Mortality Of Toxic Epidermal Necrolysis Research Articles

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Fresh Look at an Old Foe.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are some of the less common cutaneous adverse drug reactions with significant mortality. This study was undertaken with the objective of studying the demographics and clinical profile of SJS/TEN and identifying parameters associated with mortality. All patients with SJS/TEN over 10 years (2010-2020) were included in the study. Data obtained from in-patient and out-patient records were analysed. A total of 82 patients with SJS/TEN were admitted to our centre over a period of 10 years. Patients with SJS were significantly younger than those with TEN, with a male: female ratio >1 in SJS and <1 in TEN. The most commonly implicated drugs were antiepileptics (n = 29, 35.4%), antibiotics (n = 20, 24.4%). and Non-steroidal antiinflammatory drugs (NSAIDs) (n = 7, 8.5%). The mortality rate in the TEN group was 16% (n = 8). Certain factors such as cutaneous lesions preceding mucosal lesions at onset, high mean Body surface area (BSA) of denudation and a transfer to intensive care unit (ICU) more than 7 days after admission were significantly associated with higher mortality. There was no difference between survivors and deaths in terms of delay in hospitalisation, total disease duration, implicated drug, delay in initiation of therapy, the onset of re-epithelialisation, Severity-of-illness score for TEN (SCORTEN) and total duration of hospital stay. Factors significantly associated with increased mortality in TEN were cutaneous onset of lesions, mean BSA of involvement and transfer to the intensive care unit (ICU) beyond day 7 of admission.

Accuracy of SCORTEN in predicting mortality in toxic epidermal necrolysis

BackgroundToxic epidermal necrolysis (TEN) patients require multi-directional and multi-disciplinary treatment. In most cases, they are hospitalised at intensive care units and require multi-directional, burn-complication preventive care. Choosing the most appropriate treatment option might be troublesome even when predicting scores are used. SCORTEN is the most renowned prognostic score for TEN patients, however, there are some data indicating that the accuracy of this test may be limited. The credibility of not just the predicted mortality risk, but also componential laboratory results and clinical features subject to debate. The aim of this study was to evaluate the efficacy and credibility of SCORTEN in clinical practice, on proprietary material.MethodsA retrospective analysis of 35 patients with diagnosed in histopathology TEN was performed. The inclusion criteria were as follows: day of submission before 5th day from the onset of the symptoms, full protocol of plasmaphereses and IVIGs according to our scheme. Our protocol includes cycle of plasmapheresis with frozen fresh plasma twice daily for the first 2 days following admission, and once daily for the subsequent 5 to 7 days. IVIGs were administered after the first two sessions of plasmapheresis, for 4 to 7 days. The dosage was calculated according to body weight, at 0.4 to 0.5 g/kg per dose.ResultsThe sensitivity of SCORTEN for the analysed cohort was 100%, with a specificity of 24%. The estimated death was 41,9%, while the actual death rates were 12,5%. Our protocol improved the survival, OR = 26,57, RR = 6,34, p = 0,022. Decrease in mortality was caused by a combined treatment protocol we use- plasmaphereses with IVIGs. No independent risk factor was significant in death evaluation.ConclusionOur data suggest that the scoring system for predicting death among TEN patients are reliable when they are high. New prognostic factors should be found to improve the evaluation of patients with low SCORTEN.

Immunomodulatory Treatment of Lyell's Syndrome: A Simultaneous Plasmapheresis and Intravenous Immunoglobulins Therapy.

Lyell's syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P &lt; .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients' outcome in TEN.

Toxic Epidermal Necrolysis (TEN) in an elderly with comorbidities: a case report

Background: In Toxic Epidermal Necrolysis (TEN), age has been reported to be not only a risk factor but also associated with increased mortality. The presence of underlying illness and comorbidities also increased the burden of TEN in elderly patients.Case: A-70-years old male patient was consulted with a history of pulmonary tuberculosis and skin detachment. Symptoms started since four weeks before admitted to the hospital with redness in the face and extremities that spread to the chest and back accompanied by fever and malaise. The patient also complained of a wound in the lips and genitalia. Physical examination found multiple erosion, geographical shape, varied in size with positive nickolsky sign. The detachment covered 40% of the body surface area. From the laboratory, a result found a decrease in hemoglobin, blood glucose, albumin, and potassium. The patient was diagnosed with TEN, treated in the burn care unit, given supportive care and intravenous dexamethasone 10 mg every 8 hours, and then tapered off. The mortality rate from SCORTEN count was 12,1%.Discussion: The incidence and mortality of TEN were higher in the elderly than among younger adults. Supportive care was the key feature of management with various adjunctive therapy, including systemic corticosteroids, intravenous immunoglobulin, and other immunosuppressant agents. Giving more comorbidities, more observation, and a multidisciplinary approach for TEN in elderly patients might be needed.Conclusion: In the elderly, the risk and mortality of TEN were even higher, and the presence of comorbidities require more observation and supportive care.

The role of malignancy in the mortality of Stevens‐Johnson syndrome and toxic epidermal necrolysis

Background Stevens-Johnson syndrome (SJS) / Toxic epidermal necrolysis (TEN) is a rare, severe, and occasionally fatal skin reaction caused mainly by medications. The reported mortality associated with TEN varies from 10-70%. SCORTEN, a severity-of-illness score which estimates the mortality in TEN has been developed and validated. Malignancy was considered as 1 of the 7 independent prognostic factors of SCORTEN. However, the studies focused on the associated factors of malignancy in the mortality of SJS/TEN were limited. In this study, we tried to analyze the true role of malignancy in the mortality of SJS/TEN. Method

Postoperative Stevens-Johnson syndrome secondary to piperacillin-tazobactam: A case report

Introduction: Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are severe, potentially fatal cutaneous reactions to medications affecting only 1–2 per million individuals each year. They present as tenderness, erythema and blistering of both the skin and mucus membranes. We describe a case of Stevens–Johnson syndrome linked to piperacillin–tazobactam treatment, which is a previously unreported cause and a rare occurrence in postoperative patients. Case Report: A 37­year­old female with chronic pancreatitis post­total pancreatectomy with auto­islet transplant was re­admitted on postoperative day 12 with abdominal pain and leukocytosis. Her workup revealed a small intra­ abdominal fluid collection suspicious for an abscess and she was empirically started on piperacillin–tazobactam. She developed hives on her extremities with associated itching after four days of treatment. Piperacillin–tazobactam was discontinued, diphenhydramine was administered for symptomatic relief, and she was discharged on an oral regimen of ciprofloxacin and metronidazole. She returned the following day with a rash extending onto her chest, abdomen, feet, face, lips and mouth, with newly appeared bullae covering approximately 35–50% of body surface. A skin biopsy was consistent with SJS, with piperacillin–tazobactam identified as the likely causative agent. Conclusion: The most common medications linked to TEN/SJS are sulfonamide antibiotics (especially sulfamethoxazole/trimethoprim), cephalosporins, quinolones, allopurinol, carbamazepine, phenytoin, phenobarbital, and NSAIDs (oxicam­type). While medications the most common cause, mycoplasma pneumoniae and herpes simplex virus (HSV) have also been linked to SJS. The mortality rate of biopsy­ confirmed SJS ranges from 1–5%, whereas the mortality of TEN ranges from 25–35%. Though many patients experience pruritis and/or rashes as side­effects to medications given post­ operatively, it is important to keep in mind more serious reactions such as TEN and SJS as these conditions as they have a substantial associated morbidity and even mortality.

Serum Bicarbonate as a Marker to Predict Mortality in Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a rare life-threatening disorder characterized by extensive epidermal necrolysis. Its mortality which varies from 20% to 60% is related to risk factors such as age, extent of epidermal detachment, and base deficit. The purpose of this study is to investigate the risk factors of mortality in our patients with TEN. From the year 2000 to 2006, the patients with TEN admitted to the National Taiwan University Hospital Burn Center were studied retrospectively using chart review. Eleven potential risk factors including age, gender, underlying disease, malignancy, extent of epidermal detachment, tachycardia, serum urea, glucose, base deficit, leucopenia, and intravenous infusion of immunoglobulin (IVIG) were analyzed. Patients were grouped into survivors (n ¼ 11) and nonsurvivors (n ¼ 5) after intensive care treatment. Logistic regression was used in multivariate analysis for identifying important predictors of mortality. The mean age of the patients with TEN was 58 years, while the mean total body surface area of epidermal necrolysis was 66.3%. The overall mortality rate was 31.3%. Among the potential risk factors, only serum bicarbonate <20 mmol/L was found to have significant association with mortality (P ¼ .0128) in our patients with TEN. The odds of mortality in the patients with TEN having serum bicarbonate <20 mmol/L was 40 times higher than those without. This study has shown that serum bicarbonate <20 mmol/L is the most important risk factor of mortality in our patients with TEN and it may be used as a marker to predict hospital mortality.

Does hypernatremia impact mortality in Toxic Epidermal Necrolysis?

Introduction: In-hospital hypernatremia is associated with increased mortality rates. We want to elucidate the impact of in-hospital acquired hypernatremia in mortality of Toxic Epidermal Necrolysis (TEN).Purpose: Is there an association between hypernatremia and mortality in patients with TEN?Method: Retrospective study of 25 patients with TEN. Laboratory electrolyte results, diuresis and survival were analyzed. Patients were separated in two groups without (Group A) or with (Group B) hypernatremia.Results: In Group A 10 patients with a TBSA of 74±25% (mean ± standard deviation), and a SCORTEN-Score of 2.7±0.9 were summarized. Diuresis within the first 10 days after admission was 1±0.3 ml/kg/hour. In Group B 15 patients with a TBSA of 76±19%, and a SCORTEN-Score of 3.5±1 were included. Diuresis within the first 10 days after admission was 1.4±0.4 ml/kg/hour. Hypernatremia occurred on day 3.3±2.4 after admission and persisted for 5.3±2.9 days. Statistical analysis showed a significantly higher diuresis (p=0.007) and SCORTEN-Score (p=0.04) in the hypernatremic patients. One normonatremic and 8 hypernatremic patients died during ICU-stay (overall mortality rate 36%). A significantly higher mortality rate was found in Group B (odds ratio: 13,5; 95% confidence interval: 1.34–135.98; p=0.01) during ICU-stay.Conclusion: TEN patients with an in-hospital acquired hypernatremia have an increased mortality risk. Close electrolyte monitoring is advisable in these patients.

SCORTEN Accurately Predicts Mortality Among Toxic Epidermal Necrolysis Patients Treated in a Burn Center

SCORTEN is a scoring system used to predict mortality in toxic epidermal necrolysis (TEN) patients. The accuracy of SCORTEN among TEN patients treated in burn centers has not been established. The purpose of this study was to assess the discriminative power and calibration of SCORTEN among TEN patients treated at an adult regional burn center. Retrospective analysis of a consecutive series of TEN patients was used to compare actual mortality with that predicted by SCORTEN. A standardized mortality ratio was obtained to compare the actual number of deaths to the predicted number based on SCORTEN. Discrimination was measured using the area under the receiver operator characteristic curve, and model fit (calibration) was measured using the Hosmer-Lemeshow goodness-of-fit statistic. A total of 61 adult patients were analyzed. The actual overall mortality rate of 29.5% was not significantly different than the mortality rate of 25.2% predicted by SCORTEN (standardized mortality ratio, 1.17; 95% confidence intervals, 0.695-1.853; P = .08). The area under the receiver operator characteristic curve was 0.82 and the Hosmer-Lemeshow statistic was 1.381 (P = .710). SCORTEN is an accurate scoring system for estimation of mortality among TEN patients treated in a burn center setting.

Analysis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Japan from 2000 to 2006

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions with high mortality. To present the current clinical characteristics and treatment of SJS and TEN in Japan, we retrospectively analyzed reports of SJS and TEN published in medical journals from 2000 to 2006. Fifty-two cases of SJS (19 males and 33 females; mean age, 45.2 years) and 65 cases of TEN (31 males and 34 females; mean age, 45.7 years) were reported. Thirty-six cases of SJS (69.2%) and all cases of TEN were caused by drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and anticonvulsant drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction and respiratory disorders were also involved in some cases. The major complication was sepsis, but in only 1.9% of SJS and 10.8% of TEN. Most cases were treated systemically with corticosteroids, and 42 cases (80.8%) of SJS and 39 cases (60.0%) of TEN were treated with corticosteroids alone. Plasmapheresis and/or immunoglobulin therapy was combined with corticosteroid therapy in some cases. The mortality rates for patients with SJS and TEN were 1.9% and 6.2%, respectively. The mortality in TEN decreased remarkably from 21.6% (58/269) during the previous 17 years (1981 to 1997). Improvement of treatment may be one of the reasons for the decrease in mortalities of both SJS and TEN.

Increased mortality in toxic epidermal necrolysis with thalidomide: corroborating or exonerating the pathogenetic role of TNF-α ?

Conflicts of interest: none declared. Sir, I read with great interest the article by Chave et al.,1‘Toxic epidermal necrolysis: current evidence, practical management and future directions’, which appeared in the August 2005 issue of the British Journal of Dermatology. Referring twice to a randomized, placebo‐controlled study by Wolkenstein et al.2 showing increased mortality in toxic epidermal necrolysis (TEN) with the use of thalidomide, a TNF‐α inhibitor, Chave et al. support the notion that TNF could be antiapoptotic in this condition. However, the referenced work is not supportive of this notion at all—in fact, it supports the opposite notion, i.e. the pathogenetic involvement of TNF in TEN. Wolkenstein et al.’s data suggest that thalidomide does not inhibit TNF‐α production in TEN, rather, it might result in the paradoxical overproduction of it. In this study, plasma concentrations of this cytokine tended to increase after treatment with thalidomide in comparison with the placebo group. A similar unexpected increase in TNF‐α has been observed in the thalidomide therapy of oral aphthous ulcers in patients with human immunodeficiency virus infection.3

SCORTEN: A Severity-of-Illness Score for Toxic Epidermal Necrolysis

The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to develop and validate a specific severity-of-illness score for cases of toxic epidermal necrolysis admitted to a specialized unit and to compare it with the Simplified Acute Physiology Score and a burn scoring system. A sample of 165 patients was used to develop the toxic epidermal necrolysis-specific severity-of-illness score and evaluate the other scores, a sample of 75 for validation. Model development used logistic regression equations that were translated into probability of hospital mortality; validation used measures of calibration and discrimination. We identified seven independent risk factors for death and constituted the toxic epidermal necrolysis-specific severity-of-illness score: age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic epidermal necrolysis-specific severity-of-illness score point the odds ratio was 3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) = elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis-specific severity-of-illness score). Calibration demonstrated excellent agreement between expected (19. 6%) and actual (20%) mortality; discrimination was also excellent with a receiver operating characteristic area of 82%. The Simplified Acute Physiology Score and the burn score were also associated with mortality. The discriminatory powers were poorer (receiver operating characteristic area: 72 and 75%) and calibration of the Simplified Acute Physiology Score indicated a poor agreement between expected (9.1%) and actual (26.7%) mortality. This study demonstrates that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidermal necrolysis-specific severity-of-illness score. The Simplified Acute Physiology Score and burn score appear to be less adequate.

Thalidomide causes higher mortality in toxic epidermal necrolysis

Thalidomide causes higher mortality in toxic epidermal necrolysis

Antibiotic drug allergy in children

Cutaneous reactions to penicillin-type antibiotics are usually caused by IgE-mediated reactions directed toward the beta-lactam ring (in penicillin, ampicillin-amoxicillin, and cephalosporins). These allergic reactions may be reliably diagnosed (96% to 99% of the time) with a battery of skin tests derived from penicillin. A few individuals have been identified in Spain, and now Canada, who react to side chains of the beta-lactam antibiotics (and not the beta-lactam ring). Nonallergic cutaneous or systemic reactions to trimethoprim sulfamethoxazole (TMP-SMX) are now an emerging problem among HIV-infected patients. Life-threatening reactions have been described in HIV-infected infants who were rechallenged with TMP-SMX. New 10-day and 48-hour desensitization procedures have been used successfully in some TMP-SMX-reactive patients. Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis) are the most serious of the antibiotic-associated cutaneous reactions. These reactions may be caused by an immune reaction similar to graft-versus-host syndrome. Corticosteroids have been shown to be helpful in the management of Stevens-Johnson syndrome. Although the mortality of toxic epidermal necrolysis is usually high, several children with this disorder have been successfully treated in a burn unit.

Toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a life-threatening condition in which the epidermis blisters and peels in large sheets. The clinical syndrome and diagnosis are reviewed. Current treatment and prevention of complications are discussed. The key to low morbidity and mortality in TEN is early intervention. Physicians should be knowledgeable about TEN and the appearance of the skin in its initial presentation.