Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis.
BACKGROUND
Toxic epidermal necrolysis (TEN) is associated with a 30% death rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN.


METHODS
The patients received a 5-day course of thalidomide 400 mg daily or placebo. The main endpoint was the progression of skin detachment after day 7. Secondary endpoints were the severity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were measured.


RESULTS
The study was stopped because there was excess mortality in the thalidomide group--ten of 12 patients died compared with three of ten in the placebo group (Fisher's exact test with Katz's approximation, relative risk=2.78, p=0.03). After adjustment for SAPS, mortality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was higher in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p=0.07).


CONCLUSIONS
Even though few patients were included, our data suggest that thalidomide is detrimental in TEN, possibly because of a paradoxical enhancement of TNF-alpha production.
Wolkenstein
P
P
Department of Dermatology, Hôpital Henri-Mondor, University Paris XII, Créteil, France.
Latarjet
J
J
Roujeau
J C
JC
Duguet
C
C
Boudeau
S
S
Vaillant
L
L
Maignan
M
M
Schuhmacher
M H
MH
Milpied
B
B
Pilorget
A
A
Bocquet
H
H
Brun-Buisson
C
C
Revuz
J
J
D000328:Adult; D000368:Aged; D002423:Cause of Death; D003879:Dermatologic Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013262:Stevens-Johnson Syndrome / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
D003879:Dermatologic Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide