Article

Clinical Evaluation Comparing the Efficacy of Aquacel Ag with Vaseline Gauze versus 1% Silver Sulfadiazine Cream in Toxic Epidermal Necrolysis

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Abstract

The purpose of this study was to determine whether using Aquacel Ag (ConvaTec, Skillman, New Jersey) with Vaseline (Unilever, London, England) gauze instead of silver sulfadiazine cream (SSD) as the wound care protocol to treat toxic epidermal necrolysis (TEN) can improve wound healing, pain control, and reduction of labor costs. A retrospective chart review. A burn center with 2 plastic surgeons and 11 nursing staff. A pathologist diagnosed TEN in 35 patients admitted to the burn center from 1995 to 2009. Parameters included the patient's profile, dressing choice, severity-of-illness score for TEN, time to 95% re-epithelialization, visual analog scale pain scores before second dressing change, and labor cost. The exclusion criterion was wound care with neither Aquacel Ag with Vaseline nor SSD exclusively. Twenty patients were enrolled in this study. In the group using Aquacel Ag with Vaseline gauze, the visual analog scale score was significantly less than that of the SSD group (P = .02). Labor costs were significantly lower in the Aquacel Ag with Vaseline gauze group (P < .01). Commencement of specific dressing to 95% re-epithelialization (P = .09) and time spent in the second dressing change (P = .05) had no statistical significance between the 2 groups. This study showed that Aquacel Ag with Vaseline gauze decreased pain and labor costs but did not shorten wound healing time. Thus, Aquacel Ag with Vaseline gauze can be an efficient method for treating TEN wounds.

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... Nangole found that treatment with Aquacel Ag silver Hydrofiber dressings can decrease mortality in patients with Toxic epidermal necrolysis [12]. Huang et al. showed that Aquacel Ag with Vaseline gauze decreased pain and labor costs [13]. ...
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Burn depth and burn size are crucial determinants for assessing patients suffering from burns [1]. Therefore, a correct evaluation of these factors is optimal for adapting the appropriate treatment in modern burn care. Burn surface assessment is subject to considerable differences among clinicians [2]. This work investigated the accuracy among experts based on conventional surface estimation methods (e.g. "Rule of Palm", "Rule of Nines" or "Lund-Browder Chart"). The estimation results were compared to a computer-based evaluation method. Survey data was collected during one national and one international burn conference. The poll confirmed deviations of burn depth/size estimates of up to 62% in relation to the mean value of all participants. In comparison to the computer-based method, overestimation of up to 161% was found. We suggest introducing improved methods for burn depth/size assessment in clinical routine in order to efficiently allocate and distribute the available resources for practicing burn care.
Article
Toxic epidermal necrolysis (TEN) represents the most severe drug-related skin condition that is potentially life-threatening with no well-established treatments. The application of corticosteroid therapy is controversial, whereas recently intravenous immunoglobulin (IVIG) therapy is emerging as a promising new method. A severity-of-illness score for TEN (SCORTEN) has gained acceptance in some western countries. In this study, the authors' objectives were to assess the applicability of SCORTEN in Chinese patients with TEN and to evaluate the efficacy of the combination therapy of IVIG and corticosteroid in these patients. The authors performed a retrospective review of data from 61 patients with TEN treated at their intensive care unit from 2000 to 2010 to assess the performance of SCORTEN. In particular, 55 patients between 2002 and 2010 were grouped as a series to compare the therapeutic effects of corticosteroid therapy and IVIG combined therapy contemporaneously. During this period, 16 patients were administered with corticosteroid therapy and 39 were treated with the combination therapy. An initial dose of 1.5 mg/kg/day of methylprednisolone was given to all TEN patients. The combination therapy was combined with a total dose of 2 g/kg IVIG within 5 days. Areas under receiver operating characteristic curves and Hosmer-Lemeshow statistic were analyzed to illustrate the performance of SCORTEN. The comparison of the efficacy of the two therapies was conducted on the basis of clinical outcomes, standardized mortality ratio (SMR), and survival analysis. The overall actual mortality of patients between 2000 and 2010 was 16% (10/61), statistically insignificantly lower than predicted (24%, SMR = 67.98). Excellent discriminatory power (the areas under the receiver operating characteristic curves: 88.9, 88.2, 90.6%) and good calibration (P = .637, .833, .530) were found in all the groups. In patients admitted between 2002 and 2010, IVIG combined therapy showed a trend toward reducing the mortality rate (13%, SMR = 52.35), whereas corticosteroid monotherapy suggested no such difference (31%, SMR = 123.92). Besides, the cumulative survival rates of the combination therapy were higher at almost all the levels of SCORTEN, especially at the score of 5 (P = .039). Compared with corticosteroid alone, the combination therapy arrested progression earlier (P = .013), although it did not significantly lead to a tapering of corticosteroid or a reduction of the time of hospitalization. SCORTEN was generally applicable to Chinese patients with TEN. The comparison of the effect indicated that the combination therapy might achieve a better therapeutic effect than the administration of corticosteroid alone, especially in severe TEN patients.
Article
Toxic epidermal necrolysis (TEN) is associated with a significant mortality of 30-50% and long-term sequelae. Treatment includes early admission to a burn unit, where management with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. We have treated the cutaneous lesions of seven patients of TEN with collagen sheet dressings and have found a significant reduction in morbidity. The sheets are a one-time dressing, easy to apply and they reduce fluid loss, prevent infection, reduce pain, avoid repeated dressings and gradually peal off as the underlying lesions heal.
Article
Toxic epidermal necrolysis (TEN) is a severe cutaneous drug reaction with a mortality rate of approximately 30%. The hallmark of TEN is widespread epidermal sloughing due to keratinocyte apoptosis. Multiple genetic associations between TEN and specific ethnic populations have been determined. The pathophysiology of TEN has yet to be fully elucidated; however, current pathogenic models implicate Fas ligand, granulysin, and reactive oxygen species. The value of current therapies, such as intravenous immunoglobulin and corticosteroids, remains under evaluation.
Article
An open, parallel, randomized, comparative, multicenter study was implemented to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing (Mepilex Ag) vs silver sulfadiazine cream (control) in the treatment of partial-thickness thermal burns. Individuals aged 5 years and older with partial-thickness thermal burns (2.5-20% BSA) were randomized into two groups and treated with the trial products for 21 days or until healed, whichever occurred first. Data were obtained and analyzed on cost (direct and indirect), healing rates, pain, comfort, ease of product use, and adverse events. A total of 101 subjects were recruited. There were no significant differences in burn area profiles within the groups. The cost of dressing-related analgesia was lower in the intervention group (P = .03) as was the cost of background analgesia (P = .07). The mean total cost of treatment was $309 vs $513 in the control (P < .001). The average cost-effectiveness per treatment regime was $381 lower in the intervention product, producing an incremental cost-effectiveness ratio of $1688 in favor of the soft silicone foam dressing. Mean healing rates were 71.7 vs 60.8% at final visit, and the number of dressing changes were 2.2 vs 12.4 in the treatment and control groups, respectively. Subjects reported significantly less pain at application (P = .02) and during wear (P = .048) of the Mepilex Ag dressing in the acute stages of wound healing. Clinicians reported the intervention dressing was significantly easier to use (P = .03) and flexible (P = .04). Both treatments were well tolerated; however, the total incidence of adverse events was higher in the control group. The silver-containing soft silicone foam dressing was as effective in the treatment of patients as the standard care (silver sulfadiazine). In addition, the group of patients treated with the soft silicone foam dressing demonstrated decreased pain and lower costs associated with treatment.
Article
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.
Article
The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome. PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases. Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. Stevens-Johnson syndrome affects <10%, whereas involvement of 10%-30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%-50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. Profound knowledge of exfoliative skin diseases is needed to improve therapy and outcome of these life-threatening illnesses.
Article
For decades silver-containing antibiotics such as silver sulfadiazine (SSD) have been applied as standard topical therapy for patients with partial-thickness burns and venous stasis ulcers. This evidence-based review intends to answer the following research question: in ambulatory patients with partial-thickness burns or stasis dermatitis ulcers, does the use of topical SSD compared with nonantibiotic dressings improve mortality, wound healing, re-epithelialization, or infection rates? MEDLINE, EMBASE, Cochrane Library, and other databases were searched. We considered trials that enrolled patients of any age with partial-thickness burns or venous stasis ulcers and randomized them to either topical SSD or placebo, saline-soaked gauze, paraffin gauze, sterile dry dressing, or nonantibiotic moist dressing. Outcomes included mortality, wound healing, speed of re-epithelialization, and infection rates. For burns, our search revealed 400 potential articles. No human studies met the inclusion criteria. Only 7 animal studies (1 mouse, 4 rat, and 2 pig) were relevant to the proposed question. These animal studies provided conflicting results. Whereas some support the use of SSD for treatment of partial-thickness burns, others question its effectiveness. For stasis dermatitis ulcer, the search identified 50 articles for review, of which 20 abstracts were reviewed, and one article met the inclusion criteria. This study did not show any significant improvement in the rate of complete healing in SSD group compared with placebo either at 4 weeks (relative risk 6.2, 95% confidence interval 0.8-48) or at 1 year (relative risk 5.2, 95% confidence interval 0.6-41.6) of follow-up. There is insufficient evidence to either support or refute the routine use of SSD for ambulatory patients with either partial-thickness burns or stasis dermatitis ulcers to decrease mortality, prevent infection, or augment wound healing in human beings.
Article
Silver sulfadiazine has been used as a topical burn wound treatment for many years. Pain associated with dressing changes is a common problem in burn wounds. Aquacel Ag, a hydrofiber dressing coated with ionic silver has been reported to reduce burn wound infection and promote antimicrobial activity. The purpose of this study was to show the benefits of Aquacel Ag for the treatment of partial thickness burns. This prospective randomized study was conducted in 70 patients who had partial thickness burns less than 15% of total body surface area and were treated at Siriraj outpatient burn clinic during December 2006-February 2008. Patients were divided into two groups: Aquacel Ag-treated group with dressing changes every 3 days (35 patients) and 1% silver sulfadiazine-treated group, with daily dressing changes (35 patients). There was no difference in demographic data including age, gender, burn percentage between groups. Time-to-wound healing pain score during dressing change and cost of treatment were compared between both groups. Time-to-wound closure was significantly shorter in the Aquacel Ag-treated group (10 +/- 3 versus 13.7 +/- 4 days, P < 0.02) as well as pain scores at days 1, 3 and 7 (4.1 +/- 2.1, 2.1 +/- 1.8, 0.9 +/- 1.4 versus 6.1 +/- 2.3, 5.2 +/- 2.1, 3.3 +/- 1.9, respectively, P < 0.02). Total cost of treatment was 52 +/- 29 US dollars for the Aquacel Ag-treated group versus 93 +/- 36 US dollars for the silver sulfadiazine-treated group. This study showed that Aquacel Ag increased time to healing, decreased pain symptoms and increased patient convenience because of limiting the frequency of replacement of the dressing at lower total cost. This study confirms the efficacy of Aquacel Ag for the treatment of partial thickness burns at an outpatient clinic.
Aquacel Ag((R)) (ConvaTec, Princeton, NJ, USA) is a new hydrofiber wound dressing consisting of soft non-woven sodium carboxymethylcellulose fibers integrated with ionic silver. It is a moisture-retention dressing, which forms a gel on contact with wound fluid and has antimicrobial properties of ionic silver. We present a current literature review on Aquacel Ag((R)), of both in vitro and in vivo efficacy and clinical applications. In vitro and in vivo studies have demonstrated the wide antimicrobial properties of Aquacel Ag((R)), and additionally demonstrated the cytotoxicity of ionic silver to keratinocytes and fibroblasts that cause delay in wound re-epithelialization. Clinical studies confirmed that Aquacel Ag((R)) is an effective and safe dressing for a variety of wound types, both acute and chronic. Incorporation of ionic silver into the hydrofibers does not cause undue alteration in the performance properties of the base dressing, which continues to provide favorable wound moisture and exudate management. The addition of ionic silver reduces local pain and dressing changes, and provides significant broad-spectrum antimicrobial properties, with no delay in wound healing.
Article
This study established human body surface area (BSA) database and estimation formula based on three-dimensional (3D) scanned data. For each gender, 135 subjects were drawn. The sampling was stratified in five stature heights and three body weights according to a previous survey. The 3D body surface shape was measured using an innovated 3D body scanner and a high resolution hand/foot scanner, the total body surface area (BSA) and segmental body surface area (SBSA) were computed based on the summation of every tiny triangular area of triangular meshes of the scanned surface; and the accuracy of BSA measurement is below 1%. The results of BSA and sixteen SBSAs were tabulated in fifteen strata for the Male, the Female and the Total (two genders combined). The %SBSA data was also used to revise new Lund and Browder Charts. The comparison of BSA shows that the BSA of this study is comparable with the Du Bois and Du Bois' but smaller than that of Tikuisis et al. The difference might be attributed to body size difference between the samples. The comparison of SBSA shows that the differences of SBSA between this study and the Lund and Browder Chart range between 0.00% and 2.30%. A new BSA estimation formula, BSA=71.3989 x H(.7437) x W(.4040), was obtained. An accuracy test showed that this formula has smaller estimation error than that of the Du Bois and Du Bois'; and significantly better than other BSA estimation formulae.
Article
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions, characterized by a low incidence but high mortality, initially described as separate entities, but today considered variants of the same pathologic process and differing only for severity. The majority of cases appear to be related to idiosyncratic drug reactions. The drugs most commonly involved are: antibiotics such as sulfonamides, beta-lactam, tetracyclines and quinolones; anticonvulsants such as phenytoin, phenobarbital and carbamazapine; antiretroviral drugs; nonsteroidal anti-inflammatory drugs, allopurinol. There is common agreement to consider TEN as the manifestation of a disregulated immune reaction against epithelial cells. During the first stages of TEN, apoptosis mediates keratinocyte death and the pivotal role of Fas-FasL pathway activation during TEN is undoubted. T cell cytotoxicity, demonstrated during TEN, has been shown to be mediated by the perforin-granzyme pathway. It seems, also, clear that a peculiar cytokine pattern plays an important role in TEN pathogenesis. The cutaneous findings result in an acute macular erythematous rash with bullae. These lesions rapidly exhibit Nikolsky's sign and a separation of large sheets of epidermis from the dermis and a subsequent localised shedding develops rapidly, which can become very extensive. When feasible, admission in burn or intensive care unit, positioning the patients in air-fluidised beds, is universally considered crucial in TEN treatment. The prompt withdrawal of the suspected drug, fluid and electrolyte replacement and topical wound care are the first line of therapy. The use of corticosteroids has been abandoned and the role of immunosuppressants, despite some success, is not well defined and is not considered as a standard. A trial comparing thalidomide versus placebo in TEN patients was suspended because mortality rate increased in the treated group. Infliximab, a chimeric monoclonal antibody to TNF-alpha, has been administered to a patient, in single infusion, with a favourable outcome. Plasmapheresis is reported to lead to some success in TEN treatment, with improvement of clinical conditions and high percentage of survival. Different authors reported good results in terms of decreasing mortality and morbidity or improving clinical conditions of the use of human intravenous immunoglobulins (IVIGs). Regardless, the true utility of this treatment remains controversial. In 2005, the authors (ML and RC), dealing with a number of severe TEN cases, proposed a new protocol based on the combination of these last two techniques reporting their preliminary results in the treatment of severe TEN patients.
Article
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. Nine women with histologically confirmed TEN (>30% total body surface area, TBSA) were treated at our burn intensive care unit. All patients received hydrotherapy and wounds were covered with Aquacel Ag and Vaseline gauzes onlay. Following this, elastic cotton bandage was wrapped around the dressing. The dressing was changed and the wound evaluated twice a week. Efficacy was established by the wound achieving>or=95% re-epithelialisation of the study area. The mean age was 60.1 years (range from 7 to 88 years). The percentage of body surface area affected by epidermal slough ranged from 30% to 85% TBSA, with a mean of 51%. One patient expired due to severe sepsis on day 3. Eight patients achieved over 95% wound healing. All wounds healed well without the need for skin grafting. However, two of them expired on day 14 and day 20 because of pneumonia and retention of carbon dioxide, respectively. The average duration to achieve 95% wound healing was 10.4 days in eight cases (range from 7 to 14 days). No adverse reactions were noted. Aquacel Ag dressing can be easily removed during hydrotherapy. The wound pain is reduced. By changing the dressing just twice a week, we were able to evaluate the wound directly, decrease the odour and increase the quality of life of the patients. In addition, lower frequency of dressing changes decreases the manpower requirements and is cost effective. Use of Aquacel Ag with Vaseline gauze is a good alternative for the management of TEN wounds.
Article
Silver sulfadiazine cream has an enviable safety record in burn treatment. However, it side effects, exemplified by allergic reactions to its sulfadiazine moiety, silver staining of the treated burn wound, hyperosmolality, methemoglobinemia, and hemolysis due to a congential lack of glucose-6-phospate dehydrogenase, may be missed or misinterpreted. Early post burn leukopenia, once thought to be a side effect of the use of silver sulfadiazine in burn wound therapy, is no longer regarded as such since it has been found to occur with the use of other burn topical agents. Its presence is no longer an indication to discontinue silver sulfadiazine burn wound therapy. Because these side effects are uncommon, any one physician or burn facility usually has limited experience in diagnosing and treating them.
Article
The pathogenetic mechanisms, the clinical aspects, diagnosis, complications, sequelae, prognosis and treatment are discussed.
