Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases

OBJECTIVE: To evaluate the effect of high-dose intravenous immunoglobulin (IVIG) in toxic epidermal necrolysis (TEN), parameters that may affect response to treatment, and the effect of different IVIG batches on Fas-mediated cell death. DESIGN: Multicenter retrospective analysis of 48 consecutive TEN patients treated with IVIG. SETTING: Fourteen university hospital dermatology centers in Europe and the United States. PATIENTS: Forty-eight patients with TEN (skin detachment >10% of their body surface [mean, 44.8%; range, 10%-95%]). INTERVENTIONS: Infusion of IVIG in all patients (range, 0.8-5.8 g/kg), and analysis of the ability of different IVIG batches to inhibit Fas-mediated cell death. MAIN OUTCOME MEASURES: Objective response to IVIG treatment, final outcome at day 45, parameters that may affect response to IVIG treatment, and tolerance. RESULTS: Infusion of IVIG (mean total dose, 2.7 g/kg [range, 0.65-5.8 g/kg]; mean consecutive days, 4 [range, 1-5 days]) was associated with a rapid cessation (mean, 2.3 days [range, 1-6 days]) of skin and mucosal detachment in 43 patients (90%) and survival in 42 (88%). Patients who responded to IVIG had received treatment earlier in the course of disease and, on average, higher doses of IVIG. Furthermore, analysis of 35 IVIG batches revealed significant batch-to-batch variations in the capacity of IVIG to inhibit Fas-mediated cell death in vitro. CONCLUSIONS: Early infusion of high-dose IVIG is safe, well tolerated, and likely to be effective in improving the survival of patients with TEN. We recommend early treatment with IVIG at a total dose of 3 g/kg over 3 consecutive days (1 g/kg per day for 3 days).     

High-dose intravenous immunoglobulins in the treatment of toxic epidermal necrolysis: an Asian series

Toxic epidermal necrolysis (TEN) is a severe, immune-mediated, mucocutaneous reaction resulting in extensive keratinocyte apoptosis. High-dose human intravenous immunoglobulins (IVIG) have been proposed as an effective treatment for TEN. Retrospective data from 8 patients with TEN and 4 patients with Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap treated with high-dose IVIG were analysed. The total dose of IVIG administered was 2 g/kg body weight, with the exception of 2 patients who received a total dose of 1.5 g/kg body weight. Their mean age was 49.9+/-18.8 years (range, 19 to 70 years). The mean time from the first sign of skin lesion or mucosal or epidermal detachment to commencement of IVIG was 8.7+/-5.5 days (range, 3 to 22 days). Of the 11 patients who survived, the mean time to objective response was 3.6+/-1.9 days (range, 2 to 8 days). The length of stay (LOS) in hospital was 20.4+/-8.0 days (range, 10 to 37 days). The survival rate was 91.6%. One patient developed permanent mucocutaneous sequelae following TEN. There were no adverse reactions to IVIG. We conclude that high-dose IVIG may be a safe and effective therapy for Asian patients with TEN.     

Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression

BACKGROUND: It has been proposed that Fas-Fas ligand interaction was responsible for the apoptosis of epidermal cells in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and that high doses of intravenous immunoglobulin (IVIG) could help patients by blocking the apoptosis. OBJECTIVE: To study the effects of IVIG on SJS and TEN. DESIGN: Prospective open trial. SETTING: Referral center of a university hospital. PATIENTS: Thirty-four consecutive patients admitted for SJS (n = 9), SJS-TEN (n = 5), or TEN (n = 20) a mean of 4.3 days after onset. INTERVENTION: A dose of 2 g/kg of IVIG was administered within 2 days (half doses or full doses over a longer period for patients with low creatinine clearance). MAIN OUTCOME MEASURES: Detached plus detachable proportions of the total body surface area measured before and after treatment and predicted death rate estimated on admission with a validated prognostic score. RESULTS: Epidermal detachment involved a mean +/- SD 19% +/- 16% of the total body surface area on admission and 32% +/- 26% after IVIG treatment (progression in 22 of 34 cases, including most patients referred early). The prognostic score predicted 8.2 deaths (24%); 11 were observed (32%; 95% confidence interval, 17%-51%). Most deaths occurred in elderly patients who had initially impaired renal function. CONCLUSIONS: The confidence interval of the observed death rate excludes a dramatic decrease in mortality. No measurable effect was observed on the progression of detachment or on the speed of reepidermalization. These results do not support the routine use of IVIG treatment for patients with SJS or TEN, especially in cases of impaired renal function.     

Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens–Johnson syndrome and toxic epidermal necrolysis

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life‐threatening cutaneous adverse drug reactions. While there is no established therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v. immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still controversial because total doses of IVIG used vary greatly from one study to another. The aim of this study was to evaluate the efficacy of IVIG, administrated for 5 days consecutively, in an open‐label, multicenter, single‐arm study in patients with SJS or TEN. IVIG (400 mg/kg per day) administrated for 5 days consecutively was performed as an additional therapy to systemic steroids in adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated. Parameters to assess clinical outcome were enanthema including ophthalmic and oral lesions, cutaneous lesions and general condition. These parameters were scored and recorded before and after IVIG. We enrolled five patients with SJS and three patients with TEN who did not respond sufficiently to systemic steroids before IVIG administration. All of the patients survived and the efficacy on day 7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin lesions and enanthema in the patients in whom IVIG therapy was effective. Serious side‐effects from the use of IVIG were not observed. IVIG (400 mg/kg per day) administrated for 5 days consecutively seems to be effective in patients with SJS or TEN. IVIG administrated together with steroids should be considered as a treatment modality for patients with refractory SJS/TEN. Further studies are needed to define the therapeutic efficacy of IVIG.     

重症多形红斑与中毒性表皮坏死松解症患者的临床对比研究

目的探讨重症多形红斑(SJS)与中毒性表皮坏死松解症(TEN)的临床特点与临床治疗。方法对9例SJS和4例TEN住院患者的临床资料进行回顾性分析。结果 SJS组和TEN组患者中药物为最常见病因。TEN组的皮损范围、损害程度、粘膜病变均较SJS组更广泛、更严重。TEN患者主要表现为全身表皮松解,而SJS患者以靶形红斑为特征。TEN患者较SJS患者更易出现并发症。TEN患者病程急性期和恢复期时间均长于SJS患者。9例SJS和4例TEN患者早期均予以足量糖皮质激素治疗,TEN患者同时联用免疫球蛋白,13例患者均获痊愈。结论药物是SJS和TEN发病最主要的原因。TEN患者较SJS患者病变广泛且严重。药物诱发的SJS和TEN患者早期使用足量激素十分必要,TEN患者尚需静脉联用免疫球蛋白,提高抢救成功率。     

Prospective, noncomparative open study from Kuwait of the role of intravenous immunoglobulin in the treatment of toxic epidermal necrolysis

BACKGROUND: High-dose intravenous immunoglobulin (IVIG) is emerging as a promising new therapy for treating the rare but potentially fatal drug reaction toxic epidermal necrolysis (TEN). Experimental in vitro studies support that IVIG can block the Fas-FasL-mediated apoptosis in TEN. METHODS: Twelve consecutive patients (7M, 5F) with TEN admitted over a 5-year period from January 1998 to December 2002 were treated with a dose of 0.5-1.0 g/kg/d of IVIG for 4-5 days along with standard care protocol. Clinical outcome in terms of average duration to arrest the progression, complete healing, hospital stay, side-effects and complications were determined to find the efficacy of IVIG treatment. RESULTS: Average age was 27.16 years (7-50 years). There were four children (2M, 2F) aged 7-12 years. One patient had an underlying malignancy. No patient had HIV infection. The average total body surface area involvement was 57.5% (30-90%). An IVIG infusion was started, on average, 1.58 days (1-3 days) after admission. All patients responded well to the treatment. There was no mortality. The disease progression was arrested in a mean of 2.83 days (1-5 days). Time taken for complete healing (re-epithelialization) was 7.33 days (5-13 days). The average duration of hospital stay was 12.5 days (7-21 days). No side-effects of the IVIG treatment were observed in these patients. The drugs triggering TEN in these patients were phenytoin (four patients), followed by penicillin (three), cotrimoxazole (two), phenobarbital and furosemide (one patient each), respectively. In one patient, the offending drug could not be ascertained. CONCLUSION: Our experience of treating 12 patients with TEN using IVIG, in Kuwait, confirms that it is a safe and effective treatment for these patients.     

Toxic epidermal necrolysis treated with intravenous high-dose immunoglobulins: our experience

BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare severe acute exfoliative drug-induced skin disorder which has recently been ascribed to alterations in the control of keratinocyte apoptosis, mediated by an interaction between the cell surface death receptor Fas and its respective ligand. A therapeutic approach with intravenous immunoglobulins (IVIG) associated with pulse methylprednisolone, based on the inhibition of Fas-mediated keratinocyte death by naturally occurring Fas-blocking antibodies included in human immunoglobulin preparations, has produced good preliminary results. OBJECTIVE: To analyse the efficacy of IVIG in the treatment of TEN. Patients: Nine patients with erythematous body surface area ranging from 38 to 85% and dermo-epidermal detachment from 4 to 37% were treated. RESULTS: Eight patients were healed and 1 died of septic shock and multiple organ failure. Interruption of further epidermal detachment occurred after an average of 4.8 days from the onset of IVIG therapy. Complete wound healing occurred after an average of 12 days. Concerning complications, 3 out of 8 surviving patients had acute respiratory failure requiring mechanical ventilation and 1 acute renal failure was treated with dialysis. Late sequelae were limited to dyschromia and nail dystrophies. No hypertrophic scars were observed. CONCLUSION: IVIG therapy represents a safe and valid approach for TEN.     

High-dose intravenous immunoglobulins in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese patients: a retrospective study of 82 cases

Stevens-Johnson Syndrome (SJS) and Toxic epidermal necrolysis (TEN) are drug-induced diseases with a low incidence but high mortality. While there is no standard treatment, corticosteroids and intravenous immunoglobulin (IVIG) therapy have been widely used, with controversy. Our objective was to summarize the etiology and therapeutic regimen of SJS or TEN in 82 hospitalized patients in China. A retrospective study was performed on 82 patients who were diagnosed with SJS or TEN and hospitalized in Peking Union Medical College Hospital from July 1994 to August 2009. Of them, 24 were treated with IVIG plus corticosteroids (IVIG group) and the other 58 were treated with corticosteroids only (corticosteroids group). SCORTEN was used to evaluate the severity and prognosis of the patients. The efficacy of therapeutic modalities was assessed by the following parameters: starting and the maximum dose of corticosteroids, cumulative dose of corticosteroids before tapering, cumulative dose of IVIG, days of corticosteroid application before its tapering and the hospitalization days. The common agents triggering SJS/TEN in these patients were non-steroidal anti-inflammatory drugs (31 cases), anti-epileptics (18 cases), antibiotics (14 cases), antipodagrics (4 cases), sulfanilamides (4 cases) and others (11 cases), respectively. Carbamazepine was the most common drug, and induced 15 cases of SJS/TEN. The SCORTEN was significantly higher in the IVIG group than that in the corticosteroid group (2.0 ± 1.7 vs 0.8 ± 1.0, P = 0.001). Whereas no differences were observed between the two groups in the parameters including starting and maximum dose of corticosteroids, cumulative dose and the number of application days of corticosteroids before tapering and hospitalization days. However, in patients whose SCORTEN scores were 2, application of IVIG and corticosteroids shortened the duration of hospitalization from 26.4 ± 9.5 d to 18.1 ± 5.3 d (P < 0.05). No significant difference was observed in the incidence of complications between the two groups (54.2% vs 39.7%, P > 0.05). The actual mortalities were 12.5% in the IVIG group and 3.4% in corticosteroid group respectively, which were significantly lower than the predicted values (22.0% and 7.2%, respectively). Standardized mortality ratio (SMR) analysis showed a trend to a lower actual mortality (not significant) with corticosteroid treatment than the predicted mortality (SMR = 0.480; 95% CI: 0.075-1.923) and combination therapy had a tendency to reduce the mortality (not significant) rate of TEN (SMR = 0.569; 95% CI: 0.318-1.910). No significant difference in SMR was found between the two groups (P = 0.1474). Survival analysis showed that a favorable overall survival was associated with younger age (P = 0.0405). Our data indicated that early application of corticosteroids presented beneficial effects on SJS/TEN, and that combination therapy of corticosteroids and IVIG achieved a better therapeutic effect than the administration of corticosteroids alone. We recommend early treatment with IVIG at total doses of more than 2 g/kg in SJS/TEN patients whose SCORTEN are higher than 0.     

Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis

Mortality in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is high. Apart from intensive supportive therapy, no generally accepted specific treatment regimen exists. The role of corticosteroids in SJS/TEN is controversial. It is possible that high-dose pulse therapy with corticosteroids might be an improvement on long-term lower dose therapy, by combining higher efficacy with a diminished risk both of infection and of delayed wound healing. The aim of this study was to evaluate the efficacy of dexamethasone pulse therapy with respect to mortality and healing time of patients with SJS/TEN. A small, uncontrolled series of consecutive inpatients with SJS/TEN was treated with dexamethasone pulse therapy. The efficacy of this treatment was assessed retrospectively using SCORTEN. Twelve patients were included over a period of 10 years. One patient died, while SCORTEN predicted a fatal outcome of 4 patients. Stabilization was reached after 2.3 days on average, total re-epithelialization after 13.9 days. The results of this study bear no statistical relevance due to the small number of patients. In conclusion, short-term dexamethasone pulse therapy, given at an early stage of the disease, may contribute to a reduced mortality rate in SJS/TEN without increasing healing time. A larger controlled trial is warranted to investigate further the use of dexamethasone pulse therapy in SJS/TEN.     

Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens–Johnson syndrome/toxic epidermal necrolysis

Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe, skin blistering conditions in which areas of skin die and detach. They actually represent a single disease with a spectrum of severity: less than 10% body surface area detachment in SJS and more than 30% in TEN. It affects around 500 people in the UK each year and is most commonly caused by a reaction to a wide-range of commonly prescribed drugs. This study brought together researchers and patients from the U.K., Spain, Taiwan and the U.S.A. and aimed to determine levels of a protein called high mobility group box 1 (HMGB1) in the serum (part of the blood), blister fluid and skin biopsy tissue of SJS/TEN patients. HMGB1 is a protein which is known to be a marker (biological sign) of a) tissue/cell injury and b) activation of the immune response, both of which occur in SJS/TEN. The authors detected elevated serum HMGB1 levels in SJS/TEN patients at the time of reaction in three independent patient populations, and also extremely high levels in patients’ blister fluid. Levels of HMGB1 in the epidermal (upper) layer of the skin were considerably decreased in SJS/TEN patients but not healthy control or drug-induced rash skin. The decrease in HMGB1 levels in the epidermis of the skin appears to occur prior to blistering and may represent an early indicator. In addition, levels of HMGB1 appear to be retained at the junction between the epidermis and the next layer of skin, called the dermis, which may suggest a potential role for HMGB1 in the mechanism by which the layers become detached in SJS/TEN patients. The authors conclude that serum HMGB1 may not represent a good clinical marker of SJS/TEN, but that decreased levels of it in the skin may be a sign of the early onset of skin blistering, and could have a key role in the mechanism by which this occurs.     

Clinical manifestations and outcomes in 17 cases of Stevens–Johnson syndrome and toxic epidermal necrolysis

The clinical features and outcomes of 17 patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) were retrospectively reviewed. There were 11 males and six females with an average age of 61.5 years. Ten patients with SJS (seven males, three females) and seven patients with TEN (four males, three females) were identified. Antibiotics, mainly beta-lactams, were the most common cause of SJS/TEN in this series. The mean skin loss in TEN was 45.7% total body surface area in contrast to the lesser skin loss (< 10%) observed in three patients with SJS. Complications included septicaemia, pneumonia and multi-organ failure, mainly in the TEN group. Two patients died from TEN-related complications and one patient with SJS died from unrelated causes. Ocular involvement and skin pigmentary changes represented the most significant long-term sequelae.     

IVIG for the treatment of toxic epidermal necrolysis

Intravenous immunoglobulin (IVIG) has been proposed as a treatment for toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS). A number of retrospective and prospective studies have been conducted, with varying levels of evidence for the efficacy of IVIG. Recent publications provide opposing conclusions. A multi-center, comparative, long-term analysis needs to be conducted to determine the role of IVIG in the management of patients with SJS/TEN.     

Combination therapy of intravenous immunoglobulin and corticosteroid in the treatment of toxic epidermal necrolysis and Stevens–Johnson syndrome: a retrospective comparative study in China

Background Toxic epidermal necrolysis (TEN) and Stevens–Johnson Syndrome (SJS) are drug‐induced diseases with no well‐established treatments. The application of corticosteroid therapy is controversial. Intravenous immunoglobulin (IVIG) therapy is emerging as a promising new method for the treatment of these two diseases. The efficacy of combination therapy of IVIG and corticosteroid in the treatment of TEN/SJS has seldom been reported. Methods Sixty‐five consecutive patients with either TEN or SJS, admitted over a 14‐year period from January 1993 to October 2007, were treated with corticosteroid and analyzed retrospectively using SCORTEN, a severity‐of‐illness scoring system for TEN/SJS prognosis, to evaluate efficacy. For patients admitted after January 2001, additional therapy with a dose of 0.4 g/kg/day of IVIG for 5 days was applied. Results In the 45 patients with TEN treated without IVIG, 8.63 patients were expected to die based on the SCORTEN system, but 10 deaths were observed. Standardized mortality ratio (SMR) analysis [(Σobserved deaths/Σexpected deaths) × 100] suggested that patients with TEN treated with systemic corticosteroid were 16% more likely to die than those treated with routine therapy (SMR = 1.16; 95% confidence interval, 0.56–2.13). In the further study of combination therapy, 12 patients with TEN and eight patients with SJS were admitted. There were two deaths in the TEN group and one death in the SJS group, with 3.51 deaths expected on the basis of the SCORTEN system. SMR analysis showed that combination therapy had a tendency to reduce the mortality rate of TEN (SMR = 0.85; 95% confidence interval, 0.18–2.50). Nevertheless, in both the TEN and SJS groups, the difference in mortality rate between the two therapies was not statistically significant (P = 0.651 and P = 1, respectively). In patients with TEN, combination therapy also reduced significantly the time of arrested progression (P = 0.019) and the total hospitalization time (P = 0.043), but could not reduce the time to the tapering of corticosteroid (P = 0.96). In SJS patients, the times of arrested progression and hospitalization were also reduced significantly (P = 0.019 and P = 0.0475, respectively). Likewise, the time to the tapering of corticosteroid was not reduced (P = 0.122). Conclusion Combination therapy with corticosteroid and IVIG exhibited a tendency to reduce the mortality rate in comparison with the solo administration of corticosteroid. The decrease in the mortality rate, however, was not statistically significant. Combination therapy also arrested progression earlier and decreased the hospitalization time, meaning that the total dose of corticosteroid may be reduced. Combination therapy, however, did not lead to earlier tapering of corticosteroid. No severe adverse effects of IVIG were found during treatment.     

人免疫球蛋白和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的对比研究

目的:评价静脉注射人免疫球蛋白（IVIG）及重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rhTNFR：Fc）治疗中毒性表皮坏死松解症（TEN）的疗效。方法:收集2013—2019年武汉市第一医院使用IVIG及rhTNFR：Fc治疗的TEN患者资料。IVIG组11例,男3例,女8例,年龄25 ~ 72岁,中位TEN疾病严重...     

静脉注射丙种球蛋白和糖皮质激素治疗重症大疱性药疹65例

目的 比较静脉注射丙种球蛋白(IVIG)联合糖皮质激素与糖皮质激素单用治疗莺症大疱性药疹的疗效.方法 从1993-2007年共收集65例重症大疱性药疹病例.使用中毒性表皮坏死松解症评分(SCORTEN)进行分析.2001年后的病例采用联合治疗,丙种球蛋白剂量0.4 g·kg-1·d-1连用5 d,此前糖皮质激素治疗的病例作为对照.结果 在45例糖皮质激素治疗的病例中10例死亡,而预期死亡数8.63.标准死亡比(SMR)分析显示接受糖皮质激素治疗患者的死亡率较常规治疗高16%(SMR=1.16;95%CI 0.56-2.13).20例接受联合治疗患者中3例死亡,而预期死亡数3.51(SMR=0.85;95%CI 0.18-2.50).在中毒性表皮坏死松解症(TEN)、Stevens-Johnson综合征(SJS)患者中两种疗法死亡率差异均无统计学意义(P>0.05).在TEN患者中,联合疗法较之糖皮质激素疗法疾病停止进展时间及总住院时间缩短(t=2.46,3.14,P值均<0.05).但糖皮质激素减量时间无差异(t=-0.045,P>0.05);SJS患者结果相同(t=2.334,t=2.275,t=1.655,P<0.05,<0.05,>0.05 o结论 IVIG和糖皮质激素联合治疗较之仅用糖皮质激素治疗显示出死亡率降低的趋势,并能早期控制病情,缩短住院时间;但联合治疗并不能使糖皮质激素早期减量.     

Intravenous Immunoglobulin Use in Patients with Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome

Intravenous immunoglobulin (IVIg) has been proposed as a treatment for toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). A comprehensive search of the literature was conducted to examine the efficacy and safety of IVIg in TEN and SJS patients. Seventeen relevant articles (14 TEN, 3 SJS) were identified. Only three of the TEN studies and one of the SJS studies were prospective; retrospective studies were the most common study design published. Information regarding disease severity, IVIg use, response, and hospitalization were recorded and cumulated. Aggregate level statistics were calculated. The average IVIg doses used were 0.8 +/- 0.4 g/kg/day for a mean duration of 4.0 +/- 1.0 days in TEN patients and 0.8 +/- 0.2 g/kg/day for 3.4 +/- 1.0 days in SJS patients. The clinical experience of IVIg use in TEN and SJS patients was positive in most cases. However, more studies need to be conducted to confirm the benefit of IVIg use in patients with TEN or SJS.     

Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/Stevens–Johnson syndrome overlap

Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are severe mucocutaneous eruptions. There is currently no defined optimal approach to wound care. The objective of this study was to evaluate silver dressings in the wound‐care management of TEN and SJS/TEN syndrome overlap with a retrospective case review of nine patients with TEN and SJS/TEN overlap presenting to our institution. Nanocrystalline silver dressings appear to be useful in the rapid commencement of healing in these patients. TEN and SJS/TEN overlap are rare conditions. This contributed to a relatively small number of cases included in the study. The ease of application, antimicrobial properties and low frequency of change make nanocrystalline silver dressings ideal in TEN/SJS.     

Critical factors differentiating erythema multiforme majus from Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)

Erythema multiforme majus (EMM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are severe cutaneous reactions characterised by targetoid erythematous lesions and mucocutaneous involvement. The initial skin manifestations are similar, making early diagnosis difficult. We retrospectively reviewed 36 cases of EMM and 18 cases of SJS/TEN and also evaluated 6 patients with unclassified EMM. 13 patients in the EMM group and 16 patients in the SJS/TEN group presented with a high fever (>38.5?C; p<0.001). Two or more mucous membranes were affected in 6 patients in the EMM group and 18 patients in the SJS/TEN group. Significantly more SJS/TEN than EMM patients had high levels of C-reactive protein and severe hepatic dysfunction. Thirteen EMM and 13 SJS/TEN cases were caused by medications/drugs. Skin biopsy samples showed stronger mononuclear cell infiltration in the EMM than in the SJS/TEN group (p<0.001). The mean dose of initial systemic corticosteroid used to treat EMM was lower than that used to treat SJS/TEN. No patients died in either group. Clinically, the unclassified cases mostly behaved like EMM. The results of our investigation suggest that EMM and SJS/TEN are distinct conditions and they help in differentiating these syndromes at an early stage.     

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous reactions that are medication-induced in most instances. While the clinical manifestations of SJS and TEN are well-defined, the optimal treatment for these disorders is not. Case reports have shown benefit with the use of a variety of agents including tumor necrosis factor-alpha inhibitors and cyclophosphamide, whereas thalidomide was associated with an increased mortality. Plasmapheresis and cyclosporine have also demonstrated efficacy anecdotally, albeit with an even smaller number of cases in the literature. Most of the reporting has focused on the use of systemic corticosteroids and intravenous immunoglobulin (IVIG) for these severe reactions. The majority of studies analyzing the use of IVIG in the treatment of SJS/TEN show a benefit, though more recent series cast doubt upon this conclusion. The results of these studies are summarized in this present review study.     

The role of prior corticosteroid use on the clinical course of Stevens-Johnson syndrome and toxic epidermal necrolysis: a case-control analysis of patients selected from the multinational EuroSCAR and RegiSCAR studies

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologically mediated, severe cutaneous adverse reactions involving cytotoxic T cells, natural killer cells and various mediators. In large studies, up to 15% of SJS/TEN occurred in patients with chronic corticosteroid use. It is unclear if this prior exposure to corticosteroids modified the disease course. Objectives To evaluate whether systemic corticosteroid usage prior to the onset of SJS/TEN modified the clinical course and outcome. If a disease‐modifying effect is present, information from such an analysis may have implications on the therapeutic use of corticosteroids in SJS/TEN. Methods This is a case–control study based on data collected in the EuroSCAR and RegiSCAR studies. Ninety‐two cases of SJS/TEN with exposure to corticosteroids prior to the onset of disease, and 321 randomly selected SJS/TEN patients without prior exposure were included. Primary outcomes included progression of disease, disease severity and mortality. A secondary analysis of latency between the beginning of drug use and the onset of disease, based on exposure to a single high‐risk drug, was also performed. Results On multivariate analysis, cases with prior exposure to corticosteroids had a longer progression of disease by 2·2 days [95% confidence interval (CI) 1·1–3·2]. The disease severity and mortality outcome were unaffected. In addition, there is evidence that corticosteroids delayed the onset of SJS/TEN in patients with exposure to high‐risk drugs by 7·1 days (CI ?0·2 to 14·5). Conclusions The prior use of corticosteroids prolonged the period of disease progression without influencing the disease severity or mortality. In addition, when SJS/TEN is preceded by use of a single high‐risk drug, the latency between the drug intake and the onset of SJS/TEN may also be increased. These findings suggest that corticosteroids have a mild impact on the course of SJS/TEN, and further studies are required to clarify any potential therapeutic effects.