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Background: Factors implicated in the severity of drug reaction with eosinophilia and systemic symptoms (DRESS) have not been identified. We retrospectively describe and analyze severe cases of DRESS defined by history of intensive care unit admission and death due to DRESS.Observations: Of 15 patients retrospectively recruited in France, 14 were admitted to the intensive care unit and 3 died. The culprit drugs were already known to cause or trigger DRESS: allopurinol, minocycline hydrochloride, anticonvulsants, sulfonamides, and antibiotics. Visceral involvement with severe manifestations responsible for intensive care unit admission or death was variable and often multiple (pneumonitis, hepatitis, renal failure, encephalitis, hemophagocytosis, cardiac failure, and pancytopenia) and resulted in multior-gan failure in 11 patients. These severe complications sometimes developed late in DRESS. Human herpesvirus 6 infection was demonstrated in 6 of 7 patients. In addition, human herpesvirus 6 infection was demonstrated in involved viscera in 2 patients. Conclusions:Severe DRESS is rare. Some specificities of visceral involvement were associated with allopurinol and minocycline. However, visceral involvement comprising multiorgan failure seemed to be unpredictable. Better knowledge of DRESS is necessary to propose specific and prompt treatment. Early demonstration of human herpesvirus 6 reactivation could be considered a prognostic factor for identifying patients at higher risk and, hence, needs to be evaluated.

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe forms of hypersensitivity reactions affecting the skin. They are best considered severity variants of a single disease on the basis of similar pathology (epidermal necrolysis), risk factors, causes and frequent progression from SJS to TEN in a few days. Most cases occur in patients with normal metabolic pathways, after taking for a mean of 2 weeks a normal dosage of a medication for the first time. A few 'high-risk' drugs account for half of the cases of SJS as well as of TEN. Drug-specific cytotoxic T lymphocytes (hypersensitivity type IVc) induce the diffuse apoptosis of epidermal cells, probably in conjunction with amplification mechanisms not yet deciphered. Animal models point to the resemblance of epidermal necrolysis with acute graft-versus-host disease. Since mortality and morbidity of epidermal necrolysis are high, patients should be referred to specialized wards, burn units for the most severe cases. Symptomatic treatment is of tremendous importance in the absence of any intervention proven yet as capable of stopping the disease. Recent observations suggest that corticosteroids, more than highdose immunoglobulins, may deserve a formal study.

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