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Allergic rhinoconjunctivitis and chronic urticaria are common histamine-driven diseases, exerting detrimental effects on cognitive functions, sleep, daily activities, and quality of life. Non-sedating second-generation H1-antihistamines are the first-line treatment of choice. Aim of the study was to define the role of bilastine among second-generation H1-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria in patients of different ages. An international Delphi study was carried out to assess consensus among experts from 17 European and extra-European countries on three main topics: 1) Burden of disease; 2) Current treatment options; 3) Specific characteristics of bilastine among second-generation antihistamines. Here, we present the results obtained for a selection of 15 out of 27 consensus statements, focused on disease burden, role of second-generation antihistamines and bilastine profile. The rate of concordance was ≥98% for 4 statements, ≥ 96% for 6, ≥ 94% for 3, and ≥90% for 2. The high degree of agreement obtained suggests a wide awareness of the burden of allergic rhinoconjunctivitis and chronic urticaria among experts from all over the world and reflects a broad consensus on the role of second-generation antihistamines in general and of bilastine in particular for their management. [ABSTRACT FROM AUTHOR]

A 38-year-old woman presented to the emergency department with recurrent severe headaches. Although initial computer tomography (CT) brain imaging was unremarkable, a later CT venogram demonstrated a small subarachnoid haemorrhage. Magnetic resonance angiogram (MRA) brain imaging subsequently confirmed reversible cerebral vasoconstriction syndrome (RCVS). In the acute setting, RCVS rarely falls into a differential diagnosis for headache presentations, as in this case. The radiological variability can make diagnosis of RCVS challenging. However, there are clinical consistencies that can aid physicians into accurately diagnosing RCVS. A thorough history, including a medication history, can help identify potential triggers of RCVS. As in this case, the combination of commonly used drugs, including antihistamines, provides a plausible trigger for RCVS. The direct vasoactive role of antihistamines is unclear, yet there is suggestion for its ability to potentiate the vasoactive action of other drugs. In this case we propose a causal relationship between the use of antihistamine and the development of RCVS.

Neelaveni Padayachee,1 Alan D Rothberg,2 Ilse Truter,3 Neil Butkow11Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, Gauteng, South Africa; 2School of Therapeutic Sciences, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, Gauteng, South Africa; 3Department of Pharmacy, Nelson Mandela University, Port Elizabeth, South AfricaIntroduction: In South Africa there is an easy access to over-the-counter (OTC) medicines and expenditure is high. Certain OTC products are available to the public in general stores, while others may only be available at pharmacies. It is also common for OTC medicines to be prescribed by a doctor for treatment of minor illnesses. Individuals with medical insurance usually have cover for these products, but typically only to a limited extent.Aim: To investigate the utilization patterns in two medical insurance schemes of OTC analgesic products in the Anatomical Therapeutic Chemical (ATC) category N02BE51 which includes medicines containing paracetamol and varying combinations of codeine, caffeine and antihistamines.Methodology: Data were obtained for two benefit plans, one with generous, high benefits (HI), the other with lower benefits (LO). Data covered utilization of OTC medicines in the N02BE51 group, indicating whether the medicines were purchased at a pharmacy or dispensed by a doctor. Doctors were further categorised as contracted/network or non-network providers. Product costs and volumes were analysed according to access directly by the beneficiary, recommendation by a pharmacist, or prescription from a doctor.Results: Compared to doctors, pharmacists issued more-expensive products. Average costs were higher in the HI plan compared to the LO plan. Pharmacists showed a preference for dispensing larger and more expensive pack sizes. Doctors showed better cost containment: the average cost of products in HI was twice that of LO. Doctors dispensing directly to patients issued smaller pack sizes and lower-priced products. Contracted network doctors did not appear to impact on costs.Conclusion: Among the privately-insured individuals studied, the avaiIability, cost and formulation of N02BE51 OTC products appeared to be poorly regulated, whether by the consumer, pharmacist, medical insurance scheme or legislation. Doctors demonstrate better cost containment by prescribing less costly, smaller pack-size alternatives compared to pharmacists.Keywords: paracetamol, codeine, anti-histamines, pharmacists, doctors, cost, pack size

Background: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods: The Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. Conclusions: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year. [ABSTRACT FROM AUTHOR]

Background: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross‐sectional real‐world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods: The Allergy Diary –MASK ‐air –mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1‐antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1‐antihistamines. Conclusions: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year. [ABSTRACT FROM AUTHOR]

We sought to study adenoidectomy rates in children with adenoid hypertrophy (AH) who were either treated with medical therapy or not during a 2-year follow-up period in a longitudinal population-based study. We retrospectively identified healthy children aged 1–18 years between 2014 and 2020 with AH diagnosis from the Clalit Health Services database, the largest healthcare maintenance organization in Israel. The main outcome was adenoidectomy alone or in combination with other procedures performed within 2 years after diagnosis. The treatment group consisted of children who received medical therapy, defined as a pharmacy purchase of montelukast, nasal steroid sprays and/or antihistamines (medical therapy aimed to reduce AH) for ≥2 consecutive months, while the control group consisted of untreated children. We identified 68,356 unique children with AH, of them 56 % were boys, with a mean age of 4.9 ± 3.3 years. Of them, 5310 (7.7 %) received medical therapy. Overall, 6633 (9.7 %) underwent adenoidectomy within 2 years following diagnosis. There was no significant difference in surgery referral rates between the treatment and the control groups, 10 % vs. 9.7 %, respectively (p = 0.3). When adjusted for age and sex, the likelihood of undergoing adenoidectomy was similar in both groups (HR = 0.98, 95 % CI = 0.90–1.07, p = 0.6). Among operated children, the average time from diagnosis to surgery was statistically significantly longer in the treatment group than in the control group, 346 ± 180 vs 311 ± 175 days (p < 0.001). Prescribing montelukast, nasal steroids and/or oral antihistamines was not associated with a reduction in adenoidectomy rates and was associated with an average surgery delay of 35 days. [ABSTRACT FROM AUTHOR]

Abstract Rationale Angioedema without co-existent urticaria is due to a limited number of causes, including hereditary and acquired C1 esterase inhibitor deficiency, drug-induced angioedema or idiopathic histaminergic or non-histaminergic angioedema. We describe a cohort of patients with recurrent angioedema whose clinical features and response to medications are distinct from the causes above. Methods Patients were accrued retrospectively from an academic allergy practice between 2007 and 2014. After institutional research ethics board approval, patients’ charts were reviewed and demographic, clinical and laboratory data were extracted. Results A total of 11 patients were recruited. The mean age at presentation was 54.9 years (range 19–70 years) and 6 of 11 were male. The mean number of episodes per year was 18.7 (range 2–60) and mean duration of episodes was 22.4 h (range 4–96). About half of episodes (52%) began overnight. Areas of involvement were lips (73%), tongue (64%), eyelids (18%), feet (36%) and hands (27%). None of the patients had low C3, C4, or CH50; none had significantly positive ANA; C1 esterase inhibitor level and function and C1q were normal in all patients tested. In these 11 patients, complete suppression of recurrences by the combination of cetirizine 20 mg daily and montelukast 10 mg daily was reported by 9 (82%) of patients; whereas 2 (18%) of patients had a partial response to this combination of medications. Conclusions Herein, we report a form of angioedema without urticaria, mediated by a combination of histamine and leukotrienes. Clinical, demographic and therapeutic characteristics differentiate this from other recognized causes of angioedema.

Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU.

Rationale: Angioedema without co-existent urticaria is due to a limited number of causes, including hereditary and acquired C1 esterase inhibitor deficiency, drug-induced angioedema or idiopathic histaminergic or non-histaminergic angioedema. We describe a cohort of patients with recurrent angioedema whose clinical features and response to medications are distinct from the causes above. Methods: Patients were accrued retrospectively from an academic allergy practice between 2007 and 2014. After institutional research ethics board approval, patients' charts were reviewed and demographic, clinical and laboratory data were extracted. Results: A total of 11 patients were recruited. The mean age at presentation was 54.9 years (range 19-70 years) and 6 of 11 were male. The mean number of episodes per year was 18.7 (range 2-60) and mean duration of episodes was 22.4 h (range 4-96). About half of episodes (52%) began overnight. Areas of involvement were lips (73%), tongue (64%), eyelids (18%), feet (36%) and hands (27%). None of the patients had low C3, C4, or CH50; none had significantly positive ANA; C1 esterase inhibitor level and function and C1q were normal in all patients tested. In these 11 patients, complete suppression of recurrences by the combination of cetirizine 20 mg daily and montelukast 10 mg daily was reported by 9 (82%) of patients; whereas 2 (18%) of patients had a partial response to this combination of medications. Conclusions: Herein, we report a form of angioedema without urticaria, mediated by a combination of histamine and leukotrienes. Clinical, demographic and therapeutic characteristics differentiate this from other recognized causes of angioedema. [ABSTRACT FROM AUTHOR]

Background: Cold urticaria is often resistant to first line treatment with second-generation H1-antihistamines. Case summary: We report a case of a fifty year-old woman with a history of cold urticaria showing no response to classic treatments, treated successfully with hydroxychloroquine initially prescribed to treat her frontal fibrosing alopecia. Conclusion: Hydroxychloroquine may be a successful treatment option for recalcitrant cold urticaria.

Coroners files and toxicological records of fatally-injured drivers in Victoria from 2000 to 2006 and from 2007 to 2013 were reviewed in separate studies to establish the role of prescribed drugs on crash risk. 2638 driver fatalities were included in the study, which represented over 97% of all driver fatalities in this period. The detection limits of the drugs were at the low end of those seen with common illicit drugs or prescribed drugs. Drugs of any type were found in 34.4% of the study group, medicinal drugs 21.2%, and alcohol (≥0.05 gram/100mL) was found in 24.8%. The prevalence of the most common drugs detected that are legally available by prescription were anti-depressants (7.9%), benzodiazepines (7.0%), opiates/opioids (6.6%), and sedating anti-histamines (1.1%). Each driver was assessed for responsibility using a previously published and validated method. The crash risk of drivers taking opioids, benzodiazepines, or anti-depressants (primarily the serotonin reuptake inhibitors), were not significantly over-represented compared to the drug-free control group, although there was a suggestion of increased crash risk for benzodiazepines. Crash risk was elevated for drivers using cannabis (by presence of THC in blood at>2ng/mL) and amphetamines. These data show that drivers using medicinal drugs alone are unlikely to show significant crash risk even if drugs are potentially impairing. [ABSTRACT FROM AUTHOR]

Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU. [ABSTRACT FROM AUTHOR]

Objectives: Tramadol is a centrally acting synthetic analgesic. It has a cardioprotective effect against myocardial ischemia-reperfusion (I/R) injury in isolated rat heart. We hypothesized that tramadol may exert a similar protective effect on hepatic I/R injury. Hence, the current investigation was designed to study the possible protective effects of tramadol on experimentally-induced hepatic I/R injury in rats. Materials and Methods: Tramadol was administered 30 min before ischemia following which the rats were subjected to 45 min of ischemia followed by 1 h of reperfusion. Results: Tramadol attenuated hepatic injury induced by I/R as evidenced by the reduction of transaminases, structural changes, and apoptotic cell death. It decreased the level of inflammatory markers such as tumor necrosis factor-alpha (TNF-α), TNF-α/interleukin-10 (IL-10) ratio, and nuclear factor-κB gene expression. It also increased the anti-inflammatory cytokine, IL-10 levels in hepatic tissues. Furthermore, it reduced oxidative stress parameters except manganese superoxide dismutase activity. Conclusion: The results suggest that tramadol has hepatoprotective effects against hepatic I/R injury via anti-inflammatory, antiapoptotic, and antioxidant effects. [ABSTRACT FROM AUTHOR]

Objective: Treatment of chronic urticaria (CU) can be difficult in many patients. Achieving long-term remission and reducing the requirement of antihistamines are vital in CU. The objective of this study was to assess the effectiveness of injection histaglobulin, a complex of histamine and human immunoglobulin, in producing relief in patients with CU. Materials and Methods: Fifty-one patients with CU were enrolled into this prospective clinical study. Patients were administered 1 ml of injection histaglobulin subcutaneous for 8 consecutive weeks. They were also prescribed tablet levocetirizine 5 mg to be taken when required (but not more than the permitted dosage). Efficacy was assessed using urticaria activity score (UAS) which has a maximum score of 33/day, during each weekly visit. Final assessment was done after 24 weeks. Results: Twenty-nine patients had completed the entire 8-week drug regimen. Mean basal UAS was 18.9 ± 6.3 and it reduced to 80.4% by 8 weeks. The angioedema sub-score reduced by 89.8%. Anti-histamine pill burden also reduced significantly. By 24 weeks of starting the therapy, 23 patients (45%) had attained complete remission. No adverse effects to the drug were observed. Conclusions: Histaglobulin was found to be effective in producing long-term remission and it reduced the antihistamine requirement as well. Thus, it can serve as an effective alternative to existing treatment modalities. [ABSTRACT FROM AUTHOR]

Background: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods: The Allergy Diary-MASK-air-mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. Conclusions: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year. [ABSTRACT FROM AUTHOR]

Non-sedating H1-antihistamines are the recommended first-line treatment for chronic spontaneous urticaria. While efficacy studies usually apply continuous daily treatment regimens, many patients take their medication on demand. In this randomized, double-blind trial we tested whether on-demand Ht-antihistamine desloratadine in standard and higher doses is able to improve the resolution of existing wheals. Symptoms of 29 patients with chronic spontaneous urticaria were followed without treatment on one day and again on another day during the next 3 weeks after a single dose of either 5 mg or 20 mg desloratadine, using different objective measures. While the intervention with both doses of desloratadine was effective in terms of a reduction in hyperthermic skin area, there was no improvement in wheal area and wheal volume compared with no treatment. Wheal numbers were reduced after treatment with 20 mg, but not 5 mg, desloratadine. In conclusion, the beneficial effects of non-sedating H1- antihistamines given on demand appear to be low. Thus, a preventive treatment strategy should be preferred in chronic spontaneous urticaria. [ABSTRACT FROM AUTHOR]

To evaluate the antihistaminic activity of Moringa oleifera (Moringaceae) to validate its traditional use, The antihistaminic activity of ethanolic seed extract of Moringa oleifera was evaluated on horse serum and triple antigen induced active anaphylaxis Wistar albino rats. Ethanolic seed extract (500 mg/kg body weight) significantly decreases histamine secretion and de-granulation of mast cells in rats (09.35±2.32). Phytochemical study revealed the presence of steroid saponins, alkaloids, flavonoid and glycoside. The glycoside saponin was reported to possess mast cell degranulation inhibiting and antihistaminic activity. [ABSTRACT FROM AUTHOR]

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Abstract: A cellular membrane affinity chromatography (CMAC) column has been created using cellular membrane fragments from a 1321N1 cell line stably transfected with the P2Y1 receptor. The CMAC(1321N1P2Y1) column contained functional P2Y1 and histamine 1 receptors, which independently bound receptor-specific ligands. The data obtained with the CMAC(1321N1P2Y1) column demonstrate that multiple-G-protein coupled receptor (GPCR) columns can be developed and used to probe interactions with the immobilized receptors and that endogenously expressed GPCRs can be used to create CMAC columns. The results also establish that the histamine 1 receptor can be immobilized with retention of ligand-specific binding. [Copyright &y& Elsevier]

A fixed drug eruption (FDE) is a cutaneous adverse drug reaction due to Type IV or delayed cell-mediated hypersensitivity. Antihistamines, which antagonize the action of histamine during an allergic reaction by blocking the H1 histamine receptors, are used routinely for the treatment of various allergic disorders such as urticaria, eczemas, and also in itchy lesions of skin like scabies.Levocetirizine, an active (R)-enantiomer of cetirizine, is a newer or second generation antihistamine, with more specific actions and fewer side effects, including cutaneous reactions. FDE due to levocetirizine as well as with cetirizine are rare. We report a case of levocetirizine induced FDE in a 49-year-old male patient with scabies. The patient had a history of cetirizine induced FDE in the past. [ABSTRACT FROM AUTHOR]

Patients with urticaria make up a large proportion of the referrals to allergy clinics. There are many causes of urticaria and it is the clinical history which is most important when attempting to identify potential causes; however, urticaria is very often idiopathic. In a small minority of patients urticaria may be a symptom of a serious underlying medical illness or the allergic symptoms may progress to cause systemic reactions, and it is important to identify these patients and to remember that severe urticaria is a distressing and disabling condition. This review will discuss classification, investigation and treatment of urticaria and will consider some of the more unusual types of urticaria that may be encountered in the out-patient clinic. [ABSTRACT FROM AUTHOR]

Background: Allergic reaction is characterized by a complex inflammatory process. Some of the new antihistamines have antiallergic effects and can affect the inflammatory cell recruitment via adhesion molecule downregulation. We aimed to assess in a 12‐month study whether continuous treatment with an antihistamine (terfenadine) can reduce respiratory symptoms and local inflammation in children with mite allergy. Methods: The study was double‐blind and placebo‐controlled: it involved two parallel groups of children suffering from rhinoconjunctivitis and/or mild intermittent asthma due to mite allergy. They received either terfenadine (1 mg/kg per body weight per day) or placebo for 1 year. Nasal, conjunctival, and bronchial symptoms were recorded by diary cards; at each of the programmed control visits, a nasal scraping for inflammatory cells and ICAM‐1 was performed. Some additional clinical parameters were also recorded: days of school absence, extra visits for acute respiratory symptoms, and days of hospital admission. Results: Only children treated with terfenadine achieved significant control of symptoms (P<0.05 in 8 out of 12 months) and allergic inflammation, as shown by inflammatory cell infiltrate and ICAM‐1 expression at nasal level (P<0.001), and had significantly fewer extra visits and school absences than the placebo group (P<0.03). No side‐effects were reported in either group. Conclusions: The present study demonstrates that continuous terfenadine treatment (1 mg/kg body weight per day) could decrease respiratory symptoms and allergic inflammation, and it had an additional antiallergic effect in reducing ICAM‐1 expression on nasal epithelial cells. Therefore, the present results confirm the efficacy of a long‐term therapeutic strategy in controlling allergic inflammation. [ABSTRACT FROM AUTHOR]