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Allergy. 2016 Aug;71(8):1103-34. doi: 10.1111/all.12886. Epub 2016 May 25.

In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

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Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
Division of Immunology and Allergy, Department of Chest Diseases, Ankara University School of Medicine, Ankara, Turkey.
Department of Immunology and ERTICa Research Group, University Hospital of Clermont-Ferrand and Auvergne University, Clermont-Ferrand, France.
Regional Adult Cystic Fibrosis Unit, St James's Hospital, Leeds, UK.
Allergy Unit, Azienda Ospedaliera Universitaria Intergata of Verona, Verona, Italy.
Immunoallergology Department, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
Immunoallergology Unit, Department of Biomedicine, Careggi Hospital, Florence, Italy.
Department of Dermatology and Allergology Biederstein, Technische Universität München, Munich, Germany.
Pediatric Allergy Unit, Department of Child and Adolescent, University Hospitals of Geneva, Geneva, Switzerland.
Department of Immunology, Rheumatology and Allergy, Healthy Ageing Research Center, Medical University of Łódź, Łódź, Poland.
Allergy and Immunology Clinic, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK.
Allergy Unit Complesso Integrato Columbus, Rome and IRCCS Oasi Maria S.S., Troina, Italy.
BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Malaga, Spain.
Allergy Unit, Hospital de la Cruz Roja, Madrid, Spain.
Section of Immunology, Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
Department of Molecular Medicine and Personalized Therapeutics and Inserm UMRS 954N-GERE (Nutrition-Genetics-Environmental Risks), University Hospital of Nancy and University of Lorraine, Nancy, France.
Department of Allergology, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Allergy Section, Alicante University Hospital, UMH, Alicante, Spain.
Laboratory of Immunology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France.
Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, and Sorbonne Universités, UPMC Paris 06, UMR-S 1136, IPLESP, Equipe EPAR, Paris, France.


Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.


IgE; T cells; diagnosis; drug hypersensitivity; in vitro

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