Second-generation Antihistamines Research Articles

Synthesis Methods of Loratadine and Its Clinical Application Comparison in Antihistamines

Loratadine is a second-generation antihistamine widely used in treating allergic diseases such as allergic rhinitis, urticaria, and conjunctivitis. Compared to first-generation antihistamines, loratadine has fewer central nervous system side effects, such as drowsiness and cognitive impairment, and exhibits prolonged efficacy. This paper comprehensively reviews the chemical structure, mechanism of action, and organic synthesis methods of loratadine. Loratadine’s tricyclic structure and selective binding to peripheral histamine H1 receptors allow it to effectively relieve allergic symptoms at low doses while minimizing side effects. The article also analyzes various classical and improved loratadine synthesis routes, comparing their advantages and disadvantages in terms of reaction conditions, yields, and environmental impact. By introducing novel catalysts and optimizing reaction conditions, the improved synthesis methods not only enhance yields and cost-effectiveness but also reduce environmental pollution. Additionally, this paper discusses the comparison of loratadine with other antihistamines in terms of efficacy and safety, highlighting its significant clinical advantages. Nonetheless, there remains a need for further optimization of its synthesis process and exploration of its potential in personalized treatment to meet the needs of different patients.

Sublingual Fast-Dissolving Thin Films of Loratadine: Characterization, In Vitro and Ex Vivo Evaluation.

Loratadine (LOR) is a second-generation antihistamine that exhibits a low and variable oral bioavailability (10-40%) and delayed onset owing to poor solubility and an extensive first-pass effect. Therefore, in light of the clinical need, the main goal of the present study was to develop sublingual fast-dissolving thin films of LOR-citric acid co-amorphous systems (LOR-CAs) with the aim of eliciting a faster onset and improving the bioavailability. We formulated sublingual fast-dissolving thin films of LOR by a film-casting technique using hydrophilic polymers like hydroxypropyl methylcellulose (HPMC E15), polyvinyl pyrrolidone K30 (PVP K30), and hydroxypropyl cellulose EL (HPC-EF) and citric acid as a pH modulator, while glycerin served as a plasticizer. The sublingual fast-dissolving thin films were characterized by FTIR, SEM, DSC, and XRD and evaluated for in vitro dissolution and ex vivo mucoadhesion. The best formulation (F1) developed using HPMC E15 as a polymer, glycerin as a plasticizer, and citric acid as a pH modulator was found to be the optimized formulation as it was smooth, clear, flexible, and displayed good mucoadhesion (11.27 ± 0.418 gm/cm2) and uniform thickness (0.25 ± 0.02 mm). The formulation F1 was found to display a significantly shorter DT (30.30 ± 0.6 s) and rapid release of LOR (92.10 ± 2.3% in 60 min) compared to other formulations (ANOVA, p < 0.001). The results indicated that the prepared sublingual films are likely to elicit a faster therapeutic effect, avoid first-pass metabolism, and improve the bioavailability.

Bilastine Reimagined: A Comprehensive Exploration of Pruritus Management With a Novel Antihistamine.

Managing pruritic conditions is essential due to their significant impact on patients' quality of life. Chronic urticaria (CU), characterized by persistent itching and hives, severely affects daily activities and sleep. CU includes chronic inducible urticaria and chronic spontaneous urticaria, with the latter lacking identifiable triggers, making treatment especially challenging.CUis a condition that occurs across all age groups, with a higher prevalence among young adults and middle-aged women. Current antihistamine treatments include first-generation antihistamines, which are associated with sedation, and second-generation antihistamines such as cetirizine and fexofenadine, which cause less sedation but have varying efficacy and safety profiles. Bilastine, a novel second-generation H1-antihistamine, offers advantages due to its potent antihistaminic activity, rapid onset of action, and minimal sedation. This narrative review thoroughly synthesizes the evidence for the efficacy and safety of bilastine in treating CU and other pruritic conditions. By analyzing clinical trials, real-world evidence, and comparative studies, this review aims to provide a comprehensive understanding of the role of bilastine in managing pruritic conditions, emphasizing its pharmacokinetic properties, clinical efficacy, and safety profile compared to other antihistamines.

Usefulness of driver’s eye movement measurement to detect potential risks under combined conditions of taking second-generation antihistamines and calling tasks

BackgroundConcerns persist regarding the potential reduction in driving performance due to taking second-generation antihistamines or performing hands-free calling. Previous studies have indicated a potential risk to driving performance under an emergency event when these two factors are combined, whereas a non-emergency event was operated effectively. Currently, there is a lack of a discriminative index capable of detecting the potential risks of driving performance impairment. This study aims to investigate the relationship between driving performance and eye movements under combined conditions of taking second-generation antihistamines and a calling task, and to assess the usefulness of eye movement measurements as a discriminative index for detecting potential risks of driving performance impairment.MethodsParticipants engaged in a simulated driving task, which included a calling task, both under taking or not taking second-generation antihistamines. Driving performance and eye movements were monitored during both emergency and non-emergency events, assessing their correlation between driving performance and eye movements. The study further evaluated the usefulness of eye movement as a discriminative index for potential driving impairment risk through receiver operating characteristic (ROC) analysis.ResultsIn the case of a non-emergency event, no correlation was observed between driving performance and eye movement under the combined conditions. Conversely, a correlation was observed during an emergency event. The ROC analysis, conducted to assess the discriminative index capability of eye movements in detecting the potential risk of driving performance impairment, demonstrated a high discriminative power, with an area under the curve of 0.833.ConclusionsThe findings of this study show the correlation between driving performance and eye movements under the concurrent influence of second-generation antihistamines and a calling task, suggesting the usefulness of eye movement measurement as a discriminant index for detecting potential risks of driving performance impairment.

A case of chronic spontaneous urticaria with wheals lasting for more than a week.

Urticaria is characterized by the development of wheals which usually disappear within a day, and are not present beyond a few days. A 58-year-old man began to develop edematous, partially ring-shaped erythematous lesions accompanied by severe body itching without any particular cause, approximately 2 months before his first visit to our hospital. Each rash emerged as being about 5 mm in diameter, gradually enlarging over several days, and disappeared in up to 10 days. Despite oral treatment with several antihistamines and 10 mg of prednisolone, there was no improvement. Most eruptions disappeared without a trace, but the erythema that appeared on the palms left desquamation. The patient had a history of shellfish allergy, but otherwise no atopic diseases. Drug eruption was ruled out due to a lack of regular taking other medications. Histopathological findings of the skin lesions showed moderate lymphocytic and few eosinophilic infiltrates with edema, but no evidence of vasculitis. Despite the concomitant use of two second-generation antihistamines and montelukast, the rash did not improve. The symptoms began to improve following oral intake of 1.5 mg of betamethasone, which was tapered off with the addition of 150 mg of cyclosporin. The use of all medications was stopped at 4 months from the first visit without recurrence. Wheals of chronic spontaneous urticaria may last for longer than a week without apparent histopathological findings of vasculitis.

Exploring the Impact of Pre-existing Allergic Conjunctivitis on the Efficacy of Refractory Medications in Chronic Spontaneous Urticaria: A TrinetX Database Analysis

Chronic Spontaneous Urticaria, often characterized by pruritic hives, can significantly impact quality of life [1][4]. Standard treatment involves second-generation antihistamines, but some cases may become refractory, requiring stronger medications such as cyclosporine A [2]. Purpose: To investigate the association of allergic conjunctivitis alongside CSU and use of cyclosporine A compared to those without pre-existing AC in treating CSU, using TrinetX database. Methods: Analysis included ICD-10 codes ‘urticaria, unspecified, ‘idiopathic urticaria,’ or ‘other urticaria’ for patients seen during 2020-2024, with at least two consecutive visits at least 4-6 weeks apart, in addition to receiving a second-generation H1-antihistamine treatment. Compare prevalence of cyclosporine use between two cohorts: AC (+) x urticaria x pretreated with H1 and AC (-) x urticaria x pretreated with H1 and patients with and without AC, requiring the addition of cyclosporine A to H1 for treatment of CSU over an observation period of 5 years. Propensity score matching to pair the two cohorts for age, sex, and race [3]. Results: In AC (+) x urticaria x pretreated with H1 group, there were 38,530 patients, out of which 446 required the addition of cyclosporine treatment, resulting in a risk percentage of 1.158%. In AC (-) x urticaria x pretreated with second-generation antihistamine group, with 415,786 patients, 2,812 required the addition of cyclosporine treatment, resulting in a lower risk percentage of 0.676%. Risk Ratio (RR) is calculated as 1.711, with a 95% confidence interval of (1.55, 1.89). Conclusion: A greater proportion of CSU patients with AC required cyclosporine compared to those without AC.

Comparative inhibition by oral bilastine, parenteral dexchlorpheniramine, and a new bilastine parenteral (i.v. and i.m.) formulation of histamine-induced wheal and flare response: A randomised phase I trial

BackgroundBilastine is a well-known non-sedating second-generation antihistamine authorised worldwide for the symptomatic treatment of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria with proven efficacy and good safety and tolerability profile. When the oral route is not suitable or a rapid onset of action is preferred, parenteral formulations represent an effective treatment option. However, the parenteral formulations currently available are sedating antihistamines. The objective of this research was to compare the peripheral anti-H1 activity of different bilastine formulations (i.v., i.m. and oral) and dexchlorpheniramine among them also versus placebo. MethodsThis was a single-dose, randomized, crossover, double-blind, placebo-controlled, phase I clinical study performed on 25 adult healthy volunteers that compared the peripheral antihistaminic activity of a single dose of bilastine 12 mg i.v., bilastine 12 mg i.m., bilastine 20 mg oral tablets and dexchlorpheniramine 5 mg i.m. among them and versus placebo by inhibiting the histamine-induced wheal and flare (W&F) response. Pharmacokinetics, safety, and tolerability were also evaluated. ResultsAll bilastine formulations showed a rapid onset of action (15 min for parenteral and 30 min for the oral formulation), and the maximum effect in both wheal (i.v. 74.44 %; i.m.:74.29 %; oral 70,27 %) and flare area reduction (i.v. and i.m. 80.63 %; oral 77.67 %), was significantly larger compared to dexchlorpheniramine i.m. (25.85 % for wheal and 28.65 % for flare) and placebo (1.35 % for wheal and 4.02 % for flare). A more pronounced reduction in itching score was reached for bilastine oral, followed by i.m. and i.v. formulations. No serious adverse events (SAEs) were reported during the study, and 8 treatment-emergent adverse events (TEAEs) were reported by 5 subjects, all resolved without sequelae. For psychomotor assessments, dexchlorpheniramine i.m. showed a fast onset of drowsiness, as well as decreased attention and coordination when compared to all bilastine formulations and placebo. ConclusionsAll bilastine formulations showed a peripheral H1-blocking effect inducing a significantly greater inhibition of the wheal and flare response as compared to dexchlorpheniramine i.m. or placebo and provided a greater reduction of the itching sensation score. This study reconfirmed that bilastine has no sedative effect, even in a parenteral formulation. These results suggest that new bilastine parenteral formulation (i.v. or i.m.) may represent a suitable alternative for patients requiring immediate treatment of histamine-mediated type I hypersensitivity reactions, such as acute urticaria, or in those cases where oral administration is not possible.

The impact of COVID-19 on hay fever treatment in Japan: A retrospective cohort study based on the Japanese claims database.

Hay fever (HF) presents with various symptoms, including allergic conjunctivitis and rhinitis, and requires cross-organ treatment. This study assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HF treatment trends. This retrospective cohort study utilized data from the JMDC database collected between January 2018 and May 2021. Patients with HF were identified based on the relevant International Classification of Diseases 10th Revision diagnosis codes and the prescription of HF-related medications. The treatment approaches were compared during the cedar and cypress pollen allergy season (January to May in Japan) before and during the COVID-19 pandemic (2018 and 2019, and 2020 and 2021, respectively). This study included 2,598,178 patients with HF. The numbers of prescribed HF-related claims in 2018, 2019, 2020, and 2021 were 3,332,854, 3,534,198, 2,774,380, and 2,786,681 times, respectively. Oral second-generation antihistamine prescriptions decreased by >10% from 2019 to 2020, with a <10% change in the subsequent year. Anti-allergic eye drop prescriptions also decreased by >10% from 2019 to 2020 but increased by >10% from 2020 to 2021. Compared with 2018, 2019, and 2020, the number of claims in the rhinitis symptoms dominant group was significantly decreased in 2021 (p<0.001, all). In contrast, the number of claims in the eye symptoms dominant group and the rhinitis and eye symptoms dominant group increased in 2021 compared with that in 2018, 2019, and 2020 (p<0.001, all). Changes in HF treatment and related outcomes could be attributed to lifestyle modifications resulting from the COVID-19 pandemic. Measures, such as limiting outdoor activities and adopting mask-wearing practices may have influenced HF symptoms, preventive behaviors, and the overall approach to treating HF.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n=326, ROR 6.75), sneezing (n=251, ROR 15.24), and nasal congestion (n=185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n=2556, ROR 10.52 vs. Loratadine, n=1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n=233, ROR 3.3), while Loratadine was associated with nervousness (n=145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n=138, ROR 8.13), potentially leading to serious adverse consequences. Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Autologous Serum Therapy in Recalcitrant Chronic Spontaneous Urticaria: Experience from Three Dermatology Clinics in Malaysia

Abstract Autohemotherapy is a commonly used treatment for recalcitrant chronic urticaria in some countries. Herein we report our experience using autologous serum therapy in eight patients with recalcitrant chronic spontaneous urticaria. Autologous serum therapy was initiated weekly for nine weeks followed by every fortnightly. Urticaria Activity Score (UAS) 7, Dermatology Life Quality Index (DLQI), and reduction of antihistamine usage were used to assess the treatment response. Eight patients (age range: 25–76 years old; four females and four males) had one to ten years of duration of recalcitrant chronic spontaneous urticaria. All failed to respond to high doses of second-generation antihistamines and five to immune-modulating agents. Three did not respond to omalizumab. At week nine, the reduction of UAS7 ranged from 76.2% to 100%. There was more than an 80% improvement in DLQI in all patients. The number of wheals seemed to be reduced first followed by pruritus. Three patients had stopped antihistamines by week eight of treatment. No adverse events were reported in all eight patients. Autologous serum therapy may serve as an alternative treatment for recalcitrant chronic spontaneous urticaria. Apart from the practicality, which requires frequent clinic visits, venipuncture, and centrifugation, it is cheap and effective with minimal adverse events.

Epidemiological and clinical characteristics of adult patients with chronic spontaneous urticaria in Latvia: insights from a two-centre study.

Chronic spontaneous urticaria (CSU) significantly impacts the quality of life of affected individuals. This study aimed to elucidate the epidemiological and clinical profiles of adult CSU patients in Latvia. Patient interviews and electronic medical records from two study centres in Riga, Latvia, were reviewed. PROMs, including UCT, UAS7, USS, and CU-Q2oL, were used to assess disease control, activity, severity, and quality of life. Statistical analysis was performed using Jamovi v. 2.3.28 and IBM SPSS v. 29.0.0.0. The cohort included 140 CSU patients (76.4% female; mean age 41.3 ± 14.9 years), mostly urban residents (87.1%) and non-smokers (53.6%). Urticaria with angioedema occurred in 52.1% and isolated urticaria in 47.9%, with 40% experiencing CSU for 1-5 years. Accompanying symptoms were reported by 63% and triggers by 72.9%. Allergy history and autoimmune disease diagnosis were noted in 49.3% and 29.3%. Treatment mainly involved second-generation antihistamines (85.7%) and omalizumab (17.9%). Mean scores for USS, UCT, and UAS7 were 28.8 (SD: 17.8), 8.2 (SD: 3.7), and 17.2 (SD: 14.1). UAS7 indicated severe CSU in 28.6%, and UCT suggested poorly controlled disease in 77.9%. CU-Q2oL total scores revealed mental status as the most affected domain (mean score: 51.7, SD: 28.7), with a significant association between accompanying symptoms and questionnaire scores. This study provides insights into the demographic and clinical aspects of CSU patients in Latvia, highlighting areas for potential improvement in patient care and emphasizing the need for further investigation into treatment outcomes and patient quality of life.

Navigating allergies safely: tailored solutions in special circumstances – a comprehensive review of antihistamines

Personalised medicine is critical in managing allergic diseases, with the variety of second-generation antihistamines necessitating tailored approaches to individual patient needs. This encompasses considerations of age, pregnancy, breastfeeding, hepatic and renal failure, drug interactions, and aging. This paper synthesises current research and guidelines on the use of antihistamines across diverse clinical scenarios, paying special attention to paediatric allergy treatment, including safety profiles of first- and second-generation antihistamines, their use during pregnancy, breastfeeding, and interactions with other drugs, as well as considerations for elderly patients. Second-generation antihistamines are preferred for allergy treatment due to their safety, minimal adverse effects, and efficacy, with a strong recommendation against the use of first-generation antihistamines due to their potential to induce severe adverse reactions. Cetirizine, levocetirizine, and desloratadine are favoured in infants; whereas loratadine, rupatadine, and bilastine are recommended for preschoolers and older children. The safety of selected second-generation antihistamines during pregnancy (notably cetirizine, levocetirizine, desloratadine) and breastfeeding (notably loratadine, desloratadine, fexofenadine), in patients with renal failure and elderly patients (bilastine, desloratadine, fexofenadine), and patients with hepatic failure (bilastine, fexofenadine) is highlighted. The choice of second-generation antihistamines should be based on the patients’ individual needs and conditions to achieve optimal therapeutic outcomes and ensure safety, emphasising the importance of drug selection in varying clinical contexts.

Bioavailability of Bilastine Oral Self-nanoemulsion: Comparative Study with Commercial Formula in Rats

Background: Bilastine (BL) is a novel non-sedating second-generation antihistamine, and its bioavailability is about 60%. Objective: To compare the bioavailability of prepared oral self-nanoemulsions of BL (BL-SNE) with that of pure BL and marketed tablets. Methods: Four groups of Wistar rats were used in this study, each with six rats weighing between 200 and 250 g. They were treated orally using a a gavage tube. The groups were fed either with conventional tablets ("Alerbix®") after being ground and dispersed with deionized water (DIW), treated with BL-SNE or fed with pure BL powder suspension. The fourth group did not receive any medication. The concentration of BL in the rat’s plasma was measured using HPLC. We used Trandolapril as an an internal standard. Results: The bioavailability results for the the prepared formula, tablet, and pure BL were 24289.91 ng/ml, 0.75 h, 12.81, 97844.7 ng.h/ml, and 98732.9 ng/ml, respectively, for the BL-SNE formula, and 15840.37, 1.0, 13.014, 66140.4, and 67088.3 for the tablets. Meanwhile, the BL suspension demonstrates 10830.12, 1.0 h, 12.96, 59397.12 ng/ml, and 60534.64 ng/ml, respectively. Conclusions: The relative bioavailability of BL-SNE was 1.47 and 1.6 times higher than that of marketed tablets and pure BL, respectively. This indicates an improvement in BL's bioavailability.

Formulation and Evaluation of Bilastine Thermosensitive Mucoadhesive Ophthalmic in situ Gel

Background: Bilastine is a non-sedating, second-generation antihistamine used to treat urticaria and allergic conjunctivitis. Objective: to formulate and test bilastine as a mucoadhesive ophthalmic in situ gel in order to extend its presence at site for longer time and help treat conjunctivitis and allergic rhinitis. Methods: We prepared formulations using different concentrations of poloxamers (Poloxamer 407 (P407) and Poloxamer 188 (P188)) in combination with hydroxypropyl methyl cellulose (HPMC). The prepared formulas were evaluated for their physicochemical properties, sol-gel transition temperature, viscosity, mucoadhesive strength, drug release, and kinetic modeling. Results: The prepared in situ gels were clear and transparent, having a pH ranging from 7.4 to 7.5 and a gelation temperature between 29.5 and 34.7 °C. Increasing the concentrations of P-407 and HPMC increased viscosity, gel strength, and mucoadhesion force, but caused a decrease in gelation temperature and drug release. Formula (F 14) containing P 407/P 188/HPMC as 19/4/0.75% w/v, respectively, exhibited favorable characteristics, including optimal gelation temperature (33°C), drug content (93%), gel strength (40 sec), mucoadhesive force (6125 dyne/cm2), and 91.4% in vitro drug release over 5 hours. Conclusions: The bilastine mucoadhesive in situ gel formulation is presented as a promising ophthalmic formulation for the treatment of allergic conjunctivitis.

Evaluating the Efficacy of Omalizumab in Severe Cedar Seasonal Allergic Rhinitis in Japan.

Traditional treatments for cedar seasonal allergic rhinitis include second-generation antihistamines, nasal corticosteroids, and sublingual immunotherapy (SLIT). Omalizumab (Xolair®), an anti-immunoglobulin E (IgE) monoclonal antibody, is an additional option for severe cases unresponsive to existing therapies. Numerous studies have demonstrated the therapeutic effectiveness of omalizumab for cedar seasonal allergic rhinitis; however, most reported results after only up to four weeks of follow-up. Therefore, this study evaluates the clinical efficacy of omalizumab throughout one whole cedar pollen season. Subjects and methods: This study included patients from our department and the Otorhinolaryngology Department of Minami Osaka Hospital between 2021 and 2023 who were ≥ 12 years old and had serum total IgE levels of 30-1,500 IU/mL, a baseline weight of 30-150 kg, and persistent severe nasal symptoms despite conventional treatments. Patients taking oral steroids at the time of enrollment or had fewer than two omalizumab doses were excluded. Forty-six patients (26 males, 20 females; mean age, 19.1 ± 11.2 years) met these criteria and received subcutaneous omalizumab every 2 or 4 weeks based on their IgE levels and weight. Symptoms were assessed at baseline and 4, 8, and 12 weeks post-administration using the Total Nasal Symptom Score (TNSS) and the Japanese Standard Quality of Life Questionnaire (JRQLQ No. 1) for allergic rhinitis. Results: Thirty-six patients were followed up for 8 weeks and 13 for 12 weeks. TNSS significantly improved from 6.6 to 4.5 at 4 weeks, 4.2 at 8 weeks, and 4.1 at 12 weeks (p<0.05). Nasal discharge, sneezing, nasal obstruction, itchy eyes, and tearfulness showed significant improvements (p<0.05). Quality of life scores improved in daily activities, sleep, and physical health from week 4 to week 12. Discussion: Consistent with previous findings, omalizumab significantly improved nasal and ocular symptoms and quality of life in patients with severe cedar seasonal allergic rhinitis. Despite many patients discontinuing the drug after eight weeks due to high costs, the drug's effectiveness in preventing symptom recurrence suggests potential long-term benefits. Combining omalizumab with SLIT showed no significant differences in outcomes; however, further pharmacoeconomic studies are warranted to evaluate cost-effectiveness. Conclusion: Omalizumab proved to be an effective treatment for severe cedar seasonal allergic rhinitis, providing significant symptom relief and quality of life improvements. Further studies should investigate its long-term efficacy and safety, including potential adverse effects and the development of anti-omalizumab antibodies.

Chronic spontaneous urticaria: diagnosis, treatment, and management

Chronic spontaneous urticaria (CSU) is a disabling condition in which recurrent wheals, with or without angioedema, occur for over 6 weeks. CSU occurs in up to 1% of the general population at any time and, on average, lasts 2–5 years in duration. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, 25%–50% of patients are refractory to these treatments. CSU profoundly impairs patients’ quality of life and has a substantial societal impact, including significant health care costs and decreased work productivity. These factors underscore the importance of health care providers to be familiar with the diagnosis and management of this condition. This article reviews the epidemiology, pathogenesis, aggravating factors, clinical manifestations, diagnostic assessment, and treatment of CSU.

Correlation between the expression of the iNOS, caspase-3 and α-SMA genes in the parotid glands of albino rats following the administration of two antihistamines from two different generations.

Several medications, including antihistamines, can alter salivary gland function, causing dry mouth or xerostomia. Antihistamines are commonly used for treating allergic rhinitis. The aim of the present study was to compare and correlate the effects of first-generation vs. second-generation H1-antihistamines on the parotid glands of rats. Twelve adult male albino rats were used; 4 rats served as a control group (group I) and the remaining rats were divided into 2 groups: group II received promethazine hydrochloride; and group III received cetirizine dihydrochloride for 3 weeks. The parotid salivary glands were dissected, and examined histologically and analyzed histomorphometrically for the acinar area percentage. In addition, mRNA gene expression of iNOS, caspase-3 and α-SMA was assessed using quantitative realtime polymerase chain reaction (qRT-PCR). Finally, all the obtained data was statistically analyzed. Histologically, group I showed the typical architecture of the gland. In group II, degenerative changes were noticed, including acinar degeneration and shrinkage with widened connective tissue septa, intracellular vacuolization, and increased inflammatory cell infiltration. In group III, similar histological features were detected as in group II, but to a lesser extent. Histomorphometric results revealed significant differences in the acinar area percentage between various groups. In addition, qRT-PCR results showed a significant increase in iNOS expression in both groups II and III as compared to group I, caspase-3 gene expression was significantly increased in group II, while in group III, it increased non-significantly. Finally, α-SMA gene expression non-significantly decreased in both groups II and III. A significant positive correlation was observed between caspase-3 and iNOS gene expression, while an inverse correlation was noticed between caspase-3 and α-SMA gene expression. The administration of antihistamines resulted in changes in the rat salivary glands, which could be due to the induction of oxidative stress and the resultant apoptotic effect. These changes were suggested to occur mainly through action on muscarinic receptors; yet, action on histamine receptors could not be excluded. However; these effects were less marked with the second-generation antihistamine.

