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Correlations Between Clinical Patterns and Causes of Erythema Multiforme Majus, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis
Results of an International Prospective Study
Ariane Auquier-Dunant, MS;
Maja Mockenhaupt, MD;
Luigi Naldi, MD;
Osvaldo Correia, MD;
Werner Schröder, MD;
Jean-Claude Roujeau, MD;
for the SCAR Study Group
Arch Dermatol. 2002;138:1019-1024.
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.
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).
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