H1-antihistamines for primary mast cell activation syndromes: a systematic review

Background Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release. Objectives To assess the effectiveness and safety of orally administered H1-antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments. Methods We systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials. Results A total of 36 potentially relevant studies were identified. Of these, five crossover trials, enrolling a total of 71 patients (63 adults), met the eligibility criteria. All five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H1-antihistamine with placebo, two compared two different H1-antihistamines, and one study compared H1- and H2-antihistamines with oral cromolyn sodium. Four of the five randomized controlled trials were historic (reported from 1983–1993), small (enrolling 8–15 patients), and used agents and/or dosing regimens that are now less commonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine, and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found 4 weeks of treatment with the second-generation H1-antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation to elicit Darier's sign. Conclusions There is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness, and safety of second-generation H1-antihistamines in treatment of primary MCAS

Allergen immunotherapy for IgE-mediated food allergy : a systematic review and meta-analysis

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.Peer reviewe

Monitoring of coronavirus infection in the kyrgyz population

Purpose of the study: to study the dynamics of developing herd immunity against SARS-CoV-2 in the population of the Republic of Kyrgyzstan during COVID-19. Materials and methods. The work was carried out using the methodology for assessing population immunity developed by Rospotrebnadzor (Russia) as well as the Ministry of Health (Kypgyzstan) and the St. Petersburg Pasteur Institute. The selection of participants was carried out by questionnaire using a cloud (Internet server) service. To monitor population immunity, a cohort of 2421 subjects was formed, who participated in all stages of seromonitoring. Volunteers were randomized according to age groups (1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70+ years), regional and professional factors. Antibodies (Abs) against SARS-CoV-2 nucleocapsid (Nc) and the receptor binding domain (RBD) of S-glycoprotein were determined by qualitative and quantitative methods. The study was carried out in 3 stages according to a single scheme: 1st stage — 06/28–07/03/2021, 2nd — 21–25/02/2022 and 3rd — 31/10–04/11/2022. Since 2021, Kyrgyzstan has been vaccinating the population against SARS-CoV-2 mainly using inactivated whole-virion vaccines. Results. Population immunity against SARS-CoV-2 was predominantly accounted for by both Ab types (Nc+RBD+). By the 3rd stage, the percentage of such persons reached 99.2%, Nc–RBD– volunteers — up to 0.8%. At the 1st stage, middle-aged people dominated, but age differences were leveled out by the 2nd stage. The greatest impact on seroprevalence was found among medical workers, the smallest — among businessmen and industrial workers. Populational vaccination significantly impacted on the state of herd immunity that reached 25% by the 3rd stage. The refusals of the population in Kyrgyz Republic from vaccination noted at the 2nd and especially 3rd stages did not significantly affect level of herd immunity, which could probably be associated with asymptomatic cases of COVID-19, against which primary vaccination had a booster effect. Conclusion. The dynamics of population humoral immunity against SARS-CoV-2 included a number of changes in the level of circulating antibodies (Nc, RBD), caused by both primary infection and vaccination. The herd immunity formed in population of Kyrgyzstan allowed to reduce the incidence of COVID-19 to almost sporadic level

WAO consensus on definition of food allergy severity (DEFASE)

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice

Managing food allergy: GA2LEN guideline 2022

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy

WAO consensus on DEfinition of Food Allergy SEverity (DEFASE).

BACKGROUND: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. AIM: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. METHODS PHASE 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. PHASE 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. RESULTS: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. CONCLUSIONS: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice