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.     

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.     

Skin Allograft in the Treatment of Toxic Epidermal Necrolysis (TEN)

BACKGROUND: TEN is a severe form of exfoliative dermatitis. Its course is acute and its outcome fatal in 40% of cases. Wound cover to prevent fluid/protein loss and infections and to control pain, is the first step, as for burns. Skin allograft can be successfully used for this purpose. OBJECTIVE: We report two cases of TEN with de-epithelialization of 50 and 70% of the total body surface area. The patients were given support therapy and treated with human glycerol-preserved skin allografts for wound cover. METHODS: Patients were grafted with glycerol-preserved donor skin, obtained from a skin bank. RESULTS: Re-epithelization of treated areas was complete in 8 days; pain relief was obtained soon after the graft. CONCLUSIONS: Glycerol-preserved skin allograft is an effective treatment in extensive skin loss, for its barrier and analgesic effect. Quality standards of this product ensure safety and simplicity of use at limited cost.     

Lyell syndrome revisited: analysis of 18 cases of severe bullous skin disease in a burns unit.

Over the last few years, understanding of the pathophysiology of toxic epidermal necrolysis (TEN), or Lyell's disease, has substantially increased. However, differentiation of severe bullous skin disease remains a challenge for the clinician, and one that is often complicated by late patient referral. We performed a retrospective analysis of all patients with severe bullous skin disease, admitted between 1997 and 2002 to the Burn Centre, which is an integrated part of the Division for Plastic, Hand- and Reconstructive Surgery at the University Hospital of Zurich, Switzerland. We present an overview of our strategies and of the diagnostic and therapeutic difficulties encountered. The final diagnoses of the 18 patients referred to the unit were as follows: eight cases of TEN, one case of staphylococcal scalded-skin syndrome (SSSS), two cases of generalised drug eruption, one case of acute generalised exanthematic pustulosis and one case of febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta (PLEVA). In two cases, the diagnosis remained unclear. In three cases, paraneoplastic origins were suspected but not demonstrated. The overall mortality rate was 33% (six of 18 patients). Remarkably, all patients with histologically confirmed TEN survived. Six of these patients were successfully treated with intravenous immunoglobulins (IVIG). The most common single causative drug inducing TEN (four cases out of eight) was Phenytoin. Establishing an accurate diagnosis-based on a skin biopsy, harvested at an early stage-is more important than ever, because more specific and effective therapeutic modalities are available. As these potentially life-threatening bullous skin disorders are rare, we recommend, that care be provided by an experienced interdisciplinary team, comprising a dermatologist, or dermatopathologist, an intensive care specialist and a plastic surgeon.     

Characterization of a transplantable hormone-responsive human prostatic cancer xenograft TEN12 and its androgen-resistant sublines

BACKGROUND: Models for human prostate cancer can facilitate the study of resistance to endocrine therapy, aid drug discovery, and pre-clinical assessment. METHODS: Characteristics thought relevant to the growth in athymic nude mice of TEN12, an androgen-dependent transplantable prostatic cell line derived from a primary prostate carcinoma, and its two androgen-independent sublines, TEN12F and TEN12C, have been assessed immunocytochemically. RESULTS: The xenografts of the parental TEN12 line are moderately differentiated with both papillary and glandular regions, pleomorphic nuclei and abundant mitotic figures and are extremely vascular. The cells express androgen receptor (AR), PSA, VEGF, EGFR, c-erbB2, and TGFalpha. Both TEN12F and TEN12C xenografts possessed a more anaplastic morphology and displayed significantly lower growth rates, reduced blood vessel density (BVD), decreased MIB-1 antigen and E-cadherin expression and increased cytoplasmic AR and HSP90 staining. Elevated EGFR (membrane) but not c-erbB2 expression was demonstrated in the TEN12F line only. Castration of mice bearing TEN12 xenografts rapidly induced the appearance of cytoplasmic AR in the cells, PSA levels decreased initially but recovered to below pre-castration levels whilst reduced TGFalpha and loss of VEGF expression was seen in the long-term castrates. CONCLUSIONS: TEN12 and its sublines offer additional in vivo models to study the factors involved in the progression of prostatic cancer to androgen-independence.     

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.     

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.     

