Hipersensiblidad a los agentes antineoplásicos y a los fármacos biológicos: ¿un nuevo paradigma diagnóstico y terapeútico?

Las reacciones de hipersensibilidad frente a agentes antineoplásicos y biológicos se han convertido en un problema de incidencia creciente. Su aparición afecta gravemente al pronóstico de los pacientes porque, además de poner en peligro su vida, pueden ocasionar que no reciban el tratamiento de primera elección para su enfermedad oncológica o inflamatoria. La valoración de estas reacciones por parte de alergólogos expertos permite realizar un diagnóstico correcto, identificar la naturaleza de estas reacciones, realizar estratificaciones personalizadas del riesgo en cada paciente y, mediante la técnica terapéutica de la desensibilización rápida (que induce una tolerancia temporal y específica de antígeno), permiten que el paciente pueda recibir de forma eficaz y segura el fármaco frente al que es alérgico. En esta Tesis Doctoral se valida a lo largo de un periodo de tres años la implantación de un Programa Multidisciplinar de Desensibilización para agentes antineoplásicos y biológicos, así como sus técnicas diagnósticas y terapéuticas. Se aportan los datos de dos estudios principales y otros cuatro estudios secundarios que se llevaron a cabo en el Hospital Universitario Ramón y Cajal, Madrid. Los pacientes se sometieron, tras su reacción inicial con diversos fármacos antineoplásicos y agentes biológicos, a un procedimiento diagnóstico que incluyó anamnesis, pruebas cutáneas, marcadores de riesgo, estratificación individualizada del riesgo, determinación sérica de IgE específica, determinación de triptasa sérica y provocación controlada. Tras completar el procedimiento diagnóstico, se identificaron a los candidatos a recibir la medicación frente a la que son alérgicos mediante desensibilización rápida. Se presentan los datos de los pacientes que, gracias al Programa de Desensibilización, han podido continuar con su tratamiento quimioterápico o biológico pese a ser alérgicos al mismo. Se presentan los primeros datos publicados con más de cien provocaciones controladas con diversos agentes antineoplásicos y biológicos. Al tomar como Patrón Oro la provocación controlada, se presentan datos de alta calidad de validación de pruebas diagnósticas (anamnesis, pruebas cutáneas, IgE específica, etc.). Se valida la técnica de desensibilización rápida como efectiva y segura en nuestra población, mediante un nuevo protocolo diseñado para ser más corto y aportar importantes mejoras en cuanto a seguridad con respecto a protocolos previos

Flow-based basophil activation test in immediate drug hypersensitivity. An EAACI task force position paper

Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) “Basophil activation test in the evaluation of Drug Hypersensitivity Reactions” from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus-based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug-specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti-inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory.Funding for open access charge: Universidad de Málaga/CBUA. The authors would like to thank EAACI for their financial support in the development of this Task Force Position Paper

Risk and safety requirements for diagnostic and therapeutic procedures in allergology : World Allergy Organization Statement

Peer reviewe

Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement

Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe , might leave pa-tients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics , antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first -choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy)