Blockade of histamine receptor H1 augments immune checkpoint therapy by enhancing MHC-I expression in pancreatic cancer cells.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. METHODS: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. RESULTS: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. CONCLUSIONS: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

Discovery of the novel and potent histamine H1 receptor antagonists for treatment of allergic diseases.

Desloratadine, a second-generation histamine H1 receptor antagonist, has established itself as a first-line drug for the treatment of allergic diseases. Despite its effectiveness, desloratadine exhibits an antagonistic effect on muscarinic M3 receptor, which can cause side effects such as dry mouth and urinary retention, ultimately limiting its clinical application. Herein, we describe the discovery of compound Ⅲ-4, a novel H1 receptor antagonist with significant H1 receptor antagonistic activity (IC50 = 24.12 nM) and enhanced selectivity towards peripheral H1 receptor. In particular, Ⅲ-4 exhibits reduced M3 receptor inhibitory potency (IC50 > 10,000 nM) and acceptable hERG inhibitory activity (17.6 ± 2.1 µM) compare with desloratadine. Additionally, Ⅲ-4 exhibits favorable pharmacokinetic properties, as well as in vivo efficacy and safety profiles. All of these reveal that Ⅲ-4 has potential to emerge as a novel H1 receptor antagonist for the treatment of allergic diseases. More importantly, the compound Ⅲ-4 (HY-078020) has recently been granted clinical approval.

Effectiveness of promethazine on preoperative and intraoperative sequelae in cleft palate surgeries.

INTRODUCTION: Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries. MATERIALS AND METHODS: This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor. RESULTS: Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group. CONCLUSION: As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

A systematic review and meta-analysis of efficacy and safety of compound glycyrrhizin combined with second-generation non-sedated antihistamine for the treatment of chronic urticaria.

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.

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks.

BACKGROUND: Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU. OBJECTIVE: We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines. METHODS: In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7 = 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks. RESULTS: Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean ± SD change from baseline in UAS7 was -17.6 ± 13.40 and -21.8 ± 10.70; UAS7 = 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively. CONCLUSIONS: Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

BACKGROUND: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. METHODS: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. FINDINGS: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. INTERPRETATION: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. FUNDING: Novartis Pharma.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.

The Added-on of Ziziphus jujube Syrup in the Treatment of Chronic Spontaneous Urticaria Resistant to Standard-Dose of Secondary-generation H1 Antihistamine: A Double-Blind Randomized Clinical Trial.

Background: Although antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU), 50% of patients don't respond to standard doses. In this study, the effectiveness of Ziziphus jujube fruit syrup in combination with antihistamines was assessed in patients with CSU. Methods: This double-blind randomized clinical trial was conducted in Shiraz between December 2019 and December 2020. 64 patients with CSU who had experienced hives for at least six weeks and did not respond to the usual treatments were enrolled in the study. They were randomly assigned to intervention and control groups using permuted block random allocation. For four weeks, the intervention group received 7.5 mL Ziziphus jujube syrup twice a day, while the control group received 7.5 mL simple jujube syrup twice a day. Both groups received cetirizine 10 mg every night. Urticaria activity score (UAS) and CU-Q2oL questionnaires were used to assess urticaria state and sleep quality before and after each week for four consecutive weeks. Data were analyzed using SPSS software version 18, and P<0.05 was considered statistically significant. Results: Before the intervention, there was no statistically significant difference between the two groups' mean of UAS (P=0.490) and sleep quality (P=0.423). During the follow-up, UAS in the intervention group was significantly lower (P=0.001). Moreover, this difference was significant on the day 28 (P=0.046). During the follow-up, the quality of sleep in both groups improved significantly, and this improvement was more significant in the intervention group. Conclusion: Ziziphus jujube syrup could be an effective adjuvant treatment for CSU.Trial Registration Number: IRCT20190304042916N1.

Interleukin-33, endothelin-1, and inflammatory parameters in chronic spontaneous urticaria.

Background: Endothelin-1 (ET-1) and interleukin-33 (IL-33) can modulate the activation of mast cells and basophils in the pathophysiology of allergic diseases, interplaying with other mediators of "low-grade inflammation." Objective: To compare ET-1, IL-33, the neutrophil-lymphocyte ratio (NLR), eosinophil-lymphocyte ratio (ELR), platelet-lymphocyte ratio (PLR), eosinophil-basophil ratio (EBR), systemic immune inflammation index (SII), and system inflammation response index (SIRI) in patients with chronic spontaneous urticaria (CSU) and are antihistamine sensitive (AHS), antihistamine resistant (AHR), omalizumab sensitive (OmS), and omalizumab resistant (OmR). Methods: A prospective observational study enrolled 68 consecutive patients with CSU diagnosed and managed according to the dermatology section of the European Academy of Allergology and Clinical Immunology (EAACI), the European Union funded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization guidelines. Patients with a urticaria control test score of >12 are considered treatment sensitive, and ≤ 12 are considered resistant. The control group consisted of 20 sex-matched subjects without urticarial diseases. Total immunoglobulin E (IgE), antinuclear antibodies (ANA), thyroid stimulating hormone, antithyroid peroxidase, mean platelet volume (MPV), NLR, ELR, PLR, EBR, SII, SIRI, ET-1, and IL-33 were measured at the study entry and compared between the study groups. Results: Thirty AHS group, 38 AHR group, and 20 control group patients were included. The AHS, AHR, and control groups did not differ in demographic parameters, but the CSU groups were characterized by higher indicators of inflammation. In comparison with the AHS group, the AHR group was characterized by higher levels of IL-33 (p = 0.007), ET-1 (p = 0.032), C-reactive protein (p = 0.016), MPV (p = 0.002), and higher rates of positive ANA (p = 0.019). Of the 38 patients from the AHR group, 30 (79%) were included in the OmS group and 8 (21%) were included in the OmR group. The OmR group was characterized by higher levels of C-reactive protein (p = 0.022), EBR (p < 0.001), higher rates of ANA (p = 0.004), and lower levels of ET-1 (p = 0.025) than the OmS group. Conclusion: Our study did not confirm NRL, PRL, SII, and SIRI, PLR as the biomarkers of treatment response to antihistamines and/or omalizumab in CSU. Higher blood levels of IL-33 and ET-1 characterize AHR CSU.

Comparing four immunosuppressive agents for chronic spontaneous urticaria-A network meta-analysis.

BACKGROUND: Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents. OBJECTIVE: The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU. METHODS: PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects. RESULTS: This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples. CONCLUSION: Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.

Novel H2S-Releasing Bifunctional Antihistamine Molecules with Improved Antipruritic and Reduced Sedative Actions.

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with anti-inflammatory actions that also reduces itching. To test whether a combination of an antihistamine with a H2S donor has improved antipruritic efficacy, bifunctional molecules with antihistamine and H2S-releasing pharmacophores were synthesized and tested in vitro and in vivo. H2S release from the hybrid molecules was evaluated with the methylene blue and lead acetate methods, and H1-blocking activity was assessed by determining tissue factor expression inhibition. All new compounds released H2S in a dose-dependent manner and retained histamine blocking activity. Two compounds with the highest potency were evaluated in vivo for their antipruritic as well as sedative action; they proved to possess higher efficacy in inhibiting histamine-induced pruritus and decreased sedative effects compared to the parent compounds (hydroxyzine and cetirizine), suggesting that they exhibit superior antipruritic action and limited side effects that likely arise from the H2S-releasing moiety.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report.

BACKGROUND: Panic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy. CASE PRESENTATION: This report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly. CONCLUSIONS: The immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient's clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Efficacy of different oral H1 antihistamine treatments on allergic rhinitis: a systematic review and network meta-analysis of randomized controlled trials.

INTRODUCTION: Oral H1 antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more effective in improving symptoms of patients. OBJECTIVE: To evaluate the efficacy of different oral H1 antihistamine treatments on patients with allergic rhinitis by performing a network meta-analysis. METHODS: The search was executed in PubMed, Embase, OVID, the Cochrane Library and ClinicalTrials.gov for relevant studies. The network meta-analysis was performed by using Stata 16.0, and the outcome measures of the analysis were symptom score reductions of patients. Relative risks with 95% Confidence Intervals were used in the network meta-analysis to compare the clinical effect of treatments involved, and Surface Under the Cumulative Ranking Curves (SUCRAs) were also calculated to rank the treatments' efficacy. RESULTS: 18 eligible randomized controlled studies, involving a total of 9419 participants, were included in this meta-analysis. All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction. According to the results of SUCRA, rupatadine 20 mg and rupatadine 10 mg were ranked relatively high in reductions of total symptom score (SUCRA: 99.7%, 76.3%), nasal congestion score (SUCRA: 96.4%, 76.4%), rhinorrhea score (SUCRA: 96.6%, 74.6%) and ocular symptom score (SUCRA: 97.2%, 88.8%); rupatadine 20 mg and levocetirizine 5 mg were ranked relatively high in reductions of nasal itching score (SUCRA: 84.8%, 83.4%) and sneezing score (SUCRA: 87.3%, 95.4%); loratadine 10 mg was ranked the lowest in each symptom score reduction besides placebo. CONCLUSION: This study suggests that rupatadine is the most effective in alleviating symptoms of patients with allergic rhinitis among different oral H1 antihistamine treatments involved, and rupatadine 20 mg performs better than rupatadine 10 mg. While loratadine 10 mg has inferior efficacy for patients to the other antihistamine treatments.

Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.

Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARß). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.

Potential Therapeutic Approaches for Chronic Urticaria: Beyond H1-Antihistamines and Biologics.

Chronic urticaria is a disease that can significantly impact a patient's quality of life and ability to function. There are effective treatment options, such as nonsedating antihistamines or biologics, but some patients do not respond to these therapies, or the therapies are not available or affordable to all patients. This review aims to summarize potential treatment strategies for patients (1) who do not respond to antihistamines and (2) cannot readily access or do not respond to biologics. The review emphasizes the importance of sound clinical practice, including correct diagnosis of chronic urticaria phenotypes, treatment of associated comorbidities, and consideration of add-on pharmacological and nonpharmacological approaches. Although some treatments may lack high-quality evidence, they may still be justifiable in certain cases, provided that there is shared decision-making, regular reassessment, and early recognition of adverse events.

Highlights of the treatment of allergic rhinitis according to Chinese guidelines.

PURPOSE OF REVIEW: This review aimed to introduce the pharmacotherapy of allergic rhinitis according to the 2022 updated Chinese guidelines. RECENT FINDINGS: Despite recent advances in basic and clinical research worldwide, pharmacotherapy remains a mainstream in allergic rhinitis treatment. Usually, the first-line drugs, involving intranasal corticosteroids, second-generation oral and intranasal H1-antihistamines, or leukotriene receptor antagonists, can achieve acceptable outcomes in the treatment of allergic rhinitis. The second-line drugs, such as oral corticosteroids, intranasal decongestants and intranasal anticholinergics, can assist in controlling severe symptoms, like nasal congestion/blockage and watery rhinorrhea. For those with moderate-to-severe allergic rhinitis, evidence-based stepwise strategies are suitable, in which the types and dosages of drugs are de-escalated or upgraded according to their therapeutic efficacy. Meanwhile, omalizumab, a novel biological agent, has burgeoned to satisfy the need of patients. SUMMARY: This review highlights the staples in Chinese guidelines about the pharmacotherapy for allergic rhinitis to better understand the guidelines and promote the clinical practice.