Treatment issues in the care of patients with toxic epidermal necrolysis.

A review of current medical literature is presented to summarize treatment issues of ongoing controversy in the care of patients with toxic epidermal necrolysis. Terminology for the disease spectrum may be confusing and is discussed. Steroid treatment recommendations from the allergy and immunology literature are contrasted with burn center findings for optimal treatment. Issues of when to stop offending trigger medications, the value of a diagnostic biopsy, timing of hospitalization and the importance of prospective organ system monitoring are addressed.     

Secondary abdominal compartment syndrome in patients with toxic epidermal necrolysis

Introduction

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

Patients and methods

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

Results

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

Conclusion

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

Burn unit management of toxic epidermal necrolysis.

Toxic epidermal necrolysis is the name given to a group of dermatologic disorders characterized by a separation of epidermis and dermis with a subsequent skin slough. The denuded areas have the appearance of a second-degree burn. The complications of infection, negative nitrogen balance, severe pain, and emotional instability are identical to those seen in the patient with major burns. There are difficulties in patient management and advantages in burn unit care. As with the major burn, care of the patient with skin loss from toxic epidermal necrolysis is extremely complex, requiring the expertise of a burn team along with that of the dermatologist.     

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.     

Anesthesia in a patient with toxic epidermal necrolysis

We report the case of a 16-month-old boy weighing 11 kg who presented toxic epidermal necrolysis secondary to phenobarbital administration and underwent emergency laparotomy under general anesthesia because of gastrointestinal bleeding. The boy presented epidermal detachment on the slightest friction (Nikolsky's sign) so monitoring was difficult; in these cases it is advisable to use padded sphygmomanometers and weighted electrodes. Owing to the great extension of denuded skin, these patients must be considered as hypovolemic and ketamine is the drug of choice for anesthesia induction. The maintenance of airways and the proper replacement of fluids and electrolytes are essential for the correct anesthetic treatment of these patients.     

Postoperative Clostridium septicum dermatitis simulating toxic epidermal necrolysis.

Widespread detachment of the epidermis as a result of Clostridium septicum infection after a laparotomy for intestinal obstruction is described. A clinicopathological picture, hitherto undescribed, is outlined.     

Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid arthritis

IntroductionLeflunomide is an immunomodulating agent with proven efficacy in rheumatoid arthritis. Although its overall safety profile is good, a few cases of toxic epidermal necrolysis have been reported.Case reportThis 36-year-old woman had rheumatoid arthritis that proved refractory to sulfasalazine and methotrexate, which were used successively in combination with symptomatic drugs. Leflunomide was started. A maculopapular rash and a fever developed 2 weeks later. The skin lesions spread rapidly to most of the body, and ulcers of the ocular and oral mucosa appeared. Leflunomide was stopped. Cholestyramine washout and prednisolone (60 mg/day) were given. The skin lesions healed over the next month. Punctate keratitis with keratinization of the cornea led to complete loss of vision.DiscussionThe main adverse effects of leflunomide consist of diarrhea, nausea, liver enzyme elevation, hypertension, alopecia, and allergic skin reactions. A few cases of severe skin reactions such as toxic epidermal necrolysis have been reported. They require immediate discontinuation of the drug and a washout procedure to hasten drug elimination from the body.ConclusionClose monitoring for severe skin reactions is in order when using leflunomide.     

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

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

Intravenous immunoglobulins and plasmapheresis combined treatment in patients with severe toxic epidermal necrolysis: preliminary report.

Toxic epidermal necrolysis (TEN) is an acute drug-induced life-threatening disorder characterised by extensive epidermal exfoliation and high rate of mortality. Between October 2000 and April 2003, five severe TEN patients were evaluated using a specific TEN severity-of-illness scale (SCORTEN) and treated for the first time, with a combined therapy using Intravenous Human Immunoglobulins (IVIG) and plasmapheresis. The standardised mortality ratio (SMR) analysis ([Sigma observed deaths/Sigma expected deaths]x100) was applied to establish how IVIG and plasmapheresis treatment could reduce TEN patient mortality. The observed mortality was one out of five patients corresponding to 20%. The expected mortality based on SCORTEN was 3.319 corresponding to 66%. The SMR analysis revealed a 70% reduction in mortality (SMR=0.30; 95% confidence interval, 0.0-0.96). Our series show a low mortality rate (20%) related to the severity of the patients (66% expected mortality). The use of IVIG in association with plasmapheresis has a rational basis and may be effective in severe TEN patients.     

Survival after a second episode of toxic epidermal necrolysis

Toxic epidermal necrolysis resulting from severe hypersensitivity to medication has a reported mortality of up to 66%. A patient surviving two episodes with more than a 50% skin loss is unprecedented in the medical literature. Mortality has been associated with many factors, including delayed reepithelialization, persistent skin slough, coagulopathy, severe hypoproteinemia, and sepsis. It may be possible to decrease morbidity and mortality by preventing the shearing of epidermis, thereby limiting the denuded areas. This case report describes the successful management of our patient's second episode of toxic epidermal necrolysis. The treatment of this patient in our specialized burn center consisted of careful fluid and electrolyte management, nutritional support, standard topical antimicrobials, and new modalities of local wound management.     

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.     

重症急性胰腺炎并发中毒性表皮坏死松解症的诊断和治疗

中毒性表皮坏死松解症(TEN)是一种急性皮肤炎症反应,属于重型药疹的一类.随着抗生素、非甾体类解热镇痛等药物在救治危重患者中的广泛应用,TEN在临床上,特别是ICU病房中其发病率有增高趋势.TEN病死率较高,且对危重患者的整体预后有较大影响.本文报道南京军区南京总医院普通外科收治的1例重症急性胰腺炎患者,应用阿司匹林预防血栓及栓塞并发症过程中并发TEN,总结该病的诊断和治疗经验以供临床医师参考.     

Bronchial obstruction due to respiratory mucosal sloughing in toxic epidermal necrolysis.

A 17 year old woman is described who nearly asphyxiated because of sloughing of the bronchial mucosa as a result of toxic epidermal necrolysis. Bronchoscopic aspiration of bronchial slough proved life saving.     

Management of toxic epidermal necrolysis in a 15-year-old girl

Toxic epidermal necrolysis, a life-threatening reaction to certain types of drugs, is characterised by epidermal sloughing of more than 30% of the total body surface area. Patient survival depends on prompt referral to a specialist burns unit.     

Collagen sheet dressings for cutaneous lesions of toxic epidermal necrolysis

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.KEY WORDS: Toxic epidermal necrolysis, Stevens Johnson''s Syndrome, collagen sheet     

Drug-induced toxic epidermal necrolysis with involvement of the intestinal and respiratory tract. A case report

Toxic epidermal necrolysis (TEN) is a disease occurring with low-incidence but has a relatively high mortality rate. Sepsis is the predominant cause for life-threatening complications in TEN but severe mucosal damage represents a further complication which may delay convalescence. We report a case of TEN in a 51-year-old man which eventually spread to include the whole skin surface. The long-term and comprehensive treatment focused on support of the organ failure as well as wound treatment. The extent of involvement of the intestinal tract, the sustained laryngeal stenosis and the pronounced saddle-nose were unusual. It appears necessary to treat TEN in facilities which offer intensive care and are able to manage extensive skin damage. Burns units offer the best conditions for its management.     

Treatment of toxic epidermal necrolysis and a review of six cases

Six cases of drug-induced toxic epidermal necrolysis treated in a burns unit are presented. The mean skin loss was 67.3 per cent of the total body surface area. Two patients developed renal failure and two had ocular symptoms. The mortality rate was 50 per cent, with two patients dying from septicaemia and one from respiratory and renal failure. The diagnosis of toxic epidermal necrolysis can be confirmed by skin biopsy. We recommend that this disease is treated in a burns unit so that both adequate wound care and essential intensive supportive treatment can be given. Antibiotics are indicated only for specific infections such as septicaemia or pneumonia. Steroids have been shown to increase greatly the mortality from septic complications and are not recommended. The mortality ranges from 10 per cent to 70 per cent and bad prognostic factors include increasing age, greater than 50 per cent of body surface skin loss and neutropenia.