Treatment Of Toxic Epidermal Necrolysis Research Articles

Intravenous Immunoglobulin in the Treatment of Vancomycin-Induced Toxic Epidermal Necrolysis = الغلوبيولين المناعي الوريدي في علاج إنحلال البشرة السمي الناتج عن الفانكوميسين

Toxic epidermal necrolysis (TEN), an uncommon but potentially life-threatening skin reaction, is frequently induced by drugs. The mucocutaneous reaction is characterised by bullous detachment of the epidermis and mucous membranes. We present a 9-month-old male with methylmalonic acidaemia, generalised hypotonia, and global developmental delay. He presented with a 3-day history of fever, cough, shortness of breath, and vomiting. Eruption appeared after 5 days of vancomycin treatment. The eruption involved almost 60% of the total body surface area and both eyes. He was successfully treated with intravenous immunoglobulin (IVIG), antibiotics, and appropriate wound management and made a full recovery with negligible sequelae despite the severity of his disease. Important components of successful treatment include early recognition, intensive care, prompt withdrawal of the causative agent, early administration of IVIG, appropriate fluid resuscitation, and control of infection. IVIG might be beneficial in the treatment of TEN; however, controlled studies are needed to evaluate IVIG compared to other modalities.

Successful Treatment of Toxic Epidermal Necrolysis More Than 70% Body Surface Area Involved with Imunosuppressive Therapy and Amniotic Membrane Craft in Cornea

Medicine Today 2009 Volume 21 Number 02 Page 74-76 DOI: http://dx.doi.org/10.3329/medtoday.v21i2.12552

Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous drug-induced syndrome that causes massive keratinocyte apoptosis and therefore hydro-electrolytic disorders and systemic infection. TEN approximately affects one to two cases per million per year. Mortality rate may reach thirty percent of cases. Thus, TEN constitutes a therapeutic emergency at diagnosis. Typically, clinical examination shows a mucocutaneous detachment involving more than thirty percent of body area. Definitive diagnosis is made on cutaneous biopsy with histological exam that shows the blister of necrotic keratinocytes. Main differential diagnosis are acute staphylococcus epidermis, acute generalized exanthematous pustulosis, linear IgA bullous dermatosis, paraneoplastic pemphigus, bullous fixed pigmented erythema, acute lupus erythematosus. In the early days, SCORTEN gives a good estimation and is now widely used as prognostic score. Drugs are generally considered as the main etiology of TEN but in some cases bacterial or viral infections could be involved. Physiopathology remains unclear even if recent advances have reported the possible implication of immune pathways based on activation of T and NK cells. Treatment of TEN requires to be instituted as soon as the diagnosis is made and the patient is preferentially referred to a specialized unit. Supportive care consist of covering areas of cutaneous detachment. No other therapy has demonstrated its efficiency, but high-dose intravenous immunoglobulin might improve the prognosis.

Toxic Epidermal Necrolysis in a Child Successfully Treated with Infliximab

A 7-year-old boy developed severe toxic epidermal necrolysis (TEN) secondary to carbamazepine and was transferred to our center after further deterioration despite receiving one dose of intravenous immunoglobulin. After administration of one dose of infliximab, there was a clear halting of progression of blistering and an apparent dramatic improvement. We consider it likely that the administration of infliximab led to the improvement in this child and that anti-tumor necrosis factor-alpha therapy may be a logical treatment for TEN, given the possible underlying pathologic process. Well-conducted studies on the safety and efficacy of any such treatment are urgently required.

Use of etanercept to treat toxic epidermal necrolysis in a human immunodeficiency virus-positive patient

Toxic epidermal necrolysis (TEN) is an uncommon and severe cutaneous adverse drug reaction that causes disseminated necrosis of epidermal cells and mucocutaneous detachment. Here, we report the case of a 32-year-old man with human immunodeficiency virus infection who presented with generalized violaceous macules and blister formation 4 days after the administration of mefenamic acid and amoxicillin for a dental procedure. Additional symptoms included oral ulcers and conjunctivitis. Results of skin biopsy were compatible with Stevens–Johnson syndrome (SJS). SJS progressed to TEN within 2 days. Etanercept treatment showed a dramatic improvement in the symptoms of mucocutaneous lesions. To our knowledge, this is the first report on the treatment of TEN using etanercept in a human immunodeficiency virus-positive patient.

The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis

Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking. To provide a meta-analysis evidence-based examination of IVIg efficacy against TEN. A systematic review and meta-analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high-dose and low-dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg. Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19.9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1.00 [95% confidence interval (CI) 0.58-1.75; P=0.99]. The pooled OR for mortality in patients treated with high-dose IVIg vs. supportive care was 0.63 (95% CI 0.27-1.44; P=0.27). Adults treated with high-dose IVIg exhibited significantly lower mortality than those treated with low-dose IVIg (18.9% vs. 50%, respectively; P=0.022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0.494; 95% CI 0.106-2.300; P=0.369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21.6%; P=0.001). Although high-dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.

Treatment of toxic epidermal necrolysis with intravenous immunoglobulin: a series of three cases

Stevens-Johnson's syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening dermatoses, that lead to keratinocyte apoptosis induced by interactions between Fas (cell death receptor) and soluble Fas-ligand, present in serum of Stevens-Johnson's syndrome / toxic epidermal necrolysis patients. Anti-Fas antibodies in intravenous immunoglobulin (IVIG) would block the apoptosis cascade. Three cases of toxic epidermal necrolysis occurred in one male and two female patients, after use of allopurinol, leprosy multidrug therapy concomitant with dipyrone, and diclofenac. The cases were treated with intravenous immunoglobulin 2-3 mg/kg and prednisone 20-50 mg/day. The interruption of new lesions outbreak and reepithelization were extremely fast after the use of intravenous immunoglobulin, without adverse effects. Controlled studies are needed to confirm the efficacy of intravenous immunoglobulin in Stevens-Johnson's syndrome / toxic epidermal necrolysis, but the results seem promising.

Reaction to biological drugs: infliximab for the treatment of toxic epidermal necrolysis subsequently triggering erosive lichen planus

Toxic epidermal necrolysis (TEN) is a rare, life-threatening skin reaction for which there is currently has no standardized treatment, despite its significant mortality. Biological agents such as tumour necrosis factor (TNF)-α antagonists are emerging as a novel treatment for patients with TEN. We report a 32-year-old woman who developed TEN secondary to sulfasalazine, which was treated with infliximab. The infliximab treatment subsequently triggered erosive lichen planus (LP) involving the mouth and vulva. Clinicians should be aware that TNF-α antagonists can cause LP as a paradoxical complication of treatment.

Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: A series of four cases

Toxic epidermal necrolysis (TEN) is a rare, life-threatening disease with a high mortality rate that is linked to drug toxicity. There is a lack of data about the underlying pathophysiologic mechanisms and treatment options. The only widely accepted treatment of TEN is withdrawal of the offending drug followed by supportive care. The potential roles of corticosteroids, intravenous immunoglobulin (IVIG) and plasmapheresis (TPE) remain controversial. We present four patients with severe TEN (all with >80% involvement of body surface) who were treated with TPE following unsuccessful treatment with corticosteroids/IVIG. TPE was performed using a COBE Spectra blood cell separator. ACD-A was used as anticoagulant fluid and the target-washed plasma volume was one body volume. Plasma was replaced by a 5% solution of human albumin + Ringer's lactate. The mean number of TPE sessions was 5.25 ± 2.22 (range 3-8). Drugs were implicated as an etiologic agent in each case. TPE led to prompt improvement of acute condition and general health as well as halting of disease progression. Additionally, the restoration of the epithelium began in all four patients. Plasmapheresis should be considered as an alternative treatment modality for patients with the most severe form of TEN if initial treatment with other agents, including corticosteroids and/or IVIG, fails. Drugs were suspected to be the cause of TEN in all four cases.

Issues about diagnosis and treatment of toxic epidermal necrolysis

Issues about diagnosis and treatment of toxic epidermal necrolysis

中毒性表皮壊死症の治療法の確立をめざして

中毒性表皮壊死症の治療法の確立をめざして

An update on diagnosis and treatment of toxic epidermal necrolysis / Novine u dijagnostici i lečenju toksične epidermalne nekrolize

Abstract Toxic epidermal necrolysis is an idiosyncratic drug reaction which manifests with extensive epidermal detachment due to the massive keratinocyte apoptosis, mucous membrane involvement, and potentially lethal outcome. It is caused by adverse reactions to drugs, mostly idiosyncratic, unpredictable and independent of the applied dose, which develops 7-21 days after initiation of the drug, and is most commonly caused by the following drugs: sulfonamides, allopurinol, carbamazepine, phenobarbitone, phenytoin and oxycam group of nonsteroidal anti-inflammatory drugs. The treatment outcome depends on several factors, while older age, multiple drug use, late exclusion of the drug inducing toxic epidermal necrolysis, raised serum levels of urea, creatinine and cytopenia are poor prognostic indicators which are rated in SCORTEN scoring which proved to be of great help in the assessment of disease outcome. The basic approach to the treatment is early diagnosis, immediate suspension of the probable inducing drug, and emergency transport to the closest burn center, since treatment in burn units is associated with a lower risk of infection and mortality of these patients. Exclusion of the drug that induced toxic epidermal necrolysis, and supportive therapy, is the first and only therapy for which there is a consensus in different centers. Various forms of adjuvant therapy are also applied: in France, supportive therapy is a standard of care, in Germany it is short-term use of high-dose corticosteroids, while in USA, in the last decade high-dose intravenous immunoglobulins are the most widely accepted treatment modalities. Case reports and small patients’ series described therapeutic effects of plasmapheresis, cyclosporine and other immunosuppressants. In conclusion, elimination of the possible causal agent, rapid transport to the burn unit, and multidisciplinary approach to treatment are of utmost importance for favorable outcome of the disease with 20-30% mortality rate. An update on diagnosis and the treatment of toxic epidermal necrolysis is provided in this review.

Skin manifestations of drug allergy

Cutaneous adverse drug reactions range from mild to severe and from those localized only to skin to those associated with systemic disease. It is important to distinguish features of cutaneous drug reactions which help classify the underlying mechanism and likely prognosis as both of these influence management decisions, some of which necessarily have to be taken rapidly. Severe cutaneous reactions are generally T cell-mediated, yet this immunological process is frequently poorly understood and principles for identification of the culprit drug are different to those of IgE mediated allergic reactions. Furthermore, intervention in severe skin manifestations of drug allergy is frequently necessary. However, a substantial literature reports on success or otherwise of glucocorticoids, cyclophsphamide, ciclosporin, intravenous immunoglobulin and anti-tumour necrosis factor therapy for the treatment of toxic epidermal necrolysis without clear consensus. As well as reviewing the recommended supportive measures and evidence base for interventions, this review aims to provide a mechanistic overview relating to a proposed clinical classification to assist the assessment and management of these complex patients.

Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: Is cytokine expression analysis useful in predicting its therapeutic efficacy?

Toxic epidermal necrolysis (TEN) is a life-threatening, drug-induced disorder characterized by severe epidermal injury. Although there is no standard therapeutic intervention in TEN, plasmapheresis (PP) is being used increasingly to treat extremely ill TEN patients. In addition to conventional PP, double-filtration PP (DFPP) has been recently used for severe and refractory TEN. In this review, we focus on the clinical usefulness of PP by both demonstrating three cases of TEN refractory to conventional therapies, who were successfully treated with conventional PP or DFPP, and evaluating its therapeutic efficiency. We also provide evidence to suggest the mechanisms of action of PP by investigating the correlation between disease intensity and serum cytokine levels before and after treatment with PP or DFPP in these patients with TEN. At present, PP is a much more effective option for treatment of severe and/or recalcitrant TEN than any other treatment, such as pulsed corticosteroids and i.v. immunoglobulin.

Topical Ophthalmic Cyclosporine in the Treatment of Toxic Epidermal Necrolysis

Aim. To describe a case of toxic epidermal necrolysis (TEN) with ocular involvement treated with topical ophthalmic cyclosporine. Case Presentation. A 20-year-old woman developed TEN following administration of carbamazepine that was prescribed for epilepsy. Ophthalmic examination revealed bilateral pseudomembranous conjunctivitis. She was hospitalized in the intensive care unit and treated with intravenous corticosteroid and immunoglobulin. Topical cyclosporine was used in combination with topical corticosteroids for ocular surface disease. Following two months of ocular treatment, she recovered without any severe ocular complication. Ocular examination at the four-month followup showed a 2 mm of symblepharon in the lower fornix as the sole pathologic finding. Conclusion. Topical ophthalmic cyclosporine may contribute to decrease the ophthalmic complications of TEN and should be considered in the acute stage of the disease.

Quoi de neuf en thérapeutique dermatologique ?

Although the isolated clinical cases published are sometimes helpful in individual situations in which the therapeutic options have been exhausted, this type of publication cannot be generalized. For this reason, the selection presented covering the period from November 2009 to October 2010 is to a very large extent based on controlled trials, either because they contribute important information or because they raise great hope for a significant number of patients. For the first time in cutaneous oncology, a treatment (ipilimumab) has significantly increased overall survival in patients with metastatic melanoma (phase III), although this gain remains modest (4-6 months) and adverse immunological effects are frequent (30-40%). A phase I trial with treatment specifically targeting the mutant BRAF protein has shown an objective response in 81% of the patients treated in the metastatic phase of melanoma, thus allowing its development to be pursued. Grouping two studies in a rare tumor such as dermatofibrosarcoma also gives hope with imatinib as a neoadjuvant treatment when the initial tumor is inoperable, with, however, an inconsistent response of approximately 50% and only if the tumor presents reorganization of chromosomes 17 and 22. Cutaneous inflammatory diseases are still dominated by dual therapies in psoriasis, with, notably, an effectiveness trial on etanercept at different doses not showing a difference in efficacy depending on dose for the joint component of psoriasis, but also by the publication of a direct comparison of two dual therapies, ustekinumab versus etanercept. In atopic dermatitis, a controversial article invites one to reflect upon the progress made in the management of children by clinical nurses, as in the Netherlands and in Great Britain, in an attempt to contend with the shortage of dermatologists. Since the use of biotherapies is not the prerogative of psoriasis, infliximab was assessed in a phase II trial in Verneuil disease without demonstrating significant efficacy on the main criterion, but it did show a tendency to reduce the score used. This trial suffered from a weakness both in methodology and statistical power, thus precluding any conclusion. The rarity of therapeutic trials on drug eruptions warrants their mention. A French phase II study gives a glimpse of a trend toward efficacy in terms of survival in the treatment of toxic epidermal necrolysis with cyclosporine. As for infectious dermatosis and sexually transmitted infections, a French multicenter study has shown significantly higher efficacy with ivermectin than with malathion in treating pediculosis without increasing the side effects. Today, however, this systemic treatment cannot be a first-line treatment outside of certain specific situations. A large cohort study (somewhat unsatisfactory in its methodology) has not demonstrated the teratogenicity of antiherpes treatments in 830,000 infants. In prevention of HIV transmission, no microbicidal gel had shown efficacy to date. This has now been accomplished in South Africa with a 1% tenofovir gel. The results of a preliminary trial on therapeutic vaccination against HPV16 proposed to women who are carriers of cervical intraepithelial neoplasia opens the way for wide vaccine therapy of cutaneous virus-induced neoplasia. In conclusion, several articles analyzing the dermatology literature provide an opportunity to reflect on the quality of such articles, Boutron's being absolutely in-dis-pen-sa-ble!

Facing up to toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a rare but life-threatening mucocutaneous adverse drug reaction. The disease is characterized by a specific and extensive destruction of the epidermis and mucosal epithelia, particularly of the mouth, genitalia and eyes. The TEN pathomechanism is probably initiated by a toxic drug metabolism inside keratinocytes, leading to a self-activation of apoptosis and necrosis. These events are boosted by additional effects of T lymphocytes and macrophages. At present there is still a lack of validated mainstay treatment for TEN. However, a few treatment modalities have been reported to halt TEN progression in some patients.

Basic measures and systemic medical treatment of patients with toxic epidermal necrolysis

With an incidence of 1.5-1.8/1 million inhabitants per year, toxic epidermal necrolysis is a rare but life threatening disease. It is almost always drug-induced and its lethality is pronounced with up to 50 %. Several therapeutic options are described in literature; however, there is still lack of a universally accepted and specific therapy of toxic epidermal necrolysis. This survey considers 8 cases of toxic epidermal necrolysis diagnosed and treated in our clinic from 2003 to 2007. The epidermal sloughing was > 30 % of the body surface in each case. After immediately discontinuing the drug suspected of being responsible for toxic epidermal necrolysis, we treated with systemic corticosteroids in an initial dose of up to 1.5 mg/kg. Moreover, special emphasis was put on basic measures such as control of vital parameters. With this treatment we reached good results; none of the patients died. conclusions: Immediate beginning of therapy is essential for a successful treatment of toxic epidermal necrolysis. Besides systemic therapy with corticosteroids, certain basic measures such as isolation of patients at adequate room temperature to prevent hypothermia, strict control of circulation, temperature and laboratory parameters, daily smears of skin and mucous membranes and a diet rich in calories due to the catabolic metabolic status are very important for successful outcome.

A Clinical Study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Efficacy of Treatment in Burn Intensive Care Unit

Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), potentially life-threatening skin diseases with organ failures caused by drugs, require specialized intensive care. However, SJS and TEN have usually been managed in general wards and intensive care units by most doctors. This study describes the efficacy of treatment in the burn intensive care unit (BICU) compared to previous general treatments. Methods: To investigate the clinical features, outcomes and benefits of 11 patients with SJS and TEN treated in our burn intensive care unit. Data on 11 patients who were treated between January 2004 and December 2008 were collected via a retrospective chart review. Also, the data were reviewed with previous literatures on SJS and TEN treatments. Results: Patients were classified with overlap SJS/TEN (n=4, 36.36%) or TEN (n=7, 63.64%). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common causative agents. Hepatitis was the most common organ involvement in both overlap SJS/TEN (n=1, 9.1%) and TEN (n=4, 36.36%). Renal dysfunction (n=4, 36.36%) and respiratory disorders (n=3, 27.27%) were seen in some cases. Mean time of total reepithelization was 9 days and mean hospital day was 14.66 days. Two patients with TEN died from sepsis with multi-organ failure, and the mortality rate was 18.18%. Conclusion: Adequate treatment of SJS and TEN in the BICU supports efficacy with a low mortality rate, short healing time, short hospitalization and fewer complications.

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

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