Article
Toxic epidermal necrolysis (TEN), is an exfoliative dermatological disorder of unknown cause. A patient with TEN loses epidermis in sheet-like fashion, leaving extensive areas of denuded dermis that must be treated like a large, superficial, partial-thickness burn wound. Methods of coverage described in the English literature over the last decade include the use of several dressings such as fresh-frozen or cryopreserved cadaver allograft, porcine xenograft, and amnionic membrane. Successful use of the biosynthetic dressing, Biobrane, has been described after burn injuries and Stevens-Johnson syndrome; however, its use in TENS has not. We present three patients with TEN treated successfully in our burn center over the past 12 months using Biobrane. The patients were men aged 20, 58, and 77 years, with 58% to 95% total body surface area slough. Diagnosis was confirmed by skin biopsy on admission, and drug ingestion was implicated in each instance. Each patient was thoroughly debrided in the operating room shortly after admission, and denuded areas were covered with Biobrane within 24 to 48 hours of admission. Biobrane demonstrated greater than 90% adherence by 48 hours, and no wound sepsis occurred. Each patient demonstrated epithelialization within 9 days. Patients were ambulatory at 72 hours. Corticosteroids and prophylactic antibiotics were avoided. Enteral nutritional support and aggressive septic surveillance was routine. Hospital stay was between 13 and 30 days without mortality. Early use of Biobrane in patients with TEN appears to provide a reasonable means of wound coverage.
Article
36 Key opinion leaders in the field of burn care from countries all over the world participated in a survey on their preferences for ways of treating different types of burns. The article describes the results of the survey and analyses the different treatment preferences.
Article
Toxic epidermal necrolysis (TEN) is an exfoliative skin disorder that may involve a large body surface area and mucosal surfaces. The microscopic changes that occur with this condition are similar to those that occur with superficial dermal burns, such as dermal detachment from the underlying dermis. Complications of TEN are related to the loss of the epithelial skin barrier and include pain, fluid and electrolyte loss, and an increased risk of sepsis. The treatment of a patient with TEN is best accomplished in a burn unit, where expert treatment of these complications can be provided. Medical treatment includes the administration of immunosuppressive therapy and the discontinuation of any previous corticosteroid treatment. Surgical management includes the debridement of necrotic areas. In this article, the surgical management of 8 consecutive patients with TEN who were admitted to the intensive care burn unit at the Hospital Universitario de Getafe in Madrid, Spain, from 1996 to 1998 is described. These patients were treated with extensive early debridement of necrotic skin areas followed by wound coverage with Biobrane (Dow B. Hickam, Inc, Sugarland, Tex), a temporary semisynthetic skin substitute. Skin coverage with this material decreases pain and fluid loss, and it possibly facilitates epithelization and decreases the risk of sepsis, without adverse side effects. This semisynthetic material meets some standards of an ideal skin substitute: it is easy to use, provides several beneficial physiologic effects, and improves patients' comfort. In the 8 cases of patients with TEN that were studied, the use of Biobrane skin substitute for the coverage of massive areas of detached skin was found to be an important aspect of treatment.
Article
The accuracy and variability of burn size calculations using four Lund and Browder charts currently in clinical use and two Rule of Nine's diagrams were evaluated. The study showed that variability in estimation increased with burn size initially, plateaued in large burns and then decreased slightly in extensive burns. The Rule of Nine's technique often overestimates the burn size and is more variable, but can be performed somewhat faster than the Lund and Browder method. More burn experience leads to less variability in burn area chart drawing estimates. Irregularly shaped burns and burns on the trunk and thighs had greater variability than less irregularly shaped burns or burns on more defined anatomical parts of the body.
Article
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.
Article
The purpose of this study was to examine burn patients' pain and anxiety experiences during resting conditions and procedures. The relationship of contextual factors and interventions to pain and anxiety were also explored. Procedural pain was significantly higher than resting pain (P = .02); however, there were no significant differences in anxiety between resting conditions and procedures (P = .16). There was a significant difference between burn patients' acceptable level of pain, resting pain, and procedural pain (P = .01). Resting pain was significantly lower than patients' acceptable level of pain (P = < .01). Procedural pain was slightly lower than patients' acceptable level of pain, but these results were not statistically significant (P = .37). Percent of total body surface burned was associated with increased procedural anxiety (P = .022). Family presence correlated with decreased procedural pain (P = .011) and midazolam use (P = .047). Prior experience with the procedure was associated with increased morphine(P = .003) and midazolam use (P = .029). These findings support the multifactorial nature of burn pain and anxiety and provide guidance for practice.
Article
Toxic epidermal necrolysis, a rare and often fatal disease, mimics second degree burns and requires the expertise of an interdisciplinary team approach as used in burn centers. This article explores the diagnosis and acute and long-term treatment approaches. Readers will learn how effective treatment can improve outcomes and maximize recovery from this devastating disease.
Article
Toxic epidermal necrolysis (TEN) is a potentially fatal disorder that involves large areas of skin desquamation. Patients with TEN are often referred to burn centers for expert wound management and comprehensive care. The purpose of this study was to define the presenting characteristics and treatment of TEN before and after admission to regional burn centers and to evaluate the efficacy of burn center treatment for this disorder. A retrospective multicenter chart review was completed for patients admitted with TEN to 15 burn centers from 1995 to 2000. Charts were reviewed for patient characteristics, non-burn hospital and burn center treatment, and outcome. A total of 199 patients were admitted. Patients had a mean age of 47 years, mean 67.7% total body surface area skin slough, and mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 10. Sixty-four patients died, for a mortality rate of 32%. Mortality increased to 51% for patients transferred to a burn center more than one week after onset of disease. Burn centers and non-burn hospitals differed in their use of enteral nutrition (70 vs 12%, respectively, P < 0.05), prophylactic antibiotics (22 vs 37.9%, P < 0.05), corticosteroid use (22 vs 51%, P < 0.05), and wound management. Age, body surface area involvement, APACHE II score, complications, and parenteral nutrition before transfer correlated with increased mortality. The treatment of TEN differs markedly between burn centers and non-burn centers. Early transport to a burn unit is warranted to improve patient outcome.
Article
Silver products have two key advantages: they are broad-spectrum antibiotics and are not yet associated with drug resistance. This article, the first in a two-part series, describes the main mechanism of action of this metallic element.
Article
The aim of this study was to determine any occupationally relevant allergic contact sensitizations in hand dermatitis in a jeweler. Patch test with European Standard, vehicle, medicaments, and metal series (Finn chambers on Scanpor) was performed. Readings were taken on day 2 and day 4. Allergic positive reaction to colophonium 20% pet and silver nitrate 0.5% aq was detected. The contact sensitivities to silver and colophonium seem to be occupationally relevant in this case.
Article
Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease characterized by extensive destruction of the epidermis. It apparently results from the formation of specific toxic drug metabolites by the keratinocytes. The mortality rate which averages 25-30% is mainly due to secondary septicemia, and to ionic and metabolic disturbances following loss of epidermal integrity. Apoptosis is the likely mechanism leading to massive keratinocyte death in TEN. Dysregulations in the tumor necrosis factor-alpha (TNF-alpha) pathway, CD95 system (Fas ligand, CD95L; Fas receptor, CD95R) and calcium homeostasis in the epidermis are involved in this apoptotic process. An active role has also been ascribed to T lymphocytes, macrophages and factor XIIIa-positive dermal dendrocytes. Despite progress, treatment of TEN remains controversial. In the past, systemic glucocorticoids were used in order to target the inflammatory reaction in TEN. However, there was no evidence for improvement of the healing process, while corticosteroids worsened the prognosis by increasing the risk of septicemia. Only a few cases have been treated with other drugs including cyclophosphamide, pentoxyfilline, thalidomide, anti-TNF-alpha antibodies and cyclosporin A. In the recent past, some TEN patients were treated with intravenous human immunoglobulins (IVIG). The rationale for such a treatment was to block the CD95 system on keratinocytes. The early promising clinical results of IVIG treatment in TEN were subsequently challenged. This review compares the effectiveness and drawbacks of the major drugs presently used in TEN treatment. Some future prospects in TEN management are also discussed.
Article
Toxic epidermal necrolysis (TEN) is a rare disorder characterized by extensive epidermal death. Almost all cases appear to be caused by an idiosyncratic drug reaction. Proposed pathogenic mechanisms are conflicting, and the evidence for the benefits of individual treatments is inadequate, and in some cases contradictory. The mortality rate remains high. We review the literature pertaining to the pathogenesis of TEN and drug reactions in general. The rationale for therapeutic interventions, together with reported evidence of efficacy, are considered. We present a composite model of TEN, based on previous work and suggested pathogeneses of TEN, mechanisms of drug reactions and reported cytotoxic lymphocyte (CTL) cytolytic pathways. In this system, TEN, like some other cutaneous drug eruptions, is an HLA class I-restricted, specific drug sensitivity, resulting in clonal expansion of CD8+ CTLs. Cytotoxicity is mediated by CTL granzyme and possibly death receptor (DR) ligand (DR-L), probably Fas ligand (FasL). Particular to TEN, there is then an amplification sequence involving further DR-L expression. FasL is likely to be particularly important but tumour necrosis factor (TNF) may well contribute, via the TNF receptor 1 (TNF-R1) death pathway. Alternatively, we suggest the possibility of upregulation of an antiapoptotic TNF-R1-nuclear factor kappaB pathway, which would proscribe treatments which downregulate this pathway. None of the published data on individual treatment efficacies is sufficiently strong to suggest a definitive single treatment. Currently a multifaceted regimen appears indicated, targeting various likely intermediary mechanisms, including elimination of residual drug, immunosuppression, inhibition of DR pathways, general antiapoptotic strategies, and aggressive supportive care. Particular attention has been directed at avoiding potential conflicts between different treatments and avoiding agents that theoretically might have a net proapoptotic rather than antiapoptotic effect. Nursing on a specialized unit is of paramount importance.
Article
Conflicting recommendations and clinical applications have been given concerning best practices for the management of burn blisters associated with partial-thickness burns. Arguments for the preservation of intact blisters center on the idea of naturally occurring biologic protection whereas the débridment of blisters has been advocated because of the perceived decreases in wound infection and complications. Recurring themes in burn wound management that are considered in this debate include infection, healing, functional and aesthetic outcome, patient comfort, ease of dressing care, and cost efficiency. The management of burn blisters should be supported by evidence across these six categories, should match the expertise of the provider, and should use the available resources in the practice setting. The purpose of this review is combine the findings of a comprehensive review of the published literature with respect to the management of blisters in the partial-thickness burn into a clinical guideline for best practice based on available evidence.
Article
This prospective, randomized study compared protocols of care using either AQUACEL Ag Hydrofiber (ConvaTec, a Bristol-Myers Squibb company, Skillman, NJ) dressing with silver (n = 42) or silver sulfadiazine (n = 42) for up to 21 days in the management of partial-thickness burns covering 5% to 40% body surface area (BSA). AQUACEL Ag dressing was associated with less pain and anxiety during dressing changes, less burning and stinging during wear, fewer dressing changes, less nursing time, and fewer procedural medications. Silver sulfadiazine was associated with greater flexibility and ease of movement. Adverse events, including infection, were comparable between treatment groups. The AQUACEL Ag dressing protocol tended to have lower total treatment costs (Dollars 1040 vs. Dollars 1180) and a greater rate of re-epithelialization (73.8% vs 60.0%), resulting in cost-effectiveness per burn healed of Dollars 1,409.06 for AQUACEL Ag dressing and Dollars 1,967.95 for silver sulfadiazine. A protocol of care with AQUACEL(R) Ag provided clinical and economic benefits compared with silver sulfadiazine in patients with partial-thickness burns.
Article
Silver products have been used for thousands of years for their beneficial effects, often for hygiene and in more recent years as antimicrobials on wounds from burns, trauma, and diabetic ulcers. Silver sulfadiazine creams (Silvazine and Flamazine) are topical ointments that are marketed globally. In recent years, a range of wound dressings with slow-release Ag compounds have been introduced, including Acticoat, Actisorb Silver, Silverlon, and others. While these are generally accepted as useful for control of bacterial infections (and also against fungi and viruses), key issues remain, including importantly the relative efficacy of different silver products for wound and burn uses and the existence of microbes that are resistant to Ag+. These are beneficial products needing further study, although each has drawbacks. The genes (and proteins) involved in bacterial resistance to Ag have been defined and studied in recent years.
Article
Silver compounds have been exploited for their medicinal properties for centuries. At present, silver is reemerging as a viable treatment option for infections encountered in burns, open wounds, and chronic ulcers. The gold standard in topical burn treatment is silver sulfadiazine (Ag-SD), a useful antibacterial agent for burn wound treatment. Recent findings, however, indicate that the compound delays the wound-healing process and that silver may have serious cytotoxic activity on various host cells. The present review aims at examining all available evidence about effects, often contradictory, of silver on wound infection control and on wound healing trying to determine the practical therapeutic balance between antimicrobial activity and cellular toxicity. The ultimate goal remains the choice of a product with a superior profile of infection control over host cell cytotoxicity.
Article
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). A review of the hospital and acute wound center patient records and the recent English medical literature regarding TEN and nanocrystalline silver dressing. 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. The use of nanocrystalline silver dressing should be considered for the treatment of TEN.
Article
Unlabelled: Toxic epidermal necrolysis (TEN) is an unpredictable, life-threatening drug reaction associated with a 30% mortality. Massive keratinocyte apoptosis is the hallmark of TEN. Cytotoxic T lymphocytes appear to be the main effector cells and there is experimental evidence for involvement of both the Fas-Fas ligand and perforin/granzyme pathways. Optimal treatment for these patients remains to be clarified. Discontinuation of the offending drug and prompt referral to a burn unit are generally agreed upon steps. Beyond that, however, considerable controversy exists. Evidence both pro and con exists for the use of IVIG, systemic corticosteroid, and other measures. There is also evidence suggesting that combination therapies may be of value. All the clinical data, however, is anecdotal or based on observational or retrospective studies. Definitive answers are not yet available. Given the rarity of TEN and the large number of patients required for a study to be statistically meaningful, placebo controlled trials are logistically difficult to accomplish. The absence of an animal model further hampers research into this condition. This article reviews recent data concerning clinical presentation, pathogenesis and treatment of TEN. Learning objectives: At the conclusion of this learning activity, participants should have acquired a more comprehensive knowledge of our current understanding of the classification, clinical presentation, etiology, pathophysiology, prognosis, and treatment of TEN.
Article
Since their first descriptions in 1922 and 1948, respectively, Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) have become recognized as manifestations--with different severity--of the same disease process along a spectrum of illness. Even today, decades after their description, there is still disagreement about when a particular bullous disease evolves from erythema multiforme to SJS/TEN. There is no disagreement, however, about the potentially life-threatening nature of the disease. Many cases are misdiagnosed, especially in their early stages. In this paper we address our current understanding of this disease spectrum and discuss both accepted and more controversial modes of therapy.
Article
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. 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. 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. 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.
Article
We wished to determine whether changing our centre's practice of using Acticoat instead of Silvazine as our first-line burns dressing provided a better standard of care in terms of efficacy, cost and ease of use. A retrospective cohort study was performed examining 328 Silvazine treated patients from January 2000 to June 2001 and 241 Acticoat treated patients from July 2002 to July 2003. During those periods the respective dressings were used exclusively. There was no significant difference in age, %BSA and mechanism of burn between the groups. In the Silvazine group, 25.6% of children required grafting compared to 15.4% in the Acticoat group (p=0.001). When patients requiring grafting were excluded, the time taken for re-epithelialisation in the Acticoat group (14.9 days) was significantly less than that for the Silvazine group (18.3 days), p=0.047. There were more wounds requiring long term scar management in the Silvazine group (32.6%) compared to the Acticoat group (29.5%), however this was not significant. There was only one positive blood culture in each group, indicating that both Silvazine and Acticoat are potent antimicrobial agents. The use of Acticoat as our primary burns dressing has dramatically changed our clinical practice. Inpatients are now only 18% of the total admissions, with the vast majority of patients treated on an outpatient basis. In terms of cost, Acticoat was demonstrated to be less expensive over the treatment period than Silvazine . We have concluded that Acticoat is a safe, cost-effective, efficacious dressing that reduces the time for re-epithelialisation and the requirement for grafting and long term scar management, compared to Silvazine.
Article
Wound dressings containing silver as antimicrobial agents are available in various forms and formulations; however, little is understood concerning their comparative efficacy as antimicrobial agents. Eight commercially available silver-containing dressings, Acticoat 7, Acticoat Moisture Control, Acticoat Absorbent, Silvercel, Aquacel Ag, Contreet F, Urgotol SSD and Actisorb, were tested to determine their comparative antimicrobial effectiveness in vitro and compared against three commercially available topical antimicrobial creams, a non treatment control, and a topical silver-containing antimicrobial gel, Silvasorb. Zone of inhibition and quantitative testing was performed by standard methods using Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococcus aureus. Results showed all silver dressings and topical antimicrobials displayed antimicrobial activity. Silver-containing dressings with the highest concentrations of silver exhibited the strongest bacterial inhibitive properties. Concreet F and the Acticoat dressings tended to have greater antimicrobial activity than did the others. Topical antimicrobial creams, including silver sulfadiazine, Sulfamylon and gentamicin sulfate, and the topical antimicrobial gel Silvasorb exhibited superior bacterial inhibition and bactericidal properties, essentially eliminating all bacterial growth at 24 hours. Silver-containing dressings are likely to provide a barrier to and treatment for infection; however, their bactericidal and bacteriostatic properties are inferior to commonly used topical antimicrobial agents.
Article
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. 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. 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). 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.