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Usefulness of Cutaneous Provocation Tests to Study Drugs Responsible for Cutaneous Adverse Drug Reactions

  • Margarida GonçaloEmail author
Contact Dermatitis (A Giménez-Arnau, Section Editor)
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Part of the following topical collections:
  1. Topical Collection on Contact Dermatitis

Abstract

Purpose of Review

Cutaneous adverse drug reactions, particularly immune-mediated idiosyncratic reactions, are a very challenging area of Dermatology. For confirming the culprit drug, after a complete history of drug exposure with its chronologic relation with the eruption and characterization of the pattern of the drug eruption, skin provocation tests can be performed after resolution of the acute phase.

Recent Findings

Patch tests are indicated in the study of non-immediate T cell–mediated drug eruptions (maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis, fixed drug eruption, and drug photoallergy). It is recommended to test with pure drugs usually at 10% pet commercialized as patch test allergens, but in most cases, drugs have to be prepared in house, whenever possible in a final dilution at 10% pet. Methods are similar to patch testing in allergic contact dermatitis except in fixed drug eruptions where duplicate tests are needed; one of them applied for 24 h on a residual lesion.

Summary

Patch tests are safe and highly specific when performed according to the recommendations, but sensitivity is highest in exanthemas, DRESS, and fixed drug eruptions and particularly for abacavir, carbamazepine, aminopenicillins and other antibiotics, diltiazem, and tetrazepam. Allopurinol is never positive, and reactivity is low in SJS/TEN. Therefore, a negative patch test cannot exclude a possible culprit, but a positive patch test is almost always relevant.

Patch tests with drugs are also useful for evaluating cross-reactions and studying effector mechanism involved in the cutaneous adverse reaction.

Keywords

Patch testing Non-immediate drug eruptions Drug patch tests Cross-reactions 

Notes

Compliance with Ethical Standards

Conflict of Interest

Margarida Gonçalo declares that she has no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:• Of importance •• Of major importance

  1. 1.
    Gonçalo M, Bruynzeel D. Mechanisms in cutaneous drug hypersensitivity reactions. In: Wilhem K, Zhai H, Maibach H, editors. Dermatotoxicology. 2nd ed. Boca Raton. Florida: CRC Press; 2012. p. 78–92.CrossRefGoogle Scholar
  2. 2.
    Peter JG, Lehloenya R, Dlamini S, Risma K, White KD, Konvinse KC, et al. Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice. J Allergy Clin Immunol Pract Elsevier Inc. 2017;5(3):547–63.The authors provide an extensive review on the mechanisms of the more frequent and severe cutaneous adverse drug reactions.Google Scholar
  3. 3.
    Pinto Gouveia M, Gameiro A, Coutinho I, Pereira N, Cardoso JC, Gonçalo M. Overlap between maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms among cutaneous adverse drug reactions in a dermatology ward. Br J Dermatol. 2016;175(5):1274–83.CrossRefGoogle Scholar
  4. 4.
    Wang C, Dao R, Chung W. Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions. Curr Opin Allergy Clin Immunol. 2016;16(4):339–45.CrossRefGoogle Scholar
  5. 5.
    Hjortlund J, Mortz CG, Skov PS, Bindslev-Jensen C. Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge. Allergy. 2013;68(8):1057–64.CrossRefGoogle Scholar
  6. 6.
    Barbaud A, Gonçalo M, Bircher A, Bruynzeel D. Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Contact Dermatitis. 2001;45:321–8.CrossRefGoogle Scholar
  7. 7.
    Johansen J, Aalto-Korte K, Agner T, Andersen K, Bircher A, Bruze M, et al. European Society of Contact Dermatitis guideline for diagnostic patch testing—recommendations on best practice. Contact Dermatitis. 2015;73(4):195–221.Recommendations on the practical use of patch testing for diagnosing cutaneous hypersensitivity, namely in cutaneous adverse drug reactions.Google Scholar
  8. 8.
    Redwood AJ, Pavlos RK, White KD, Phillips EJ. Human leukocyte antigens: key regulators of T cell mediated drug hypersensitivity. HLA. 2018;91(1):3–16.CrossRefGoogle Scholar
  9. 9.
    Lachapelle J-M. Historical aspects. In: Johansen J, Frosch P, Lepoittevin J, editors. Contact dermatitis. 5th ed. Berlin-Heidelberg: Springer-Verlag; 2011. p. 1–9.Google Scholar
  10. 10.
    Barbaud A. Tests cutanés dans l’investigation des toxidermies: de la physiopathologie aux résultats des investigations. Therapie. 2002;57:258–62.PubMedGoogle Scholar
  11. 11.
    Lammintausta K, KorteKangas-Savolainen O. The usefulness of skin tests to prove drug hypersensitivity. Br J Dermatol. 2005;152:968–74.CrossRefGoogle Scholar
  12. 12.
    Pinheiro V, Pestana C, Pinho A, Antunes I, Gonçalo M. Occupational allergic contact dermatitis caused by antibiotics in healthcare workers—relationship with non-immediate drug eruptions. Contact Dermatitis. 2018;78(4):281–6.CrossRefGoogle Scholar
  13. 13.
    Hausermann P, Harr T, Bircher A. Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis. 2004;51:297–310.CrossRefGoogle Scholar
  14. 14.
    Pinho A, Marta A, Coutinho I, Gonçalo M. Long-term reproducibility of positive patch test reactions in patients with non-immediate cutaneous adverse drug reactions to antibiotics. Contact Dermatitis. 2017;76(4):204–9.In this original study it was shown that patch test reactivity to drugs can be reproduced after long intervals confirming the long lasting hypersensitivity and PT usefulness as a retrospective diagnosis.Google Scholar
  15. 15.
    Braun V, Darrigrade A-S, Milpied B. Positive patch test reaction to carbamazepine after a very long delay. Contact Dermatitis. 2018;79(4):240–1.CrossRefGoogle Scholar
  16. 16.
    Serra D, Gonçalo M, Mariano A, Figueiredo A. Pustular psoriasis and drug-induced pustulosis. G Ital Dermatol Venereol. 2011;146(2):155–8.PubMedGoogle Scholar
  17. 17.
    Serra D, Ramos L, Brinca A, Gonçalo M. Acute generalized exanthematous pustulosis associated with acyclovir, confirmed by patch testing. Dermatitis. 2012;23(2):99–100.CrossRefGoogle Scholar
  18. 18.
    Gonçalo M, Santiago F, Julião M, Tellechea O. Postive patch test in toxic epidermal necrolysis with clinical and histopathological aspect typical of TEN. Contact Dermatitis. 2010;63(S1):22–3.Google Scholar
  19. 19.
    Gonçalo M, Cardoso J, Coutinho I, Gameiro A, Tellechea O. Histopathology of patch tests depends on the pattern of CADR, not on the culprit drug. Contact Dermatitis. 2014;70(S1):36–7.Google Scholar
  20. 20.
    Yawalkar N, Hari Y, Frutig K, Egli F, Wendland T, Braathen L, et al. T cells isolated from positive epicutaneous test reactions to amoxicillin and ceftriaxone are drug specific and cytotoxic. J Invest Dermatol. 2000;115(4):647–52.CrossRefGoogle Scholar
  21. 21.
    Andrade P, Brinca A, Gonçalo M. Patch testing in fixed drug eruptions. a 20-year review. Contact Dermatitis. 2011;65(4):195–201.CrossRefGoogle Scholar
  22. 22.
    Alanko K. Topical provocation of fixed drug eruption. A study of 30 patients. Contact Dermatitis. 1994;31:25–7.CrossRefGoogle Scholar
  23. 23.
    Gonçalo M, Ferguson J, Bonevalle A, Bruynzeel D, Giménez-Arnau A, Goossens A, et al. Photopatch testing: recommendations for a European photopatch test baseline series. Contact Dermatitis. 2013;68(4):239–43.CrossRefGoogle Scholar
  24. 24.
    Brajon D, Menetre S, Waton J, Poreaux C, Barbaud A. Non-irritant concentrations and amounts of active ingredient in drug patch tests. Contact Dermatitis. 2014;71(3):170–5.CrossRefGoogle Scholar
  25. 25.
    Assier H, Valeyrie-allanore L, Gener G, Carvalh MV, Chosidow O, Wolkenstein P. Patch testing in non-immediate cutaneous adverse drug reactions: value of extemporaneous patch tests. Contact Dermatitis. 2017;77(5):297–302.CrossRefGoogle Scholar
  26. 26.
    Pinho A, Santiago L, Gonçalo M. Patch testing in the investigation of non-immediate cutaneous adverse drug reactions to metamizole. Contact Dermatitis. 2017;76(4):238–9.CrossRefGoogle Scholar
  27. 27.
    Santiago F, Gonçalo M, Vieira R, Coelho S, Figueiredo A. Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS). Contact Dermatitis. 2010;62(1):47–53.CrossRefGoogle Scholar
  28. 28.
    Barbaud A, Collet E, Milpied B, Assier H, Staumont D, Avenel-Audran M, et al. A multicenter study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol. 2013;168(3):555–62.The authors show the safety and utility of patch testing in cutaneous adverse drug reactions. in a multicenter study with a very large number of patients and different classes of drugs.Google Scholar
  29. 29.
    Shebe K, Ngwanya MR, Gantsho N, Lehloenya RJ. Severe recurrence of drug rash with eosinophilia and systemic symptoms syndrome secondary to rifampicin patch testing in a human immunodeficiency virus-infected man. Contact Dermatitis. 2014;70(2):125–7.CrossRefGoogle Scholar
  30. 30.
    Romano A, Gaeta F, Valluzzi R, Alonzi C, Maggioletti M, Zaffiro A, et al. Absence of cross-reactivity to carbapenems in patients with delayed hypersensitivity to penicillins. Allergy. 2013;68(12):1618–21.CrossRefGoogle Scholar
  31. 31.
    Pinho A, Coutinho I, Gameiro A, Gouveia M, Gonçalo M. Patch testing—a valuable tool for investigating non-immediate cutaneous adverse drug reactions to antibiotics. J Eur Acad Dermatol Venereol. 2017;31(2):280–7.CrossRefGoogle Scholar
  32. 32.
    Pereira N, Canelas MM, Santiago F, Brites MM, Gonçalo M. Value of patch tests in clindamycin-related drug eruptions. Contact Dermatitis. 2011;65(4):202–7.CrossRefGoogle Scholar
  33. 33.
    Wolkenstein P, Chosidow O, Fléchet M-L, Robbiola O, Paul M, Dumé L, et al. Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Contact Dermatitis. 1996;35(4):234–6.CrossRefGoogle Scholar
  34. 34.
    Barbaud A, Trechot P, Weber-Muller F, Ulrich G, Commun N, Schmutz JL. Drug skin tests in cutaneous adverse drug reactions to pristinamycin: 29 cases with a study of cross-reactions between synergistins. Contact Dermatitis. 2004;50(1):22–6.CrossRefGoogle Scholar
  35. 35.
    Barbaud A, Girault P-Y, Schmutz J-L, Weber-Muller F, Trechot P. No cross-reactions between tetrazepam and other benzodiazepines: a possible chemical explanation. Contact Dermatitis. 2009;61:53–6.CrossRefGoogle Scholar
  36. 36.
    Vander Hulst K, Kerre S, Goossens A. Occupational allergic contact dermatitis from tetrazepam in nurses. Contact Dermatitis. 2010;62(5):303–8.CrossRefGoogle Scholar
  37. 37.
    Cravo M, Gonçalo M, Figueiredo A. Fixed drug eruption to cetirizine with positive lesional patch tests to the three piperazine derivatives. Int J Dermatol. 2007;46:760–2.CrossRefGoogle Scholar
  38. 38.
    Oliveira H, Gonçalo M, Reis J, Figueiredo A. Fixed drug eruption to piroxicam. Positive patch tests with cross-sensitivity to tenoxicam. J Dermatol Treat. 1999;10:209–12.CrossRefGoogle Scholar
  39. 39.
    Andrade P, Gonçalo M. Fixed drug eruption caused by etoricoxib-2 cases confirmed by patch testing. Contact Dermatitis. 2011;64(2):118–20.CrossRefGoogle Scholar
  40. 40.
    Gonçalo M, Figueiredo A, Tavares P, Fontes Ribeiro C, Teixeira F, Poiares Baptista A. Photosensitivity to piroxicam: absence of cross reaction with tenoxicam. Contact Dermatitis. 1992;27:287–90.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Clinic of Dermatology, University Hospital and Faculty of MedicineUniversity of CoimbraCoimbraPortugal

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