药物所致重症多形红斑和中毒性表皮坏死松解症的临床研究

对药物所致征症多形红斑（ＳＪＳ）和中毒性表皮松解症（ＴＥＮ）进行了对比研究。两者最常见的致敏解药物是解镇痛药，其次是抗生素类和镇静抗癫痫药。ＳＪＳ和ＴＥＮ的发病年龄、性别和潜伏期无差异，但ＴＥＮＲ 发热时间、急性期和恢复期时间明显长于ＳＪＳ，发热程度、粘膜损害程度和合并症发生率明显高于ＳＪＳ。ＳＪＳ预后良好，无１例死亡，ＴＥＮ的死亡率高达３９％。关于皮质类固醇激素在治疗ＴＥＮ中的应用，我们认为早期     

Open trial of ciclosporin treatment for Stevens–Johnson syndrome and toxic epidermal necrolysis

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute mucocutaneous reactions associated with poor prognosis. The treatment is mainly symptomatic, based on supportive care. Until now, several curative treatments have been proposed without evidence of effectiveness. Objectives To evaluate the effect of ciclosporin on SJS and TEN after a short series had suggested a benefit. Methods We conducted an open, phase II trial to determine the safety and possible benefit of ciclosporin. Among the 45 consecutive patients admitted for SJS/TEN from March 2005 to September 2007, 29 fulfilled inclusion criteria. Ciclosporin was administered orally (3 mg kg^?1 daily for 10 days) and tapered over a month. Clinical and biological evaluations were performed sequentially. Predicted death rate was estimated with a validated prognostic score (SCORTEN). Results Twenty‐nine patients were included at a mean ± SD of 2·8 ± 1·8 days after onset. The final diagnosis was SJS (n = 10), SJS/TEN overlap (n = 12) and TEN (n = 7). One month of treatment was completed in 26. Ciclosporin was stopped after more than 10 days in three cases for side‐effects including posterior leucoencephalopathy (n = 1), neutropenia (n = 1) and nosocomial pneumopathy (n = 1). Ciclosporin dosage was tapered earlier than scheduled in two cases for alteration in renal function. The prognostic score predicted 2·75 deaths; none occurred (P = 0·1). Mean epidermal detachment remained stable in 18 of 29 cases (62%). The mean ± SD hospital stay was 16·2 ± 9·1 days. Conclusions Both the death rate and the progression of detachment seemed lower than expected, suggesting a possible usefulness of ciclosporin in SJS and TEN that needs to be confirmed.     

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.     

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.     

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.     

Mycoplasma pneumoniae and mucositis – part of the Stevens‐Johnson syndrome spectrum

Background: Mycoplasma pneumoniae may induce mucosal inflammation, referred to as M. pneumoniae‐associated mucositis (MPAM). There is no generally accepted definition of MPAM, since there may be mucosal lesions only, or mucosal and minimal skin lesions. Patients and Methods: We conducted a literature review of MPAM, paying particular attention to pathogenesis, clinical manifestations, treatment decisions, and prognosis. Results: We identified 32 cases of MPAM (median age 13.5 years), whereof 23 patients were otherwise healthy children and young adolescents (72%). M. pneumoniae infection was associated with fever and respiratory symptoms in all calls; it was confirmed by serology (n = 30) and/or PCR (n = 9). Oral lesions were present in all cases, followed by ocular (97%) and uro‐genital lesions (78%). Despite the syndrome's name postulating the absence of cutaneous involvement, minimal skin lesions occurred in 31%. Treatment regimens included systemic antibiotics (100%) and systemic anti‐inflammatory treatment with corticosteroids (31%) or immunoglobulins (9%). Macrolides were given in 81%, with failure, relapse, and/or worsening in one‐third of patients. No patient suffered long‐term sequelae. Conclusion: MPAM is a distinct extra‐pulmonary manifestation falling into the continuum of Stevens‐Johnson syndrome. This entity may be due to inflammatory mechanisms suggesting that systemic anti‐inflammatory treatment is even more important than antimicrobials.     

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.     

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.     

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.     

Case of fertility treatment‐induced Stevens‐Johnson syndrome with a severe ocular complication

Pharmacological regimens with multiple medications are being used in fertility treatments. Herein, we report a case of a 40‐year‐old Japanese woman who developed Stevens‐Johnson syndrome (SJS) with a severe ocular complication during fertility treatment. Despite early multimodal interventions, including methylprednisolone pulse therapy and plasma exchange, her ocular complications persisted for more than a year. The four drugs administered in this case (cabergoline, medroxyprogesterone acetate, clomiphene, and intravenous human chorionic gonadotropin) have never been reported to induce SJS. Based on this case, we suggest that obstetricians, gynecologists, and dermatologists should be aware of fertility treatment‐induced severe drug eruptions.     

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.