Approach for delabeling beta-lactam allergy in children.

A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of in vitro testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.

Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

Corrigendum: Approach for delabeling beta-lactam allergy in children.

[This corrects the article DOI: 10.3389/falgy.2023.1298335.].

Peptide hydrogel with self-healing and redox-responsive properties.

We have rationally designed a peptide that assembles into a redox-responsive, antimicrobial metallohydrogel. The resulting self-healing material can be rapidly reduced by ascorbate under physiological conditions and demonstrates a remarkable 160-fold change in hydrogel stiffness upon reduction. We provide a computational model of the hydrogel, explaining why position of nitrogen in non-natural amino acid pyridyl-alanine results in drastically different gelation properties of peptides with metal ions. Given its antimicrobial and rheological properties, the newly designed hydrogel can be used for removable wound dressing application, addressing a major unmet need in clinical care.

Polymorphisms in eicosanoid-related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity. OBJECTIVES: To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA. METHODS: Two independent cohorts of patients were recruited in Spain, alongside NSAID-tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID-exacerbated respiratory disease (NERD). A set of tagging single-nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction. RESULTS: The study included 1272 individuals. Thirty-five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 [95% confidence interval (CI) 1·34-2·14; Pcorrected = 2·83 × 10-4 ) and 2·19 for rs28395868 (95% CI 1·43-3·36; Pcorrected = 0·002). CONCLUSIONS: Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID-hypersensitivity and shedding light on their genetic basis.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization.

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available (AU)

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure (AU)

La desensibilización a medicamentos ha permitido la administración de fármacos de primera línea en pacientes con reacciones dehipersensibilidad (RH) a quimioterápicos (QT), incluyendo los anticuerpos monoclonales (AcM). La desensibilización es un procedimientoseguro y altamente efectivo, no únicamente para las reacciones mediadas por IgE sino también para aquellas relacionadas con un mecanismoindependiente de IgE. El riesgo de reacciones durante la desensibilización es bajo y frecuentemente las reacciones observadas son leves,considerándose infrecuentes las reacciones moderadas o graves.En este documento, dieciséis Servicios de Alergia pertenecientes a la red española de investigación ARADyAL presentan una revisiónde la evidencia científica disponible y sugieren unas pautas de actuación generales para el diagnóstico y manejo de las RH a QT y AcM,centrándose en el proceso de desensibilización (AU)

Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

Statement of the Spanish Society of Allergology and Clinical Immunology on Provocation Tests With Aspirin/Nonsteroidal Anti-inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated.

Statement of the Spanish Society of Allergology and Clinical Immunology on provocation tests with aspirin/nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated

Los antiinflamatorios no esteroideos (AINE) son medicamentos ampliamente utilizados a nivel mundial y frecuentemente implicados en reacciones de hipersensibilidad que pueden comprender desde reacciones locales y/o leves a reacciones sistémicas y graves. La complejidad del diagnóstico ante la falta de pruebas cutáneas o de laboratorio estandarizadas y/o validadas, hace que en muchos casos debamos realizar pruebas de provocación de alto riesgo. Por ello, es necesario un exhaustivo estudio de estos pacientes en los que tienen gran importancia el correcto diagnóstico y la búsqueda de procedimientos más seguros ante pacientes con reacciones graves, así como también la búsqueda de opciones alternativas de tratamientos antiinflamatorios. Actualmente existen diversas guías y protocolos de actuación que describen el manejo de la hipersensibilidad a los AINE aunque con importante variabilidad entre diferentes países. Desde los distintos comités de Asma, Rinoconjuntivitis y Alergia a Fármacos de la Sociedad Española de Alergología e Inmunología Clínica (SEAIC) proponemos un documento de posicionamiento sobre las opciones en las pruebas de provocación con aspirina/ AINE. Este documento es el resultado de una revisión exhaustiva de la evidencia actual, basada en publicaciones recientes sobre el diagnóstico de pacientes con hipersensibilidad a AINE, y de la discusión consensuada de un grupo de expertos de la SEAIC. El objetivo fundamental ha sido elaborar una guía práctica de fácil lectura dirigida a profesionales sanitarios de atención especializada implicados en el estudio y manejo de pacientes con sospecha de hipersensibilidad a AINE. Además, se ha realizado una actualización sobre las indicaciones, contraindicaciones y procedimientos de las pruebas de provocación oral, bronquial y nasal con aspirina/AINE

Spanish guidelines for diagnosis, management, treatment, and prevention of DRESS syndrome

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. OBJECTIVE: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided

ANTECEDENTES: El síndrome DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) es una reacción cutánea grave inducida por hipersensibilidad a fármacos, compleja y multisistémica. Su diagnóstico y manejo es difícil e implica a diferentes especialistas. Es muy importante una correcta identificación del fármaco responsable para que el paciente disponga de opciones terapéuticas seguras en el futuro. No hay guías ni documentos de consenso españoles previos sobre el síndrome DRESS. OBJETIVO: Realizar una revisión y guía sobre el diagnóstico clínico y alergológico, manejo, tratamiento y prevención del DRESS según la evidencia científica disponible y la experiencia de expertos de diferentes especialidades médicas. MÉTODOS: Esta guía ha sido elaborada por un grupo de alergólogos del Comité de Alergia a Fármacos de la SEAIC, junto a otros especialistas involucrados en el manejo del DRESS e investigadores del Consorcio PIELenRed. Se realizó una búsqueda de publicaciones científicas sobre DRESS y el grupo de expertos evaluó la evidencia científica de la literatura y aportaron grados de recomendación. Cuando no existía evidencia se alcanzó un consenso entre expertos. RESULTADOS: Se publica la guía española sobre DRESS. Incluye aspectos prácticos importantes sobre el diagnóstico clínico, la identificación de fármacos causales a través del algoritmo del Sistema Español de Farmacovigilancia y guía para el diagnóstico alergológico. Se realizan recomendaciones sobre el manejo, tratamiento y prevención del DRESS. Se aportan algoritmos sobre el manejo en la fase aguda y en la de recuperación. Se ha elaborado una guía terapéutica escalonada consensuada por expertos especialistas implicados en el tratamiento del DRESS

Accuracy of the Diagnosis of Allergic Reactions in the Emergency Department.

BACKGROUND AND OBJECTIVE: Suspicion of an acute allergic reaction is a common reason for attending the emergency department (ED). However, there are few comparisons between the initial diagnosis of suspected allergic reaction made in the ED with the definitive diagnosis made subsequently in the allergy department (AD). Objective: To compare details of the initial diagnosis made in the ED relating to allergy with the final diagnosis made in the AD. METHODS: Patients attending the ED of 2 hospitals with suspected allergic reactions were prospectively enrolled based on key words. A certified allergy specialist reviewed the ED records of these patients and, if these were suggestive of an allergic reaction, the patients were scheduled for further evaluation at the allergy clinic. RESULTS: In total, 2000 patients were enrolled between April 2013 and October 2015. Of these, 1333 passed the initial assessment and underwent further evaluation. Of the 1333 patients, 528 underwent an allergological study, and 206 were confirmed as being allergic. With respect to drug allergy, nonsteroidal anti-inflammatory drugs were the most common triggers, followed by ß-lactams; in food allergy, plant-based foods were the most common. Only 16.4% of patients confirmed as having anaphylaxis in the AD were initially diagnosed with the condition in the ED. CONCLUSION: Of the 528 patients who finally underwent the full allergological study, fewer than half were confirmed as allergic. Moreover, anaphylaxis appears to be underdiagnosed in the ED. Better communication between the ED and the AD is necessary to improve the diagnosis and management of these patients.

Accuracy of the diagnosis of allergic reactions in the emergency department

Background: Suspicion of an acute allergic reaction is a common reason for attending the emergency department (ED). However, there are few comparisons between the initial diagnosis of suspected allergic reaction made in the ED with the definitive diagnosis made subsequently in the allergy department (AD).Objective: To compare details of the initial diagnosis made in the ED relating to allergy with the final diagnosis made in the AD. Methods: Patients attending the ED of 2 hospitals with suspected allergic reactions were prospectively enrolled based on key words. A certified allergy specialist reviewed the ED records of these patients and, if these were suggestive of an allergic reaction, the patients were scheduled for further evaluation at the allergy clinic. Results: In total, 2000 patients were enrolled between April 2013 and October 2015. Of these, 1333 passed the initial assessment and underwent further evaluation. Of the 1333 patients, 528 underwent an allergological study, and 206 were confirmed as being allergic. With respect to drug allergy, nonsteroidal anti-inflammatory drugs were the most common triggers, followed by ß-lactams; in food allergy, plant-based foods were the most common. Only 16.4% of patients confirmed as having anaphylaxis in the AD were initially diagnosed with the condition in the ED. Conclusion: Of the 528 patients who finally underwent the full allergological study, fewer than half were confirmed as allergic. Moreover, anaphylaxis appears to be underdiagnosed in the ED. Better communication between the ED and the AD is necessary to improve the diagnosis and management of these patients

Antecedentes: La sospecha de una reacción alérgica aguda es un motivo frecuente de consulta en urgencias. Sin embargo, hay pocos trabajos que comparen el diagnóstico inicial realizado en las unidades de urgencias con el diagnóstico definitivo realizado en las unidades de alergia. Objetivo: Analizar en detalle la sospecha diagnóstica inicial dada en urgencias con el diagnóstico definitivo en las consultas de alergia. Métodos: Estudio prospectivo, que consistió en la selección, en base a palabras claves, de pacientes con sospecha de reacción alérgica. En la fase de screening, se seleccionaron los pacientes en base a las palabras claves, finalmente aquellos pacientes que presentan reacción sugestiva de alergia se seleccionaron para evaluación final. Resultados: Se revisaron 2.000 pacientes entre abril de 2013 y octubre de 2015, de los cuales 1.333 se seleccionaron para la evaluación. Finalmente, 528 se sometieron a un estudio alergológico y 206 se confirmaron como alérgicos. Con respecto a las reacciones por fármacos, los AINE y ß-lactámicos fueron los mayormente implicados; en relación con los alimentos, los de origen vegetal fueron los más frecuentes. Sólo el 16,4% de los pacientes con anafilaxia confirmada tras el estudio de alergia, fueron diagnosticados inicialmente en urgencias. Conclusión: Sólo la mitad de los pacientes que finalizaron en estudio fueron confirmados como alérgicos. Un dato importante es el infradiagnóstico de la anafilaxia en las urgencias. Por ello pensamos que es necesaria una mejor comunicación entre las unidades de urgencias y alergia para mejorar el manejo clínico y terapéutico de estos pacientes

An EAACI task force report: recognising the potential of the primary care physician in the diagnosis and management of drug hypersensitivity.

Adverse drug reactions include drug hypersensitivity reactions (DHRs), which can be immunologically mediated (allergy) or non-immunologically mediated. The high number of DHRs that are unconfirmed and often self-reported is a frequent problem in daily clinical practice, with considerable impact on future prescription choices and patient health. It is important to distinguish between hypersensitivity and non-hypersensitivity reactions by adopting a structured diagnostic approach to confirm or discard the suspected drug, not only to avoid life-threatening reactions, but also to reduce the frequent over-diagnosis of DHRs. Primary care physicians are often the first point of contact for the sufferer of a reaction, as such they have a key role in deciding whether to discard the diagnosis or send the patient for further investigation. In this review, we highlight the importance of diagnosing DHRs, analysing in detail the role of primary care physicians. We describe the common patterns of DHRs and signs of its progression, as well as the indications and contraindications for referring the patient to an allergist. The diagnostic process is described and the possible tests are discussed, which often depend on the drug involved and the type of DHR suspected. We also describe recommendations regarding the avoidance of medication suspected to have caused the reaction and the use of alternatives.

Practical Guidelines for Perioperative Hypersensitivity Reactions.

Perioperative hypersensitivity reactions constitute a first-line problem for anesthesiologists and allergists. Therefore, hospitals should have a consensus protocol for the diagnosis and management of these reactions. However, this kind of protocol is not present in many hospitals, leading to problems with treatment, reporting of incidents, and subsequent etiological diagnosis. In this document, we present a systematic review of the available scientific evidence and provide general guidelines for the management of acute episodes and for referral of patients with perioperative hypersensitivity reactions to allergy units. Members of the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) have created this document in collaboration with members of the Spanish Anesthesia Society (SEDAR). A practical algorithm is proposed for the etiologic diagnosis, and recommendations are provided for the management of hypersensitive patients.

Practical guidelines for perioperative hypersensitivity reactions

Perioperative hypersensitivity reactions constitute a first-line problem for anesthesiologists and allergists. Therefore, hospitals should have a consensus protocol for the diagnosis and management of these reactions. However, this kind of protocol is not present in many hospitals, leading to problems with treatment, reporting of incidents, and subsequent etiological diagnosis. In this document, we present a systematic review of the available scientific evidence and provide general guidelines for the management of acute episodes and for referral of patients with perioperative hypersensitivity reactions to allergy units. Members of the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) have created this document in collaboration with members of the Spanish Anesthesia Society (SEDAR). A practical algorithm is proposed for the etiologic diagnosis, and recommendations are provided for the management of hypersensitive patients

Las reacciones de hipersensibilidad perioperatorias constituyen un problema de primera línea para los anestesiólogos y alergólogos, por lo que es recomendable que los hospitales tengan un protocolo de consenso para el diagnóstico y el tratamiento de estas reacciones. Sin embargo, este tipo de protocolos no está presente en muchos hospitales, lo que conlleva problemas en el tratamiento, la comunicación de incidentes y el posterior diagnóstico etiológico. Este documento ha sido creado por miembros del Comité de Alergia a Medicamentos de la Sociedad Española de Alergia e Inmunología Clínica (SEAIC) en colaboración con miembros de la Sociedad Española de Anestesia (SEDAR). Se ha realizado una revisión sistemática de la evidencia científica disponible y se proporcionan pautas generales para el manejo de episodios agudos y para la derivación de pacientes con reacciones de hipersensibilidad perioperatoria a los Servicios de Alergología. Se propone un algoritmo práctico para el diagnóstico etiológico y se brindan recomendaciones para el manejo de pacientes con reacciones alérgicas perioperatorias

Update on the Genetic Basis of Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to ß-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists.

Dermatophagoides pteronyssinus immunotherapy changes the T-regulatory cell activity.

Subcutaneous specific immunotherapy (SCIT) has been shown to modify the Dermatophagoides pteronissinus (DP) allergic response, characterized by generation of Treg cells. However, studies have reported no changes in the proportion of Treg cells after immunotherapy, indicating that the effects may be due to modifications in their regulatory activities. We aimed to determine whether Tregs generated by DP-SCIT can switch the allergic response to tolerant and study the involvement of suppressive cytokines on it. Twenty-four DP-allergic rhinitis patients were recruited, 16 treated with DP-SCIT and 8 untreated. Treg and T effector cells were isolated before and after DP-SCIT, and cocultured in different combinations with α-IL-10, α-TGF-ß blocking antibodies and nDer p 1. Treg cells after DP-SCIT increased Th1 and decreased Th2 and Th9 proliferation. Similarly, they increased IL-10 and decreased IL-4 and IL-9-producing cells. α-IL-10 affected the activity of Treg cells obtained after DP-SCIT only. Finally, DP-specific IgG4 levels, Treg percentage and IL-10 production were correlated after DP-SCIT. These results demonstrate that DP-SCIT induces Treg cells with different suppressive activities. These changes could be mediated by IL-10 production and appear to play an important role in the induction of the tolerance response leading to a clinical improvement of symptoms.