[Recent advances in the practical management of allergic rhinitis.] / Recenti progressi nella gestione pratica della rinite allergica.

Allergic rhinitis (AR) is a widespread disease, and its prevalence is still growing. AR may be associated with other diseases, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on history, physical examination, documentation of sensitization, such as the production of allergen-specific IgE, also using molecular diagnostics in selected patients. Treatments is based on education, engagement, allergen avoidance, non-pharmacological and pharmacological remedies, and allergen-specific immunotherapy (Ait). Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This article also aims to discuss new management strategies for AR patients. The self-management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered to intranasal corticosteroids and antihistamines without medical prescription, probiotics and other natural substances, and new formulations (tablets) of Ait.

Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

Nonprescription Treatment Options.

The pathogenesis of atopic dermatitis (AD) is complex and multifactorial. However, recent advancements in the genetics and pathophysiology of AD suggest that epidermal barrier dysfunction is paramount in the development and progression of the condition (Boguniewicz M, Leung DYM, Immunol Rev 242(1):233-246, 2011). In addition to standard therapy for AD, there are a plethora of nonprescription treatment modalities which may be employed. Over-the-counter treatments for atopic dermatitis can come in the form of topical corticosteroids, moisturizers/emollients, and oral antihistamines. Though these treatments are beneficial, prescription treatments may be quicker acting and more efficacious in patients with moderate to severe disease or during flares. OTC agents are best used for maintenance between flares and to prevent progression of mild disease. Alternative and complementary treatments lack strong efficacy evidence. However, wet wraps, bleach baths, and other treatments appear to be promising when used in conjunction with conventional treatments. With the financial burden of atopic dermatitis ranging from 364 million to 3.8 billion dollars each year in the United States, we suspect this topic will gain further research attention.

Oral Prescription Management.

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.

Atopic Dermatitis: Managing the Itch.

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ nonpharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, nonsedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.

Allergic Rhinitis.

Allergic rhinitis is a common ailment in primary and acute care settings. Diagnosis is clinical, by means of history and physical examination. Referral to an allergist is considered when symptoms are difficult to manage and/or confirmation by means of further testing is desired. Management of allergic rhinitis should not be considered trivial, as multiple secondary effects can present as the course progresses. Several treatment modalities exist but should begin with glucocorticoid nasal sprays and systemic second- or third-generation antihistamines.

Clinical efficacy of Zhiyang Xiaozhen granules combined with second-generation antihistamine in the treatment of chronic urticaria. / 止痒消疹颗粒联合第2ä»£æŠ—ç»„èƒºè¯æ²»ç–—æ ¢æ€§è¨éº»ç–¹çš„ä¸´åºŠç–—æ•ˆ.

OBJECTIVES: Chronic urticaria presents a chronic process of recurrent attacks, and its first-line treatment is second-generation antihistamine with limited treatment options. The efficacy of antihistamine varies among individuals and cannot meet the needs of all patients. This study aims to explore the clinical efficacy and safety of Zhiyang Xiaozhen granules combined with antihistamine in the treatment of chronic urticaria patients. METHODS: We retrospectively analyzed the clinical data of patients with chronic urticaria who visited the Xiangya Hospital of Central South University from April 2020 to March 2021. The patients who received conventional second-generation antihistamine treatment were selected as a control group, while the patients who received combined treatment with Zhiyang Xiaozhen granules on the basis of conventional second-generation antihistamine treatment were selected as an observation group. The differences in the Weekly Urticaria Activity Score (UAS7) and Dermatology Life Quality Index (DLQI) between the 2 groups before and 4 weeks after treatment were compared. The Symptom Score Reduce Index (SSRI) was used to evaluate and compare the efficacy of the 2 treatment regimens. RESULTS: After 4 weeks of treatment, the UAS7 levels in both groups were significantly reduced (P=0.001 and P<0.001, respectively). The effective rates of the control group and the observation group were 61.11% and 59.38%, respectively when converting UAS7 to SSRI for efficacy evaluation, and there was no statistically significant difference in efficacy between the 2 groups (P>0.05); however, when converting DLQI to SSRI for efficacy evaluation, the effective rates of the control group and the observation group were 33.33% and 46.88%, respectively, and the difference in efficacy between the 2 groups was statistically significant (P<0.001). There were 3 patients with adverse drug reactions related to drowsiness in both groups. CONCLUSIONS: The combination of Zhiyang Xiaozhen granules and second-generation antihistamine can effectively improve disease activity in patients with chronic urticaria, and the improvement in quality of life is better than that with the second-generation antihistamine alone.

Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

An update on the use of antihistamines in managing chronic urticaria.

INTRODUCTION: Urticaria, a mast cell-mediated skin disease, manifests as acute or chronic, with the latter divided into spontaneous and inducible types and requires individualized management, including identifying triggers and comorbidities. Antihistamines, particularly the second generation group, form the mainstay of primary treatment plans consisting of dosage adjustments and/or in combination with other treatment modalities depending on underlying disease control. AREAS COVERED: A literature search was conducted using 'antihistamines,' 'urticaria,' 'pharmacogenomics,' 'genomics,' 'biomarkers' and 'treatment response' as key words. In this review, we focus on the comprehensive understanding and application of antihistamines in managing adult and adolescent patients with chronic urticaria. EXPERT OPINION: Using antihistamines to treat urticaria is set to change significantly, focusing more on personalized medicine and identifying key biomarkers to enhance treatment response prediction. These changes aim to make treatments more specific and cost-effective by avoiding unnecessary tests. Applying new approaches in everyday clinical care faces challenges like proving the biomarkers' reliability, updating current guidelines, and incorporating individualized treatments into standard procedures. Efforts should now concentrate on finding easy-to-use biomarkers, improving access to pharmacogenomics, understanding why some patients are resistant to treatment, and creating more specific treatment options based on patient needs.

H2 antihistamines: May be useful for combination therapies in cancer?

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.

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.

Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review.

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

Risk calculator of the clinical response to antihistamines in chronic urticaria: Development and internal validation.

Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk.

Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial.

BACKGROUND: Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects. OBJECTIVES: To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression. METHODS: This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability. RESULTS: Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (> 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R. CONCLUSIONS: This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.

Cholinergic urticaria (CholU) is a common subtype of an inflammatory skin condition called chronic inducible urticaria, where signs and symptoms (e.g. hives and swelling in the skin) are triggered by sweating caused by physical exercise, passive warming and other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines (a type of medication), approximately 90% of people with the condition report that these medications do not control the disease. Targeting the histamine 4 receptor (H4R) has shown promise in studies of allergic/inflammatory diseases. CholU is driven by histamine (a chemical released in the body) and characterized by high skin levels of H4R. Izuforant is a medication that may reduce itch and inflammation. In our study, which was carried out across multiple sites in Germany, we assessed the effects of izuforant 100 mg in 18 patients with CholU using a range of measures covering symptom control, disease severity, provocation response and quality of life. The primary endpoint (the main result measured at the end of the study to see if the treatment worked) was change from baseline in the post-provocation Urticaria Activity Score, where areas of skin were provoked and the time until common symptoms of CholU appeared (sweating and whealing (hives)) was measured. Overall, the primary endpoint and most of the exploratory endpoints were not met. There were significant improvements in patients' global assessment for izuforant versus placebo. This was the first study to explore the role of H4R as a therapeutic target in urticaria. Our findings suggest that targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements versus placebo in the primary endpoint, and all but one prespecified exploratory endpoint in CholU.

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.

The pharmacotherapeutic management of allergic rhinitis in people with asthma.

INTRODUCTION: Up to 90% of asthmatic patients have comorbid allergic rhinitis (AR). Although appropriate therapy of AR can improve asthma symptoms and management, AR is often underdiagnosed and under-treated in asthmatics.A non-systematic literature research was conducted on AR as a comorbidity and risk factor of asthma. Latest international publications in medical databases, international guidelines, and the Internet were reviewed. AREAS COVERED: Based on the conducted literature research there is proved evidence of the necessity of diagnosis and treatment of AR in patients with asthma because it affects health care utilization. Therefore, it is recommended in national and global guidelines. EXPERT OPINION: AR increases the risk of asthma development and contributes to the severity of an existing asthma. Early treatment of AR with drugs as intranasal steroids, antihistamines, leukotriene receptor antagonists, and especially allergen-specific immunotherapy can reduce the risk of asthma development and the concomitant medication use in addition to severity of symptoms in AR and asthma.