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Guideline for the diagnosis of drug hypersensitivity reactions

S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM)

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An Erratum to this article was published on 30 January 2018

Abstract

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1–6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks–6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an „allergy passport“ in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AGEP:

Acute generalized exanthematous pustulosis

CAST:

Cellular antigen stimulation test

DRESS:

Drug reaction with eosinophilia and systemic symptoms

EBV:

Epstein-Barr virus

ELISpot:

Enzyme-Linked ImmunoSpot

ENDA:

European Network on Drug Allergy

HIV:

Human immunodeficiency virus

HLA:

Human leukocyte antigen

Ig:

Immunoglobulin

NA:

Not applicable or no concentration recommended

NSAID:

Non-steroidal anti-inflammatory drug

sIgE:

Specific immunoglobulin E

SJS:

Stevens-Johnson syndrome

TEN:

Toxic epidermal necrolysis

ADR:

Adverse drug reactions

UV:

Ultraviolet radiation

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Author information

Authors and Affiliations

  1. Department of Dermatology and Allergology Biederstein, Technical University of Munich, Biedersteiner Straße 29, 80802, Munich, Germany

    Knut Brockow & Johannes Ring

  2. Department of Dermatology and Allergology, Allergy Center, Ludwig Maximilian University of Munich, Munich, Germany

    Bernhard Przybilla

  3. Department of Dermatology, Medical University of Graz, Graz, Austria

    Werner Aberer

  4. Department of Allergology, University Hospital Basle, Basle, Switzerland

    Andreas J. Bircher

  5. Department of Dermatology, Münster University Hospital, Münster, Germany

    Randolf Brehler

  6. Department of Dermatology, Venereology and Allergology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany

    Heinrich Dickel

  7. Department of Dermatology, Venereology and Allergology, Göttingen University Hospital, Göttingen, Germany

    Thomas Fuchs

  8. Department of Dermatology and Venereology, Freiburg University Hospital, Freiburg, Germany

    Thilo Jakob

  9. Department of Pediatrics, Marien Hospital Bonn, Bonn, Germany

    Lars Lange

  10. Department of Dermatology and Allergology, Gießen and Marburg University Hospital, Marburg, Germany

    Wolfgang Pfützner

  11. German Center for the Documentation of Severe Skin Reactions, Department of Dermatology and Venereology, Freiburg University Hospital, Freiburg, Germany

    Maja Mockenhaupt

  12. Children’s and Adolescents’ Hospital „Auf der Bult,“, Hannover, Germany

    Hagen Ott

  13. ENT at Mannheim University Hospital, Center for Rhinology and Allergology, Wiesbaden, Germany

    Oliver Pfaar

  14. Federal Institute for Drugs and Medicinal Products, Bonn, Germany

    Bernhardt Sachs

  15. Institute of Theoretical Surgery, Philipps University, Marburg, Germany

    Helmut Sitter

  16. Department of Dermatology and Allergology, Mainfranken Allergy, Würzburg University Hospital, Würzburg, Germany

    Axel Trautmann

  17. Department of Dermatology, Venereology and Allergology, Leipzig University, Leipzig, Germany

    Regina Treudler

  18. Department of Dermatology, Venereology and Allergology, Hannover Medical University, Hannover, Germany

    Bettina Wedi

  19. Department of Dermatology, Venereology and Allergology, Charité University Hospital, Berlin, Germany

    Margitta Worm & Torsten Zuberbier

  20. Department of Dermatology and Allergology, RTWH Aachen, Aachen, Germany

    Gerda Wurpts & Hans F. Merk

Authors
  1. Knut Brockow
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  2. Bernhard Przybilla
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  3. Werner Aberer
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  4. Andreas J. Bircher
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  5. Randolf Brehler
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  6. Heinrich Dickel
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  7. Thomas Fuchs
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  8. Thilo Jakob
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  9. Lars Lange
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  10. Wolfgang Pfützner
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  11. Maja Mockenhaupt
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  12. Hagen Ott
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  13. Oliver Pfaar
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  14. Johannes Ring
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  15. Bernhardt Sachs
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  16. Helmut Sitter
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  17. Axel Trautmann
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  18. Regina Treudler
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  19. Bettina Wedi
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  20. Margitta Worm
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  21. Gerda Wurpts
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  22. Torsten Zuberbier
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  23. Hans F. Merk
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Corresponding author

Correspondence to Knut Brockow.

Additional information

Conflict of interests

The information on potential conflicts of interest have been reviewed by a steering-group which did not find any conflicts of interest which may affect the authors’ independency in the process of the development of this guideline. The authors’ disclosures are available in a table (together with the working-report on this guideline) on the AWMF-page of the S2k-Guideline for the diagnosis of drug hypersensitivity reactions via www.awmf.org/leitlinien/detail/ll/061-021.html.

Cite this as

Brockow K, Przybilla B, Aberer W, Bircher AJ, Brehler R, Dickel H, Fuchs T, Jakob T, Lange L, Pfützner W, Mockenhaupt M, Ott H, Pfaar O, Ring J, Sachs B, Sitter H, Trautmann A, Treudler R, Wedi B, Worm M, Wurpts G, Zuberbier T, Merk HF. Guideline for the diagnosis of drug hypersensitivity reactions. S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group, the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int 2015;24:94–105 DOI: 10.1007/s40629-015-0052-6

A correction to this article is available at http://dx.doi.org/10.1007/s15007-018-1526-x

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Brockow, K., Przybilla, B., Aberer, W. et al. Guideline for the diagnosis of drug hypersensitivity reactions. Allergo J Int 24, 94–105 (2015). https://doi.org/10.1007/s40629-015-0052-6

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  • DOI: https://doi.org/10.1007/s40629-015-0052-6

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