Case Of Toxic Epidermal Necrolysis Research Articles

Toxic Epidermal Necrolysis Associated with Acetaminophen Ingestion

OBJECTIVE:To report a case of toxic epidermal necrolysis (TEN) associated with acetaminophen ingestion.SUMMARY:A seven-year-old girl developed TEN after acetaminophen ingestion. The diagnosis was based on clinical evaluation and skin biopsy. A later acetaminophen challenge, undertaken by an allergist who questioned the diagnosis, resulted in a similar skin reaction.DISCUSSION:TEN is a severe disease with a high mortality rate. TEN may be either idiopathic or associated with several clinical conditions, such as viral infections, autoimmune disorders, malignancy, and drug hypersensitivity. Because of the rarity of its association with acetaminophen, the diagnosis in our patient was questioned by an allergist who performed an oral acetaminophen rechallenge test despite the potential risk. This caused a severe skin reaction that required rehospitalization.CONCLUSIONS:TEN can be caused by over-the-counter medications such as acetaminophen. Rechallenge with the causative drug carries a risk of severe complications and should be avoided.

Toxic epidermal necrolysis following morbilli-parotitis-rubella vaccination

We present the first reported case of toxic epidermal necrolysis (TEN) caused by morbilli-parotitis-rubella (MPR) vaccine. A 13-year-old girl developed TEN 7 days after she received live, attenuated, triple MPR vaccine. The history of drug intake and any illness was negative. At admission the patient was acutely ill with high fever. The whole body was erythematous. The epidermis was wrinkled and the Nikolsky sign was positive. Numerous erosions were present on the lips and genital region. On the seventh day of illness, the eruption involved 80% of the skin. Systemic corticosteroid therapy was not employed. The skin and mucosal defects completely epithelized by the end of the third week of illness. Mild keratoconjunctivitis sicca remained because of permanent cup cell damage.

Toxic epidermal necrolysis following morbilli‐parotitis‐rubella vaccination

We present the first reported case of toxic epidermal necrolysis (TEN) caused by morbilli-parotitis-rubella (MPR) vaccine. A 13-year-old girl developed TEN 7 days after she received live, attenuated, triple MPR vaccine. The history of drug intake and any illness was negative. At admission the patient was acutely ill with high fever. The whole body was erythematous. The epidermis was wrinkled and the Nikolsky sign was positive. Numerous erosions were present on the lips and genital region. On the seventh day of illness, the eruption involved 80% of the skin. Systemic corticosteroid therapy was not employed. The skin and mucosal defects completely epithelized by the end of the third week of illness. Mild keratoconjunctivitis sicca remained because of permanent cup cell damage.

Apoptosis in selected skin diseases

Ten cases each of lupus erythematosus (discoid or systemic, LE), pemphigus foliaceus (PF) and erythema multiforme (EM), seven cases of toxic epidermal necrolysis (TEN) and two specimens of normal canine skin have been evaluated for the presence of apoptotic cells by immunohistochemistry using a commercially available in situ apoptosis detection kit (ApopTag, Oncor). In normal skin sections cells located in the centre of sebaceous glands and in catagen hair follicles were stained. In TEN no epidermal cell was positive, whereas in LE scattered basal and low suprabasal cells stained, and in EM single suprabasal epidermal cells stained. In PF acantholytic cells were predominantly negative, but there were single positive suprabasal cells in the neighbourhood of the acantholytic foci. Satellitosis, phagocytosis of apoptotic material and apoptosis of dermal inflammatory cells were also observed. The special staining procedure, if compared with light microscopic observation of haematoxylin/eosin specimens, resulted in a reliable tool for identification of apoptotic cells in normal and lesional skin. Data on the presence or absence of apoptotic cells in the dermatopathies examined may cast a new light on the pathogenesis of these diseases.

A case of toxic epidermal necrolysis treated with intravenous immunoglobulin

A case of toxic epidermal necrolysis treated with intravenous immunoglobulin

Diaminopyrimidines and Severe Cutaneous Adverse Reactions

The occurrence of cutaneous adverse reactions with the use of lamotrigine (Lamictal, Glaxo-Wellcome Inc, Research Triangle Park, NC) should prompt a reevaluation of rashes seen with the use of drugs of similar structure, specifically diaminopyrimidines. Trimethoprim and pyrimethamine both contain diaminopyrimidine ring structures. Lamotrigine has a triazine ring structure but is strikingly similar in other respects (Figure). Lamotrigine is currently marketed as an anticonvulsant in the United States and in more than 67 countries worldwide. During premarketing clinical trials of lamotrigine in 3400 subjects, one case of Stevens-Johnson syndrome and one case of toxic epidermal necrolysis were reported.1This incidence rate of 2 per 3400 individuals exposed is comparable to (if not greater than) the risks of severe cutaneous adverse reactions reported for the combination products trimethoprim-sulfamethoxazole (1-3 per 100 000 exposed) and pyrimethamine-sulfadoxine (10-20 per 100 000 exposed).2,3Pyrimethamine-sulfadoxine is marketed in the United States (Fansidar, Roche

Hospitalization for serious blood and skin disorders following co-trimoxazole.

To quantify the risk of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole. We conducted a population-based cohort study at Group Health Cooperative of Puget Sound (GHC). During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Hospitalization for serious blood and skin disorders following use of co-trimoxazole.

The objective of this study was to quantify the risk of serious blood and skin disorders associated with co-trimoxazole. We conducted a population-based cohort study of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole at Group Health Cooperative and Puget Sound (GHC). During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Toxic epidermal necrolysis after mifepristone/gemeprost-induced abortion

In France, mifepristone (Myfegine [RU 486]), an oral antiprogesterone, has been available in hospitals since 1990. It is administered to women requesting abortion during early pregnancy (amenorrhea <50 days) together with an intravenous injection or vaginal suppository of a prostaglandin analogue. 1 We describe the first case of toxic epidermal necrolysis (TEN) after administration of mifepristone and gemeprost, a prostaglandin analogue.

Patch testing in an unusual case of toxic epidermal necrolysis

Patch testing in an unusual case of toxic epidermal necrolysis

Amiodarone-induced linear IgA disease

Drug-inducedlinear IgA diseaseis histologically identical to sporadic linear 19A disease. The eruption typically ceases after the offending agent is stopped, and it recurs when rechallenged. We describe the first reported patient with drug-induced linear IgA disease caused by amiodarone. Amiodarone, a benzofuran derivative, is an antiarrhythmic medication. It has beenassociated with several cutaneous side effects. Photosensitivity to UVA is common. 1Dermallipofuscinosis manifesting as peculiar blue-graypigmentationhas beenreported.? A fatal case of toxic epidermal necrolysis caused by arniodarone has been described.' Arniodarone-induced pseudoporphyria that resolved on cessation of the drug has also been reported.

Macrophages and Tumor Necrosis Factor a in Toxic Epidermal Necrolysis

<h3>Background:</h3> We studied the immunopathologic characteristics of five cases of toxic epidermal necrolysis by using a large panel of antibodies. <h3>Observations:</h3> The pattern and amount of the inflammatory cell infiltrate varied according to the stage of the disease. The main constant feature was the prominent involvement of the monocyte-macrophage lineage, including factor XIIIa⁺HLA-DR⁺dendrocytes and CD68⁺Mac 387⁺macrophages, before and during the epidermal ne- crosis. The number of CD4⁺and CD8⁺lymphocytes was comparatively small. This was associated with a dense labeling of the epidermis for tumor necrosis factor a. <h3>Conclusions:</h3> Cells of the monocyte-macrophage lineage largely outnumber lymphocytes in the lesions of toxic epidermal necrolysis. Tumor necrosis factor a is likely a major cytokine that is responsible for necrosis. (Arch Dermatol. 1994;130:605-608)

Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis

We studied the immunopathologic characteristics of five cases of toxic epidermal necrolysis by using a large panel of antibodies. The pattern and amount of the inflammatory cell infiltrate varied according to the stage of the disease. The main constant feature was the prominent involvement of the monocyte-macrophage lineage, including factor XIIIa+HLA-DR+ dendrocytes and CD68+ Mac 387+ macrophages, before and during the epidermal necrosis. The number of CD4+ and CD8+ lymphocytes was comparatively small. This was associated with a dense labeling of the epidermis for tumor necrosis factor alpha. Cells of the monocyte-macrophage lineage largely outnumber lymphocytes in the lesions of toxic epidermal necrolysis. Tumor necrosis factor alpha is likely a major cytokine that is responsible for necrosis.

Clinical Classification of Cases of Toxic Epidermal Necrolysis, Stevens-Johnson Syndrome, and Erythema Multiforme

To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema. The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts. This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.

Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme

Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme

Toxic epidermal necrolysis (Lyell syndrome) in 77 elderly patients.

Toxic epidermal necrolysis is a rare, severe drug-induced disorder characterized by extensive epidermal loss. This study used the data of a national survey looking for all cases which occurred during a five-year period. The incidence of toxic epidermal necrolysis (cases/million/year) was 2.7 times higher among elderly than among younger adults. In the elderly population no female preponderance was found but clinical patterns were similar. The fatality of toxic epidermal necrolysis was twice as high in the elderly patients (51%) as in the younger (25%). The drugs incriminated in most cases of toxic epidermal necrolysis were the same in both groups (NSAIDs, antibacterials and anticonvulsants).

Drug-induced toxic epidermal necrolysis (Lyell syndrome) in patients infected with the human immunodeficiency virus

Although patients infected with the human immunodeficiency virus (HIV) are predisposed to cutaneous adverse drug reactions, only a few cases of toxic epidermal necrolysis (TEN) have been reported in this setting. Our purpose was to examine the features of TEN in HIV-infected patients. We performed a retrospective analysis of all HIV-infected patients in a series of 80 consecutive cases of TEN during a 6-year period. Fourteen patients were HIV infected. They had typical TEN, with epidermal detachment involving 20.6% +/- 8.0% of the skin surface. Suspected drugs were sulfadiazine, trimethoprim-sulfamethoxazole, sulfadoxine, clindamycin, phenobarbital, and chlormezanone. Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a dramatically increased risk of TEN. During our study period 15 cases of AIDS-associated TEN occurred in the greater Paris area, whereas 0.04 case would have been expected if the incidence of TEN were the same in these patients as in the general population. HIV-infected patients, especially those with AIDS, may develop TEN that shares many similarities with the disease in immunocompetent patients.

Work-Related Toxic Epidermal Necrolysis?

A case of toxic epidermal necrolysis is described in an employee of a company that carries out plastic extrusion using various resins, including cellulose acetate, co-polyester, polyvinyl chloride, acrylonitrile-butadienestyrene, and polyethylene. Air sampling during normal operating conditions indicated only trace amounts of hydrogen chloride and the plasticizer diethylphthalate. However, pyrolysis products of resin plugs could include compounds such as formaldehyde, acrylonitrile, and chlorinated hydrocarbons that have been associated with previous case reports of either erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. The development of toxic epidermal necrolysis in this worker was directly preceded by exposure to a vapor from a machine used to dry cellulose acetate. The problems in determining work relatedness and advising about return to work are discussed.

Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases

Toxic epidermal necrolysis is a potentially severe mucocutaneous affliction whose cause is usually drug related. To further characterize the nature of the dermal mononuclear infiltrate as well as the epidermal alterations observed by standard microscopy, we studied five cases of toxic epidermal necrolysis using labeled monoclonal antibodies. On clinically involved areas of skin, the following occurs: (1) the dermal infiltrate is composed mainly of activated T lymphocytes, with a predominant helper phenotype; (2) the number of Langerhans cells is decreased; and (3) keratinocytes express HLA-DR molecules, normally absent on their surface. These findings, although not specific, are consistent with an immune cellular reaction, but they could also be linked to an inflammatory reaction initiated by epidermal damages whatever its primary mechanism.

Common histopathological processes of phenytoin drug eruption.

Fifteen patients (6 males and 9 females) with phenytoin drug eruptions which ultimately resulted in various skin manifestations were analyzed histopathologically. The following types of skin manifestations were noted; 2 cases of toxic epidermal necrolysis, 2 cases of mucocutaneous ocular syndrome, 6 cases of erythema exudative multiform, 3 cases of lichenoid, and 2 cases of the maculopapular type. All of the biopsied specimens from these different skin manifestations exhibited some of the more common histopathological findings: 1) adhesion of the infiltrated cells to the basal layer of the epidermis, 2) cell infiltration into the epidermis, 3) vacuolation of the basal cells, 4) dyskeratotic cells in the epidermis, and epidermal necrosis. Immunohistopathological examinations in 5 typical cases with different skin manifestations revealed that epidermal cells and infiltrating cells were HLA-DR antigen positive. The infiltrating cells in the dermis consisted of almost equal numbers of CD4+ and CD8+ cells; CD8+ cells were predominant in the cells infiltrating into the epidermis. These findings suggest a possibility that the various clinical features in phenytoin drug eruptions may share some common mechanisms.