Skip to main content
SpringerLink
Log in

Introduction: Classification, Terminology, Epidemiology, and Etiology of Cutaneous Adverse Drug Reactions

  • Chapter
  • First Online:
Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions

Abstract

Whenever a cutaneous adverse drug reactions (cADR) is suspected, it is important to establish the dermatological diagnosis, since reaction patterns may differ in causality, time latency between the beginning of drug use and reaction onset, and prognosis. Few epidemiologic studies have been performed on frequent non-life-threatening cADR, such as maculopapular exanthema, fixed drug eruption, and urticaria. For rare but life-threatening severe cutaneous adverse reactions, e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms, several epidemiologic studies have been or are currently performed. They allow for estimation of incidence rates, demographic data, and drug risks.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Abbreviations

ADR:

Adverse drug reactions

AGEP:

Acute generalized exanthematous pustulosis

BSA:

Body surface area

cADR:

Cutaneous adverse drug reactions

DIHS:

Drug-induced hypersensitivity syndrome

DRESS:

Drug reaction with eosinophilia and systemic symptoms

E(E)M:

Erythema (exsudativum) multiforme

EMM:

EM majus

EN:

Epithelial necrolysis

FDE:

Fixed drug eruption

GBFDE:

Generalized bullous fixed drug eruption

HSS:

Hypersensitivity syndrome

MPE:

Maculopapular exanthema

NSAIDs:

Nonsteroidal anti-inflammatory drugs

SCAR:

Severe cutaneous adverse reactions

SJS:

Stevens–Johnson syndrome

TEN:

Toxic epidermal necrolysis

WHO:

World Health Organization

References

  • Auquier-Dunant A, Mockenhaupt M, Naldi L et al (2002) Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol 138:1019–1024

    Article  PubMed  Google Scholar 

  • Barbaud A, Collet E, Milpied B et al (2013) 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 168:555–562. https://doi.org/10.1111/bjd.12125

    Article  CAS  PubMed  Google Scholar 

  • Bastuji-Garin S, Rzany B, Stern RS et al (1993) Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 129:92–96

    Article  CAS  PubMed  Google Scholar 

  • Bocquet H, Bagot M, Roujeau JC (1996) Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 15:250–257

    Article  CAS  PubMed  Google Scholar 

  • Bork K (2009) Cutaneous adverse drug reactions. In: Burgdorf W, Plewig G, Wolff HH, Landthaler M (eds) Braun-Falco’s dermatology, 3rd edn. Springer, Heidelberg, pp 456–472

    Chapter  Google Scholar 

  • Bouvy JC, De Bruin ML, Koopmanschap MA (2015) Epidemiology of adverse drug reactions in Europe: a review of recent observational studies. Drug Saf 38:437–453. https://doi.org/10.1007/s40264-015-0281-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN et al (2001) Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. AIDS Lond Engl 15:1843–1848

    Article  CAS  Google Scholar 

  • Fiszenson-Albala F, Auzerie V, Mahe E et al (2003) A 6-month prospective survey of cutaneous drug reactions in a hospital setting. Br J Dermatol 149:1018–1022

    Article  CAS  PubMed  Google Scholar 

  • Grosber M, Carsin H, Leclerc F (2006) Epidermal necrolysis in association with Mycoplasma pneumoniae infection. J Invest Dermatol 126:S3–S116. https://doi.org/10.1038/sj.jid.5700514

    Article  Google Scholar 

  • Haddad C, Sidoroff A, Kardaun SH et al (2013) Stevens-Johnson syndrome/toxic epidermal necrolysis: are drug dictionaries correctly informing physicians regarding the risk? Drug Saf 36:681–686. https://doi.org/10.1007/s40264-013-0070-6

    Article  PubMed  Google Scholar 

  • Halevy S, Ghislain P-D, Mockenhaupt M et al (2008) Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 58:25–32. https://doi.org/10.1016/j.jaad.2007.08.036

    Article  PubMed  Google Scholar 

  • Hernández-Salazar A, Rosales SP-L, Rangel-Frausto S et al (2006) Epidemiology of adverse cutaneous drug reactions. A prospective study in hospitalized patients. Arch Med Res 37:899–902. https://doi.org/10.1016/j.arcmed.2006.03.010

