Combining dipyridamole and cilostazol with up-dosing antihistamines improves outcomes in chronic spontaneous urticaria with high D-dimer levels: A randomized controlled trial.

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.

[Second-Generation Antihistamines for Preventing Hypersensitivity Reactions during Anticancer Therapy-A Retrospective Study].

Hypersensitivity reactions are an adverse effect of anticancer drug therapy. Prophylactic administration of antiallergic drugs and steroids is recommended when administering drugs associated with a high hypersensitivity reaction incidence. First-generation antihistamines are generally used in this setting. These medications, however, induce drowsiness and sedation due to their inhibitory effects on the central nervous system. They are contraindicated in patients with angle-closure glaucoma and prostatic hyperplasia. Second-generation antihistamines are used as alternative drugs for such cases in our hospital. This study investigated the use of second-generation antihistamines at our hospital and examined their efficacy and safety. A total of 7 second-generation antihistamines were used at our hospital. Approximately 90% of the target patients were shifted from first-generation antihistamines to bilastine or desloratadine. The most frequent reasons for changing to second- generation antihistamines were drowsiness(32.3%)and car driving(24.2%). No central inhibitory side effects were observed upon consumption of second-generation antihistamines. Only 2 patients(3.2%)developed hypersensitivity reactions after changing to second-generation antihistamines. Our findings suggest that second-generation antihistamines are effective in preventing hypersensitivity reactions. These medications may be used in patients who have concerns regarding the central inhibitory side effects of first-generation antihistamines or their potential to exacerbate comorbidities. Their use can help improve the safety of anticancer drug therapy.

In utero exposure to antihistamines and risk of hepatocellular carcinoma in a multigenerational cohort.

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes. METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records to identify those prescribed antihistamines during pregnancy, and diagnoses of HCC in adult (age ≥18 y) offspring were identified by linkage with a population-based cancer registry. Cox proportional hazard models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact. RESULTS: About 15% of offspring (n=2759 of 18,751) were exposed in utero to antihistamines. Chlorpheniramine (51.8%) and diphenhydramine (15.4%) were the 2 most commonly prescribed antihistamines. Any in utero exposure was not associated with HCC (adjusted hazard ratio: 2.76, 95% CI: 0.70, 10.89), but the association differed by timing of exposure. Offspring exposed to antihistamines in the first or second trimester had a higher risk of HCC compared to offspring not exposed (adjusted hazard ratio: 4.64, 95% CI: 1.21, 17.78). Similarly, incidence rates were 4.3 per 100,000 (95% CI: 0.9, 12.6) for offspring exposed in the first or second trimester compared to 1.0 per 100,000 (95% CI: 0.3, 2.1) for offspring not exposed. CONCLUSIONS: In utero exposure to antihistamines in early pregnancy may increase the risk of HCC in adulthood.

The role of histamine and its receptors in breast cancer: from pathology to therapeutic targets.

Breast cancer is the most common malignancy in women, and despite the development of new treatment methods and the decreasing mortality rate in recent years, one of the clinical problems in breast cancer treatment is chronic inflammation in the tumor microenvironment. Histamine, an inflammatory mediator, is produced by tumor cells and can induce chronic inflammation and the growth of some tumors by recruiting inflammatory cells. It can also affect tumor physiopathology, antitumor treatment efficiency, and patient survival. Antihistamines, as histamine receptor antagonists, play a role in modulating the effects of these receptors in tumor cells and can affect some treatment methods for breast cancer therapy; in this review, we investigate the role of histamine, its receptors, and antihistamines in breast cancer pathology and treatment methods.

Urticarial Vasculitis.

Urticarial vasculitis is a rare autoimmune disorder characterized by persistent edematous papules and plaques on the skin that last longer than 24 hours, often accompanied by systemic symptoms such as joint pain and fever. Unlike common urticaria, this condition involves inflammation of small blood vessels, leading to more severe and long-lasting skin lesions with a tendency to leave a bruiselike appearance. Diagnosis is challenging and may require a skin biopsy. Associated with underlying autoimmune diseases, treatment involves managing symptoms with medications such as antihistamines and corticosteroids, addressing the immune system's dysfunction, and treating any concurrent autoimmune conditions.

Chronic Spontaneous Urticaria: An Update on the Evaluation and Management.

Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases.

Treatment with Antihistamines and the Risk of Liver Cancer in Patients with Viral Hepatitis: A Multi-Center Cohort Study.

Background: The effects of antihistamines on cancer risk and prognosis have been inconsistent across cancers. The aim of this multi-center cohort study was to investigate the association between antihistamine use and the risk of liver cancer in individuals with viral hepatitis. Methods: This multi-center cohort study included individuals diagnosed with hepatitis B or hepatitis C between January 2008 and March 2022. For antihistamine-treated patients, the index date was the date of antihistamine prescription, and for non-users, it was the date of hepatitis diagnosis. Participants were followed for five years, with the primary outcome of interest being new-onset liver cancer. The incidence rate and the adjusted hazard ratio (aHR) along with its 95% confidence interval (CI) of the outcome were calculated. Subgroup analyses were conducted, stratified by types of viral hepatitis including hepatitis C and hepatitis B. An additional validation study was performed. Results: The study included a total of 7748 patients with viral hepatitis. The incidence rate was 12.58 per 1000 person-years in patients with viral hepatitis on antihistamines, compared to 3.88 per 1000 person-years in those without antihistamine use. After adjusting for factors including age, sex, body mass index (BMI), comorbidities, laboratory data of liver function tests, comedications, and the use of antiviral therapies, the risk of new-onset liver cancer was significantly higher in patients on antihistamines (aHR = 1.83, 95% CI, 1.28-2.60). In patients with hepatitis C, the incidence rate in the antihistamine group was 15.73 per 1000 person-years, while non-users had a rate of 4.79 per 1000 person-years. Patients with hepatitis C on antihistamines had a significantly higher risk of developing liver cancer (aHR = 3.24, 95% CI, 2.16-4.86). Conclusions: This multi-center cohort study reported an increased risk of liver cancer in patients with hepatitis B or hepatitis C treated with antihistamines. Long-term follow-up studies are warranted to validate the findings.

Plant Dermatitis.

Plant dermatitis is a common pathology that plagues those who work and recreate in the North American outdoors. The most common plant family to cause dermatitis is the Toxicodendron genus, which includes the plants known by the common names of poison ivy, poison oak, and poison sumac. While mortality is usually quite low for this pathology, the incidence and prevalence of the disease leads to substantial healthcare burden and financial implications across the population. The mainstays of treatment have focused on prevention, corticosteroids, and antihistamines.

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

Clinical Aspects of Chronic Idiopathic Postnasal Drip: An Entity Not to Be Overlooked.

BACKGROUND/AIM: Postnasal drip may be related to several diseases, but not all patients are clearly diagnosed. Patients with chronic, idiopathic postnasal drip symptoms are easily overlooked, and their clinical features are yet to be identified. This study aimed to analyze the clinical features and response to first generation antihistamine-decongestant therapy in patients with chronic idiopathic postnasal drip, suggesting it as a distinct entity. PATIENTS AND METHODS: A retrospective cohort study involving 157 chronic idiopathic postnasal drip patients was conducted, analyzing demographics, symptoms, and treatment response to first-generation antihistamines and nasal decongestants. RESULTS: Mean age of patients was 55.4±17.0 years old. Median duration of symptom was 36 months (range=12-66 months) and severity in the visual analogue scale was 7 (range=5-8). Throat discomfort was the most frequently associated symptom (73.7%). Cough was recorded in 30.3% of patients. Viscosity of postnasal drip was associated with rhinorrhea and throat discomfort. Of the patients, 71.6% responded positively to 1st generation antihistamine-decongestant medication. However, 25.9% of patients presented symptom re-occurrence. Patients with nasal stiffness or persistent symptoms presented a higher re-occurrence rate compared to others. CONCLUSION: This study outlines the clinical features of patients with chronic idiopathic postnasal drip and suggests it as a distinctive entity., This proposal aims to enhance diagnostic precision and promote further research in the field.

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.

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.

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.

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.

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.

[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.

Over-the-counter medications encountered in the postmortem pediatric population from 2010-2020.

In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days-18 years), particularly those given to individuals <5 years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from 11 years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine and pseudoephedrine), gastrointestinal aids (dicyclomine and loperamide) and/or sleep aids (melatonin). Antihistamines, cold/flu medications and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5 U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g. antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse and suicidal overdoses can occur in the vulnerable, pediatric population.

Evaluation of Guideline Line-Care Approach to the Treatment of Chronic Inducible Urticaria.

BACKGROUND: Chronic inducible urticaria (CIndU) management often follows chronic spontaneous urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in CIndU is lacking. OBJECTIVE: To assess the clinical impact of adapting CSU international guidelines for CIndU management. METHODS: We conducted a prospective cohort study involving patients diagnosed with CIndU based on challenge tests and a Urticaria Control Test (UCT) score of ≤11 points. Following the guidelines, a stepwise approach was used: avoidance measures, antihistamines, omalizumab, and cyclosporine. Treatment steps were added based on individual response, with control defined as UCT ≥12 points. Pharmacological steps were evaluated for at least 1 month, with the next step initiated in case of a UCT score ≤11 points. RESULTS: We enrolled 194 patients with CIndU. Of them, 134 patients had CIndU with concomitant CSU and 60 had CIndU only. Following the step-by-step approach outlined in the guidelines, a total of 159 (81.9%) patients reach a UCT ≥12 points, with avoidance measures 23 (11.8%) patients, antihistamines 84 (43.2%), omalizumab 35 (18%), and cyclosporine 17 (8.7%). CONCLUSIONS: This study supports the use of a stepwise approach based on CSU guidelines for CIndU management. However, a significant proportion of patients, particularly those with CIndU only, did not achieve adequate control. This highlights the heterogeneity within CIndU and the need for further research to develop new therapies for patients with CIndU who remain uncontrolled.