Drug-induced Toxic Epidermal Necrolysis Research Articles

Plasmapheresis in Severe Drug-Induced Toxic Epidermal Necrolysis

Five patients with severe drug-induced toxic epidermal necrolysis improved rapidly after one to two plasma exchanges. The improvement of all five patients treated with plasmapheresis contrasts with the disease's mortality rate of up to 50%, as reported in the literature and as observed among our previously treated patients. Since there is no effective treatment for toxic epidermal necrolysis, a controlled clinical trial to evaluate the effectiveness of plasma exchange would seem worthwhile.

Plasmapheresis in severe drug-induced toxic epidermal necrolysis

• Five patients with severe drug-induced toxic epidermal necrolysis improved rapidly after one to two plasma exchanges. The improvement of all five patients treated with plasmapheresis contrasts with the disease's mortality rate of up to 50%, as reported in the literature and as observed among our previously treated patients. Since there is no effective treatment for toxic epidermal necrolysis, a controlled clinical trial to evaluate the effectiveness of plasma exchange would seem worthwhile. (<i>Arch Dermatol</i>1985;121:1548-1549)

SJÖGREN-LIKE SYNDROME AFTER DRUG-INDUCED TOXIC EPIDERMAL NECROLYSIS

7 of 9 patients recovering from a drug-induced toxic epidermal necrolysis (TEN) which they had had 2 months to 4 years before had xerostomia, or keratoconjunctivitis sicca, or both. 5 patients had symptoms; 2 had severe visual impairment. In 5 cases there was lymphocytic infiltration of small salivary glands; in 2 patients this was identical to that of Sjögren syndrome. None of the patients had antinuclear antibody. TEN may occur during acute graft-versus-host disease (GVHD) and these observations are reminiscent of the sicca syndromes reported during chronic GVHD. They suggest that autoimmune mechanisms may be involved in drug-induced TEN and that Sjögren syndrome may occur as the result of a drug reaction.

Lymphocyte transformation test in drug-induced toxic epidermal necrolysis.

Lymphocyte transformation tests (LTT) to drugs remain widely used in drug reactions, despite controversies about their real usefulness. We tested the lymphocytes of 12 patients recovering from a drug-induced Toxic epidermal necrolysis (TEN). There was no difference between the amounts of thymidine incorporated when patients' lymphocytes were cultivated with culprit or innocent drugs. In both situations the lymphocytes from patients reacted like the lymphocytes from controls cultivated with the same panel of drugs. These negative results do not exclude that a hypersensitivity reaction may play a role in the physiopathology of TEN. Anyhow, they clearly indicate that testing lymphocyte transformation to drugs has no practical value in the diagnosis of TEN.

Delayed hypersensitivity in drug-induced toxic epidermal necrolysis

Delayed hypersensitivity in drug-induced toxic epidermal necrolysis

Toxic Epidermal Necrolysis

Drug-induced toxic epidermal necrolysis is a disease of severe morbidity and high mortality. In the ten cases reported herein, therapeutic measures, including antibiotics, closed mechanical ventilation, maintenance of fluid and electrolyte balance, and management in special burn-care units, failed to alter a poor prognosis. The administration of corticosteroids was of no apparent benefit and may have been detrimental. Young age seemed to have a favorable influence on survival. There developed a pattern of leukopenia due to severe granulocytopenia that proved to be of prognostic importance. Persistence of the granulocytopenia portended a fatal outcome, whereas recovery of the granulocyte count to normal indicated, overall, a more favorable trend. The cause of the granulocytopenia could not be determined.

Toxic epidermal necrolysis. Granulocytic leukopenia as a prognostic indicator.

Drug-induced toxic epidermal necrolysis is a disease of severe morbidity and high mortality. In the ten cases reported herein, therapeutic measures, including antibiotics, closed mechanical ventilation, maintenance of fluid and electrolyte balance, and management in special burn-care units, failed to alter a poor prognosis. The administration of corticosteroids was of no apparent benefit and may have been detrimental. Young age seemed to have a favorable influence on survival. There developed a pattern of leukopenia due to severe granulocytopenia that proved to be of prognostic importance. Persistence of the granulocytopenia portended a fatal outcome, whereas recovery of the granulocyte count to normal indicated, overall, a more favorable trend. The cause of the granulocytopenia could not be determined.

Observations on drug-induced toxic epidermal necrolysis in Singapore

Fifteen patients with toxic epidermal necrolysis (TEN) were studied. In all of them the TEN was related to drug ingestion and believed to be drug-induced. The drugs implicated include pyrazolone derivatives, allopurinol, barbiturates, tetracycline, phenytoin, and penicillamine. Possible etiologic co-factors are infections, cancer, and the systemic lupus erythematosus diathesis. The extent of skin loss varied from 25% to almost 100% involvement of the total body surface. Seven of the fifteen patients had more than 75% epidermal loss. Three deaths were recorded (20%). From observations on these fifteen patients it was found that a single drug can cause two "reaction" patterns, namely, Stevens-Johnson syndrome (or erythema multiforme) and TEN, at the same time or at different times in one and the same patient. It is stressed that from the prognostic and therapeutic viewpoints patients with TEN may be equated to patients with extensive partial-thickness burns and should be treated in a burn unit.

