Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS): experience with high-dose intravenous immunoglobulins and topical conservative approach. A retrospective analysis

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, drug-induced, severe acute exfoliative skin and mucosal disorders. Several treatments previously proposed have produced contradictory results in small series; in 1998 the use of intravenous immunoglobulins (IVIG) was introduced with excellent clinical findings. Our experience (1999-2005) using IVIG in the therapy of TEN/SJS, together with a local conservative approach, is reported and related to our previous treatments (1993-1998). The SCORTEN and the standardized mortality ratio (SMR) was used to evaluate the efficacy of our therapeutic modalities. Eight patients were treated before IVIG era and 23 patients have been treated with IVIG. There was no significant difference in SCORTEN between the two groups. Concerning the local approach, a conservative wound management in IVIG series replaced an extensive epidermal debridment and coverage with artificial skin substitutes of the pre-IVIG series. Overall mortality in patients treated before IVIG was 75% (6/8), in the IVIG group it decreased to 26% (6/23) with a cessation of further epidermal detachment after an average of 5 days (3-10 days) from the onset of the therapy. The SMR showed a trend to lower actual mortality (not significative) with IVIG treatment than the predicted mortality (SMR=0.728; 95% CI: 0.327-1.620).     

Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal necrolysis: A regional burns centre experience

Introduction

Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, potentially fatal desquamative disorders characterised by large areas of partial thickness skin and mucosal loss. The degree of epidermal detachment that occurs has led to SJS/TEN being described as a burn-like condition. These patients benefit from judicious critical care, early debridement and meticulous wound care. This is best undertaken within a multidisciplinary setting led by clinicians experienced in the management of massive skin loss and its sequelae. In this study, we examined the clinical outcomes of SJS/TEN overlap & TEN patients managed by our regional burns service over a 12-year period. We present our treatment model for other burn centres treating SJS/TEN patients.

A systematic review of the management and outcome of toxic epidermal necrolysis treated in burns centres

IntroductionToxic epidermal necrolysis (TEN) is a rare condition characterised by mucocutaneous exfoliation of greater than 30% total body surface area (%TBSA), increasingly being treated in burns centres. The rate of mortality varies significantly in the literature, with recent prospective studies in non-burns centres reporting percentage mortality of approximately 45%. We undertook a systematic review of published studies that included TEN patients treated specifically in burns centres to determine a cumulative mortality rate.MethodsElectronic searches of MEDLINE, EMBASE and The Cochrane Library (Issue 4, 2010) databases from 1966 onwards were used to identify English articles related to the treatment of TEN in burns centres.ResultsThe systematic literature search identified 20 studies which specifically described patients with TEN grater than 30% %TBSA. Treatment regimens varied amongst studies, as did mortality. The overall percentage mortality of the combined populations was 30%. Risk factors commonly described as associated with mortality included age, %TBSA and delay to definitive treatment.ConclusionThe review highlights the variation between principles of treatment and mortality amongst burns centres. It offers a standard that burns centre can use to internationally compare their mortality rates. The review supports the ongoing reporting of outcomes in TEN patients with epidermal detachment greater than 30%.     

Secondary abdominal compartment syndrome in patients with toxic epidermal necrolysis

Introduction

Secondary abdominal compartment syndrome (ACS) is a severe complication in patients admitted to burn intensive care units (BICUs). Unlike patients with thermal burns, patients with toxic epidermal necrolysis (TEN) present with a different pathophysiology and usually require less fluid.

Patients and methods

We reviewed our registry of adult patients presenting with TEN in our 8-bed BICU over the course of 11 years and identified and analyzed patients treated for ACS and decompressive laparotomy (DL).

Results

From a total of 29 patients with bioptic confirmed TEN, 5 underwent DL due to ACS with a mean age of 57 years, mean percentage of total body surface area (TBSA) affected of 54 ± 25%, complete epidermolysis of 28 ± 24% TBSA, a mean severity of illness score (SCORTEN) of 3.8 ± 0.8, and a mean intra-abdominal pressure before DL of 33 ± 7 mmHg. Mortality was 100% in patients with ACS versus 33% without ACS.

Conclusion

An ACS that requires DL worsens the already critical condition of a TEN patient considerably. TEN-related impaired intestinal functionality and increasing intestinal edema due to systemic capillary leakage warrant early initiation of intra-abdominal pressure monitoring to identify patients at high risk of ACS.     

Toxic epidermal necrolysis: use of Biobrane or skin coverage reduces pain, improves mobilisation and decreases infection in elderly patients

INTRODUCTION: Toxic epidermal necrolysis is a rare disease with high mortality due to generalised infection, sepsis or lung involvement, and requires discontinuation of all potentially triggering medications and intensive care in a specialised burn centre. Apart from wound care with antiseptics, wound coverage may be achieved with a skin substitute; treatments are compared with regard to infection, protein loss, re-epithelialisation and mortality. PATIENTS AND METHODS: Of 14 people with toxic epidermal necrolysis affecting >30% body surface area, eight received daily dressing changes using Lavasept nd six received wound coverage with Biobrane. Demographic data, SCORTEN score, mortality, visual-analog pain scale, mobilisation, time to re-epithelialisation, serum protein, albumin, C-reactive protein and leukocytes, and body temperature were evaluated in all cases. RESULTS: Mean age of patients was 68.0+/-14.8 years, mean body surface area affected was 66.4%, median SCORTEN score was three and overall mortality was 36%. In the Biobrane ompared with the Lavasept control) group, mean pain was significantly reduced (2.9 versus 5.5 on the scale, p<0.05), mobilisation was significantly earlier (walking at 3 days versus 7 days, p=0.003), re-epithelialisation was complete in 12.5 days versus 16 days, and at 9 days there was reduced decrease of serum proteins and significantly lower levels of C-reactive protein and white cells (p<0.05). CONCLUSION: Early wound coverage with synthetic skin substitute such as Biobrane s beneficial compared with conservative antiseptic wound treatment, but mortality rate is not significantly different.     

Effect of N-acetylcysteine combined with infliximab on toxic epidermal necrolysis. A proof-of-concept study

IntroductionThe pathophysiology of toxic epidermal necrolysis (TEN) is thought to be related to a drug-induced oxidative stress combined with TNFα overexpression by keratinocytes. None of the current treatments for TEN including systemic corticosteroids, cyclosporine and intravenous administration of immunoglobulins has proven superior over supportive care only.MethodsA total of 10 TEN patients were enrolled to be treated at admission in burn units with the antioxidant N-acetylcysteine [NAC, 150 mg/kg in a 20-h intravenous (IV) administration], or the combination of the same IV NAC perfusion with the anti-TNFα antibody infliximab (Remicade^®), administered at a 5 mg/kg dosage as a single 2-h IV administration. TEN was confirmed by a skin biopsy taken from a bullous lesion. At entry in the trial and 48 h later, the illness auxiliary score (IAS) of clinical severity was determined and the extent in altered skin area (erythema and blisters) was assessed as a relative body area. Skin biopsies of both clinically uninvolved and erythematous areas were collected and immunohistochemistry was performed for assessing the density of inflammatory cells (CD8+ T cells, CD68+ macrophages) and keratinocytes enriched in intracellular calcium (Ca⁺⁺) identified by the Mac387 anti-calprotectin antibody.ResultsNo unexpected drug-induced adverse event was noticed. After 48 h of both treatment modalities, improvements were not observed in the extent of skin involvement and in IAS. Immunohistopathology showed the absence of reduction in the amount of intraepidermal inflammatory cells. An increased intracellular Ca⁺⁺ load in clinically uninvolved keratinocytes and in erythematous epidermis was noticed. This latter finding suggested the progression in the way of the apoptotic process. On burn unit discharge, the survival in each modality of treatment was not improved compared to the expected outcomes determined from the IAS at admission.ConclusionsIn this proof-to-concept attempt, NAC treatment or its combination with infliximab did not appear to reverse the evolving TEN process.     

Toxic epidermal necrolysis/Stevens-Johnson syndrome: current trends in management

BACKGROUND: Toxic epidermal necrolysis (TEN) is an uncommon but potentially life-threatening condition that involves sloughing of the skin at the dermoepidermal junction. TEN is a well-recognized syndrome and is part of a range of severe mucocutaneous intolerance reactions, mostly elicited by drugs and/or their metabolites. Reported mortality rates vary widely from 20 to 75%. Several systemic treatment protocols for TEN have been published; however, none has been formally standardized in a randomized controlled trial. The present study documents the current management principles and trends seen in 16 patients admitted with TEN or Stevens-Johnson syndrome over a 5-year period at the Concord Repatriation General Hospital Burns Unit. METHOD: Data were collected by retrospective chart review, and parameters included in the study were patient demographics, causative agents, percentage total body surface area and/or mucosal involvement, complications, treatment and outcome. In particular, dressing choice and documented healing of skin lesions were noted. RESULTS: Sixteen patients were identified, with the beta-lactam antibiotics most commonly implicated as the cause. Complications tended to relate to degree of sepsis and/or mucous membrane involvement. Nanocrsytalline silver dressings, such as Acticoat (Smith & Nephew, Mount Waverley, Victoria, Australia), were used predominantly in more recent cases. CONCLUSION: The shift in dressing choice from traditional Vaseline-impregnated gauze coincided with a general trend towards the use of nanocrystalline silver dressings for superficial burns after 2003. The nanocrystalline silver dressings have shown considerable advantage over previously used dressings, with no adverse reactions noted and good healing of the skin lesions for all patients.     

Nursing problems in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome in a Dutch burn centre: A 30-year retrospective study

ObjectiveMultiple studies have been published on toxic epidermal necrolysis (TEN) and Stevens-Johnsen syndrome (SJS). Nursing care is an important part of the treatment of TEN patients. Unfortunately, limited information on nursing in TEN/SJS patients has been published in the current literature. Nursing research is needed to improve the complex nursing care required for these rare patients. Therefore, the objective was to assess nursing problems in TEN patients in a burn centre setting over a 30-year period.MethodsThe data for this study were gathered retrospectively from nursing records of all patients with TEN/SJS admitted to Burn Centre Rotterdam between January 1987 and December 2016. Dutch burn centres were recently accepted as expertise centres for TEN patients. Nursing problems were classified using the classification of nursing problems of the Dutch Nursing Society.ResultsA total of 69 patients were admitted with SJS/TEN. Fifty-nine patient files were available. The most frequently reported nursing problems (>20% of the patients) were wounds, threatened or disrupted vital functions, dehydration or fluid imbalance, pain, secretion problems and fever. Furthermore, TEN-specific nursing problems were documented, including oral mucosal lesions and ocular problems. The highest number of concomitant nursing problems occurred during the period between days three and 20 after onset of the disease and varied by nursing problem.ConclusionsThe most frequently reported nursing problems involved physical functions, especially on days three to 20 after onset of the disease. With this knowledge, we can start nursing interventions early in the treatment, address problems at the first sign and inform patients and their families or relatives of these issues early in the disease process. A next step to improve nursing care for TEN patients is to acquire knowledge on the optimal interventions for nursing problems.     

Upper airway involvement in Stevens–Johnson syndrome and toxic epidermal necrolysis

BackgroundStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening hypersensitivity conditions associated with epidermal detachment and mucositis. The indication for flexible nasoendoscopy (FNE) and overall predictive factors for early intubation are unclear.ObjectivesTo describe the incidence of airway involvement and the key indicators for intubation in our SJS or TEN patient cohort. To determine the association between FNE findings and early intubation.MethodsA retrospective review of 45 patients with biopsy proven SJS or TEN admitted to an Australian tertiary burns centre from 2010 to 2017.ResultsThirty-five patients were diagnosed with TEN (77.8%), followed by overlap syndrome (SJS-TEN) (n = 6, 13.3%) and SJS (n = 4, 8.9%). Twenty (44.4%) patients were intubated; and all 20 had a diagnosis of TEN (100.0%) (p < 0.05). Intubated patients had a higher increase in total body surface area percentage(%) from day 1–3 [10.0% (IQR 0.0–23.8%)] and a longer length of stay [26.0 days (IQR 12.5–34.0)], compared to non-intubated patients [0.0% (IQR 0.0–4.0%)], [10.0 days (IQR 6.0–14.0)] (p < 0.05) respectively. The main indications for intubation were to facilitate operative and dressing management (47.4%) followed by airway involvement (26.3%). FNE was performed on 32 patients (71.1%), however FNE findings did not significantly influence intubation rates.ConclusionMore than half (n = 20, 57.1%) of the 35 patients diagnosed with TEN underwent intubation, mainly to facilitate operative and dressing management. FNE was performed on most patients, however there was no clear association between FNE findings and early intubation.     

Toxic epidermal necrolysis data from the CELESTE multinational registry. Part I: Epidemiology and general microbiological characteristics

Introduction

Toxic epidermal necrolysis (TEN) is a rare, life-threatening autoimmune disease predominantly manifested in the skin and mucous membranes. Today, infectious complications have the dominant share in mortality of TEN patients. Due to the nature of the therapy and administration of immunosuppressive medications, a wide range of potentially pathogenic microorganisms, which cause infectious complications in different compartments in these patients, is not surprising.

Treatment of toxic epidermal necrolysis in a pediatric patient with a nanocrystalline silver dressing

Background/Purpose

To report a case of toxic epidermal necrolysis (TEN) involving 90% body surface area, successfully treated with a nanocrystalline silver dressing (Acticoat, Smith & Nephew, Largo, FL).

Methods

A review of the hospital and acute wound center patient records and the recent English medical literature regarding TEN and nanocrystalline silver dressing.

Results

We found only 1 report of TEN treated with a nanocrystalline silver dressing. The nanocrystalline silver dressing was both effective in preventing wound infection and convenient for treating our patient with TEN.

Conclusion

The use of nanocrystalline silver dressing should be considered for the treatment of TEN.     

Retrospective study of 213 cases of Stevens–Johnson syndrome and toxic epidermal necrolysis from China

BackgroundStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial.MethodsA retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG).ResultsThe causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection.ConclusionThe mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.     

AQUACEL Ag in the treatment of toxic epidermal necrolysis (TEN)

Toxic Epidermal Necrolysis (TEN) is life-threatening dermatological disease characterized by extensive destruction of the epidermis is associated with a 25-60% mortality rate in adults. We presented one patient with TEN with 86% skin slough treated successfully using AQUACEL Ag exclusively. All of the wounds were healed completely 8 days after onset of TEN. AQUACEL Ag is an efficient and cost-effective adjunct in the treatment of TEN.     

Aquacel Ag with Vaseline gauze in the management of toxic epidermal necrolysis (TEN)

Toxic epidermal necrolysis (TEN) is a rare condition with potentially high mortality and involves severe exfoliative disease of the skin and mucous membranes induced by drugs. The reported fatality of TEN varies widely from 20% to 60%. The technique for TEN wound coverage described in this article involves the use of various dressings.     

Combination therapy: Etanercept and intravenous immunoglobulin for the acute treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis

BackgroundStevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an autoimmune condition with significant morbidity and mortality.MethodsA retrospective review was performed at a single institution. All patients admitted to the LAC + USC burn unit from May 1st 2015–January 1st 2018 with a histologic diagnosis of SJS/TEN were reviewed. Patient characteristics and outcomes were recorded. These outcomes were compared to our previously published cohort.ResultsThirteen total consecutive SJS/TEN patients were treated with etanercept. Compared to non-etanercept treated patients, etanercept-treated patients did not experience a significant difference in mortality (15.4% vs. 10%, P = 0.58), ICU days (6.9 vs. 15.1, P = 0.08), length-of-stay (9.8 vs 16.4, P = 0.11), or infections (38.5% vs. 57.5%, P = 0.58). The standardized mortality ratio in etanercept-treated patients was 0.44 (95% CI, 0.21, 0.65). In general, etanercept-treated patients had higher SCORTENs (3 vs. 2, P = 0.03) and longer delays to presentation (5.2 vs. 2.7 days, P < 0.01).ConclusionsEtanercept can be considered in the treatment of SJS/TEN patients in addition to IVIg, and supportive care in a burn unit.     

Obese patients in a burn care unit: A major challenge

ObjectiveObesity is an important predictor of mortality and morbidity during a hospital stay. There is very little data concerning the impact of the BMI on clinical outcomes in obese burn patients.The purpose of this study is to document the general epidemiological aspects of thermal injuries in an obese population and draw attention to topics relating to the management, rehabilitation and prognosis of burns in this emerging subpopulation of patients.MethodsAll patients >16 years of age admitted to the burn unit between January 2008 and December 2012 and fulfilling the burn center referral criteria were enrolled in the study. SPSS version 20 (SPSS GmbH Software, Illinois, USA) was employed for data analysis.ResultsEleven extreme obese patients (men:women, 6:5) had a mean BMI of 38 kg/m². Their incidence in our study was 5.5%. The mean length of stay was 41.5 days, almost twice that of the non-obese. The presence of co-morbidities such as diabetes, hypertension, cardiac disease, or pulmonary disease, the problematic wound healing and the burn wound infection were significantly higher in the obese patients than in the non-obese. The mortality of obese burned patients was 36.4%.ConclusionsThese facts indicate admission of these patients to a burn care unit for the best possible treatment although they might not always fulfill criteria for admission to burn intensive care unit. Burn centers must be also prepared in terms of special nursing equipment for obese patients.