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Direct drug provocation test (DPT) without prior skin testing (ST) has been investigated in children suspected of being at risk for beta-lactam hypersensitivity reaction (BL-HSR). However, no systematic review and meta-analysis has investigated the efficacy and safety of direct DPT for BL-HSR in children.To investigate the prevalence of BL-HSR by direct DPT, and the safety of direct DPT in children.We searched MEDLINE, EMBASE, Web of Science, and CINAHL from their inception to 23 July 2022 for studies that performed direct DPT in children with suspected BL-HSR, or for studies that performed DPT in all cases with ST results, but they ignored the ST results. The true prevalence was defined as the proportion of children who experienced a HSR during direct DPT. Safety was determined according to the proportion of children who developed a dangerous reaction following DPT.Twenty-eight studies with 8,334 direct challenges were included. Fifteen studies included patients presented with either immediate or non-immediate HSR, and majority of the index reactions were non-severe. Amoxicillin/amoxicillin-clavulanic acid were the most commonly used during the DPT. The pooled prevalence of confirmed BL-HSR was 5.23% (95%CI: 4.17-6.39, IThe prevalence of BL-HSR by direct DPT was 5.23%, and the frequency of severe reactions from direct DPT was very low (0.036%). Our findings support direct DPT as a safe and effective delabeling tool in children with suspected non-severe BL-HSR.

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.We want to expand the differential diagnosis of adverse reactions to LA by presenting rare diagnoses.We present here two patients with similar clinical presentations, namely skin necrosis after local anesthesia with lidocaine, but with two different final diagnoses.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.The allergist should be aware of these diagnoses and include them in the differential diagnosis of local anesthetic hypersensitivity.

International audience

International audience; 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.

Purpose of the review Premedication using antihistamines and/or corticosteroids has been widely used to prevent reoccurrence of immediate hypersensitivity reactions (iHR) after iodinated contrast media (ICM). However, efficacy has been debated, especially in high-risk patients. Novel findings on the role and risks of premedication and preventive strategies are summarized. Recent findings The rate and severity of iHR occurring despite premedication indicate that premedication is not a panacea and the intensity usually reflects that of the initial reaction. Next, the number needed to treat (NNT) to prevent one serious ICM-mediated event using corticosteroid-based premedication is high and associated with a diagnostic delay. Randomly changing the ICM has been suggested as an additional preventive measure, whilst others used a skin test–based approach to identify a subgroup of ICM allergic patients and negative skin test–based alternatives with a high negative predictive value. Summary Growing evidence indicates the need to discriminate between non-allergic iHR that are most likely non-obligatory and susceptible to premedication, and rare type I allergic iHR that can be identified using skin testing, especially in those with a severe iHR. Although premedication reduces reoccurrence of mild iHR, it is not always efficacious and should be balanced against side effects, a high NNT and an uncertain efficacy physicians should not blindly rely on. Future work should evaluate combined approaches of an allergy-driven ICM selection and endotype-driven premedication regimens in patients with non-allergic iHR.