    Article  PubMed  Google Scholar 

  • Hunziker T, Künzi UP, Braunschweig S et al (1997) Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey. Allergy 52:388–393

    Article  CAS  PubMed  Google Scholar 

  • Johansson SGO, Bieber T, Dahl R et al (2004) Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 113:832–836. https://doi.org/10.1016/j.jaci.2003.12.591

    Article  CAS  PubMed  Google Scholar 

  • Kardaun SH, Sidoroff A, Valeyrie-Allanore L et al (2007) Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 156:609–611. https://doi.org/10.1111/j.1365-2133.2006.07704.x

    Article  CAS  PubMed  Google Scholar 

  • Kardaun SH, Sekula P, Valeyrie-Allanore L et al (2013) Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol 169:1071–1080. https://doi.org/10.1111/bjd.12501

    Article  CAS  PubMed  Google Scholar 

  • Kauppinen K (1972) Cutaneous reactions to drugs with special reference to severe bullous mucocutaneous eruptions and sulphonamides. Acta Derm Venereol Suppl (Stockh) 68:1–89

    CAS  Google Scholar 

  • Lipowicz S, Sekula P, Ingen-Housz-Oro S et al (2013) Prognosis of generalized bullous fixed drug eruption: comparison with Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 168:726–732. https://doi.org/10.1111/bjd.12133

    Article  CAS  PubMed  Google Scholar 

  • Mardivirin L, Valeyrie-Allanore L, Branlant-Redon E et al (2010) Amoxicillin-induced flare in patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): report of seven cases and demonstration of a direct effect of amoxicillin on Human Herpesvirus 6 replication in vitro. Eur J Dermatol 20:68–73. https://doi.org/10.1684/ejd.2010.0821

    Article  CAS  PubMed  Google Scholar 

  • Mockenhaupt M (2009) Severe cutaneous adverse reactions. In: Burgdorf W, Plewig G, Wolff HH, Landthaler M (eds) Braun-Falco’s dermatology, 3rd edn. Springer, Heidelberg, pp 473–484

    Chapter  Google Scholar 

  • Mockenhaupt M, Viboud C, Dunant A et al (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 128:35–44. https://doi.org/10.1038/sj.jid.5701033

    Article  CAS  PubMed  Google Scholar 

  • Park CS, Kim T-B, Kim SL et al (2008) The use of an electronic medical record system for mandatory reporting of drug hypersensitivity reactions has been shown to improve the management of patients in the university hospital in Korea. Pharmacoepidemiol Drug Saf 17:919–925. https://doi.org/10.1002/pds.1612

    Article  PubMed  Google Scholar 

  • Paulmann M, Mockenhaupt M (2016) Severe drug hypersensitivity reactions: clinical pattern, diagnosis, etiology and therapeutic options. Curr Pharm Des 22:6852–6861. https://doi.org/10.2174/1381612822666160928125152

    Article  CAS  PubMed  Google Scholar 

  • Paulmann M, Mockenhaupt M (2017) Fever in Stevens-Johnson syndrome and toxic epidermal necrolysis in pediatric cases: laboratory work-up and antibiotic therapy. Pediatr Infect Dis J 36:513–515. https://doi.org/10.1097/INF.0000000000001571

    Article  PubMed  Google Scholar 

  • Roujeau JC, Guillaume JC, Fabre JP et al (1990) Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981–1985. Arch Dermatol 126:37–42

    Article  CAS  PubMed  Google Scholar 

  • Roujeau JC, Kelly JP, Naldi L et al (1995) Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 333:1600–1607. https://doi.org/10.1056/NEJM199512143332404

    Article  CAS  PubMed  Google Scholar 

  • Rzany B, Mockenhaupt M, Baur S et al (1996) 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 49:769–773

    Article  CAS  PubMed  Google Scholar 

  • Salopek TG (1997) Nikolsky’s sign: is it “dry” or is it “wet”? Br J Dermatol 136:762–767

    Article  CAS  PubMed  Google Scholar 

  • Sassolas B, Haddad C, Mockenhaupt M et al (2010) ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther 88:60–68. https://doi.org/10.1038/clpt.2009.252

    Article  CAS  PubMed  Google Scholar 

  • Schlienger RG, Shapiro LE, Shear NH (1998) Lamotrigine-induced severe cutaneous adverse reactions. Epilepsia 39(Suppl 7):S22–S26

