Skip to main content

Diagnosis of Allergic Reactions to Drugs

  • Chapter
  • First Online:
Drug Allergy
  • 1030 Accesses

Abstract

In diagnosing drug allergies, history, skin testing, some in vitro laboratory tests, and provocation (challenge) testing are the backbone of the investigation. If skin prick testing elicits no reaction, intradermal testing is usually employed. The latter test is more sensitive but produces more false positives. The COADEX classification should be used to assess clinical relevance of positive patch tests. Assays for drug-specific serum IgE antibodies are useful in cases of skin test-negative or equivocal reactors or when skin tests are unreliable/unavailable. In interpreting results of IgE antibody tests, receiver-operating characteristic (ROC) curves provide more information to aid discrimination between positive and negative results. Drug challenge is the best way to confirm an allergic reaction, and it is considered to be the “gold standard” in the diagnosis of drug hypersensitivities. In anaphylaxis, the ratio of total to mature tryptase is typically less than 10. Given the technical improvements made with BAT and the test’s validation for a number of drugs, it continues to be applied to many drug reactions. Non-proliferation-based in vitro assays of cell surface activation markers, cytokines, chemokines, and skin-homing receptors will be increasingly applied to diagnosis. ELISPOT assays (e.g., for IFN-γ and granzyme B) show potential for diagnosis and the chemokine CCL27 and CLA and are promising markers for aiding efforts to understand the relationship between T cells, drugs, and adverse delayed skin reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Further Reading

  • Aberer W, Kränke B. Provocation tests in drug hypersensitivity. Immunol Allergy Clin N Am. 2009;29:567–84.

    Article  Google Scholar 

  • Baldo BA, Pham NH. Structure-activity studies on drug-induced anaphylactic reactions. Chem Res Toxicol. 1994;7:703–21.

    Article  CAS  Google Scholar 

  • Baldo BA, Smal MA, McCaskill C. A specific, sensitive and high-capacity immunoassay for PAF. Lipids. 1991;26:1136–9.

    Article  CAS  Google Scholar 

  • Barbaud A. Drug patch testing in systemic cutaneous drug allergy. Toxicology. 2005;209:209–16.

    Article  CAS  Google Scholar 

  • Barbaud A. Skin testing in delayed reactions to drugs. Immunol Allergy Clin N Am. 2009;29:517–35.

    Article  Google Scholar 

  • Barbaud A, Gonçalo M, Bruynzeel D, et al. Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Contact Dermatitis. 2001;45:321–8.

    Google Scholar 

  • Baretto RL, Beck S, Heslegrave J, et al. Validation of international consensus equation for acute serum total tryptase in mast cell activation: a perioperative perspective. Allergy. 2017;72:2031–4.

    Article  CAS  Google Scholar 

  • Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(Suppl 3):S66–S121.

    Google Scholar 

  • Brockow K, Garvey LH, Aberer W, et al. Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2013;68:702–12.

    Google Scholar 

  • Cooney SJ, Smal MA, Baldo BA. Stability of platelet activating factor (PAF) in human saliva. Quantitation by radioimmunoassay. Clin Chim Acta. 1991;200:161–74.

    Article  CAS  Google Scholar 

  • Ebo DG, Elst J, Van Gasse AV, et al. Basophil activation experiments in immediate drug hypersensitivity: more than a diagnostic aid. In: Gibbs BF, Falcone FH, editors. Basophils and mast cells. Methods and protocols. Methods in molecular biology, vol. 2163. New York: Springer Science+Business Media; 2020. p. 197–211.

    Google Scholar 

  • Elst J, van der Poorten M-LM, Faber MA, et al. Mast cell activation test in chlorhexidine allergy: a proof of concept. Br J Anaesth. 2020; In press. https://doi.org/10.1016/j.bja.2020.06.024.

  • Gastaminza G, Lafuente A, Goikoetxea MJ, et al. Improvement of the elevated tryptase criterion to discriminate IgE- from non-IgE-mediated allergic reactions. Anesth Analg. 2018;127:414–9.

    Article  CAS  Google Scholar 

  • Gibbs BF, Falcone FH, editors. Basophils and mast cells. Methods and protocols. Methods in molecular biology, vol. 2163. New York: Springer Science+Business Media; 2020.

    Google Scholar 

  • Hamilton RG. Clinical laboratories worldwide need to report IgE antibody results on clinical specimens as analytical results and not use differential positive thresholds. J Allergy Clin Immunol. 2015;136:811–2.

    Article  Google Scholar 

  • Hamilton RG, Matsson P, Hovanec-Burns DL, et al. Analytical performance characteristics. In: Quality assurance and clinical utility of immunological assays for human IgE antibodies of defined allergen specificities (CSLI-Guidance Document ILA20-A3). Wayne: Clinical and Laboratory Standards Institute; 2015.

    Google Scholar 

  • Hausmann OV, Gentinetta T, Bridts CH, et al. The basophil activation test in immediate-type drug allergy. Immunol Allergy Clin N Am. 2009;29:555–66.

    Article  Google Scholar 

  • Kalyuzhny AE, editor. Handbook of ELISPOT. Methods and protocols. Methods in molecular biology, vol. 792. New York: Humana Press; 2012.

    Google Scholar 

  • Lachapelle JM, Maibach HI. Patch testing and prick testing. A practical guide official publication of the ICDRG. 3rd ed. Berlin: Springer; 2012.

    Google Scholar 

  • Laroche D, Dubois F, Gérard J-L, et al. Radioimmunoassay for plasma histamine: a study of false positive and false negative values. Br J Anaesth. 1995;74:430–7.

    Article  CAS  Google Scholar 

  • Mangodt EA, Van Gasse AL, Decuyper I, et al. In vitro diagnosis of immediate drug hypersensitivity: should we go with the flow? Int Arch Allergy Immunol. 2015;168:3–12. https://doi.org/10.1159/000440663.

    Article  CAS  PubMed  Google Scholar 

  • NCCLS. Protocols for determination of limits of detection and limits of quantitation: approved guideline. NCCLS document EP17-A. NCCLS, Wayne; 2004.

    Google Scholar 

  • Santamaria Babi LF, Picker LJ, Perez Soler MT, et al. Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen. J Exp Med. 1995;181:1935–40.

    Article  CAS  Google Scholar 

  • Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin N Am. 2006;26:451–63.

    Article  Google Scholar 

  • Schwartz LB, Min H-K, Ren S, et al. Tryptase precursors are preferentially and spontaneously released, whereas mature tryptase is retained by HMC-1 cells, mono-Mac-6 cells, and human skin-derived mast cells. J Immunol. 2003;170:5667–73.

    Article  CAS  Google Scholar 

  • Scolaro RJ, Crilly HM, Maycock EJ, et al. Australian and New Zealand Anaesthetic Allergy Group Perioperative Anaphylaxis Investigation Guidelines. Anaesth Intensive Care. 2017;45:543–55.

    Article  CAS  Google Scholar 

  • Sprung J, Weingarten TN, Schwartz LB. Presence or absence of elevated acute total tryptase by itself is not a definitive marker for an allergic reaction. Anesthesiology. 2015;122:713–4.

    Article  Google Scholar 

  • Steiner M, Harrer A, Himly M. Basophil reactivity as biomarker in immediate drug hypersensitivity reactions—potential and limitations. Front Pharmacol. 2016;7:171. https://doi.org/10.3389/fphar.2016.00171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39:561–77.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Baldo, B.A., Pham, N.H. (2021). Diagnosis of Allergic Reactions to Drugs. In: Drug Allergy. Springer, Cham. https://doi.org/10.1007/978-3-030-51740-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-51740-3_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-51739-7

  • Online ISBN: 978-3-030-51740-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics