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Management of severe drug reactions: a retrospective monocentric analysis

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Abstract

Background

In contrast to the classic frequently seen drug eruptions, the rare severe drug reactions such as acute generalized exanthematous pustulosis (AGEP), erythema multiforme (EM), Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN, Lyell’s syndrome), and drug reaction with eosinophilia and systemic symptoms (DRESS) are frequently associated with increased mortality. Neither their acute management nor their further allergy diagnostic testing to avoid re-exposure and enable restriction of substances prohibited due to the event are standardized.

Materials and methods

The management of severe adverse drug reactions was investigated in a 10-year monocentric retrospective study.

Results

TEN (43.5%) and EM (29.0%) were the two most common subtypes of severe adverse drug reactions, while AGEP (3.2%), SJS (6.5%), and DRESS (17.7%) were less frequent. The acute management of 62 patients with severe adverse drug reactions was generally performed using systemic glucocorticoids (58.1%) or as a combination therapy consisting of glucocorticoids and intravenous immunoglobulins (IVIG, 41.9%), which were usually used in severe clinical courses. The most commonly suspected triggers were beta-lactam antibiotics (28.8%), followed by metamizole (19.4%) and sulfonamide antibiotics (17.7%).

Conclusion

Due to the rarity and heterogeneity of this patient population, there is scant reliable data on the systemic treatment of SJS/TEN. Therefore, whether it confers an evident benefit remains unclear. Although the allergy diagnostic testing of severe adverse drug reactions is complex, it is often able to yield important insights and should be performed.

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Abbreviations

AGEP:

Acute generalized exanthematous pustulosis

CsA:

Cyclosporine A

DRESS:

Drug reaction with eosinophilia and systemic symptoms

EM:

Erythema multiforme

GC:

Glucocorticoids

IgE:

Immunoglobulin E

IVIG:

Intravenous immunoglobulins

LTT:

Lymphocyte transformation test

SJS:

Stevens–Johnson syndrome

TEN:

Toxic epidermal necrolysis (Lyell’s syndrome)

ADR:

Adverse drug reactions

References

  1. Bork K. Arzneinebenwirkungen. In: Braun-Falco O, Plewig G, Wolff HH, Burgdorf WHC, Landthaler M, editors. Dermatologie und Venerologie. 5th ed. Berlin-Heidelberg: Springer; 2005. pp. 425–6.

    Chapter  Google Scholar 

  2. Coombs RR. Immunopathology. Br Med J. 1968;1:597–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sidoroff A, Dunant A, Viboud C, Halevy S, Bavinck JN, Naldi L, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP) – results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157:989–96.

    Article  CAS  PubMed  Google Scholar 

  4. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129:92–6.

    Article  CAS  PubMed  Google Scholar 

  5. Mockenhaupt M. Severe drug-induced skin reactions. Stevens-Johnson syndrome and toxic epidermal necrolysis. Hautarzt. 2014;65:415–23.

    Article  CAS  PubMed  Google Scholar 

  6. Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169:1071–80.

    Article  CAS  PubMed  Google Scholar 

  7. Rzany B, Mockenhaupt M, Baur S, Schröder W, Stocker U, Mueller J, et al. Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990–1992): structure and results of a population-based registry. J Clin Epidemiol. 1996;49:769–73.

    Article  CAS  PubMed  Google Scholar 

  8. Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol. 1990;126:43–7.

    Article  CAS  PubMed  Google Scholar 

  9. Roujeau JC, Guillaume JC, Fabre JP, Penso D, Fléchet ML, Girre JP. Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981–1985. Arch Dermatol. 1990;126:37–42.

    Article  CAS  PubMed  Google Scholar 

  10. Sekula P, Dunant A, Mockenhaupt M, Naldi L, Bouwes Bavinck JN, Halevy S, et al. Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol. 2013;133:1197–204.

    Article  CAS  PubMed  Google Scholar 

  11. Roujeau JC, Bastuji-Garin S. Systematic review of treatments for Stevens-Johnson syndrome and toxic epidermal necrolysis using the SCORTEN score as a tool for evaluating mortality. Ther Adv Drug Saf. 2011;2:87–94.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zimmermann S, Sekula P, Venhoff M, Motschall E, Knaus J, Schumacher M, et al. Systemic Immunomodulating therapies for Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. Jama Dermatol. 2017;153:514–22.

    Article  PubMed  Google Scholar 

  13. Enk AH, Hadaschik EN, Eming R, Fierlbeck G, French LE, Girolomoni G, et al. European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology. J Eur Acad Dermatol Venereol. 2016;30:1657–69.

    Article  CAS  PubMed  Google Scholar 

  14. Mahar PD, Wasiak J, Hii B, Cleland H, Watters DA, Gin D, et al. A systematic review of the management and outcome of toxic epidermal necrolysis treated in burns centres. Burns. 2014;40:1245–54.

    Article  PubMed  Google Scholar 

  15. Ye LP, Zhang C, Zhu QX. The effect of intravenous immunoglobulin combined with corticosteroid on the progression of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis. PLoS ONE. 2016;11:e167120.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Valeyrie-Allanore L, Wolkenstein P, Brochard L, Ortonne N, Maitre B, Revuz J, et al. Open trial of ciclosporin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2010;163:847–53.

    Article  CAS  PubMed  Google Scholar 

  17. González-Herrada C, Rodríguez-Martín S, Cachafeiro L, Lerma V, González O, Lorente JA, et al. Cyclosporine use in epidermal necrolysis is associated with an important mortality reduction: evidence from three different approaches. J Invest Dermatol. 2017;137:2092–100.

    Article  PubMed  Google Scholar 

  18. Finkelstein Y, Macdonald EM, Li P, Hutson JR, Juurlink DN. Recurrence and mortality following severe cutaneous adverse reactions. JAMA. 2014;311:2231–2.

    Article  CAS  PubMed  Google Scholar 

  19. Alniemi DT, Wetter DA, Bridges AG, El-Azhary RA, Davis MD, Camilleri MJ, et al. Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996–2013. Int J Dermatol. 2017;56:405–14.

    Article  CAS  PubMed  Google Scholar 

  20. Möbs C, Pfützner W. Diagnostics of drug hypersensitivity reactions. Hautarzt. 2017;68:19–28.

    Article  PubMed  Google Scholar 

  21. Paulmann M, Mockenhaupt M. Severe drug-induced skin reactions: clinical features, diagnosis, etiology, and therapy. J Dtsch Dermatol Ges. 2015;13:625–45.

    PubMed  Google Scholar 

  22. Mashiah J, Brenner S. A systemic reaction to patch testing for the evaluation of acute generalized exanthematous pustulosis. Arch Dermatol. 2003;139:1181–3.

    Article  PubMed  Google Scholar 

  23. Vaillant L, Camenen I, Lorette G. Patch testing with carbamazepine: reinduction of an exfoliative dermatitis. Arch Dermatol. 1989;125:299.

    Article  CAS  PubMed  Google Scholar 

  24. Barbaud A, Collet E, Milpied B, Assier H, Staumont D, Avenel-Audran M, et al. A multicentre 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;168:555–62.

    Article  CAS  PubMed  Google Scholar 

  25. Santiago F, Gonçalo M, Vieira R, Coelho S, Figueiredo A. Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS). Contact Derm. 2010;62:47–53.

    Article  CAS  PubMed  Google Scholar 

  26. Yaylacı S, Demir MV, Temiz T, Tamer A, Uslan MI. Allopurinol-induced DRESS syndrome. Indian J Pharmacol. 2012;44:412–4.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Brockow K, Przybilla B, Aberer W, Bircher AJ, Brehler R, Dickel H, et al. 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). Allergo J Int. 2015;24:94–105.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Brockow K, Ring J. Anaphylaxis to radiographic contrast media. Curr Opin Allergy Clin Immunol. 2011;11:326–31.

    Article  CAS  PubMed  Google Scholar 

  29. Fernández TD, Torres MJ, Blanca-López N, Rodríguez-Bada JL, Gomez E, Canto G, et al. Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins. Allergy. 2009;64:242–8.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, Tübingen University Hospital, Liebermeisterstraße 25, 72076, Tübingen, Germany

    Jonas Ali, Bernadette Schoch, Gwendolyn Glatthaar, Jörg Fischer &  Amir S. Yazdi

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  1. Jonas Ali
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  2. Bernadette Schoch
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  3. Gwendolyn Glatthaar
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  4. Jörg Fischer
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  5. Amir S. Yazdi
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Correspondence to Amir S. Yazdi.

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Conflict of interest

J. Ali, B. Schoch, G. Glatthaar, J. Fischer, and A.S. Yazdi declare that they have no competing interests.

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Ali, J., Schoch, B., Glatthaar, G. et al. Management of severe drug reactions: a retrospective monocentric analysis. Allergo J Int 27, 49–55 (2018). https://doi.org/10.1007/s40629-017-0047-6

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  • DOI: https://doi.org/10.1007/s40629-017-0047-6

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