Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

Efficacy of a Non-Pharmacological Intervention in Seasonal Allergic Rhinitis Symptoms.

BACKGROUND: Patients suffering from allergic rhinitis seek for several therapeutic symptomatic options, including nonconventional treatments, to control their symptoms. OBJECTIVES: Through the present proof-of-concept study, we prospectively investigated the potential role of Puressentiel® nasal protection spray (SNPA) in patients suffering from cypress pollen allergic rhinitis. METHODS: In 15 adults, we performed two nasal provocation tests, with a cypress pollen extract, with a 15-day interval, with and without previous randomized administration of SNPA, and evaluated a nasal symptom score, the nasal inspiratory peak flow, and the concentration of inflammatory cytokines in the nasal lavage after the procedures. RESULTS: Comparing results in patients challenged with and without the SNPA spray before the nasal challenge, we found a 57% mean decrease in symptoms, and a 62% average difference in inspiratory peak flow, after the use of the spray. CONCLUSIONS: Puressentiel® SNPA is effective in reducing nasal symptoms, as assessed by nasal symptoms score and nasal inspiratory peak flow, and could be a valid natural non-pharmacological option in patients suffering from allergic rhinitis.

Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).

Optimization of the allergen classification of the International Classification Of Diseases, 11th Revision (ICD-11).

BACKGROUND: Accurate diagnosis of triggers or causative allergens is essential for appropriate risk assessment, providing correct advice to patients with allergy and their caregivers and personalized treatment. However, allergens have never been represented in the World Health Organization International Classification of Diseases (ICD). OBJECTIVE: In this article, we present the process of selection of allergens to better fit the ICD, 11th Revision (ICD-11) structure and the outcomes of this process. METHODS: The Logical Observation Identifiers Names and Codes database, containing 1444 allergens, was used as the basis for the selection process. Two independent experts were responsible for the first selection of the allergens according to specific technical criteria. The second step of the selection process was based on real-life relevance of the allergens according to the frequency of requests regarding each of them. RESULTS: We selected 1109 allergens (76.8%) from all 1444 present in the Logical Observation Identifiers Names and Codes database, with considerable agreement between experts (Cohen κ = 8.6). After assessment of real-life data, 297 additional relevant allergens worldwide were selected and grouped as plants (36.4%), drugs (32.6%), animal proteins (21%), mold and other microorganisms (1.5%), occupational allergens (0.4%), and miscellaneous allergens (0.5%). CONCLUSION: The stepwise approach allowed us to select the most relevant allergens in practice, which is the first step to building a classification of allergens for the WHO ICD-11. Aligned with the achievement in the construction of the pioneer section addressed to the allergic and hypersensitivity conditions in the ICD-11, the introduction of a classification for allergens can be considered timely and much needed in clinical practice.

Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS.

INTRODUCTION: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults. METHODS: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visit t. The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity. RESULTS: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association. CONCLUSION: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis. METHODS: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated. RESULTS: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions. CONCLUSIONS: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis. CLINICAL TRIAL REGISTRATION: NCT02250729.

Anaphylaxis in Brazil between 2011 and 2019.

BACKGROUND: There is a lack of population-based studies of anaphylaxis from low- and middle-income countries. This hampers public health planning and investments and may influence availability of adrenaline auto-injectors. OBJECTIVE: We conducted the first national population-based study of anaphylaxis hospitalization in Brazil. METHODS: Descriptive study using routinely reported data to the Brazilian Hospital Information System for the years 2011-2019. Information available is coded based on the International Classification of Diseases (ICD)-10 and covers main cause of hospitalization (primary cause) and any conditions contributing to it (secondary cause). RESULTS: Over 9 years, we identified 5716 admissions due to anaphylaxis for all causes. The average hospitalization rate related to anaphylaxis was 0.71/100,000 population per year, with a 2.4% (95% CI 1.9%, 2.9%) increase per annum over the study period. Admissions were more frequent among females (52.8%), except for cases due to insect sting. Most admissions occurred in adulthood, from 30 to 59 years (36.3%) but 13.8% in preschool children (0-4 years). There were more young children admitted for food-related anaphylaxis, and more adults admitted for drug/iatrogenic-related anaphylaxis. There were 334 cases (5.8% of admissions) of fatal anaphylaxis over the study period, with increased case fatality rate over time. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first study of anaphylaxis hospital admissions using nation-wide data from a low- or middle-income country. Hospital admissions and fatalities from anaphylaxis in Brazil appear to be increasing.

Diagnostic performance of serial serum total tryptase measurement to differentiate positive from negative allergy testing among patients with suspected perioperative hypersensitivity.

BACKGROUND: Serum total tryptase has been shown to increase during acute allergic reactions (acute tryptase, TA ); however, few studies have investigated the values of TA or a combination of TA and baseline tryptase (TB ) to discriminate positive from negative testing in perioperative hypersensitivity reaction (POH) allergy work-up. The aim of this study was to determine the diagnostic performance of TA in order to differentiate positive from negative allergy testing suspected POH and analyse the diagnostic performance of serial tryptase levels using several formulas. METHODS: All patients from the University hospital of Montpellier and Strasbourg, France, who presented with suspected POH and underwent complete drug allergy work-up between March 2011 and December 2019 with available TA and TB were included. Four formulas, including a change in TA  > 11 (F1), or >2 + 1.2 × TB (F2), or >3 + TB (F3), or >120%TB (F4), were applied. RESULTS: One hundred and sixty-two patients were included, and 131 of them (80.8%) had Grade III or IV reactions. Ninety patients had positive allergy testing. The optimal cut-off value of TA to distinguish positive from negative allergy testing patients was 9.8 µg/L with an AUC of 0.817 (95% CI: 0.752-0.882, p < .001). The 93% PPV threshold for TA was 33 µg/L (95.8% specificity). Paired tryptase levels according to formulas F2 and F3 yielded the highest Youden index (0.54 and 0.53, respectively). CONCLUSION: The optimal cut-off point for TA for distinguishing positive from negative allergy testing suspected POH was 9.8 µg/L. TA value of 33 µg/L was required to achieve >90% PPV.

Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. OBJECTIVE: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study. METHODS: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. RESULTS: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. CONCLUSIONS & CLINICAL RELEVANCE: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.

Allergic and hypersensitivity conditions in non-specialist care: Flow diagrams to support clinical practice.

Most patients presenting with allergies are first seen by primary care health professionals. The perceived knowledge gaps and educational needs were recently assessed in response to which the LOGOGRAM Task Force was established with the remit of constructing pragmatic flow diagrams for common allergic conditions in line with an earlier EAACI proposal to develop simplified pathways for the diagnosis and management of allergic diseases in primary care. To address the lack of accessible and pragmatic guidance, we designed flow diagrams for five major clinical allergy conditions: asthma, anaphylaxis, food allergy, drug allergy, and urticaria. Existing established allergy guidelines were collected and iteratively distilled to produce five pragmatic and accessible tools to aid diagnosis and management of these common allergic problems. Ultimately, they should now be validated prospectively in primary care settings.

Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy.

Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

Food allergy in the World Health Organization's International Classification of Diseases (ICD)-11.

There are increasing global data regarding the prevalence of food allergy and food-induced anaphylaxis. However, knowledge in morbidity and mortality epidemiological data is still not optimal, and international comparable standards remain poorly accessed. This information could in turn support better clinical practice and possibly prevent future severe reactions and avoidable fatalities. The International Classification of Diseases (ICD) is the standard diagnostic tool used for epidemiology, health management, and clinical purposes supported by the World Health Organization (WHO). It is also used to determine health care payment and reimbursement of providers and health care services in hospitals. Thanks to the academic and technical efforts under the ALLERGY in ICD-11 initiative the pioneer "Allergy and hypersensitivity conditions" section has been built under the "Disorders of the Immune System" chapter of the ICD-11. The "Food hypersensitivity" (FH) subsection is classified under the "Complex allergic or hypersensitivity conditions" section and "Food-induced anaphylaxis" is under the "Anaphylaxis" section. In order to inform the development of strategies to reduce preventable FHs/food allergies, the burden of disease in different healthcare settings and patient populations and their common etiologies need to be understood. Besides, greater specificity regarding clinical conditions and services delivered will provide payers, policy makers, and providers with better information to make major refinements to countries payment and reimbursement systems, including the design and implementation of pay-for-performance program.The new classification addressed to FHs will enable the collection of more accurate epidemiological data to support quality management of patients with FHs/food allergies, and better facilitate health care planning and decision-making and public health measures to prevent and reduce their morbidity and mortality. The improved logic and standardized definitions through the ICD-11 (and other WHO classifications) will also facilitate international comparisons of quality care and the sharing of best practice globally.

Allergy in the World Health Organization's International Classification of Diseases (ICD)-11.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes, and health management. The change in the hierarchy in ICD-11 permitted the construction of the pioneer section addressed to allergic and hypersensitivity conditions (A/H), which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology, and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. The Montpellier World Health Organization (WHO) Collaborating Centre on Classification Scientific Support was designated in 2018 and is responsible for supporting the WHO through representing A/H in the international classifications and quality care of patients from the public health perspective.

A review of allergen immunotherapy in asthma.

Asthma is one of the most common chronic diseases worldwide. Besides symptomatic treatments, allergen immunotherapy (AIT) is a possible add-on treatment for asthmatic patients. In case of an immunologically proven allergen-driven mechanism of asthma, AIT represents the only etiologic treatment for allergic symptoms. AIT has proven both its efficacy and effectiveness in reducing asthma symptoms and asthma medications. It is still debated whether its prescription in severe asthmatic patients is allowed and safe. As for uncontrolled asthma, such a condition should be considered temporary, and AIT may be started as asthma becomes at least partially controlled after treatment adjustment. Finally, randomized trials and real-life studies in recent years have proven that AIT could be administered as a preventive strategy to reduce the risk of developing asthma in patients suffering from allergic rhinitis. More studies are needed to provide more precise indications on the role in clinical practice of AIT in asthmatic patients. Nevertheless, present data are already strong enough to highlight its role as a therapeutic option for allergic asthma and as a preventive strategy to stop or at least decelerate the allergic march.

Integrating the evidence in allergen immunotherapy: Why real-world data should be important for the practicing clinician?

Data obtained from controlled clinical trials are the gold standard for evaluation of allergen immunotherapy (AIT) efficacy and safety. Less prone to biases (with a strong internal validity), they allow their use and external validation in the real world. The quantity and diversity of real-world data has increased exponentially, and access to large cohorts and electronic medical records have made this information increasingly accessible and useful for research and regulatory purposes. New retrospective database studies have confirmed the sustained benefits of grass, birch pollen, and house dust mite AIT for both allergic rhinitis and asthma symptom and medication scores, the prevention of asthma (when used in nonasthmatic rhinitics), and the real rate of adverse systemic reactions. They also have addressed clinical practice issues not elsewhere analyzed, including the management of polysensitized patients with respiratory allergies and adherence to AIT. Real-world evidence has its own biases and limits that need to be taken into account. In this article we present a concise summary of the literature about the role of real-world evidence in AIT.

A 300 IR sublingual tablet is an effective, safe treatment for house dust mite-induced allergic rhinitis: An international, double-blind, placebo-controlled, randomized phase III clinical trial.

BACKGROUND: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies. OBJECTIVE: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged ≥12) and adults with moderate to severe HDM-induced allergic rhinitis. METHODS: In a phase III, international, double-blind, placebo-controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300 IR tablet. The primary end point was the average total combined score during 4 weeks at the end of the treatment period. RESULTS: A total of 1607 participants were randomized, and 1476 (including 555 [37.6%] with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean average total combined score in the 300 IR group (3.62) was significantly lower (P < .0001) than in the placebo group (4.35), with a relative least squares mean difference of -16.9% (95% CI, -24.0% to -9.2%). All prespecified secondary end points were consistently improved in the 300 IR group, relative to placebo. The 300 IR tablet was generally well tolerated. Treatment-related adverse events (mainly mild or moderate local reactions) were reported for 51.0% of the patients in the 300 IR group and 14.9% in the placebo group. CONCLUSIONS: The 300 IR sublingual HDM tablet is an effective, safe treatment for HDM-induced allergic rhinitis.

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

BACKGROUND: ß-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE. OBJECTIVE: We sought to identify genetic predisposing factors for immediate reactions to ß-lactam antibiotics. METHODS: Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. RESULTS: Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10-14); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10-7) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10-7). Haplotype analysis identified that HLA-DRB1∗10:01 was a risk factor even without the HLA-DQA1∗01:05 allele. The association with HLA-DRB1∗10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1∗10:01 increased the risk of immediate hypersensitivity at a genome-wide level (odds ratio, 2.96; P = 4.1 × 10-9). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to ß-lactams. CONCLUSIONS: HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.

Skin necrosis following local anesthetic: Same presentation for two different diagnoses.

BACKGROUND: Local anesthetics (LA) are widely used in medicine and are generally well tolerated. Although most adverse reactions are nonallergic, LA are a frequent reason for allergy consultation. OBJECTIVE: We want to expand the differential diagnosis of adverse reactions to LA by presenting rare diagnoses. METHODS: We present here two patients with similar clinical presentations, namely skin necrosis after local anesthesia with lidocaine, but with two different final diagnoses. RESULTS: For Patient 1, skin necrosis was imputed to the vasoconstrictor effect of epinephrine in a patient with vascular background aggravated by heavy consumption of tobacco and cannabis. Patient 2 final diagnosis was Nicolau syndrome (embolia cutis medicamentosa), a cutaneous necrosis at the site of injection. CONCLUSIONS: The allergist should be aware of these diagnoses and include them in the differential diagnosis of local anesthetic hypersensitivity.