Dw. Kaufman, EPIDEMIOLOGIC APPROACHES TO THE STUDY OF TOXIC EPIDERMAL NECROLYSIS, Journal of investigative dermatology, 102(6), 1994, pp. 190000031-190000033
The appropriate epidemiologic strategy for studying the etiology of to
xic epidermal necrolysis is determined by the characteristics of the d
isease, particularly its rarity and the fact that it is caused by nume
rous drugs. Although information about drugs as risk factors can in pr
incipal be obtained from case reports and experimental studies, the fo
rmer are subject to bias and the latter ace impractical because toxic
epidermal necrolysis is so rare. Cohort studies are also impractical b
ecause of the rarity of the outcome. An automated database, even if ba
sed on a large population, can only yield valid results if it is used
as the starting point for a case-control study that includes access to
the subjects and to the medical records for information to confirm th
e diagnosis. A population-based case registry can provide a large enou
gh and well-documented series of cases, but does not allow for the val
id estimation of risks because it lacks a comparison series. This leav
es a case-control study as the only strategy that is both practical an
d valid. An ongoing international case-control study of toxic epiderma
l necrolysis and Stevens-Johnson syndrome in relation to the use of dr
ugs is described. Data collection has proceeded in France, Italy, Germ
any, and Portugal. The study in Germany is conducted within a populati
on-based case registry, and the study in Portugal is also population b
ased; this will allow for the estimation of absolute risks. Data on de
mographic factors and medical history, a detailed history of drug use
in the month before hospital admission, and various other factors are
collected by interview of the cases and hospital controls. Cases are c
onfirmed in an independent review process in which the diagnoses, and
classification a spectrum of Stevens-Johnson syndrome and toxic epider
mal necrolysis, are determined without knowledge of drug use. As of Ju
ne, 1993, 459 cases and 1299 controls have been enrolled. At the sched
uled end of data collection in 1995, the projected totals are 698 case
s and 1956 controls. These large numbers will allow for the detailed e
valuation of even relatively uncommonly used drugs, for the evaluation
of more commonly used drugs in relation to subtypes of toxic epiderma
l necrolysis/Stevens-Johnson syndrome, and for the comparison of resul
ts between countries.