UNASSIGNED: Chronic spontaneous urticaria (CSU) is a common condition treated by allergist/immunologists, but the only FDA-approved biologic medication, omalizumab, may be underutilized globally.
UNASSIGNED: This study was performed to determine the global prescription of omalizumab for treatment of CSU by allergists/immunologists.
UNASSIGNED: Anonymous questionnaire surveys were distributed online to World Allergy Organization (WAO) members worldwide. Categorical data were analyzed for descriptive analysis using one-way frequency tabulation in SAS 9.4.
UNASSIGNED: There were 348 respondents (43 missing data); Average age 51 (range 28-90); M/F 48%/52%. 58% had > 15 years of clinical experience and 10% < 5; 42% worked in private clinics, 36% public hospitals, 24% academia, 18% private hospitals, and 4% in community practice. Eighty-two percent (82%) prescribed omalizumab for CSU patients and use of omalizumab was highest among young practitioners. The most significant barriers were cost (63%) and restricted formulary (24%). Drug safety (63%) and chances of adverse events (47%) were the most significant factors deciding treatment. Twenty-two percent (22%) reported 80-100% of CSU patients were complete responders to omalizumab; 34% preferred increasing frequency (q 2-weeks), and 18% preferred increasing dose (600 mg q 4-weeks) for partial or non-responders. UAS7, UCT, and CU-QoL were used to assess CSU by 55%, 29%, and 25% of respondents, respectively. Autoimmune thyroid disease (62%), thyroid abnormality (43%) and allergic rhinitis (35%) were the most frequent comorbidities reported.
UNASSIGNED: Most clinicians favored omalizumab over other potential treatments due to safety. Although younger clinicians were more likely to prescribe omalizumab, cost and formulary access were major barriers. Only 22% of respondents reported 80% or greater of their patients had complete response to omalizumab, indicating the need for novel CSU therapies.

Endometriosis is a chronic inflammatory gynecologic condition among women of reproductive age causing a plethora of symptoms that significantly affect their quality of life and mental health. Recent literature reports mounting evidence for several inflammation-mediated pathways for endometriosis pathogenesis, where elevated levels of proinflammatory factors, such as intercellular adhesion molecule 1, tumor necrosis factor-alpha, and nuclear factor kappa B have been established. Simultaneously, the prevalent clinical use of H1-antihistamines for other pathologies along with active research into its action pathways has led to our current understanding that H1-antihistamines counteract several inflammation mediators, including intercellular adhesion molecule 1, tumor necrosis factor-alpha, and nuclear factor kappa B. Although a wide range of existing drug-based endometriosis managements act via the estrogen-dependent pathways, along with some newer ones attempting to use antagonists of targeted inflammation-modulating factors, investigations into the direct use of H1-antihistamines in the context of endometriosis are currently lacking. In this brief perspective opinion essay, correlative evidence has been placed forward that points toward a potential avenue of H1-antihistamines for endometriosis management, and some ideas have been highlighted for future research considerations.

H1-antihistamines (AHs) may exert protective effects against cancer. We investigated the association of AH use with hepatocellular carcinoma (HCC) risk in type 2 diabetes mellitus (T2DM) patients without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
The data of patients with T2DM enrolled from Taiwan\'s National Health Insurance Research Database were examined for the period of January 1, 2008, to December 31, 2018. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the AH use-HCC risk association.
After 1:1 propensity score matching was performed, the two cohorts were each divided into AH users (n = 47,990) and nonusers (n = 47,990). The risk of HCC was significantly lower in AH users than in AH nonusers (adjusted hazard ratio [aHR]: 0.55 95% confidence interval [95% CI], 0.46 to 0.67; IRR: 0.70; 95% CI, 0.60 to 0.84), respectively. The dose-response relationship between AH use and HCC risk was also observed (aHRs: 0.58, 0.56, 0.50, and 0.41 for 28-35, 36-49, 50-77, and >77 cumulative defined daily doses of AH, respectively).
AH use can reduce HCC risk in T2DM patients without HBV or HCV infection in a dose-dependent manner.

BACKGROUND: The pathogenesis of chronic spontaneous urticaria involves metabolic, immunological, and psychological factors. The thiol-disulfide exchange reactions could be a mechanism to counteract oxidative stress in patients with chronic spontaneous urticaria.
OBJECTIVE: The assessment of thiol-disulfide homeostasis parameters (TDHPs) according to disease severity and the influence of H1-antihistamine therapy in patients with chronic spontaneous urticaria.
METHODS: We have included 30 patients with chronic spontaneous urticaria in the study and we have determined the levels of native thiol, total thiol, disulfides as well as the disulfide/native thiol ratio, disulfide/total thiol ratio and the native thiol/total thiol ratio, before and after therapy with H1-antihistamines.
RESULTS: The results of the study showed altered levels of TDHPs and their normalization after treatment with H1-antihistamines in patients with chronic spontaneous urticaria. We determined a statistically significant increase in the serum levels of total thiol, native thiol, and native thiol/total thiol ratio and a significant reduction in the levels of disulfides, disulfide/native thiol ratio and disulfide/total thiol ratio after treatment with H1-antihistamines. The normalization of the serum levels of TDHPs has been associated with the relief of symptoms and reduction or resolution of pruritus and urticarial plaques.
CONCLUSIONS: These results suggest the involvement of thiol-disulfide homeostasis in the defense against the harmful effects of reactive oxygen species in patients with chronic spontaneous urticaria and the potential role of TDHPs in monitoring H1-antihistamine therapy. To the best of our knowledge, this is the first study investigating TDHPs in patients with chronic spontaneous urticaria before and after treatment.

BACKGROUND: Inconsistencies remain regarding the effectiveness and safety of leukotriene receptor antagonists (LTRAs) and selective H1-antihistamines (SAHs) for allergic rhinitis (AR). A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the medications.
METHODS: Relevant head-to-head comparative RCTs were retrieved by searching the PubMed, Embase, and Cochrane\'s Library databases from inception to April 20, 2020. A random-effects model was applied to pool the results. Subgroup analyses were performed for seasonal and perennial AR.
RESULTS: Fourteen RCTs comprising 4458 patients were included. LTRAs were inferior to SAHs in terms of the daytime nasal symptoms score (mean difference [MD]: 0.05, 95% confidence interval [CI] 0.02 to 0.08, p = 0.003, I2 = 89%) and daytime eye symptoms score (MD: 0.05, 95% CI 0.01 to 0.08, p = 0.009, I2 = 89%), but were superior in terms of the nighttime symptoms score (MD: - 0.04, 95% CI - 0.06 to - 0.02, p < 0.001, I2 = 85%). The effects of the two treatments on the composite symptom score (MD: 0.02, 95% CI - 0.02 to 0.05, p = 0.30, I2 = 91%) and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) (MD: 0.01, 95% CI - 0.05 to 0.07, p = 0.71, I2 = 99%) were similar. Incidences of adverse events were comparable (odds ratio [OR]: 0.97, 95% CI 0.75 to 1.25, p = 0.98, I2 = 0%). These results were mainly obtained from studies on seasonal AR. No significant publication bias was detected.
CONCLUSIONS: Although both treatments are safe and effective in improving the quality of life (QoL) in AR patients, LTRAs are more effective in improving nighttime symptoms but less effective in improving daytime nasal symptoms compared to SAHs.

BACKGROUND: It is important to assess the burden of chronic urticaria (CU) with real-life studies. The AWARE study was performed in 36 countries over two years in CU patients resistant to H1-antihistamines.
OBJECTIVE: To correlate patient-reported outcomes and available therapeutic options in CU patients.
METHODS: The AWARE study was a prospective, non-interventional, international study that included adult patients who have had H1-antihistamine-resistant CU for at least two months. The primary endpoints were the evolution of disease activity (UAS7), urticaria control (UCT), dermatological quality of life (DLQI) and treatment satisfaction (visual analogic scale) during a two-year follow-up. The data from French centres are reported.
RESULTS: Ninety-two patients were included (mean age: 47.8 years; women: 70.7%; mean disease duration: 6.5 years; angioedema: 34.1%). The percentage of patients with CU treatment increased from 56.5% at inclusion to 86.0% after two years (for patients with non-sedative H1-antihistamines from 52.2% to 74.4%, and omalizumab from 2.2% to 25.6%). During the follow-up, the percentage of patients with UAS7 score <6 increased from 12.5% to 60.9%, and patients with well-controlled CU (UCT score >12) increased from 11.1% to 62.2%. The negative impact on quality of life (DLQI >10) decreased from 34.1% to 10.5%. The mean score of patient satisfaction for treatment increased from 4.6 to 7.6.
CONCLUSIONS: The management of CU patients resistant to H1-antihistamines was not optimal at inclusion with uncontrolled disease, impaired quality of life and insufficient treatment. After a two-year follow-up, disease symptoms and quality of life improved, but the therapeutic management could be further optimized.

