Toxic epidermal necrolysis: a study of 22 cases

Toxic epidermal necrolysis leads to extensive exfoliative epidermal slough, fever, systemic toxic reactions, conjunctivitis and severe mucous membrane involvement. As it evolves many other organs can be affected. Whether or not toxic epidermal necrolysis is the most severe form of erythema multiform is still a subject of discussion. The pathophysiological events involved are not well understood. Indirect evidence suggests a hypersensitivity reaction, but the search for potential immunological mechanisms has resulted in little data to support this hypothesis. Drug reactions remain the most common associated factor. Twenty-two patients, 3-84 years old, have been included in this retrospective study. In 15 patients, clinical evidence points to drugs as the most important cause of toxic epidermal necrolysis. Recent infections were implicated in three patients and ulcerative colitis and lymphoma in one case each. Symptomatic therapy included fluid replacement, nutritional support and local treatment. Steroids were administered in 13 patients, followed by plasmapheresis in three. The mortality rate was approximately 27%. Elderly patients and patients with extensive lesions were at greater risk. Results of immunofluorescence and immunoblot analysis were of no significant interest.     

Lamotrigine-induced toxic epidermal necrolysis treated with intravenous cyclosporin: A discussion of pathogenesis and immunosuppressive management

There is growing evidence that the final common pathway of toxic epidermal necrolysis (TEN) is mediated by the cellular immune system which targets drug altered epithelial antigens. This provides a rationale for immunosuppressive therapy. The ideal regimen for quickly turning off epidermal damage in TEN has not yet been determined and the use or benefit of routine immunosuppression remains highly controversial. This article reviews recent advances in the pathogenesis of TEN along with the theoretical benefits of early immunosuppressive treatment in severe cases, specifically utilizing cyclosporin. We describe a 29-year-old woman with TEN due to the anticonvulsant lamotrigine whose successful management included intravenous cyclosporin. The extension of her lesions ceased within 24 hours of initiating cyclosporin (day 7 of her admission). Complications included: scarring alopecia; Enterococcus faecalis septicaemia due to an infected central line; and ulceration and squamous metaplasia of conjunctivae, The potential role of lamotrigine as a cause of TEN is discussed.     

A Case of Generalized Seizure after Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous adverse reaction characterized by extensive necrosis and epidermal detachment involving more than 30% of the body surface area (BSA). It is commonly triggered by antiepileptics, sulfonamide antibiotics, and non-steroidal anti-inflammatory drugs. A 22-year-old female without any underlying medical history presented with painful multiple erythematous bullae and plaques of varied sizes throughout the body for 1 day. On the second hospitalization day (HD), the bullae progressively coalesced, leading to epidermal detachment involving 60% of the BSA. On the fifth HD, the patient had a tonic–clonic seizure with eyeball deviation for 5 minutes. She was transferred to the intensive care unit (ICU) and administered lorazepam 4 mg and levetiracetam 1,500 mg. Brain computed tomography, magnetic resonance imaging, and cerebrospinal fluid examination showed no abnormalities. Although the patient had delirium and additional seizures while in the ICU, her condition improved without any complications after 5 weeks of inpatient treatment. Several complications of TEN such as dehydration, malnutrition, sepsis, and ophthalmic and pulmonary complications have been reported; however, seizures have not been reported yet. Herein, we report a case of seizure in a patient during treatment for TEN.     

表皮痣综合征

报告1例并发癫癎的表皮痣综合征.患者女,21岁.出生后3个月颈部、躯干、四肢即出现弥漫分布的黑褐色、疣状角化性丘疹.患者3年前出现癫癎间断发作.家族中有同样疾病患者.皮损组织病理检查示表皮角化过度,基底层黑素增多.     

Epidermal necrolysis: SCORTEN performance in AIDS and non-AIDS patients

Background Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening blistering drug reactions with high incidence of ocular sequela. The term ‘Epidermal Necrolysis’ has been recently used to better describe the full spectrum of the disease that includes Stevens-Johnson syndrome and toxic epidermal necrolysis at opposite ends, which differ by the extent of body surface area with epidermal detachment. SCORTEN is a mortality prognosis score for ‘Epidermal Necrolysis’ cases that still needed validation in acquired immunodeficiency syndrome.Objective To evaluate the SCORTEN performance in acquired immunodeficiency syndrome, and the differences in outcomes between acquired immunodeficiency syndrome and non- acquired immunodeficiency syndrome cohorts.Methods Retrospective cohort study of AIDS and non-AIDS ‘Epidermal Necrolysis’ cases admitted to a Brazilian reference center from 1990-2014.Results Five deaths (16.7%) occurred as a consequence of EN in 30 AIDS patients, and seven (17.9%) in 39 non-AIDS patients, relative risk (RR) .92 (p=1.0). SCORTEN showed great performance, with an Area Under the Receiver Operating Curve (AUC) (ROC) of 0.90 with a 95% confidence interval ranging from .81 to .99. The performance of SCORTEN was better among non-AIDS patients than AIDS patients: AUC non- acquired immunodeficiency syndrome =0.99 (CI 05% 0.96-1.00), AUC acquired immunodeficiency syndrome = 0.74 (CI 95% 0.53-0.95), p=.02.Study Limitations: Heterogeneity of cases, wide variation of systemic corticosteroid doses when used.Conclusion: SCORTEN is valid for the Brazilian population, including among those patients with acquired immunodeficiency syndrome, and, as such, its use is recommended for aiding treatment choice in this subgroup of patients.     

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

Background: 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. Methods: 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. Results: 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.     

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options

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.     

Management of drug eruptions

In this second of two articles on adverse cutaneous drug reactions, the management of drug eruptions is reviewed. This necessitates, above all, a full history and may involve observation of the effects of drug elimination. Skin testing may be helpful in some circumstances, but is hampered by false positive and negative results, and lack of knowledge of the significant antigenic determinants for most drugs. In vitro tests are for the most part unreliable and are research tools. Challenge tests are safe in fixed drug eruption, but are absolutely contraindicated in Stevens–Johnson syndrome and toxic epidermal necrolysis. The approach to the treatment of the more serious adverse cutaneous drug reactions, including angioedema/anaphylaxis, exfoliative dermatitis erythroderma and toxic epidermal necrolysis is reviewed. For those patients who develop reactions to an essential medication for which there is no alternative, desensitization is possible.     

High-dose intravenous immunoglobulins in the treatment of toxic epidermal necrolysis: an Asian series

Toxic epidermal necrolysis (TEN) is a severe, immune-mediated, mucocutaneous reaction resulting in extensive keratinocyte apoptosis. High-dose human intravenous immunoglobulins (IVIG) have been proposed as an effective treatment for TEN. Retrospective data from 8 patients with TEN and 4 patients with Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap treated with high-dose IVIG were analysed. The total dose of IVIG administered was 2 g/kg body weight, with the exception of 2 patients who received a total dose of 1.5 g/kg body weight. Their mean age was 49.9+/-18.8 years (range, 19 to 70 years). The mean time from the first sign of skin lesion or mucosal or epidermal detachment to commencement of IVIG was 8.7+/-5.5 days (range, 3 to 22 days). Of the 11 patients who survived, the mean time to objective response was 3.6+/-1.9 days (range, 2 to 8 days). The length of stay (LOS) in hospital was 20.4+/-8.0 days (range, 10 to 37 days). The survival rate was 91.6%. One patient developed permanent mucocutaneous sequelae following TEN. There were no adverse reactions to IVIG. We conclude that high-dose IVIG may be a safe and effective therapy for Asian patients with TEN.     

Treatment of epidermal cysts with Solcoderm (a copper ion and acid solution)

The treatment of epidermal cysts has often posed a problem for dermatologists. Although surgical excision has been adopted as the method of choice for the removal of these lesions, complications of surgery and recurrences have warranted the search for alternate therapeutic modalities. Use of a recently introduced compound, Solcoderm, is reported in the treatment of 116 epidermal cysts in 85 patients over a 2-year period. The satisfactory cosmetic results observed, low incidence of recurrence, low cost and ease of administration, make this drug a viable alternative in the management of epidermal cysts, particularly in those cases where surgery should be avoided.     

Epidermal nevus syndromes: New insights into whorls and swirls

Knowledge of the molecular underpinnings of many epidermal nevi and epidermal nevus syndrome has expanded rapidly in recent years. In this review and update on epidermal nevus syndrome, we will cover recent genetic discoveries involving epidermal nevi, including nevus sebaceus, keratinocytic epidermal nevus, nevus comedonicus, congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome, phakomatosis pigmentokeratotica, Becker's nevus, porokeratotic adnexal ostial nevus, inflammatory linear verrucous epidermal nevi, and cutaneous‐skeletal hypophosphatemia syndrome. We will discuss how newly defined mutations relate to the biology reflected in the cutaneous patterns seen in these mosaic disorders and how new molecular data has informed our understanding of these diseases and shaped management decisions.     

Verrucous epidermal nevus as a manifestation of a type 2 mosaic PTEN mutation in Cowden syndrome

Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4-year-old boy and review the literature.     

Stevens‐Johnson syndrome and toxic epidermal necrolysis in children: a review of the experience with paediatric patients in a University Hospital

Background Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening drug reactions considered to be part of the spectrum of a single pathological process. Objective To describe the clinical and epidemiological characteristics of SJS/TEN in children attended at our hospital. Materials and methods Retrospective study of children diagnosed with SJS/TEN between 1999 and 2009 in a University Hospital provided with regional‐level burn and paediatric intensive care units. Results We found 14 paediatric patients (eight SJS and six TEN). They presented an average of 60% of the body surface area affected and 31% of epidermal sloughing. The average of suspected drugs was 1.7 per patient, anticonvulsants (carbamazepine, phenytoin and lamotrigine) and antibiotics (penicillin and macrolides) being the most frequent ones. Silver sulfadiazine was the topical treatment most frequently used, 86% of patients received systemic steroids and 28.5% intravenous immunoglobulins. One patient died. Conclusions The SJS/TEN complex is a true dermatological critical condition that also affects children. Any drug can be the causative agent, more frequently anticonvulsants and antibiotics. Depending on the extension of the affected body surface, patients should be rapidly admitted to a critical care area with experience in the care of burn patients. Discontinuation of the suspected offending drugs is mandatory. Optimal supportive care and management of denuded skin areas are still the mainstay of treatment. The use of specific therapies remains controversial. Compared with adults, the disease in children seems to be milder with lower mortality.     

Familial papular epidermal nevus with “skyline” basal cell layer and multiple pilomatricomas: A new association?

Papular epidermal nevus with “skyline” basal cell layer is a newly described keratinocytic nevus. Recently, papular epidermal nevus with “skyline” basal cell layer has been reported in association with extracutaneous involvement, and the term papular epidermal nevus with “skyline” basal cell layer syndrome is used to indicate a neurocutaneous syndrome characterized by the presence of papular epidermal nevus with “skyline” basal cell layer and different neurologic symptoms that seem to improve during infancy and adolescence. Multiple pilomatricomas have been reported in association with various syndromes. We report herein papular epidermal nevus with “skyline” basal cell layer associated with multiple pilomatricomas in two members of a family with the aim of drawing attention to this peculiar epidermal nevus to improve our knowledge of the syndrome.     

金黄色葡萄球菌表皮剥脱毒素致病作用与机体防御机制研究进展

葡萄球菌性烫伤样皮肤综合征是由金黄色葡萄球菌产生的表皮剥脱毒素引起的以皮肤浅表水疱形成为特征的皮肤病。目前认为表皮剥脱毒素是一种独特的丝氨酸蛋白酶,能高效、特异地辨认和水解上皮细胞间的黏附分子-桥粒芯糖蛋白1,导致表皮剥脱。该病常发生在婴幼儿,在健康成人中发病极为罕见,但健康人对表皮剥脱毒素作用的保护机制现在仍不完全清楚,可能与免疫保护和肾脏对表皮剥脱毒素的快速清除有关。     

Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited PTEN mutation

A 3-year-old boy with Proteus syndrome has a novel germline p.Y68D mutation of the PTEN gene inherited from his mother who has Cowden syndrome. In addition, DNA extracted from curettings of his widespread epidermal naevus shows loss of heterozygosity for this mutation. To our knowledge, this has not been described before.     

The effect of cyclosporin on human epidermal keratinocytes in vitro

Cyclosporin A has been shown to be effective in the treatment of severe, recalcitrant psoriasis, but it is uncertain whether the mode of action is primarily by immune suppression or by other mechanisms. Cyclosporin-dependent growth-inhibition has recently been demonstrated in vitro using several non-human and transformed epithelial cell lines. In this study the effect of cyclosporin on human epidermal keratinocytes and skin fibroblasts was investigated. Secondary cultures of human epidermal keratinocytes were grown on collagen-coated dishes in the presence of increasing concentrations of cyclosporin. Inhibition of growth was observed at 6-8 microM. An almost identical dose-response curve was obtained for the cytotoxic drug, cis-platin. Short-term exposure (I h) to cyclosporin did not have any effect on epidermal cell growth, suggesting that direct membrane-related effects were not involved. Analysis of cellular proteins by SDS-PAGE indicated no effect of continuous cyclosporin exposure on in vitro differentiation. The observation that human epidermal keratinocyte growth is inhibited by cyclosporin suggests that a topical form of therapy for psoriasis may be an effective alternative to oral treatment.     

Successful Treatment of Dark-colored Epidermal Nevus with Ruby Laser

The pulsed ruby laser has a selective thermolytic effect. Recently, it has been available for the treatment of superficial pigmented disorders. We studied 5 cases of epidermal nevus treated with the pulsed ruby laser. In comparison with the usual methods including electrocautery, cryotherapy and skin abrasion, ruby laser therapy is an excellent tool due to technological ease and rapid improvement. Depigmentation after treatment in 2 cases was the only side effect of this therapy. Bose cases had a dark pigmentation of the skin. Despite of the risk of discoloration, the ruby laser is one of the most effective tools for therapy of pigmented epidermal nevus.     

成人表皮痣综合征1例

 报告1例成人表皮痣综合征。患者男,28岁,因皮疹、智力低下、多动28年,间断抽搐27年就诊。皮肤科检查：额部、眼周、颈部可见弥漫性密集的淡褐至褐黑色乳头瘤样角化性丘疹,触之坚硬,似高起鱼鳞病、先天性良性黑棘皮病样。躯干、双上肢、四肢皮损角质增厚,较额部、眼周、颈部薄,可见弧形带状或旋涡状排列,不规则斑片状或斑点状色素脱失斑,与增生性皮损及正常皮肤相互交错。颈部皮损组织病理检查示纤维上皮性息肉改变,胸部皮损组织病理检查示表皮痣样改变。脑电图：脑电图异常伴高中波幅尖波及4~7 Hz的θ节律短阵出现。诊断为表皮痣综合征。     

Toxic epidermal necrolysis; 15 years'' experience in a Dutch burns centre

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially fatal drug reaction characterized by an extensive skin rash with blisters and exfoliation, frequently accompanied by mucositis. The wounds caused by TEN are similar to second-degree burns and severe cases may involve large areas of skin loss. OBJECTIVES: Analysis of our results in patients with TEN and evaluation of the variety of therapeutic interventions that has been studied and suggested in TEN. PATIENTS/METHODS: Retrospective analysis of 19 consecutive patients with TEN treated in our burns centre between 1989 and 2004. RESULTS: Immediate withdrawal of any potentially fatal drug, maximum supportive care, and a restricted and tailored antibiotic, medical and surgical treatment regimen confined mortality to 21%, whereas prognosis scores like APACHE II and SCORTEN predicted mortality of 22 and 30%, respectively. A positive contribution of selective digestive decontamination is suggested but has yet to be established. CONCLUSIONS: Because of a potentially fatal outcome, fast referral of a patient suspected of TEN to a specialized centre (mostly a burns unit or specialized dermatology centre) for expert wound management and tailored comprehensive care is strongly advised and contributes to survival.