Severe Cutaneous Adverse Reactions: A Single-Center Retrospective Study of 173 Patients in China

BackgroundSevere cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial.ObjectiveTo analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management.MethodsA retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted.ResultsOf 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis.ConclusionPrompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.     

A patch testing and cross‐sensitivity study of carbamazepine‐induced severe cutaneous adverse drug reactions

Background The usefulness of the drug patch testing for Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is still controversial. Recent studies have shown that HLA‐B*1502 is strongly associated with CBZ‐SJS/TEN in Chinese and Southeast Asian populations. Objective To evaluate the usefulness of patch tests for patients with carbamazepine (CBZ)‐induced SJS, TEN and drug reaction with eosinophilia and systemic symptoms (DRESS) and the cross‐reactivity in patch tests among the aromatic antiepileptic drugs. Methods We measure the frequency of positive patch test reactions and cross‐sensitivity to structure‐related aromatic anti‐epileptic drugs (AEDs) for patients after SJS/TEN or DRESS episodes caused by CBZ. CBZ and other structure‐related AEDs used for patch testing were prepared in 10% and 30% petrolatum. Secondary measures included the association of HLA‐B*1502 genotype and frequency of possible side effects from the patch tests. Results Positive patch test reactions to 30% CBZ in the CBZ‐SJS/TEN were 62.5% (10/16), and 70% (7/10) in the CBZ‐DRESS. None of the 10 healthy controls displayed a positive reaction to tested agents. Cross‐sensitivity to other aromatic AEDs was observed in both the CBZ‐SJS/TEN and the CBZ‐DRESS. Only the HLA‐B*1502 genotype was present and strongly associated with the CBZ‐SJS/TEN, but not with the CBZ‐DRESS. Conclusion Drug patch testing is a safe and useful method for the identification of CBZ as the culprit drug of SJS/TEN as well as DRESS. Testing of chemically or pharmacologically related AEDs may provide information on cross‐reactivity for these patients.     

Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis

Patch testing may help to assess the culpability of a drug in an adverse reaction. Our aim was to study patch testing in severe cutaneous ad verse drug reactions [ADRs] (Stevens-Johnson syndromeitoxic epidermal necrolysis (SJS/TEN). acute genera exanthematous pustulosis (AGEP), and other cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had SJS/TEN. 14 AGEP, and 23 other cutaneous ADRs. Patients were patch tested with the suspect drug and with H standard series of drugs. 2 patients among the 22 SJSTEN cases had a relevant positive test. 7 patients among the 14 AGEP cases had a relevant positive test. 6 patients among the 23 other cutaneous ADRs had a relevant positive test. Our results suggest that patch testing has a weak sensitivity in SJS'TEN and is not appropriate in these diseases. Patch testing seems more adapted to other cutaneous ADRs, such as AC it: P. in which the proportion of positive patch tests was significantly higher (P<0.02). Nevertheless, the difference of sensitivity of patch testing in SJS TEN, AGEP or other cutaneous ADRs could be linked not only to the clinical type of eruption, but also lo the different spectrum of culprit drugs in each type of eruption.     

Cutaneous adverse drug reactions seen in a tertiary hospital in Johor,Malaysia

Background Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Objective Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. Materials and Methods This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. Results A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens‐Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). Discussion The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA‐B*1502 and HLA‐B*5801 which are genetic markers for carbamazepine‐induced SJS/TEN and allopurinol‐induced SJS/TEN/DRESS respectively. Conclusion The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine and allopurinol were the two main causative drugs of severe ADRs in our population.     

3 Severe cutaneous adverse reactions time latency between beginning of drug use and onset of reaction

Background Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are acute life‐threatening severe cutaneous adverse reactions (SCAR) with an unclear pathogenesis mainly caused by drugs. Allopurinol and trimethoprim/sulphamethoxazole (TMS) are both well known to be associated with these conditions. In addition, TMS is known to induce generalized bullous fixed drug eruption (GBFDE), a less severe condition with a very short induction period that is clinically often confused with SJS or TEN. Aim We want to further investigate the risk profile of allopurinol and TMS for inducing SCAR, as the hazard functions of these substances are different. Furthermore, the re‐review of cases using more specific criteria to differentiate between SCAR and GBFDE should allow us to detect misclassification of cases. Methods 984 cases of SJS, SJS/TEN overlap and TEN were ascertained by a population‐based registry between 1990 and 1999. The following analysis is based on a random sample of 115 cases earlier accepted as SJS or TEN, which were exposed to either allopurinol or TMS, and 38 cases excluded in the previous review. An independent expert committee blinded for possible causes re‐reviewed these cases in clinical terms, as the original review process took place over a period of 10 years. In this analysis special emphasis is given to the time latency between beginning of drug use and onset of SCAR. Results Before re‐review 162/984 patients with SCAR reported the use of allopurinol and 131/984 the use of TMS within 2 weeks prior to the onset of the adverse reaction. After the re‐review the percentage of doubtful cases was higher for TMS (28/57) than for allopurinol (30/83). For definite cases of SJS or TEN the range between the lower and upper quartile of the time latency between beginning of drug use and onset of SCAR was 14–34 days for allopurinol, in contrast to 5–15 days for TMS. The time latency for doubtful and excluded cases after the use of TMS was much shorter (2.5 and 2 days, respectively). Conclusions The high numberof doubtful cases after the re‐review reveals the difficulty of applying approved detailed definitions to the variety of clinical patterns of cutaneous adverse reactions. We could confirm a high correlation of time latency between beginning of drug use and onset of SCAR and GBFDE for allopurinol and TMS, which may have an important impact on the risk profile of these and other suspected drugs, as well as on pathogenetic and therapeutic considerations of severe adverse events. When drug exposure occurs outside the relevant interval of time latency for SJS and TEN, other risk factors and/or differential diagnoses such as GBFDE should be considered.     

Severe drug‐induced skin reactions: clinical pattern,diagnostics and therapy

The spectrum of severe drug‐induced skin reactions includes not only Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) but also generalized bullous fixed drug eruption (GBFDE), acute generalized exanthematous pustulosis (AGEP) and hypersensitivity syndrome (HSS), also called drug reaction with eosinophilia and systemic symptoms (DRESS). These reactions differ in clinical presentation as well as prognosis, causative agents and therapy. Therefore, the appropriate diagnostic measures should be undertaken rapidly, in order to prove the diagnosis. In addition to a thorough clinical examination, a skin biopsy should be taken and specific laboratory investigations should be done if AGEP or HSS/DRESS is suspected. Since these reactions are drug‐induced, the causative agent should be rapidly identified and withdrawn. Besides adequate supportive therapy, systemic immunomodulatory treatments may be considered. Despite intensive care management, the prognosis in SJS and TEN is often poor and influenced by the amount of skin detachment as well as the age of the patients and the pre‐existing underlying conditions. Severe sequelae may develop in survivors and affect especially mucosal sites. The prognosis of GBFDE is better but recurrent events may lead to more severe involvement. In HSS/DRESS sequelae have been also described as well as long lasting and recurrent courses, whereas AGEP usually heals without problems.     

Severe drug‐induced skin reactions: clinical features,diagnosis, etiology,and therapy

Drugs can induce severe skin reactions that differ in clinical presentation, prognosis, and therapy. The spectrum of these reactions not only includes bullous reactions such as Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and generalized bullous fixed drug eruption (GBFDE) but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). If AGEP or DRESS is suspected, the diagnosis should be confirmed by thorough clinical examination, a skin biopsy, and specific laboratory tests. Crucial for the patient's prognosis, the causative agent should be rapidly identified and discontinued. It is therefore important to know the most frequent triggers of severe drug reactions, some of which may induce various reaction patterns. Depending on the clinical diagnosis, symptomatic and adequate supportive therapy, as well as systemic immunomodulatory treatments are used. The prognosis in SJS/TEN is often poor and depends on the patient's age and underlying conditions as well as the extent of skin detachment. The prognosis of GBFDE is somewhat better, but recurrences may lead to more severe disease manifestations. In DRESS, protracted and recurrent courses have been described, whereas AGEP usually resolves without problems.     

Differential diagnosis of severe cutaneous drug eruptions

Adverse cutaneous reactions to drugs are frequent, mostly secondary to antibacterials, however, serious adverse cutaneous reactions are infrequent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of the same disease. They are the more severe drug eruptions, with a mortality around 30% for TEN. The confusion between erythema multiforme major and SJS means that erythema multiforme major is the main differential diagnosis. Skin disorders involving desquamation, in particular after pustulosis, are also common differential diagnoses. Mechanical or autoimmune blistering are also potential misdiagnoses of TEN/SJS. Hypersensitivity Syndrome (HSS) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a severe cutaneous drug reaction with often a long duration of eruption and serious other organ involvement. Exfoliative dermatitis, whether caused by psoriasis, dermatitis or lymphoma, can be thought of as a differential diagnosis of DRESS/HSS. Angio-immunoblastic lymphadenopathy, viral eruption and vasculitis are other differential diagnoses of DRESS/HSS. Prompt recognition of a severe drug reaction and withdrawal of the culprit drug is often the most important therapeutic action. Alternatively, a delay in starting a specific treatment for a disease misdiagnosed as a drug eruption could be deleterious.     

Pharmacogenetics of cutaneous adverse drug reactions

Drug-induced hypersensitivity reactions are of major medical concern because they are associated with high morbidity and high mortality. In addition, individual patients' reactions are impossible to predict in each patient. In the field of severe cutaneous adverse drug reactions (cutaneous ADR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DHIS) or drug rash with eosinophilia and systemic symptoms (DRESS), major advances have recently been gained through studies of an association between HLA alleles and drug hypersensitivity induced by specific drugs. The results of these pharmacogenomic studies allow prediction of the risk of adverse reactions in patients treated with certain drugs, including carbamazepine and other aromatic antiepileptic drugs, allopurinol and abacavir. However, different ethnic populations show variations in the genetic associations. A strong association between carbamazepine-induced SJS/TEN and HLA-B*1502 has been found in Southeast Asian patients but not in Caucasian and Japanese patients. Moderate associations between aromatic amine anticonvulsants and other HLA alleles have been proposed in Japanese patients. In contrast, HLA-B*5801 was found to be associated with allopurinol-induced cutaneous ADR, including SJS/TEN and DIHS/DRESS, in Caucasian and Asian patients, including the Japanese. These differences may, at least in part, be due to the differences in allele frequency in different ethnic populations. This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity.     

Drug rash with eosinophilia and systemic symptoms vs toxic epidermal necrolysis: the dilemma of classification

According to contemporary vernacular, when the cutaneous manifestations of drug rash with eosinophilia and systemic signs (DRESS) syndrome are those of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the condition is defined as "DRESS syndrome with severe cutaneous reactions". In this article, we have presented arguments for and against including patients with skin lesions of the SJS/TEN syndromes who also have fever (practically all of the patients) and internal organ involvement (most of the patients) under the definition of DRESS syndrome. After weighing the arguments for and against this alteration of definition, we conclude that it makes more sense for patients with SJS/TEN to be classified as such and not be lumped together under the misleading label of DRESS syndrome.     

Severe flucloxacillin‐induced acute generalized exanthematous pustulosis (AGEP), with toxic epidermal necrolysis (TEN)‐like features: does overlap between AGEP and TEN exist? Clinical report and review of the literature

Acute generalized exanthematous pustulosis (AGEP) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. Especially in TEN, large areas of the skin and mucosae may become detached. Although AGEP and SJS/TEN are distinct entities with a different clinical picture, pathogenesis, prognosis and treatment, they may share some features, raising the hypothesis of overlap between both entities. We present a severe case of AGEP, caused by flucloxacillin, clinically presenting with TEN‐like features and pronounced systemic symptoms with haemodynamic and respiratory instability. Furthermore, we present a review of the literature on cases of AGEP with features resembling SJS/TEN or a supposed overlap with SJS/TEN.     

Drug reaction with eosinophilia and systemic symptoms (DRESS): a clinical update and review of current thinking

Summary Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a severe medication-induced adverse reaction, which has cutaneous, haematological and solid-organ features. It is one of the triad of life-threatening drug hypersensitivity dermatoses, along with acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this article, we discuss several controversies that surround DRESS, including problems with nomenclature and the lack of consensus in diagnostic criteria.     

Epidemiological study of severe cutaneous adverse drug reactions in a city district of China

BACKGROUND: An epidemiological study of severe cutaneous adverse drug reactions (SCADRs) in China has not been reported. AIMS: To estimate the incidence of SCADRs in a city district of China. METHODS: A retrospective study was performed in Peking University Third Hospital, the only hospital in Haidian district, Beijing with a dermatology ward. The medical records of inpatients with SCADRs from January 1994 to December 2002 were studied. RESULTS: The prevalence rates for overall SCADRs, Stevens-Johnson syndrome (SJS), exfoliative dermatitis (ED), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) among hospitalized patients were 0.32, 0.15, 0.10, 0.04 and 0.07 per thousand, respectively. The risk of SCADRs from systemic drugs among hospitalized patients was 0.03/1000 (0.02/1000 for SJS, and 0.01/1000 for ED and DRESS). The reported incidence of SCADRs in Haidian district was not less than 1.8 per million person-years. The reported incidence of ED, SJS, TEN and DRESS in Haidian district was not less than 0.6, 0.8, 0.05 and 0.4 per million person-years, respectively. The most common underlying disorders were infection, pain-related diseases and epilepsy. Antibiotics were the most common offending drugs followed by anticonvulsants and traditional Chinese medicines (TCM). CONCLUSIONS: These results confirm the relatively low incidence of SCADRs in China. Antibiotics, anticonvulsants and TCM are the most common causative drugs.     

Schwere Arzneimittelreaktionen der Haut

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe drug-induced bullous skin reactions. They are rare, but often life-threatening and have a high mortality rate. Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, but after the suspected drug is withdrawn, the skin heals rapidly and mortality is low. The clinical pattern, histology and inducing drugs differ substantially between AGEP and the SJS/TEN group.     

Prognosis of generalized bullous fixed drug eruption: comparison with Stevens–Johnson syndrome and toxic epidermal necrolysis

Background Generalized bullous fixed drug eruption (GBFDE) is a rare cutaneous adverse reaction to drugs, and may resemble Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), but is usually considered less severe. Objectives To compare the severity and mortality rate in cases of GBFDE and control cases of SJS or TEN of similar extent of skin detachment. Methods This was a case–control analysis of 58 patients with GBFDE matched by age and extent of skin detachment to 170 control patients with a validated diagnosis of SJS or SJS/TEN overlap. Data for cases and controls were extracted from the EuroSCAR and RegiSCAR databases resulting from two population‐based studies of severe cutaneous adverse reactions conducted in Europe. Preselected outcome criteria were death (primary), and fever, duration of hospitalization and transfer to an intensive care or burn unit (secondary). Results GBFDE affected mainly older patients (median age 78 years, interquartile range 68–84 years); 13 of 58 cases died (22%). The mortality rate was slightly but not significantly lower for patients with GBFDE than controls [28%, multivariate odds ratio 0·6 (95% confidence interval 0·30–1·4)]. Patients with GBFDE and controls did not differ in other preselected criteria for severity. Conclusions Although our study featured limited statistical power, we were not able to confirm that GBFDE had better prognosis than SJS or SJS/TEN of similar disease extent in older patients. Severe cases of GBFDE deserve the attention and active management given to patients with SJS or TEN.     

The life-threatening eruptions of immune checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.     

Differences in immunological alterations and underlying viral infections in two well-defined severe drug eruptions

Background. Similar drugs (e.g. anticonvulsants) have been implicated in the development of two distinct forms of severe cutaneous drug reactions, Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug–induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS). Aim. To investigate immunological alterations and underlying viral infections that could contribute to the variability in the clinical presentations of these diseases. Methods. We retrospectively analysed clinical variables, serum immunoglobulin levels, numbers of circulating white blood cells, lymphocytes and their subsets, serum levels of several cytokines, and underlying viral infections in both drug reactions, using samples obtained at onset from 9 patients with SJS/TEN and 19 patients with DIHS/DRESS. Results. There were significant differences between the two drug eruptions in the duration of drug intake before onset, the levels of IgG, IgA and IgM, the numbers of circulating white blood cell, lymphocyte, CD3+ T cell and CD8+ T cells, the serum levels of interferon-γ, and the titres of anti-herpes simplex virus IgG at onset. Conclusions. The difference in the pattern of immune responses shaped in part by previous and underlying viral infections at the time of drug exposure could cause a marked deviation in the pathological phenotype of severe drug eruptions. Elucidating these host factors may provide a basis for therapeutic approaches in patients with severe drug reactions.     

Profile and pattern of Stevens-Johnson syndrome and toxic epidermal necrolysis in a general hospital in Singapore: treatment outcomes

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially life-threatening, reactions to medications. Both conditions have significant morbidity and mortality. The aim of this study was to document the epidemiological features, aetiologies, treatment and clinical outcomes of retrospectively reviewed data of all patients with SJS or TEN treated from January 2004 to November 2010 in a general hospital. There were 18 cases of SJS, seven cases of SJS/TEN overlap and three cases of TEN. Mean age was 50.6 years, with a range of 13-85 years. The male/female ratio was 1. Drugs accounted for 26 cases; one case was caused by Neisseria gonorrhoea infection. Anti-convulsants (35.7%) were the most common implicated drugs followed by antibiotics (28.5%), non-steroidal anti-inflammatory drugs (NSAIDS) (14.3%), allopurinol (7.1%) and traditional Chinese medication (7.1%). In seven cases, multiple drugs were implicated. Most SJS cases (88%) were treated with corticosteroids, of which 61% were given high-dose systemic corticosteroids. No infective complications were observed. Six out of the seven SJS/TEN overlap syndrome and all three TEN cases were given intravenous immunoglobulins. One patient with TEN died. In conclusion, anti-convulsants, especially carbamazepine, were the most frequently implicated drugs, followed by antibiotics and NSAIDS. High-dose corticosteroids were effective in SJS, whereas intra-venous immunoglobulin were useful in TEN and SJS/TEN overlap syndrome.     

Treatment of severe drug eruptions

Severe drug eruptions are rare, life-threatening events. The management begins with the withdrawal of the suspect drug(s). We recently confirmed that an earlier withdrawal of drugs with short elimination half-life was associated with a better survival of patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). In cases of "acute skin failure" (exfoliative dermatitis, extensive SJS or TEN), management of patients must be undertaken in specialized intensive care units or in burn units. The main principles of symptomatic therapy are the same as for major burns: warming of the environment, correction of electrolyte disturbances, high caloric intake, and prevention of sepsis. The suspected immunologic orgin of drug eruptions prompted the use of corticosteroids, immunosuppressive drugs, and anti-cytokines. Systemic corticosteroids are useful in "hypersensitivity syndrome" when visceral lesions depend on infiltration by activated cosinophils. Systemic corticosteroids were shown to be deleterious in cases of advanced TEN. Their potential usefulness at earlier stages of SJS or TEN remains controversial. High intravenous doses of cyclophosphamide or oral cyclosporin have been administered to a few patients with TEN, most often following ineffective treatment with corticosteroids for 1 to 5 days. It remains doubtful that the progression of the lesions was shortened. A few patients appeared to benefit from treatment with pentoxifyllin, a drug suppressing the production of TNF. Thalidomide, another suppressor of TNF production, significantly increased the death rate when tested in a double-blind placebo controlled trial in patients with early TEN. High dose intravenous immunoglobulins were used in 10 patients with TEN on the basis of their ability to inhibit fas-fas ligand mediated apoptosis. The potential benefit of this treatment needs confirmation by further studies. Patients and their first degree relatives should be advised to avoid the responsible drug and chemically related compounds. Regulatory agencies should be notified of such cases.