Effect of Various Herbal and Chemical Enhancers on Skin Permeability to Cetirizine: A Study of Changes in Rat Skin Cells

Background: Cetirizine is a second-generation antihistamine with anti-allergy and anti-itching properties. The topical formulation of this medicine is used in androgenic alopecia treatment. Due to the hydrophilic nature of cetirizine, its skin absorption is negligible, so to increase its absorption, various enhancers were examined to see which can be used in the design of a topical formulation. Methods: First, the skin was exposed to enhancers, including eucalyptus, menthol, Tween 80, propylene glycol, and oleic acid, for 1 or 2 hours. Then, the permeability parameters of the cetirizine solution and the structural changes of the skin after exposure to enhancers were analyzed by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) techniques. Results: The obtained results show that all used enhancers increased the permeability of the drug cetirizine compared to water. Various mechanisms, such as liquefaction of lipids, destruction of lipid structure, and irreversible denaturation of intracellular keratin, are involved in the increase in drug penetration caused by eucalyptus, mint, Tween 80, propylene glycol, and oleic acid. Conclusions: The results showed that among the studied absorption enhancers, eucalyptus and Tween 80 had the strongest, and propylene glycol had the weakest absorption enhancement effect after 2- and 1-hour pre-contact, respectively.

Delayed Pressure Urticaria Associated With Altitude Chamber Training Responsive to Cyclosporine and Omalizumab.

Delayed pressure urticaria (DPU) is a subset of chronic inducible urticaria. It is characterized by the formation of wheals anytime between 30 minutes and 24 hours after stimulus exposure of localized pressure application. In this case report, we discuss a military flight crew member with no significant past medical history who developed DPU following rapid decompression in an altitude chamber. The chamber training included an uneventful ascent to 45,000 feet, higher than he had been previously, and a rapid decompression. About 16 hours later, he developed pruritic swelling of his hands and feet, along with diffuse deep nodular swelling, erythematous plaques, and erythematous nodules. His DPU was refractory to monotherapy treatment with antihistamines, and he continued to develop lesions in weight-bearing areas. Control of symptoms was achieved through combination treatment of a second-generation antihistamine, a leukotriene receptor antagonist, and an immunosuppressant (cyclosporine). His waiver to return to flight status was denied while on cyclosporine. He was transitioned to a monoclonal antibody that binds free immunoglobin E (omalizumab) with resolution of symptoms and was cleared to return to active duty.

Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis

H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. To explore dementia risk in patients with allergic rhinitis using AHs. Taiwanese patients with new-onsetallergic rhinitis (2011-2017) constituted the study population (677,971 with FGAs or SGAs, 36,081 without AHs). AH use was measured in cumulative defined daily dose (cDDD). Patients were grouped by cDDD (nonuser, <60 cDDD, 60-120 cDDD, and >120 cDDD). A Cox proportional hazard model assessed the AH-dementia association. Sensitivity analysis explored AH effects on dementia risk across subgroups and associations between specific AHs and dementia types. FGAs in patients with allergic rhinitis were associated with elevated dementia risk. At less than 60 cDDD, adjusted hazard ratio (aHR) was 1.13 (95% CI, 1.09-1.17); at 60 to 120 cDDD, aHR was 1.29 (95% CI, 1.21-1.38); and at more than 120 cDDD, aHR was 1.51 (95% CI, 1.42-1.62). SGAs also raised dementia risk. At less than 60 cDDD, aHR was 1.11 (95% CI, 1.05-1.17); at 60 to 120 cDDD, aHR was 1.19 (95% CI, 1.12-1.26); and at more than 120 cDDD, aHR was 1.26 (95% CI, 1.19-1.33). Patients with allergic rhinitis on FGAs or SGAs face an escalating dementia risk with increasing cumulative dosage. Moreover, FGAs exhibit a higher dementia risk compared with SGAs. Nevertheless, extensive clinical trials are imperative for confirming the association between FGA use, SGA use, and dementia risk.