학술논문
"Delabeling" by direct provocation testing in children and adolescents with a suspected history of a delayed reaction to β-lactam antibiotics: Consensus paper of Gesellschaft für pädiatrische Allergologie und Umweltmedizin (GPAU), Deutsche Gesellschaft für Allergologie und klinische Immunologie (DGAKI), and Ärzteverband deutscher Allergologen (ÄDA).
Document Type
Academic Journal
Author
Neustädter I; Pediatric and Adolescent Medicine, Diakoneo Klinik Hallerwiese-Cnopfsche Kinderklinik, Nuremberg.; Blatt S; Pediatric and Adolescent Medicine, Diakoneo Klinik Hallerwiese-Cnopfsche Kinderklinik, Nuremberg.; Wurpts G; Clinic for Dermatology and Allergology, Aachen Comprehensive Allergy Center (ACAC), University Hospital of RWTH Aachen University, Aachen.; Dickel H; Clinic for Dermatology, Venereology and Allergology, St. Josef Hospital, University Hospital of the Ruhr University Bochum, Bochum.; Walter C; Practice for Pediatric and Adolescent Medicine, Allergology, Bad Homburg, Germany.; Aberer W; Department of Dermatology and Venereology, Medical University of Graz, Austria.; Bode S; University Clinic for Children and Adolescents, Ulm.; Buhl T; Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen.; Gernert S; Department of Pediatrics, St. Marien Hospital, GFO Clinics, Bonn.; Harner S; Clinic and Polyclinic for Pediatrics and Adolescent Medicine, University of Regensburg, Regensburg.; Heine G; Department of Dermatology, Venereology and Allergology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel.; Kerzel S; Clinic and Polyclinic for Pediatrics and Adolescent Medicine, University of Regensburg, Regensburg.; Köhler M; Asthma and Allergy Outpatient Clinic, Dr. von Hauner Children's Hospital, LMU University Hospital, Munich.; Lange L; Department of Pediatrics, St. Marien Hospital, GFO Clinics, Bonn.; List J; University of Freiburg, Center for Pediatric and Adolescent Medicine, Freiburg.; Merk HF; Clinic and Polyclinic for Dermatology and Allergology at Biederstein, Technical University of Munich, Munich.; Nüßlein T; Clinic for Pediatrics and Adolescent Medicine, Gemeinschaftsklinikum Mittelrhein, Koblenz.; Ott H; Children's and Youth Hospital Auf der Bult, Hanover.; Sattler F; Asthma and Allergy Outpatient Clinic, Dr. von Hauner Children's Hospital, LMU University Hospital, Munich.; Schuster A; Clinic for General Pediatrics, Neonatology and Pediatric Cardiology, University Hospital Düsseldorf, Düsseldorf.; Straube H; Princess Margaret Children's Hospital, Darmstadt.; Wedi B; Hannover Medical School, Clinic for Dermatology, Allergology and Venereology, Hanover, and.; Zuberbier T; Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Brockow K; Clinic and Polyclinic for Dermatology and Allergology at Biederstein, Technical University of Munich, Munich.
Source
Publisher: Dustri-Verlag Country of Publication: Germany NLM ID: 101722686 Publication Model: eCollection Cited Medium: Internet ISSN: 2512-8957 (Electronic) Linking ISSN: 25128957 NLM ISO Abbreviation: Allergol Select Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Background: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to β-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection.
Materials and Methods: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies.
Results: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE.
Conclusion: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
Competing Interests: The author declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article. Table 1.Warning signs of β-lactam allergy, modified according to [1, 12]. Immediate reactionDelayed reactionConjunctival erythemaPronounced facial edemaShock symptoms (arterial hypotension/dizziness)Atypical target lesions, bullous lesionsCoughing, sneezing, wheezing ErythrodermaDyspneaHemorrhagic and necrotic lesionsHoarsenessPainful skin, mucous membrane involvementDysphagiaGeneralized lymphadenopathyPathological laboratory findings (e.g., liver enzyme elevation, impaired renal function) Table 2.Provocation regime [6, 8, 15]. Day 1 (practice/clinic)Day 2 (at home)Day 3 (at home)1 single doseDaily dose distributed in 2 – 3 doses (depending on the antibiotic)Daily dose distributed in 2 – 3 doses (depending on the antibiotic)Monitoring for 1 hourStart ~ 24 hours after the first dose day 1**Wash-out period should be ~ 24 hours so that delayed reactions can be recorded after the 1st dose during the time interval between reaching the therapeutic dose and the subsequent dose. Figure 1Estimates on the likelihood of allergic cross-reactions between the various β-lactam antibiotics ([14]).
(© Dustri-Verlag Dr. K. Feistle.)
Materials and Methods: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies.
Results: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE.
Conclusion: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
Competing Interests: The author declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article. Table 1.Warning signs of β-lactam allergy, modified according to [1, 12]. Immediate reactionDelayed reactionConjunctival erythemaPronounced facial edemaShock symptoms (arterial hypotension/dizziness)Atypical target lesions, bullous lesionsCoughing, sneezing, wheezing ErythrodermaDyspneaHemorrhagic and necrotic lesionsHoarsenessPainful skin, mucous membrane involvementDysphagiaGeneralized lymphadenopathyPathological laboratory findings (e.g., liver enzyme elevation, impaired renal function) Table 2.Provocation regime [6, 8, 15]. Day 1 (practice/clinic)Day 2 (at home)Day 3 (at home)1 single doseDaily dose distributed in 2 – 3 doses (depending on the antibiotic)Daily dose distributed in 2 – 3 doses (depending on the antibiotic)Monitoring for 1 hourStart ~ 24 hours after the first dose day 1**Wash-out period should be ~ 24 hours so that delayed reactions can be recorded after the 1st dose during the time interval between reaching the therapeutic dose and the subsequent dose. Figure 1Estimates on the likelihood of allergic cross-reactions between the various β-lactam antibiotics ([14]).
(© Dustri-Verlag Dr. K. Feistle.)