Treatment of toxic epidermal necrolysis with cyclosporin A

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe skin disorder characterized by separation of the dermal-epidermal junction, as is observed in second-degree superficial burns. It has been proposed that immunosuppressive treatment may improve prognosis of patients with TEN. METHODS: We report here a case series of patients with TEN treated with cyclosporin A (CSA) without other concomitant immunosuppressive agent. These patients (n = 11) were consecutively admitted to our Intensive Care Burn Unit because of severe TEN, involving a large body surface area (83 +/- 17% [mean +/- SD], median, 90%; range, 35-96%) and were treated with CSA 3 mg/kg per day enterally every 12 hours. We compared the series of patients treated with CSA with a historical series of patients admitted to our Intensive Care Burn Unit before CSA was introduced as part of the treatment protocol These patients (n = 6) were treated with cyclophosphamide (150 mg i.v. every 12 hours) and different doses of corticosteroids (> or =1 mg/kg per day of 6-methyl-prednisolone). Both groups of patients were similar in regard to age, delay from onset of disease to Intensive Care Burn Unit admission, and body surface area involved. RESULTS: Time from the onset of skin signs to arrest of the disease progression (1.4 +/- 0.3 days, vs. 3.6 +/- 1.5 days) and to complete reepithelialization (12.0 +/- 3.6 days, vs. 17.6 +/- 3.1 days) was significantly shorter in patients treated with CSA compared with those treated with cyclophosphamide and corticosteroids (p = 0.0002, and p = 0.0058, respectively). Significantly fewer patients in the CSA group had > or =4 organs failing (2 of 11 vs. 3 of 6, respectively, p = 0.029), had severe leukopenia (<1,000 cells/microL) (0 of 11 vs. 4 of 6, respectively, p = 0.006), or died (3 of 6 vs. 0 of 11, respectively, p = 0.0029). CONCLUSION: We conclude that immunosuppressive treatment with CSA is safe and is associated with a rapid reepithelialization rate and a low mortality rate in patients with severe TEN. Our data suggest that this regimen could be more effective than treatment with cyclophosphamide and corticosteroids. Prospective controlled trials are required to test the hypothesis that CSA is more effective than cyclophosphamide or other immunosuppressive regimens for the treatment of TEN.     

Toxic epidermal necrolysis complicated by small bowel intussusception: a case report

Intestinal involvement in toxic epidermal necrolysis (TEN) has been identified only rarely. We report a case of TEN complicated by small bowel intussusception. The patient was a previously healthy 8-year-old boy who presented with TEN and extensive lesions, including up to 40% of the body surface area as well as conjunctival, oropharyngeal, respiratory, and genital mucosa. Rapidly after the onset of a constant rate of enteral feeding, he developed bilious vomiting, diarrhea, and significant abdominal distension. Abdominal sonography showed a small bowel intussusception. At abdominal exploration, an ileoileal intussusception was observed with a viable but inflamed bowel wall. Manual reduction was performed. During the postoperative clinical course, the patient was managed with total parenteral nutrition and local care of the skin and mucous membranes. Enteral feeding was introduced on the sixth postoperative day, and the child left the hospital 15 days after his admission. The association of TEN and small bowel intussusception has not been previously reported in the literature.     

Non-thermic skin affections

The Centre for Burns can help by its means (material, technical and personal) in the treatment of burns with extensive and deep losses of the skin cover and other tissue structures and in some affections with a different etiology (non-thermic affections). Indicated for admission are, in particular, extensive exfoliative affections--Stevens-Johnson's syndrome (SJS), Lyell's syndrome--toxic epidermal necrolysis (TEN) and staphylococcal scalded skin syndrome (SSSS), deep skin and tissue affections associated with fulminant purpura (PF), possibly other affections (epidermolysis bullosa, posttraumatic avulsions etc.). The similarity with burn injuries with loss of the skin cover grade II is typical, in particular in exfoliative affections with a need for adequate fluid replacement in the acute stage and aseptic surgical treatment of the affected area from the onset of the disease. In conditions leading to full thickness skin loss, in addition to general treatment rapid plastic surgical interventions dominate.     

Treatment of Toxic Epidermal Necrolysis With Moisture-Retentive Ointment: A Case Report and Review of the Literature

Toxic epidermal necrolysis (TEN) is a rare condition that was described by Lyell in 1956. It is a severe, acute, adverse, primarily drug-induced, potentially fatal, cutaneous reaction that is characterized by large areas of skin desquamation and sloughing, similar in many aspects to second-degree burns. The treatment of cutaneous drug reactions rests essentially on immediate diagnosis and recognition of the disease process, accurate history, thorough physical examination, prompt discontinuation of the offending drug, and supportive care. TEN patients are best managed in specialized burn units. Nevertheless, the management remains very much individualized, based on the clinical setting. Topical wound care remains an essential factor in the treatment of burn-like syndromes and is a main determining parameter for morbidity and mortality. As the value of moist environment in wound healing is being fully appreciated, we report on the use of a newly introduced ointment, the Moist Exposed Burn Ointment (Julphar; Gulf Pharmaceutical industries, Ras El-Khaymah, United Arab of Emirutes), a moisture-retentive ointment, in the successful management of a case of TEN.     

弹性髓内钉治疗青少年锁骨骨折的临床应用

目的:探讨弹性髓内钉治疗青少年锁骨骨折的方法和临床疗效。方法:2008年10月至2009年11月,采用弹性髓内钉治疗17例青少年急性锁骨骨折,男11例,女6例;年龄12～18岁,平均15.3岁。伤后至手术时间2～7 d,平均3.5 d。对术前和术后3个月随访时的肩关节Constant评分、术前和术后2周肩关节活动度进行比较,并通过X线片检查观察患者骨折愈合及复位情况。结果:所有患者均获得随访,时间3～8个月,平均6.5个月。没有出现感染、TEN断裂及顶破皮肤等并发症。术后3个月Constant评分(85.6±4.3)分,较术前(45.3±6.1)分明显提高(t=22.164,P<0.01)。术后2周肩关节活动度较术前明显改善(P<0.01)。术后12～16周取出髓内钉X线片显示骨性愈合,肩关节活动度恢复良好。结论:弹性髓内钉治疗青少年锁骨骨折具有疗效良好,创伤小,固定可靠等优点,其为锁骨骨折青少年治疗提供一种可靠的选择。     

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%.     

Use of the KTP laser in the treatment of rosacea and solar lentigines

Numerous techniques have evolved in facial plastic surgery to treat rosacea and solar lentigines. The treatment regimens range from avoidance of causative factors to the use of topical agents or other modalities that target the superficial layers of the skin. Of the modalities that target the epidermis, lasers offer the physician and patient the ability to target specific chromophores in the skin. Advances in laser technology led to the implementation of targeting certain characteristic pigments of abnormal areas with minimal damage to surrounding normal tissue. Rosacea and solar lentigines have characteristic cells that are targeted by a potassium-titanyl-phosphate (KTP) laser. The lesions are different in their origins but share the ability to be treated successfully with the KTP laser. A review of both conditions and other treatment options is discussed.     

Hospital management and clinical factors associated with ophthalmic involvement in Toxic Epidermal Necrolysis

Background

Toxic Epidermal Necrolysis (TEN) is characterized by an exfoliative rash resembling widespread burns. It is often considered on the same spectrum of disease as Stevens Johnson Syndrome but is distinguished by epidermal detachment of >30% of total body surface area (TBSA). Ocular involvement of TEN may result in complications requiring intensive topical, systemic or operative treatment. This study aimed to identify the current hospital management of, and factors associated with, ophthalmic involvement in adult TEN patients.

Methods

All adult TEN patients admitted to the Victorian Adult Burns Service over an 12-year period were included. Retrospective data analyzed included patient demographics, site of TEN involvement, % TBSA, complications, duration of ocular follow up and visual outcomes.

Results

TEN patients with and without ocular involvement were compared. Cutaneous involvement of the head and neck was found to be significantly associated with ocular involvement of TEN. Age, TBSA involvement, presence of a prodrome, and presence of comorbidities were not found to be significantly associated with ocular involvement. Management of ophthalmic involvement of TEN varied between patients.

Conclusions

Clinicians should have a high index of suspicion for ocular involvement when exfoliation of the head and neck is present and should seek ophthalmological advice early in the course of disease.     

The definition and treatment of pediatric subtrochanteric femur fractures with titanium elastic nails

PURPOSE: Titanium elastic nailing (TEN) has become more common in the treatment of pediatric femur fractures in many European centers and in North America over the past several years. Prior studies have shown that the use of TEN for midshaft femur fractures results in excellent outcomes with an earlier return to activity, earlier mobilization, and a shortened hospital stay. However, subtrochanteric femur fractures continue to remain a difficult subset of fractures to care for, with loss of reduction and nonunion being significant complications. Studies have differed regarding the definition of pediatric subtrochanteric femur fractures. The purpose of this study is to establish a reproducible method of defining pediatric subtrochanteric fractures and then apply that definition in a retrospective review of 13 patients who sustained subtrochanteric femur fractures treated with TEN at North Carolina Baptist Hospital using a modified technique that allows for improved fracture stability. METHODS: Charts and radiographs were retrospectively reviewed for all pediatric patients sustaining subtrochanteric femur fractures treated with TEN from the period of 2000 to 2004 at Wake Forest University. The TEN outcome measures scale was applied to determine their results. RESULTS: TEN allowed rapid mobilization with excellent or satisfactory clinical and radiographic results in all patients. CONCLUSIONS: Results suggest that the use of TEN for subtrochanteric femur fractures is a safe and effective method of fixation that benefits patients through early mobilization, shorter hospital stays, and fewer complications. SIGNIFICANCE: By applying the definition of subtrochanteric femur fractures described by the authors, results of future studies can be objectively compared and classified. TEN is a safe and effective alternative for treating most pediatric subtrochanteric fractures by decreasing the morbidity that occurs with other treatment modalities.     

保守治疗与钛制弹性髓内钉治疗移位锁骨中段骨折的疗效对比分析

目的 比较保守治疗与钛制弹性髓内钉(TEN)治疗明显移位锁骨中段骨折的疗效.方法 回顾性研究2005年2月至2007年9月间采用保守治疗(保守治疗组,100例)或TEN固定(TEN固定组,60例)治疗并获得随访的160例移位锁骨中段骨折患者资料.比较两组患者术后的肩关节功能(Constant评分和DASH评分)、患者对治疗结果的满意度、恢复正常生活的时间、并发症发生率、肩部外观及锁骨愈合后的X线表现.结果 所有患者术后获平均18个月(9～31个月)随访.保守治疗组和TEN固定组Constant评分分别为72.5分和90.5分(t=3.280,P=0.020),DASH评分分别为26.5分和2.4分(t=2.420,P=0.032);满意率分别为75.0%和96.7%(X2=1.450,P=0.042);恢复正常生活时间分别为6～8周和2～3周;并发症发生率分别为13.0%和3.3%(X2=1.890,P=0.020).保守治疗组28例肩部不对称,42例解剖位置愈合.TEN固定组肩部基本对称,56例解剖位置愈合.结论 TEN固定治疗移位的锁骨中段骨折,在肩部功能评分、满意率及并发症发生率等方面比保守治疗更有优势,因此不推荐使用保守治疗,TEN固定可作为一种有效的治疗方法.     

钛制弹性钉与重建钢板在治疗移位锁骨中段骨折中的临床疗效比较

目的 比较钛制弹性钉(TEN)与重建钢板(RP)治疗移位锁骨中段骨折的疗效.方法 2005年1月至2007年7月,对采用TEN或RP治疗且获随访的141例锁骨中段移位骨折患者的资料进行回顾性分析,其中57例患者采用TEN治疗(TEN组),84例患者用3.5 mm RP治疗(RP组).比较两组患者的一般情况、术后并发症、术后6个月及术后2年Constant评分及臂、肩、手功能障碍(DASH)评分.结果 TEN组患者获24～41个月(平均30个月)随访,RP组患者获28～48个月(平均32个月)随访.影像学显示TEN组骨折愈合时间平均为(12.4±3.4)周,RP组平均为(14.4±3.7)周.两组患者骨不连和成角畸形短缩、内置物失败、感染、短暂性神经丛刺激症、内置物移位、皮肤刺激症等并发症的发生情况,差异无统计学意义(P＞0.05).TEN组有17例内置物移位,但程度轻,多数患者无临床症状.术后6个月随访时,TEN组患者DASH评分明显低于RP组(P＜0.05),而Constant 评分明显高于RP组(P＜0.05).术后2年时,两组患者的DASH评分和Constant评分差异无统计学意义(P＞0.05).TEN组患者对术后肩部外形及综合结果较RP组更满意.结论 与RP相比,TEN治疗移位的锁骨中段骨折在术后早期功能锻炼及功能恢复方面有明显的优势.术后早期TEN组患者对肩部外形及术后综合结果方面更为满意.