OBJECTIVE: The aim of the study was to describe the clinical characteristics, management, and outcome of a series of children with chronic urticaria (CU).
METHODS: We retrospectively studied children aged <15 years diagnosed with CU in a tertiary teaching hospital in Palma de Mallorca, Spain, between January 2014 and March 2019. CU was defined as persistence of symptoms of wheals, with or without angioedema, for >6 weeks.
RESULTS: Twenty-nine patients (17 girls, mean age 8 years) were included. Family history of atopy was found in 31% of the cases. In 41.3% of patients, episodes of CU were associated with angioedema. Physical triggers were found in 34.5% of the cases. Most episodes of CU were successfully managed with the recommended (60.7%) or double the recommended dose (17.2%) of H1-antihistamines. Quadruple the recommended dose of H1 antihistamines was used in six patients, five of whom were finally treated with off-label omalizumab. Treatment with anti-leukotrienes was needed in one patient. Associated thyroiditis was diagnosed in one patient, which was controlled with levothyroxine.
CONCLUSIONS: Pediatric CU showed features similar to CU in adulthood, including a greater predominance in females and frequent association with personal or family history of atopy. Adult guidelines for the treatment of CU are currently extrapolated to the pediatric population. Specific tools for the assessment of disease activity and impairment of quality of life in pediatric CU are needed for use in prospective studies aimed to define treatment strategies for children with CU.

OBJECTIVE: To prevent infusion-related reactions (IRRs), H1-antihistamines (H1AT) are recommended as a premedication for monoclonal antibodies, such as Ramucirumab (RAM), even though there are H1AT-related side effects, such as drowsiness and dizziness. Here, we investigated the safety of H1AT-free RAM regimens in patients with solid cancer.
METHODS: We retrospectively reviewed the patients with solid cancer receiving RAM without H1AT at Osaka Medical College Hospital between 2015 and 2019.
RESULTS: Among the 123 registered patients, 58 were identified as eligible. The total number of RAM infusions was 291, and the median number of RAM administration was 4 cycles (range=1-23 cycles). IRRs were not observed in any patient.
CONCLUSIONS: Although our data are preliminary and limited, H1AT-free RAM regimens may be a treatment option for cancer patients having a significant risk of developing H1AT-related side effects. Further studies are needed to confirm the safety of H1AT-free RAM regimens.

Background: This study aimed to measure the association of various H1-antihistamines (H1A) with Torsade de Pointes (TdP), and present a comprehensive overview of H1A-induced TdP cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: All H1A-induced TdP cases (n = 406) were retrieved from the FAERS database using the preferred term \'Torsade de Pointes\' of MedDRA version-22 from 1990 to 2019. Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR); Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). H1A with >3 TdP cases were included. Results: A total of 12 signals (Astemizole, cetirizine, chlorpheniramine, clemastine, desloratadine, diphenhydramine, hydroxyzine, loratadine, meclizine, promethazine, terfenadine, and trimeprazine) were identified including six new signals (cetirizine, chlorpheniramine, clemastine, desloratadine, loratadine, and meclizine). The number of risk factors (p = 0.031) and concomitant QT-prolonging drugs (p = <0.001) were significantly lower among new signals vs old signals. Moreover, new signals were strongly associated with QT-prolongation, cardiac reactions, and electrolyte abnormalities as compared with old signals. Conclusions: Our study found the increased torsadogenic potential of new signals compared with previously known old signals, hence necessitating clinical studies to determine the actual torsadogenic potential of newly identified signals.

H1-antihistamines antagonize histamine and prevent it from binding to the histamine H1 receptor (H1R). Some of them also act as inverse agonists, which are more potent than pure antagonists because they suppress the constitutive H1R activity. Bilastine is a non-sedative antihistamine which is one of the most satisfy the requirements for oral antihistamines. However, there is no information to show the inverse agonist activity of bilastine including inositol phosphates accumulation, and its inverse agonist activity is yet to be elucidated. Here we evaluated whether bilastine has inverse agonist activity or not. Intracellular calcium concentration was measured using Fluo-8. Inositol phosphates accumulation was assayed using [3H]myo-inositol. The H1R mRNA level was measured using real-time RT-PCR. At rest, Ca2+ oscillation was observed, indicating that H1R has intrinsic activity. Bilastine attenuated this fluorescence oscillation. Bilastine suppressed the increase in IPs formation in a dose-dependent manner and it was about 80% of the control level at the dose of 3 μM. Bilastine also suppressed histamine-induced increase in IPs formation to the control level. Furthermore, bilastine suppressed basal H1R gene expression in a dose-dependent manner. Data suggest that bilastine is an inverse agonist. Preseasonal prophylactic administration with bilastine could down-regulate basal H1R gene expression in the nasal mucosa and ameliorate the nasal symptoms during the peak pollen period.