Schwere Arzneimittel-induzierte Hautreaktionen

The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to develop and validate a specific severity-of-illness score for cases of toxic epidermal necrolysis admitted to a specialized unit and to compare it with the Simplified Acute Physiology Score and a burn scoring system. A sample of 165 patients was used to develop the toxic epidermal necrolysis-specific severity-of-illness score and evaluate the other scores, a sample of 75 for validation. Model development used logistic regression equations that were translated into probability of hospital mortality; validation used measures of calibration and discrimination. We identified seven independent risk factors for death and constituted the toxic epidermal necrolysis-specific severity-of-illness score: age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic epidermal necrolysis-specific severity-of-illness score point the odds ratio was 3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) = elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis-specific severity-of-illness score). Calibration demonstrated excellent agreement between expected (19. 6%) and actual (20%) mortality; discrimination was also excellent with a receiver operating characteristic area of 82%. The Simplified Acute Physiology Score and the burn score were also associated with mortality. The discriminatory powers were poorer (receiver operating characteristic area: 72 and 75%) and calibration of the Simplified Acute Physiology Score indicated a poor agreement between expected (9.1%) and actual (26.7%) mortality. This study demonstrates that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidermal necrolysis-specific severity-of-illness score. The Simplified Acute Physiology Score and burn score appear to be less adequate.

Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case-control study to quantify the risks associated with the use of specific drugs. Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. Among drugs usually used for short periods, the risks were increased for trimethoprim-sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to infinity); valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124). For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk. The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. But for none of the drugs does the excess risk exceed five cases per million users per week.