International audience; Background: Cephalosporins, which belong to the beta-lactam therapeutic class, are increasingly used throughout the world. Few large studies on this issue have been conducted, and most of them have been performed as part of penicillin hypersensitivity studies.Objective: We described our 26-year experience exploring cephalosporin drug hypersensitivity, from which we identified epidemiological and cross-reactivity data.Methods: We included 476 patients who reported drug hypersensitivity reaction (DHR) to cephalosporin and underwent an allergy workup between January 1992 and July 2018 in the Allergy Unit of the University Hospital of Montpellier (France). According to their structural side chain R1 homology, we worked with 4 classes of cephalosporins. Logistic regression analysis was used to search for risk factors for hypersensitivity to cephalosporin (positive skin test [ST] or drug provocation test [DPT] results).Results: Cephalosporin hypersensitivity was proven in 22.3% of the patients referred in our Unit, according to positive ST (51.9%) or DPT to the culprit drug (48.1%). One in 5 patients were children, and cephalosporin hypersensitivity was confirmed in 15% (47.6% of them by means of ST). In the cephalosporin hypersensitive population, initial reactions were mostly immediate (68.9%) and anaphylactic (72.7%). Cross-reactivity with aminopenicillins was the most frequent pattern of cross-reactivity. In multivariate analysis, immediate reactions (odds ratio [OR] = 3, 95% confidence interval [CI] [1.6-5.5], P < .001), anaphylactic shock (OR = 6.5, 95% CI [3.3-13.1], P < .001) and anaphylaxis (OR = 3.1, 95% CI [1.6-6.1], P < .001), and multiple reactions to the same or several cephalosporins (OR = 2.0, 95% CI [1-3.5], P = .04) were statistically associated with confirmed DHR. DPT was generally safe, but elicited anaphylaxis in 20% of patients. Systemic reactions during skin testing occurred in 9.1% of positive patients, almost always related to anaphylactic index reactions. Nonimmediate confirmed DHR to cephalosporins were rare and occurred in less than 10% of the positive patients.Conclusion: Almost a quarter of the tested patients were confirmed as hypersensitive to cephalosporins; sensitivity of skin testing was 51.9%, and thus, half of the positive patients needed a DPT to prove the diagnosis.

International audience; Background: β-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 β-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 β-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.

International audience

In medicine, blue dyes are widely used for lymphatic mapping and biopsy of sentinel lymph nodes in patients with malignant tumors. Three dyes are used for this purpose, namely patent blue, isosulfan blue and methylene blue. They are also used to stain tissues for chromoendoscopy. Reports of anaphylactic reactions to blue dyes are increasing. The allergological work-up is based mainly on history. In the case of perioperative anaphylaxis, it relies on a thouroughly review of the perioperative record. The incorrect identification of the blue dye in the peroperative record will lead to an incorrect diagnosis which could cause serious consequences for patients in case of re-exposure. We describe here two cases of patients who presented peroperative anaphylactic shocks. Both of them had the wrong dye identified in their perioperative record., Les colorants bleus sont utilisés en médecine et en chirurgie de longue date. Injectés dans les tissus, ils sont dirigés vers le système lymphatique, ce qui permet l’identification directe des ganglions sentinelles lors de chirurgies oncologiques, dans le cadre d’un cancer du sein ou d’un mélanome. Trois d’entre eux sont utilisés à cette fin, soit le bleu patenté, le bleu isosulfan et le bleu de méthylène. Ils sont également utilisés pour marquer les tissus en hromoendoscopie de fac ̧ on à repérer les fistules et lâchages de sutures. Comptetenu de l’utilisation croissante des colorants bleus pour la cartographie lymphatique, l’incidence des réactions d’hypersensibilités (HS) immédiates à ces médicaments tend elle aussi à augmenter. Les réactions d’HS immédiates aux colorants bleus ont plusieurs particularités. Les investigations allergologiques reposent principalement sur l’histoire de la réaction. Le dossier chirurgical et anesthésique se doit donc d’être complet et bien documenté, afin de bien orienter les investigations allergologiques à entreprendre. Un dossier mal documenté, comprenant des informations inexactes, pourraient compromettre les investigations et le diagnostic allergologiques, et entraîner des conséquences néfastes pour les patients. Nous décrivons ici le cas de deux patientes ayant présenté des chocs anaphylactiques peropératoires et dont le colorant bleu utilisé avait été mal documenté au dossier.

International audience; No abstract available

Immediate and non-immediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5-3% of patients receiving non-ionic ICM. The diagnosis and management of these patients varies among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and non-immediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Reexposition or drug provocation test should only be done with skin test-negative ICMs.The decision for performing either reexposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

International audience

International audience; Allergic rhinitis, when not related to proteic allergens, is difficult to diagnose. We report a case in which no association with a high-molecular-weight allergen was identified.

International audience; BACKGROUND: The management of iodinated contrast medium (ICM) hypersensitivity has been a matter of debate. Skin testing to identify a subgroup of ICM allergic patients has been proposed, in addition to complete avoidance, provocation testing, or premedication. OBJECTIVE: The objective of this study was to assess the negative predictive value (NPV) of skin testing for ICM. METHODS: Patients with a hypersensitivity reaction to ICM who underwent skin testing during a 13.5-year period at a single center were evaluated for re-exposure to a negatively skin-tested ICM. Premedication, consisting of second-generation H1-antihistamines twice a day 48 hours before the examination, was advised only for patients with mast cell disorder or chronic urticaria who had negative skin tests. RESULTS: A total of 597 patients tested for 423 (70.9%) immediate, 118 (19.7%) nonimmediate, and 56 (9.4%) hypersensitivity reactions with undetermined chronology were included. Eighty (13.4%) patients were skin test positive. Re-exposure to ICM occurred in 233 (39.0%) patients and was tolerated in 16 of 17 (94.1%) with at least 1 positive skin test and 201 of 216 (93.1%) with all negative skin tests. Reaction intensity was similar in 4, milder in 10, unknown in 1, and worse in 1 patient although this reaction was deemed to be nonallergic in hindsight. Premedication was administered in 20.7% of patients and associated with more reactions (19.4% vs 5.7%, P~= .01). The overall NPV of skin testing for ICM was 93.1% (95% confidence interval [CI] 89.1% to 96.0%), and for immediate and nonimmediate hypersensitivity reactions 94.2% (95% CI 89.6% to 97.2%) and 86.1% (95% CI 72.1% to 94.7%), respectively. We cannot exclude some challenges occurred with a different than the initial culprit ICM, possibly overestimating the NPV. CONCLUSIONS: Skin testing for potential ICM hypersensitivity can identify safe alternative(s) for ICM re-exposure especially in patients with an immediate hypersensitivity reaction and/or skin test-proven ICM drug allergy. Reactions on re-exposure were infrequent, mostly milder, and occurred in some patients despite premedication.

Introduction Des profils de reactivite croisee connus et frequents sous-tendent la majorite des positivites observees en tests cutanes (TC) aux betalactamines (BL) mais ne permettent pas d’expliquer, seuls, l’ensemble des observations. Methodes Nous presentons le cas d’une patiente de 59 ans rapportant 6 reactions suite a des prises ou contacts avec l’amoxicilline : un choc anaphylactique en 2015 traite par adrenaline et 3 episodes avec urticaire. Cinq ans apres, elle a presente une anaphylaxie grade II lors d’un repas au cours duquel un convive etait traite par penicilline. Idem lors d’un autre repas ou son mari etait traite par penicilline. Resultats Le bilan allergologique retrouve des dosages d’IgE specifiques (ImmunoCAP Phadia) vis-a-vis de l’amoxicilline positifs a 4,11 kUA/l ; de la penicilline V a 0,36 kUA/l et de la penicilline G a 0,14 kUA/l. Les TC realises (concentrations recommandees) sont positifs pour l’amoxicilline/acide clavulanique et l’ampicilline en prick-test a 1/100e; pour la penicilline G et le cefuroxime en intradermoreaction (IDR) 1/10e ; pour la ceftriaxone en IDR 1/100e et enfin pour l’aztreonam en IDR pure. Les autres cephalosporines (cefpodoxime, cefotaxime, cefazoline, cefoxitine, ceftazidime) et l’imipeneme sont negatifs. Le test de reintroduction a la cefazoline est negatif. La tryptasemie basale est a 3,2 kUA/L. Discussion Ce cas suscite 2 interrogations. D’abord, sur un profil atypique et etendu de positivites en TC aux betalactamines incluant des penicillines, des cephalosporines et l’aztreonam, l’ensemble des positivites peut etre interprete comme des reactivites croisees (via un epitope inconnu), une co-sensibilisation ou une allergie multiple aux beta-lactamines (peu probable la patiente ne declare pas de prise de cephalosporines ou aztreonam). Le cas pose aussi le probleme de la dangerosite des beta-lactamines pouvant donner des reactions anaphylactiques par contact. Notre patiente a ete munie dans ce contexte d’une trousse d’urgence avec adrenaline. Conclusion Bien que ce genre de profil soit exceptionnel, il nous rappelle que proposer une alternative (en dehors d’un bilan allergologique) chez un patient allergique a une penicilline peut s’averer perilleux.

Introduction Jusqu’a ce jour, la declaration des suspicions d’allergies medicamenteuses (AM) se fait de facon manuelle avec pour support une carte papier ou dans des logiciels propres a chaque hopital. Ces outils restent tres peu optimaux. D’autres supports sont possibles et utilises (bracelets, colliers), mais en 2016 les experts du groupe ENDA de l’EAACI estimaient que la carte d’allergie papier restait la plus adaptee. L’unite d’allergologie du CHU de Montpellier a developpe avec ses partenaires une carte numerique d’allergie (CNA) basee sur la structuration des donnees relatives aux AM et l’utilisation d’une technologie blockchain a permission. Methodes Objectif : evaluer l’acceptabilite/la facilite d’usage de la CNA. Des entretiens semi-directifs ont ete menes pour recueillir les perceptions de la facilite d’usage, de l’utilite et de l’acceptabilite et des freins potentiels de l’utilisation de la CNA. Ces entretiens, portant sur des maquettes interactives, ont permis l’amelioration de la CNA et la conception du prototype. Resultats Onze patients et cinq medecins ont ete interviewes. La majorite des patients (80 %) disaient ne pas utiliser les applications en sante, par meconnaissance des applications disponibles, par resistance face aux technologies de l’information ou par preference d’un contact direct avec le medecin. En revanche, la plupart des medecins en utilisaient et la totalite utilisait les logiciels metier. Quatre-vingt trois pour cent des patients etaient prets a utiliser une application pour la tracabilite de leurs suspicions d’AM et 100 % etaient d’accord que l’accessibilite sur tout type de supports a tout moment etait un avantage. Si le processus d’identification etait indique comme laborieux par 80 % des patients, trois quarts estimaient que le contenu de la carte etait clair. Les freins exprimes (par patients et medecins) etaient lies principalement a la confidentialite des donnees et la longueur de l’etape d’identification. Discussion Une CNA represente une alternative attractive a la documentation actuelle en AM. Conclusion Des evaluations du prototype sont prevues, de meme que l’extension a toutes les vigilances, notamment allergiques.

Resume La prise en charge des reactions anaphylactiques perioperatoires repond a des recommandations specifiques elaborees sous l’egide de la SFAR et de la SFA et revisees en 2011. En France, l’incidence des reactions anaphylactiques d’origine allergique est estimee a 100,6 [76,2–125,3]/million d’anesthesies dans la population generale. Chez l’adulte, les substances les plus frequemment incriminees sont les curares, suivis des antibiotiques et des colorants. Les reactions au latex sont en nette regression. La majorite des reactions apparait dans les minutes suivant l’injection intraveineuse des produits. Lorsque la symptomatologie est d’apparition plus tardive, au cours de la periode d’entretien de l’anesthesie, une allergie au latex, a un colorant, un antiseptique ou aux produits de remplissage doit etre evoquee. L’expression clinique d’une reaction anaphylactique est de gravite variable. Les signes cliniques initiaux les plus frequemment rapportes sont l’absence de pouls, un erytheme, une difficulte de ventilation, une desaturation ou une baisse de la pression tele-expiratoire de CO2. Les signes cutanes peuvent parfois etre absents. Le diagnostic du mecanisme de la reaction repose sur le dosage des mediateurs (tryptase, histamine), au moment de la reaction. En cas d’allergie, l’identification de l’agent responsable se fait par la mise en evidence d’IgE specifiques au moment de la reaction ou a distance et sur la realisation de tests cutanes 6 semaines apres la reaction. Le traitement repose sur l’interruption de l’administration de l’allergene lorsqu’elle est possible, sur la prescription d’adrenaline a dose titree en fonction de la gravite clinique et de la reponse au traitement et sur le remplissage vasculaire.

Resume L’allergie aux curares est une complication souvent grave survenant en cours d’anesthesie. C’est le plus souvent une reaction immunologique IgE mediee. Tous les curares peuvent induire des reactions anaphylactiques. Le rocuronium et le suxamethonium induisent plus frequemment des reactions anaphylactiques que les autres curares. L’allergie aux curares est imprevisible en dehors d’antecedent de reaction grave inexpliquee survenue lors d’anesthesie anterieure. Le plus souvent le patient fera le choc anaphylactique sans avoir recu un curare au prealable. Ceci suggere une sensibilisation croisee avec d’autres molecules contenant l’epitope des curares l’ion ammonium quaternaire. Differents modes de sensibilisation sont actuellement en cours d’investigation. La pholcodine principe actif de sirops antitussifs pourrait etre un mode important de sensibilisation. L’antidote du rocuronium pourrait avoir un effet benefique sur les reactions anaphylactiques induites par le rocuronium. Cependant, elle a deja induit des reactions anaphylactiques. En cas de survenue d’un choc anaphylactique, un bilan de la reaction et la recherche d’allergie croisee sont necessaires determiner un curare utilisable pour les anesthesies ulterieures.

Prevalence of both asthma and food allergy is increasing in Western Europe (1,2). In France, according to recent surveys, the prevalence of asthma is 9.4% in children and 7% in adults (3). Food allergy proven by oral food challenges (OFC) affects between 1 to 10% of the population (4). Studies have been considering both disorders as comorbidities under the atopic disease concept. Asthmatic children with food allergy have an increased risk for asthma exacerbation and severe asthma, especially when developing anaphylactic reactions (1,5). Each part of the respiratory system (the nose, the larynx, and the lungs) may be involved in food-induced allergic reactions, especially in IgE-mediated allergic reactions, and food allergies play a role in the pathogenesis of respiratory tract symptoms (6). This article is protected by copyright. All rights reserved.

Introduction Les reactions d’hypersensibilite (HS) les plus frequentes aux quinolones sont immediates, et le test de provocation (TP) est incontournable (controverses liees aux tests cutanes (TC) et tests in vitro). Methodes Objectifs : Construire un protocole de TP base sur les preuves ; decrire la population exploree pour des suspicions d’HS aux quinolones. Nous avons analyse les patients explores dans deux unites d’Allergologie, au CHU de Montpellier (2004-2019) et au CHR de Metz (2015–2019). Les patients avaient ete testes par TC et TP. Les TP positifs ont ete analyses par une courbe de Kaplan–Meier pour trouver la dose reactogene (DR), exprimee comme pourcentage entre la dose declenchante de la reaction et la dose totale prevue en TP (dose therapeutique journaliere). Resultats Cent cinquante-neuf patients ont ete analyses. Trois quarts etaient des femmes. Les quinolones les plus frequemment impliquees etaient : ofloxacine (31,4 %), ciprofloxacine (26,4 %) et levofloxacine (18,9 %). La plupart des reactions initiales etaient urticariennes (40,5 %) ou anaphylactiques (20 %). Le diagnostic d’HS a ete porte chez 40 patients (25,1 %), dont 9 par TC et 31 par TP. Quarante TP etaient positifs. Plusieurs predicteurs etaient associes independamment a une HS confirmee : une histoire clinique immediate (OR = 3,1, IC95 % : 1,0–9,7), anaphylactique (OR = 8,3, IC95 % : 1,7-38,9), a la moxifloxacine (OR = 13,5, IC95 % : 2,8–63,9). Parmi les reactions declenchees lors des TP, 20 % etaient anaphylactiques, la premiere a DR = 0,1 %. Discussion Selon la distribution des reactions en TP, nous avons retenu plusieurs DR de nombreuses reactions (autour de DR = 1 %, DR = 20 %, DR = 50 %, DR = 100 % d’une dose therapeutique journaliere). En tenant compte aussi de la distribution des reactions severes en TP, nous proposons un TP du type : 5 %-10 %-15 %-20 %-50 %, precede par 0,1 et 0,5 % en cas d’histoire d’anaphylaxie. Conclusion Nous avons confirme l’HS aux quinolones dans un quart des cas ayant des suspicions cliniques et avons propose, en fonction des profils de reaction en TP (dose, severite), un TP base sur les preuves.

International audience; No abstract available

International audience; Multiple drug hypersensitivity syndrome (MDHS) is defined as confirmed drug hypersensitivity (DH) to at least 2 chemically and pharmacologically unrelated drugs. Reports of MDHS are scarce and poorly specified, and studies that diagnose MDHS on the basis of positive allergy test results are lacking.Objective: To evaluate retrospectively the frequency and characteristics of patients with MDHS in a large database.Methods: We included all patients who consulted and were tested in our Allergy Unit between September 1996 and February 2018 for a suspicion of DH. Clinical history and allergy workup results compiled in our Drug Allergy and Hypersensitivity Database were reviewed, and data of patients with a diagnosis of MDHS were retrieved and analyzed.Results: During this period a total of 9250 patients were explored and 1819 tested positive for at least 1 drug. Forty-five cases, 30 female and 15 male patients cumulating 92 DHs, were confirmed as having MDHS. An immunologic mechanism, as demonstrated by positive skin testing, accounted for 59 DHs. Drug provocation tests were performed to confirm the diagnosis for the remaining 33 DHs. Of the 92 DHs in this series, 38 were classified as type IV and 21 as type I allergies; 33 remained of undetermined mechanism. Drug class occurrences seem to differ from those in monoallergic patients.Conclusions: Our data support the concept of MDHS as a distinct and rare subgroup of DH. The prevalence in our database was 2.5% in the total DH alleged patient population and 0.5% of the demonstrated DHs. Skin testing and drug provocation tests are mandatory for confirming the diagnosis.

International audience; No abstract available

International audience; A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta-lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost-effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross-reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, as well as diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (i.e., occurring within 1 to 6 hours after the last administered dose) or nonimmediate (i.e., occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low-risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus.

International audience

International audience; INTRODUCTION:Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is of great concern because they are frequently encountered in daily clinical practice. Drug provocation tests (DPTs) are particularly needed for NSAIDs.METHODS:The aim of this retrospective study was to detect eliciting dose thresholds during NSAIDs DPT in order to suggest optimal step doses, using the survival analysis method. Our secondary objective was to describe subgroups at higher risk during DPT and evaluate the safety of our 30 minutes incremental 1-day protocol. The study comprised all the patients attended the Allergy of the University Hospital of Montpellier (France), between 1997 and 2017 for a suspicion of drug hypersensitivity reaction to NSAIDs.RESULTS:Throughout the study period, 311 positive DPT were analyzed (accounting for 285 hypersensitive patients). We identified eliciting thresholds (dose and time), and we suggest the following steps for future DPT: for the rapid absorption group (acetylsalicylic acid, ibuprofen, ketoprofen, and tiaprofenic acid), every 30 minutes: 20%-30%-50% of daily therapeutic dose, for the moderate absorption group, every 30 minutes: for diclofenac 5%-15%-30%-50%, and for celecoxib, 20%-80%. For the slow absorption group, piroxicam, 25%-75%, was separated by a 3-hours interval. A surveillance period of 3 hours after the last dose is mandatory for patients.CONCLUSION:Drug provocation test protocols for NSAID are empirical, driven by the knowledge on patterns of DHR, cross-reactivity between NSAID and pharmacological effects of these all drugs. This is the second experience in improving DPT protocols, after BL (B-lactam) antibiotics.

Resume La dysfonction des cordes vocales, definie par un blocage des cordes vocales en adduction lors de l’inspiration, est responsable d’une dyspnee inspiratoire brutale. Cette pathologie est rare et rends le diagnostique difficile a evoquer, d’autant que la reaction est souvent prise a tord pour un bronchospasme. L’allergie immediate, IgE mediee, aux glucocorticoides est rare et implique le plus souvent les esters succinate d’hydrocortisone et de methylprednisolone. Nous rapportons ici le cas d’une jeune fille de 19 ans, suivie initialement pour un asthme ayant presente plusieurs episodes de dyspnee inspiratoire brutale avec urticaire lors d’efforts physiques. Le bilan allergologique, pneumologique et ORL nous a fait fortement suspecter une dysfonction des cordes vocales a l’effort associe a une allergie IgE mediee a l’hemisuccinate de methylprednisolone avec tolerance de la prednisolone et de la methylprednisolone. Le traitement, qui a consiste en une reeducation orthophonique avec eviction du sport et contre indication a l’hemisuccinate de methylprednisolone, a permis l’absence de recidive.

International audience; There is no perfect agreement on how to perform an allergy workup in suspected beta-lactam (BL)-allergic children, since skin test (ST)-induced pain is often a limitation. The aim of the study was to assess the possibility of reducing the number of ST in children when performing a complete allergy workup for BL hypersensitivity reactions.Methods: A retrospective analysis of all patients referring to the Allergy Unit of the University Hospital of Montpellier (France) with positive responses in immediateand non-immediate-reading ST to a BL over a 16-year period was performed, to determine the positive predictive value (PPV) of ST. All pediatric patients with a suspected BL hypersensitivity were skin-tested with the suspected drug only, during the following 54 months.Results: A total of 319 patients reporting 328 BL reactions were included in the retrospective study. The PPV of ST for the reported drug was of 99.4%. Based on the results, the number of patients to include in the prospective study was estimated to be 101. In the prospective study, 229 children were included. We diagnosed a BL hypersensitivity in 12 children (5.2%): Diagnosis was reached in 6 (50.0%) through ST (delayed reading for all) and in 6 through drug provocation test (DPT).Conclusion: ST with BL should therefore be performed as a screening test, before DPT, and testing only the suspected drug may be sufficient when dealing with children.

BACKGROUND: Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure. OBJECTIVE: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France. METHODS: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform. RESULTS: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests. CONCLUSION AND CLINICAL RELEVANCE: A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

Resume Introduction L’incidence de l’anaphylaxie augmente. Le retard a l’injection d’adrenaline est un facteur de risque de deces, comme le fait d’etre asthmatique. Les medecins generalistes ont un role dans la prise en charge de cet evenement, principalement par des actions de prevention, et eventuellement par la gestion de l’episode aigu. But de l’etude Le but de l’enquete etait d’evaluer la prise en charge de l’anaphylaxie par les medecins generalistes : actions de prevention (prescription de trousses d’urgence avec ou sans adrenaline), et traitement d’une anaphylaxie (injection d’adrenaline, adressage a l’allergologue). Patients et methodes Une enquete declarative par questionnaire electronique a ete realisee parmi 1301 medecins generalistes de la region Occitanie, de fevrier a avril 2017. Resultats Au total, 141 medecins ont repondu, soit 11 %. Ils etaient pres de 75 % a avoir prescrit 1 a 5 trousses d’urgence contenant de l’adrenaline l’annee precedente. Sur les 48 medecins ayant ete en contact avec une anaphylaxie (soit 34 %), 72,9 % ont declare que leur patient avait recu de l’adrenaline, 66 % que leur patient avait ete adresse en structure hospitaliere, et 79,1 % que leurs patients avaient ete adresses en consultation d’allergologie. 66 % sont demandeurs de formations. Conclusion Les medecins generalistes sont en majorite prescripteurs et utilisateurs d’adrenaline. Toutefois, leur role peut etre optimise concernant l’education des patients, et le recours aux soins specialises post-anaphylaxie. Des formations par simulation, cours ou interventions lors de congres permettraient de renforcer ces connaissances et competences.

Large health system databases have revolutionized our understanding of the epidemiology of adverse drug reactions and immunologically mediated drug hypersensitivity. Population-based background rates of newly reported drug intolerance with each therapeutic exposure could not have been determined without large health system databases. Large databases have increased our understanding of multiple drug intolerance syndrome. Large health care systems, such as Kaiser Permanente, with a single electronic medical record system that covers all inpatient, outpatient, and pharmacy interactions, are particularly valuable in understanding the population-based incidence of severe and nonsevere adverse drug reactions, the risks of delayed-onset adverse drug reactions, such as those caused by Clostridiodes difficile, which can occur months after antibiotic exposures, and the risks and benefits associated with "allergy" delabeling, specifically penicillin allergy delabeling, which may accrue in the years after the delabeling. There currently are limitations to using electronic data, specifically billing code data, when studying adverse drug reactions. It is critical to audit electronic health records, which have temporally associated the use of a drug and an adverse reaction because of high rates of miscoding or lack of true cause and effect. Pending improvements in drug hypersensitivity coding in International Classification of Diseases, Eleventh Revision may make large databases even more useful.

ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE vol:7 issue:3 pages:1081-1082 ispartof: location:United States status: published

Introduction Cluster analysis refers to a broad set of unsupervised learning techniques used to discover distinct subgroups or clusters within a set of data. This study aimed to distinguish different clinical characteristics among patients with suspicions of drug hypersensitivity reactions (DHRs) to iodinated radiocontrast media (iRCM) based on a cluster analysis. Methodes A retrospective study was performed using data extraction from the Drug Allergy and Hypersensitivity Database (DAHD) at the Allergy Unit, University Hospital of Montpellier, France. All referred patients with suspicions of iRCM DHRs between February 2001 and December 2019 either with confirmed positive skin tests (ST)s or negative STs were included in the analysis. Resultats A total of 1439 patients with suspicion of a DHR to iRCM who underwent a drug allergy work-up were analysed. Positive STs were displayed in 153 patients (10.6 %). The solution proposed by the automatic cluster analysis categorized the 1439 patients into five clusters, with a fair quality of clustering and an optimal ratio (2.3) of the cluster sizes. Cluster 1 contained almost only patients with a non-immediate reaction. Cluster 2 comprised virtually only patients with immediate reactions (IR), all with known culprit iRCM. These were the best defined clusters. Cluster 4 and 5 were virtually identical, with one exception, namely the clinical manifestation. Where they both comprised IRs, with multiple episodes of DHR, induced by unknown culprits, tested two decades after the index reaction, cluster 5 contained virtually only anaphylactic events whereas cluster 4 included various reactions, but no anaphylaxis. Confirmed allergies were more frequent in cluster 1 (16.9 %) and 2 (16.5 %). Conclusion Five clinical phenotypes which make sense clinically were determined by cluster analysis. From a pragmatic point of view, this new knowledge can be integrated in the drug allergy work-up reasoning : patients with well-defined recent reactions are allergic in up to 17 % of cases, but the frequency of allergy is leveled down by two or more in reactions tested more than a decade after their occurrence, despite the clinical manifestation which can resemble anaphylaxis.