Erythema multiforme,Stevens–Johnson syndrome and toxic epidermal necrolysis: Frozen‐section diagnosis

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may be fatal. Although classified by body surface area skin detachment, initial stages of both may present with erythema multiforme (EM)‐like lesions. To diagnose and predict disease activity adequately as early as possible for patients revealing EM‐like lesions, we performed frozen‐section diagnosis. Thirty‐five patients clinically diagnosed as EM, SJS or TEN were biopsied to diagnose and predict disease progression within the initial‐visit day. Half of a histological section taken from a lesion was snap‐frozen and immediately cryostat‐sectioned, acetone‐fixed and stained with hematoxylin–eosin. Specimens were examined with light microscopy for presence of epidermal necrosis. A section from unaffected sites was also examined for 11 patients. Specimens were examined with light microscopy for presence of graft‐versus‐host reaction (GVHR)‐like findings: apoptotic keratinocytes and satellite cell necrosis. Epidermal necrosis was seen in nine patients. Initial diagnosis of the nine was one of overlap SJS‐TEN, four of SJS and four of EM, and final diagnosis of those was one of TEN, one of overlap SJS–TEN, four of SJS and three of EM. Dissociation between initial and final diagnosis was seen in three cases. GVHR‐like findings in the epidermis were observed in two patients finally diagnosed as overlap SJS–TEN and TEN. Frozen sections are useful not only to make a diagnosis of erythema multiforme but to assess a potential to exhibit more aggressive clinical behaviors (SJS or TEN).     

Procalcitonin as a diagnostic indicator for systemic bacterial infections in patients with Stevens–Johnson syndrome/toxic epidermal necrolysis

Elevated serum procalcitonin (PCT) level has been reported to be a diagnostic index in systemic bacterial infections, but it can also increase in some non‐infectious inflammatory diseases. Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immune‐mediated cutaneous mucosal reaction which is susceptible to bacterial infections and may have elevated PCT levels. The value of serum PCT has not been assessed in series of SJS/TEN patients. We aimed to investigate the PCT levels in SJS/TEN patients with systemic bacterial infections (systemic infected group), with skin surface bacterial infections (skin surface infected group) and without infections (non‐infected group), to assess whether PCT was a valuable indicator for systemic bacterial infections in SJS/TEN patients. The PCT and C‐reactive protein (CRP) levels of 42 inpatients with SJS/TEN were retrospectively analysis. The receiver–operator curve (ROC) was used to determine the diagnostic efficacy of PCT for systemic bacterial infections in SJS/TEN patients. The results demonstrated that PCT levels in the systemic infected group were significantly higher than those in the other two groups (P < 0.05). There was no significant difference in CRP between the three groups. The cut‐off PCT level of 0.65 ng/mL calculated by ROC had optimal diagnostic efficacy, with sensitivity and specificity of 84.6% and 89.7%, respectively. PCT and severity‐of‐illness score for toxic epidermal necrolysis were positively correlated (P < 0.05). In conclusion, PCT is a valuable index and superior to CRP in detecting systemic bacterial infections in SJS/TEN patients. The level of PCT can partially reflect the severity of the disease.     

Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens–Johnson syndrome and toxic epidermal necrolysis

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life‐threatening cutaneous adverse drug reactions. While there is no established therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v. immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still controversial because total doses of IVIG used vary greatly from one study to another. The aim of this study was to evaluate the efficacy of IVIG, administrated for 5 days consecutively, in an open‐label, multicenter, single‐arm study in patients with SJS or TEN. IVIG (400 mg/kg per day) administrated for 5 days consecutively was performed as an additional therapy to systemic steroids in adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated. Parameters to assess clinical outcome were enanthema including ophthalmic and oral lesions, cutaneous lesions and general condition. These parameters were scored and recorded before and after IVIG. We enrolled five patients with SJS and three patients with TEN who did not respond sufficiently to systemic steroids before IVIG administration. All of the patients survived and the efficacy on day 7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin lesions and enanthema in the patients in whom IVIG therapy was effective. Serious side‐effects from the use of IVIG were not observed. IVIG (400 mg/kg per day) administrated for 5 days consecutively seems to be effective in patients with SJS or TEN. IVIG administrated together with steroids should be considered as a treatment modality for patients with refractory SJS/TEN. Further studies are needed to define the therapeutic efficacy of IVIG.     

Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/Stevens–Johnson syndrome overlap

Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are severe mucocutaneous eruptions. There is currently no defined optimal approach to wound care. The objective of this study was to evaluate silver dressings in the wound‐care management of TEN and SJS/TEN syndrome overlap with a retrospective case review of nine patients with TEN and SJS/TEN overlap presenting to our institution. Nanocrystalline silver dressings appear to be useful in the rapid commencement of healing in these patients. TEN and SJS/TEN overlap are rare conditions. This contributed to a relatively small number of cases included in the study. The ease of application, antimicrobial properties and low frequency of change make nanocrystalline silver dressings ideal in TEN/SJS.     

Rapid remission of Stevens–Johnson syndrome by combination therapy using etanercept and intravenous immunoglobulin and a review of the literature

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are spectrum of rare, acute, and life‐threatening delayed‐type drug hypersensitivity reactions that are associated with high mortality rates. However, no therapeutic standard has been proposed for SJS/TEN. Here, we report a case of a patient diagnosed with Stevens–Johnson syndrome whose disease progression was halted by a single dose of etanercept and was treated successfully. In addition, we reviewed the literature reporting patients with SJS/TEN treated with similar regimens.     

Clinical risk management of Stevens–Johnson syndrome/toxic epidermal necrolysis spectrum

Clinical risk management concedes that risk is inherent to all health-care processes. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life-threatening reactions to medications. Risk management should be considered prior to starting, during, and after therapy. Prior to starting therapy, risks that need to be assessed include any specific patient groups that may be at greater risk for the development of SJS/TEN. Gene testing is in place for Chinese and Thai patients who are going to be exposed to carbamazepine. During therapy, it is important to recognize SJS/TEN as a possible adverse drug reaction. Diagnostic criteria have changed, and more data exist on drugs with an increased risk. Although there is no standardized treatment for all patients with SJS/TEN, options that have been used include cyclosporine, corticosteroids, and intravenous immunoglobulin. Standards of care are usually defined locally, but new treatments, such as amniotic membrane support for ocular damage, may need to be considered. Good communication skills are needed to allow practitioners to show empathy and to provide disclosure. Risk management after a reaction includes skills in acknowledging bad outcomes or error; freedom to say "sorry" as defined by "apology laws," and knowing the rights provided by "Quality Assurance Conferences," where the information discussed is protected. In other words, the patient is best supported after an event like SJS/TEN if the practitioner is knowledgeable about optimal care standards and their legal rights and obligations.     

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.     

Incidence of Stevens–Johnson syndrome following combination drug use of allopurinol,carbamazepine and phenytoin in Taiwan: A case–control study

The goal of our study was to investigate the incidence of Stevens–Johnson syndrome (SJS), the frequency of SJS diagnosis, and the association between SJS and prior use of allopurinol, carbamazepine or phenytoin. This case–control study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Controls visited the emergency department of the same hospital for trauma or fractures (excluding burns) and used allopurinol, carbamazepine or phenytoin during the past 3 months. We determined whether patients were prescribed a combination of drugs in addition to allopurinol, carbamazepine or phenytoin within the last 3 months. We identified 1 853 985 controls and 7327 SJS‐diagnosed patients using the Taiwan NHIRD records for 2000–2008. Higher use of allopurinol (49.8%), carbamazepine (39.1%) or phenytoin (21.3%) was observed among patients (n = 3131) than among controls (n = 2858). The overall SJS incidence rate was 3.6/1 000 000. Drug combinations were uncommon (<10%) in patients or controls taking allopurinol. However, combination drug use exceeded 10% in patients taking carbamazepine or phenytoin. Logistic regression analysis of recent combination drug use revealed that phenobarbital, valproate, non‐steroidal anti‐inflammatory drugs (NSAIDs) including piroxicam and tenoxicam, and antibiotics including amoxicillin and cephalexin were strongly associated with SJS. Patients with gout or epilepsy taking allopurinol, carbamazepine or phenytoin should be evaluated carefully by physicians. Concurrent use of piroxicam, tenoxicam, phenobarbital, valproate, amoxicillin or cephalexin, in addition to carbamazepine or phenytoin, may increase the incidence of SJS.     

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.     

Treatment of erythema multiforme, Stevens–Johnson Syndrome, and toxic epidermal necrolysis

The "erythema multiforme disease spectrum" comprises four distinct, severe, clinical subvariants: (1) bullous erythema multiforme (bullous-EM), (2) Stevens–Johnson syndrome (SJS), (3) SJS–toxic epidermal necrolysis (TEN)-overlap syndrome, and (4) TEN. These diseases are closely related to severe mucocutaneous intolerance reactions that are mostly elicited by drugs/drug metabolites and associated with a high mortality rate. Old age and area of detached skin negatively influence the course of disease, and early withdrawal of causative drugs with short half-life is a positive prognostic factor. Therapeutic management represents a multidisciplinary challenge for colleagues from various specialities including specialized nurses and usually can be performed at a dermatologic ward unless technical equipment of an intensive care unit is needed. Topical therapy with biologic and (semi-)synthetic dressings is aimed at early re-epithelialization and the prevention of scarring, synechia formation, and infection. Systemic treatment includes antibiotics, fluid and electrolyte replacement, protein preparations and blood products, etc. Various anti-inflammatory and immunosuppressive treatment regimens with corticosteroids, cyclosporine A, cyclophosphamide, plasmapheresis have been considered to halt ongoing immunologic pathomechanisms, and some of these have shown significant efficacy. However, because we lack formal clinical trials, none of these regimens can be definitively proposed as a therapy of choice in any of the severe clinical variants of the EM spectrum.     

Efficacy and safety of cyclosporine in Stevens–Johnson syndrome and toxic epidermal necrolysis

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life threatening cutaneous reactions that are most commonly caused by exposure to medications. This review assesses the efficacy and safety of cyclosporine therapy for SJS, TEN, and SJS/TEN overlap. A literature review was conducted in PubMed using the MeSH terms TEN, SJS, and cyclosporine. Five case series and one meta‐analysis were analyzed. From review of the existing literature, cyclosporine appears to not only have a mortality benefit in the treatment of SJS/TEN, but also a relatively safe side effect profile.     

Pediatric toxic epidermal necrolysis treated successfully with infliximab

Successful management of toxic epidermal necrolysis (TEN) with tumor necrosis factor‐α inhibitors has been described in adults. We present a case of a 7‐year‐old boy with infection‐associated TEN, diagnosed by typical clinical and histopathological features, most likely caused by Mycoplasma pneumoniae. Treatment with a single dose of infliximab 5 mg/kg intravenously on day 5 after the onset of symptoms was followed by cessation of all blister formation over 3 days and complete resolution within a week. Sequelae were mild, consisting of postinflammatory hyperpigmentation and dry eyes.     

Successful treatment of interstitial lung disease related to Stevens–Johnson syndrome/toxic epidermal necrolysis overlap with etanercept: A case report and published work review

Interstitial lung disease (ILD) is a rare complication of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this study, we present the case of a 33‐year‐old woman who was diagnosed with ILD related to SJS/TEN overlap syndrome. Surprisingly, the patient did not respond to combination therapy with steroids and i.v. immunoglobulin, but rapidly improved after two doses of etanercept treatment. To our knowledge, this is the first case of SJS/TEN‐induced ILD that was successfully treated with etanercept. We reviewed another two cases of ILD associated with SJS/TEN, and found that unlike the other cases, in the present case, ILD occurred early in the course of the disease and rapidly improved after etanercept injection. We discovered that in the present patient, the serum interleukin‐6 level increased during the progressive stage and declined after the initiation of treatment with etanercept.     

Update on pathobiology in Stevens-Johnson syndrome and toxic epidermal necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions (SCARs), which are mainly induced by a variety of drugs. Once considered to be unpredictable, significant progress has been achieved in understanding the pathological mechanisms underlying such reactions. Recent studies suggested that SJS/TEN is a specific immune reaction where human leukocyte antigen (HLA) alleles specific for certain drugs in defined populations are involved in the activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Upon the activation, various cytotoxic and immunological signals, including but not limited to Fas/Fas ligand, perforin/granzyme B, and granulysin are launched to mediate the disseminated keratinocyte death in SJS/TEN. This review provides an update on the pathobiology of SJS/TEN in both the genomic and immunologic perspectives. The knowledge gained from these cutting-edge studies will form the basis for better prevention and management of SJS/TEN.     

中毒性表皮坏死松解症12例临床分析

目的：探讨中毒性表皮坏死松解症(TEN)药疹的临床特点和治疗。方法：回顾性分析12例TEN药疹患者的临床特点和治疗。结果：TEN药疹患者潜伏期1～60天，平均18．7天。发热11／12例(91．7％)，肝损害10／12例(83．3％)，粘膜损害9／12例(75％)。经糖皮质激素治疗，加强护理，加强营养及预防感染，11例痊愈(91．7％)，1例死亡。结论：糖皮质激素治疗非常有效，强化护理、支持疗法及预防感染对降低死亡率非常重要。