Correlations Between Clinical Patterns and Causes of Erythema Multiforme Majus, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis: Results of an International Prospective Study | Allergy and Clinical Immunology | JAMA Dermatology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.170.64.36. Please contact the publisher to request reinstatement.
1.
Bastuji-Garin  SRzany  BStern  RSShear  NHNaldi  LRoujeau  J-C Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.  Arch Dermatol. 1993;12992- 96Google ScholarCrossref
2.
Hebra  F Erythema exsudativum multiforme. Kaiserliche Akademie der Wissenschaften,ed. Atlas der Hautkrankheiten. Vienna, Austria Kaiserliche Akademie der Wissenschaften1866;655- 57Google Scholar
3.
Stevens  AMJohnson  FC A new eruptive fever associated with stomatitis and ophthalmia: report of two cases in children.  AJDC. 1922;24526- 533Google Scholar
4.
Kelly  JPAuquier  ARzany  B  et al.  An international collaborative case-control study of severe cutaneous adverse reactions (SCAR): design and methods.  J Clin Epidemiol. 1995;481099- 1108Google ScholarCrossref
5.
Roujeau  JCKelly  JPNaldi  L  et al.  Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.  N Engl J Med. 1995;3331600- 1607Google ScholarCrossref
6.
Kaufman  DWKelly  JPLevy  MShapiro  S The Drug Etiology of Agranulocytosis and Aplastic Anemia.  New York, NY Oxford University Press1991;103
7.
Lyell  A Requiem for toxic epidermal necrolysis.  Br J Dermatol. 1990;122837- 838Google ScholarCrossref
8.
Ruiz-Maldonado  R Acute disseminated epidermal necrosis types 1, 2, and 3: study of sixty cases.  J Am Acad Dermatol. 1985;13623- 635Google ScholarCrossref
9.
Rzany  BMockenhaupt  MBaur  S  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;49769- 773Google ScholarCrossref
10.
Assier  HBastuji-Garin  SRevuz  JRoujeau  J-C Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes.  Arch Dermatol. 1995;131539- 543Google ScholarCrossref
11.
Côté  BWechsler  JBastuji-Garin  SAssier  HRevuz  JRoujeau  J-C Clinicopathological correlations in erythema multiforme and Stevens-Johnson syndrome.  Arch Dermatol. 1995;1311268- 1272Google ScholarCrossref
12.
Rzany  BHering  OMockenhaupt  M  et al.  Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis.  Br J Dermatol. 1996;1356- 11Google ScholarCrossref
13.
Paquet  PPierard  GE Erythema multiforme and toxic epidermal necrolysis: a comparative study.  Am J Dermatopathol. 1997;19127- 132Google ScholarCrossref
14.
Kokuba  HAurelian  LBurnett  J Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-γ is expressed in HAEM lesions and tumor necrosis factor-α in drug-induced erythema multiforme lesions.  J Invest Dermatol. 1999;113808- 815Google ScholarCrossref
15.
Mockenhaupt  MSchröder  WSchlingman  JSchneck  BHering  OSchöpf  E Clinical re-evaluation of erythema exsudativum multiforme majus and Stevens-Johnson syndrome resulting in different etiology [abstract].  J Invest Dermatol. 1999;112661Google Scholar
16.
Tatnall  FMSchofield  JKLeigh  IM A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme.  Br J Dermatol. 1995;132267- 270Google ScholarCrossref
17.
Schulz  JTSheridan  RLRyan  CMMacKool  BTompkins  RG A 10-year experience with toxic epidermal necrolysis.  J Burn Care Rehabil. 2000;21199- 204Google ScholarCrossref
Study
August 2002

Correlations Between Clinical Patterns and Causes of Erythema Multiforme Majus, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis: Results of an International Prospective Study

Author Affiliations

From the Department of Biostatistics and Epidemiology, Institut Gustave-Roussy, Villejuif, France (Ms Auquier-Dunant); Dokumentationszentrum schwerer Hautreaktionen/Department of Dermatology, Albert-Ludwigs-Universität, Freiburg, Germany (Drs Mockenhaupt and Schröder); Gruppo Italiano Studi Epidemiologici in Dermatologia/Department of Dermatology, Università degli Studi di Milano, Bergamo, Italy (Dr Naldi); Grupo Português ELYS/Department of Dermatology and Immunology, Hospital S. João, Faculdade de Medicina, Porto, Portugal (Dr Correia); and Department of Dermatology, Hôpital Henri Mondor, Université Paris XII, Créteil, France (Dr Roujeau). A complete listing of the members of the Severe Cutaneous Adverse Reactions (SCAR) Study Group has been published previously (N Engl J Med. 1995;333:1606).

Arch Dermatol. 2002;138(8):1019-1024. doi:10.1001/archderm.138.8.1019
Abstract

Background  It was proposed that Stevens-Johnson syndrome and toxic epidermal necrolysis differed from erythema multiforme majus by the pattern and localization of skin lesions.

Objective  To evaluate the validity of this clinical separation.

Design  Case-control study.

Settings  Active survey from 1989 to 1995 of 1800 hospital departments in Europe.

Patients  A total of 552 patients and 1720 control subjects.

Methods  Cases were sorted into 5 groups (erythema multiforme majus, Stevens-Johnson syndrome, Stevens-Johnson syndrome–toxic epidermal necrolysis overlap, toxic epidermal necrolysis, and unclassified erythema multiforme majus or Stevens-Johnson syndrome) by experts blinded as to exposure to drugs and other factors. Etiologic fractions for herpes and drugs obtained from case-control analyses were compared between these groups.

Results  Erythema multiforme majus significantly differed from Stevens-Johnson syndrome, overlap, and toxic epidermal necrolysis by occurrence in younger males, frequent recurrences, less fever, milder mucosal lesions, and lack of association with collagen vascular diseases, human immunodeficiency virus infection, or cancer. Recent or recurrent herpes was the principal risk factor for erythema multiforme majus (etiologic fractions of 29% and 17%, respectively) and had a role in Stevens-Johnson syndrome (etiologic fractions of 6% and 10%) but not in overlap cases or toxic epidermal necrolysis. Drugs had higher etiologic fractions for Stevens-Johnson syndrome, overlap, or toxic epidermal necrolysis (64%-66%) than for erythema multiforme majus (18%). Unclassified cases mostly behaved clinically like erythema multiforme.

Conclusions  This large prospective study confirmed that erythema multiforme majus differs from Stevens-Johnson syndrome and toxic epidermal necrolysis not only in severity but also in several demographic characteristics and causes.

×