    Article  CAS  PubMed  Google Scholar 

  • Schöpf E, Stühmer A, Rzany B et al (1991) Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany. Arch Dermatol 127:839–842

    Article  PubMed  Google Scholar 

  • Schröder W, Mockenhaupt M, Schlingmann J et al (1999) Clinical re-classification of severe skin reactions and evaluation of their etiology in a population-based registry. In: Victor N, Blettner M, Edler L et al (eds) Medical informatics, biostatistics and epidemiology for efficient health care and medical research: contributions from the 44th annual conference of the GMDS… Heidelberg, September 1999. Urban und Vogel, München, pp 107–110

    Google Scholar 

  • Sekula P, Dunant A, Mockenhaupt M et al (2013) Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol 133:1197–1204. https://doi.org/10.1038/jid.2012.510

    Article  CAS  PubMed  Google Scholar 

  • Shear NH, Spielberg SP (1988) Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk. J Clin Invest 82:1826–1832. https://doi.org/10.1172/JCI113798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shiohara T, Kano Y, Takahashi R et al (2012) Drug-induced hypersensitivity syndrome: recent advances in the diagnosis, pathogenesis and management. Chem Immunol Allergy 97:122–138. https://doi.org/10.1159/000335624

    Article  PubMed  Google Scholar 

  • Sidoroff A, Halevy S, Bavinck JN et al (2001) Acute generalized exanthematous pustulosis (AGEP)—a clinical reaction pattern. J Cutan Pathol 28:113–119

    Article  CAS  PubMed  Google Scholar 

  • Sidoroff A, Dunant A, Viboud C et al (2007) Risk factors for acute generalized exanthematous pustulosis (AGEP)—results of a multinational case-control study (EuroSCAR). Br J Dermatol 157:989–996. https://doi.org/10.1111/j.1365-2133.2007.08156.x

    Article  CAS  PubMed  Google Scholar 

  • Strom BL, Carson JL, Halpern AC et al (1991) A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures. Arch Dermatol 127:831–838

    Article  CAS  PubMed  Google Scholar 

  • Thong BY-H, Leong K-P, Tang C-Y, Chng H-H (2003) Drug allergy in a general hospital: Results of a novel prospective inpatient reporting system. Ann Allergy Asthma Immunol 90:342–347. https://doi.org/10.1016/S1081-1206(10)61804-2

    Article  PubMed  Google Scholar 

  • Valeyrie-Allanore L, Poulalhon N, Fagot J-P et al (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy. Radiother Oncol J Eur Soc Ther Radiol Oncol 87:300–303. https://doi.org/10.1016/j.radonc.2008.01.021

    Article  Google Scholar 

  • World Health Organization (1972) International drug monitoring: the role of national centres. Report of a WHO meeting. World Health Organ Tech Rep Ser 498, pp 1–25

    Google Scholar 

  • Ziemer M, Mockenhaupt M (2011) Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. In: Khopkar U (ed) Skin biopsy—perspectives. InTech, Rijeka

    Google Scholar 

  • Ziemer M, Wiesend CL, Vetter R et al (2007) Cutaneous adverse reactions to valdecoxib distinct from Stevens-Johnson syndrome and toxic epidermal necrolysis. Arch Dermatol 143:711–716. https://doi.org/10.1001/archderm.143.6.711

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Medical Center and Medical Faculty—University of Freiburg, Freiburg, Germany

    Maja Mockenhaupt

Authors
  1. Maja Mockenhaupt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maja Mockenhaupt .

Editor information

Editors and Affiliations

  1. University of Toronto Medical School, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Neil H. Shear

  2. Department of Dermatology, Emek Medical Center, Afula, Israel

    Roni P. Dodiuk-Gad

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mockenhaupt, M. (2019). Introduction: Classification, Terminology, Epidemiology, and Etiology of Cutaneous Adverse Drug Reactions. In: Shear, N., Dodiuk-Gad, R. (eds) Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions. Adis, Singapore. https://doi.org/10.1007/978-981-13-1489-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-1489-6_1

  • Published:

  • Publisher Name: Adis, Singapore

  • Print ISBN: 978-981-13-1488-9

  • Online ISBN: 978-981-13-1489-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation