levocetirizine hydrochloride groups (the F values were 11.84, 3.89, 4.07, 66.15, and 44.33, respectively). The protein expressions of PTGDS, PGD2, and PGD2R in the 100 ng/mL group (0.32±0.05, 141.62±5.44, and 215.08±9.55, respectively) were significantly lower than those in the blank control group (0.73±0.06, 180.08±6.15, and 273.24±3.18, respectively) (the t values were 5.66, 45.07, and 92.05, respectively; all P<0.05), whereas the protein expressions of pAKT and pGSK3β in the 100 ng/mL group (0.59±0.05 and 0.46±0.03, respectively) were significantly higher than those in the blank control group (0.46±0.02 and 0.35±0.042, respectively) (t=16.59, t=7.73, respectively; both P<0.05)., Conclusions: Levocetirizine hydrochloride may promote the growth and proliferation of hDPC in vitro by inhibiting the PGD2-GPR44 pathway and activating the AKT signaling pathway.

Allergic rhinitis (AR) is an IgE-mediated inflammation which causes olfactory dysfunction. Antihistamines have been widely used to treat AR while few studies have investigated the effect of antihistamines on improving the sense of smell. In addition, the underlying mechanisms are not well elucidated. We established the ovalbumin (OVA)-induced allergic rhinitis rat model and administrated desloratadine to AR rats. The AR symptoms, serum level of OVA-specific IgE and IL-17, and expression of IL-4, IL-5 and IL-13 in nasal mucosa were measured. The olfactory dysfunction was monitored by buried food test and the expression of GluR1 was measured. Desloratadine treatment alleviated AR symptoms, decreased serum level of OVA-specific IgE and IL-17 in AR rats. Desloratadine decreased IL-4, IL-5, and IL-13 expression in nasal mucosa of AR rats. Desloratadine ameliorated olfactory dysfunction in AR rats and decreased GluR1 expression in AR rats. Desloratadine treatment alleviated AR symptoms and ameliorated olfactory dysfunction in AR rats. The expression of AMPA receptor subunit GluR1 in olfactory bulb was associated with olfactory disorder.

Antihistamines are currently one of the most commonly administered drugs in children. They are used to treat symptoms that depend on histamine release, namely allergic diseases, such as rhinitis, asthma, urticaria, and anaphylaxis. It is possible to distinguish first- and second-generation antihistamines. Pharmacological effects and therapeutic indications are similar, but second-generation antihistamines have fewer adverse effects because they are more selective for peripheral H1 receptors. Although they have been on the market for several years, there are still many adverse effects linked to the antihistamine safety profile, especially in the first years of life. Thus, many antihistamines are prescribed off-label, especially in children younger than 2 years of age, which is the age-group where most of the data on drug safety are lacking and many antihistamines are not recommended. This article aims to provide a practical update on the use of antihistamines in children., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Glucocorticoids are among the most effective drugs to treat asthma. However, the severe adverse effects associated generate the need for its therapeutic optimization. Conversely, though histamine is undoubtedly related to asthma development, there is a lack of efficacy of antihistamines in controlling its symptoms, which prevents their clinical application. We have reported that antihistamines potentiate glucocorticoids' responses in vitro and recent observations have indicated that the coadministration of an antihistamine and a synthetic glucocorticoid has synergistic effects on a murine model of allergic rhinitis. Here, the aim of this work is to establish if this therapeutic combination could be beneficial in a murine model of asthma. We used an allergen-induced model of asthma (employing ovalbumin) to evaluate the effects of the synthetic glucocorticoid dexamethasone combined with the antihistamine azelastine. Our results indicate that the cotreatment with azelastine and a suboptimal dose of dexamethasone can improve allergic lung inflammation as shown by a decrease in eosinophils in bronchoalveolar lavage, fewer peribronchial and perivascular infiltrates, and mucin-producing cells. In addition, serum levels of allergen-specific IgE and IgG1 were also reduced, as well as the expression of lung inflammatory-related genes IL-4, IL-5, Muc5AC, and Arginase I. The potentiation of dexamethasone effects by azelastine could allow to reduce the effective glucocorticoid dose needed to achieve a therapeutic effect. These findings provide first new insights into the potential benefits of glucocorticoids and antihistamines combination for the treatment of asthma and grants further research to evaluate this approach in other related inflammatory conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2019 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Objective: This study evaluated the role of cetirizine compared to diphenhydramine as premedications for patients receiving paclitaxel, cetuximab, and rituximab infusions. Historically, diphenhydramine has been linked with more sedation in comparison to cetirizine; however, it is unknown if cetirizine can replace diphenhydramine in the prevention of hypersensitivity reactions in patients receiving chemotherapy., Methods: This is a retrospective study designed to assess infusion reactions occurring in patients receiving diphenhydramine or cetirizine premedication for rituximab, paclitaxel, or cetuximab therapies. Infusion reactions were defined as various symptoms such as flushing, itching, alterations in heart rate and blood pressure, and dyspnea plus the clinical setting of a concurrent or very recent infusion., Results: A total of 207 patients were evaluated in this study with 83 patients receiving cetirizine and 124 diphenhydramine patients. Overall, the percentage of patients with at least one chemotherapy-related infusion event in the cetirizine group was 19.3% (95% CI 11.4-29.4) compared to diphenhydramine group 24.2% (95% CI 17.0-32.7), P  = 0.40. Of the patients who received cetirizine and then experienced an event in the first cycle, 41.7% (95% CI 13.7-74.3) of the events were due to paclitaxel, 50.0% (95% CI 19.4-80.6) were due to rituximab, and 8.3% (95% CI 0.1-43.6) were due to cetuximab. Of the patients who received diphenhydramine and then experienced an event in the first cycle, 26.1% (95% CI 5.7-51.4) were due to paclitaxel, 73.9% (95% CI 48.6-94.3) were due to rituximab and none due to cetuximab., Conclusion: Cetirizine appears to be a viable substitute for diphenhydramine for the prevention of infusions reactions with cetuximab, paclitaxel, and rituximab infusions in adults. Prospective studies are needed to determine the efficacy and safety of cetirizine compared with diphenhydramine in the prevention of chemotherapy-related infusion reactions.

Purpose of Review: This article presents an update on the clinical pharmacology, mechanisms of action, and safety of second generation antihistamines (SGAHs)., Recent Findings: Recent research has shown the efficacy and good tolerance of SGAHs supporting its indication as first line medications for the treatment of allergic rhinoconjunctivitis and urticaria., Summary: The information contained in this review is relevant for the correct utilization of SGAHs by practicing physicians who take care of these highly prevalent clinical disorders.

Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous., Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US)., Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults., Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence)., Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

Bilastine is a non-sedating second-generation H 1 antihistamine approved for treatment of allergic rhinoconjunctivitis (AR) and urticaria (U) in adults at the oral (p.o.) dose of 20 mg once daily (OD). Optimal attributes can be anticipated for its clinical use in pediatrics due to its favorable safety and tolerability and age-independent PD profile. The aim of this work was to characterize bilastine PK in children through population modeling of data from a limited sampling confirmatory clinical trial in children with AR or U. The objective was also to ascertain whether the proposed dose (10 mg/day) in the target pediatric subset aged 2-<12 years matches the systemic exposure seen in adults at the 20 mg/day dose. A popPK model characterizing bilastine PK behavior in children aged from 4 to <12 years treated with 10 mg oral bilastine daily was successfully developed and qualified. No relationship was found between bilastine PK and age or weight; stopping rules pre-stablished to finalize the trial, i.e., model completeness and no dependence of exposure on decreasing age, were thus fulfilled. On a second step, the popPK model in children was linked to the PD model in adults assuming the same PD as described in adults and used to compare the PD outcome between both populations. Finally, an allometric scaling method and a physiological approximation were used to evaluate the suitability of the selected dose in the youngest children, showing that children from 2 years were deemed to belong to the same population as well. The achievement of comparable PK (i.e., within the range) to that observed in adults after the therapeutic dose of 20 mg, together with the achievement of similar PD and additional integrative analysis, served to confirm the validity of the 10 mg daily dose for the target pediatric subset (2 to <12 years)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Antihistamines targeting the histamine H₁ receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H₁ receptor occupancy (H₁RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20⁻50%), and sedating (≥50%) groups based on H₁RO. Among the non-sedating group, fexofenadine and bilastine are classified into "non-brain-penetrating antihistamines" based on the H₁RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H₁ receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis.

Background: Up to 1% of the general population in the USA and Europe suffer from chronic urticaria (CU) at some point in their lifetime. CU has an adverse effect on the quality of life., Objective: This study aims to provide an update on the epidemiology, pathogenesis, clinical manifestations, diagnosis, aggravating factors, complications, treatment and prognosis of CU., Methods: The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "chronic urticaria" at the following links: www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com., Results: CU is a clinical diagnosis, based on the episodic appearance of characteristic urticarial lesions that wax and wane rapidly, with or without angioedema, on most days of the week, for a period of six weeks or longer. Triggers such as medications, physical stimuli, and stress can be identified in 10 to 20% of cases. C-reactive protein/erythrocyte sedimentation rate, and complete blood cell count with differential are the screening tests that may be used to rule out an underlying disorder. The mainstay of therapy is reassurance, patient education, avoidance of known triggers, and pharmacotherapy. Secondgeneration H1 antihistamines are the drugs of choice for initial therapy because of their safety and efficacy profile. If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable, the dose of second-generation H1 antihistamines can be increased up to fourfold the manufacturer's recommended dose (all be it off license). If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable after the fourfold increase in the dosage of second-generation H1 antihistamines, omalizumab should be added. If satisfactory improvement does not occur after 6 months or earlier if the symptoms are intolerable after omalizumab has been added, treatment with cyclosporine and second-generation H1 antihistamines is recommended. Short-term use of systemic corticosteroids may be considered for acute exacerbation of CU and in refractory cases. Recent patents for the management of chronic urticaria are also discussed. Complications of CU may include skin excoriations, adverse effect on quality of life, anxiety, depression, and considerable humanistic and economic impacts. On average, the duration of CU is around two to five years. Disease severity has an association with disease duration., Conclusion: CU is idiopathic in the majority of cases. On average, the duration of CU is around two to five years. Treatment is primarily symptomatic with second generation antihistamines being the first line. Omalizumab has been a remarkable advancement in the management of CU and improves the quality of life beyond symptom control., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Current treatment options for Allergic Rhinitis (AR) may have their own limitations and side effects. This study aimed to investigate the effects of Ma-al-Shaeer (MS), a novel natural formulation based on Hordeum vulgare, in the treatment of AR compared with Fexofenadine (FX)., Methods: A total of 77 patients with AR were divided into two groups: MS group (n=38) and FX group (n=39). The first group received 15 g of dried MS powder, and the second group received 60 mg of FX twice daily for 14 days. At baseline (week zero) and after the 14-day treatment period (week two), both groups were evaluated for sneezing, rhinorrhea, nasal congestion, nasal itching, post nasal drip, eye, throat, or ear symptoms, headache, cough, mental function, quality of life scores, blood eosinophil count and total IgE levels. Rhinitis control assessment tests were conducted at week zero and again at one week after cessation of treatment (week three) in both groups., Results: All symptoms of AR except cough were significantly reduced in both groups; for nasal congestion, post nasal drip, and headache, the MS treatment was found to be superior. Rhinitis control was significantly increased after treatment in both groups (p value < 0.001). Both drugs significantly reduced total IgE levels. There was no significant change in eosinophil count in either group., Conclusion: MS formulation based on H. vulgare may be an effective treatment for AR. Further studies are needed to confirm the effect of MS as an alternative treatment in AR., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis., Objective: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system., Methods: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group., Results: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected., Conclusion: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown., Clinical Trial Registration Number: UMIN ID: UMIN000029653., (© 2019 S. Karger AG, Basel.)

Background: Despite the current knowledge of UV, there is a lack of consensus among diagnostic criteria and management. In general, antihistamine therapy is regularly used for the symptomatic management of pruritus but does not control inflammation or alter the course of the disease. Monoclonal antibodies such as omalizumab (anti-IgE) have been proposed as a potential treatment for urticarial vasculitis. A few studies have reported the benefits of omalizumab in patient-reported outcome measures (PROMs). Herein we describe a female patient with urticarial vasculitis who was treated with omalizumab. We discuss the response to treatment and possible implications of PROMs in guiding the management of the disease., Case Presentation: We describe the case of a 57-year-old woman with a diagnosis of urticarial vasculitis. Due to lack of response to first-line treatment and the severity of the disease, treatment with omalizumab was initiated. Omalizumab 150 mg was administered every four weeks for three months. Second-generation antihistamines were used as needed. Both CU-Q2oL and UAS 7 improved. After three-month therapy with omalizumab, disease severity improved from moderate severity (UAS7 = 19) to well controlled (UAS7 = 6). However, 5 months after the last administration of omalizumab, the patient complained of worsening symptoms and active disease with quality of life impairment. A single dose of omalizumab (150 mg) was prescribed with corticosteroids. Thereafter, the patient presented a disease activity and quality of life with a fluctuating pattern that was controlled with additional doses of omalizumab., Conclusion: In chronic urticaria, patient-reported outcome measures (PROMs) are important for assessing disease status and the impact of symptoms on patients' lives. However, to our knowledge, there is no validated tool to measure such outcomes in UV patients. Although UAS7 and CU-Q2oL were not designed for UV assessment, they might be useful in the clinical setting as objective measures to determine treatment efficacy. However, some domains in the CU-Q2oL questionnaires do not correlate well with UAS7, which might serve as a relative indication to continue treatment despite disease severity improvement. Based on our observations, we believe omalizumab 150 mg might be a feasible therapeutic alternative when first-line treatment is unsuccessful.

Objective: To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.