Delayed Hypersensitivity in Ampicillin-Induced Toxic Epidermal Necrolysis

A patient with ampicillin-induced toxic epidermal necrolysis (TEN) showed pronounced delayed hypersensitivity to ampicillin sodium by both intradermal and patch tests. In addition, a positive lymphocyte transformation test to ampicillin was demonstrated by an in vitro study. On the basis of these findings and the data found in the literature, we believe that delayed hypersensitivity plays a crucial role in the development of drug-induced TEN. We recommend patch testing with suspected medication in such cases.

Toxic shock syndrome or toxic epidermal necrolysis: Case reports showing clinical similarity and histologic separation

A case of toxic shock syndrome and a case of drug-induced toxic epidermal necrolysis with renal involvement are described. The two patients had similar early clinical manifestations and therefore posed a difficult differential diagnosis. Diagnostic distinction is important because therapy differs considerably. A skin biopsy in each case proved helpful in establishing the correct diagnosis, since there appears to be a different histologic pattern for each condition: superficial perivascular dermatitis for toxic shock syndrome and an interface dermatitis for toxic epidermal necrolysis.

Human Cadaver Homograft in Toxic Epidermal Necrolysis

Burn-unit management is described of severe drug-induced toxic epidermal necrolysis, with 90% skin and mucosal involvement. In this patient, in whom acidosis and sepsis complicated the case, wound coverage with heterograft was ineffective but cadaver skin homograft “take” occurred and the wound was closed. Some homograft remained on the healthy patient at 5 months after discharge.

Toxic Epidermal Necrolysis in Childhood: Differentiation from Staphylococcal Scalded Skin Syndrome

The staphylococcal scalded skin syndrome usually occurs in children less than 5 years old, whereas drug-induced toxic epidermal necrolysis is considered a disease of adults.1 Except for the age differential, the two often cannot be distinguished clinically. Therefore, rapid and definitive biopsy diagnosis is essential in the management of patients with acute exfoliative skin disorders. We wish to report the case of a young child with proven toxic epidermal necrolysis and review the manifestations of this disease, as well as the staphylococcal scalded skin syndrome. CASE REPORT A 4-year-old white girl was admitted to Strong Memorial Hospital because of a generalized bullous eruption.

Frozen section differentiation of drug-induced and staphylococcalinduced toxic epidermal necrolysis

Frozen section differentiation of drug-induced and staphylococcalinduced toxic epidermal necrolysis

Studies Of The Mechanism of Epidermal Injury By A Staphylococcal Epidermolytic Toxin

Experimental animal models of the two forms of toxic epidermal necrolysis have been reviewed: a murine model of staphylococcal-induced epidermolysis and a hamster model of graft-versus-host disease. In the former, a protein exotoxin, epidermolysin, has been purified and characterized. The exotoxin has a molecular weight of approximately 30,000 and causes a split beneath the granular layer. It is effective at 3 times 10(-12) moles. Epidermolysin does not require an intact complement system for its action since B10D2 mice deficient in C5 or mice injected with the decomplementing agent in cobra venom factor were susceptible to its epidermolytic effects. Neither are immunocompetent thymocytes required for the action of the toxin since hairless, athymic adult (nu/nu) mice are susceptible. A few reports of epidermolysis due to an exotoxin of group I Staphylococcus aureus have appeared. This toxin is antigenically different from the exotoxin of group II organisms. A model of drug-induced toxic epidermal necrolysis has been described in hamsters, but the toxic principle released from sensitized lymphoid cells has not yet been characterized.

Letter: Staphylococcal scalded skin syndrome in adults.

To the Editor.— Reid et al 1 have admirably documented a case of staphylococcal toxic epidermal necrolysis (TEN) in an adult who had renal failure and impaired delayed hypersensitivity. As recently stated, 2 the distinctive histologic features of drug-induced vs staphylococcal TEN allow rapid differentiation between these two entities, which can then be treated by appropriate therapy, pending results of culture studies. Isolation of group 2 organisms and demonstration of their exfoliative capacity in neonatal mice is usually much more time-consuming (and perhaps less reliable, since such organisms could be secondary invaders 2 ). In seeking to explain the generalized TEN in their patient, Reid et al focused on the immunological defect discovered. The fact that in this case, as well as in the case reported earlier by Levine and Norden, 3 the patients had renal insufficiency was not considered important per se. I suggest that while immune factors may have