Score Of Toxic Epidermal Necrosis Research Articles

Effectiveness of Corticosteroids Alone versus Corticosteroids and Cyclosporine in the Management of Patients with Severe Cutaneous Drug Reaction

Introduction: Severe Cutaneous Adverse Reactions (SCADRs) are emergency dermatologic manifestations associated with high morbidity and mortality. Their management includes immediate withdrawal of suspected causal agent followed by prompt management with drugs such as corticosteroids, cyclosporine and cyclophosphamide. Aim: To compare the effectiveness of corticosteroids alone versus cyclosporine and corticosteroids in management of SCADRs. Materials and Methods: This was a prospective observational study carried out in Indoor patients of Dermatology Department, Civil Hospital Ahmedabad, Gujarat, India, from October 2019 to September 2022. Twenty six patients were diagnosed with SCADRs and grouped according to the treatment received in two groups: corticosteroids alone (group B), and corticosteroids along with cyclosporine (group A). The efficacy was assessed based on: the days of disease arrest, days of complete reepithelialisation, duration of hospitalisation and final outcome. To know the prognosis of the patients, Score of Toxic Epidermal Necrosis (SCORTEN) score was used. Data was entered and analysed with the help of Microsoft excel ® 2019. Results: There were 14 patients in group A and 12 in group B. In a total 26 cases majority were of Stevens-Johnson Syndrome (SJS) (50%) followed by SJS-Toxic Epidermal Necrolysis (TEN) (27%) TEN (15%), Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) (8%). The mean duration of disease arrest was significantly shorter in group A (n=14) when compared to group B (n=12) (p-value <0.001**). Also, the time for complete re-epithelisation was significantly shorter in group A than group B (p-value=0.025*) While no significant difference between the two groups was observed in SCORTEN score. Mortality was 3/12 in group B, nil in group A. Conclusion: Combination therapy with corticosteroids and cyclosporine leads to an early arrest of the disease progression, better prognosis and outcome in patients of SCADRs.

Combined use of cyclosporine in the treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis.

The exact efficacy of cyclosporine in the treatment of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) still needs evidence from more clinical data. This study was designed to compare the effectiveness and side-effects of combined use of cyclosporine in the treatment TEN with glucocorticoids (GC)/i.v. immunoglobulin G (IVIG). A total of 46 patients with SJS/TEN were enrolled and classified into two groups based on the therapeutic drugs used. Clinical characteristics, interventions, outcomes, and disease progressions were collected and compared between the two groups. In our cohort, seven patients eventually died and the overall fatality rate was 15.2%, but there was no difference between the two groups (p=0.557). On discharge, the median SCORe of Toxic Epidermal Necrosis (SCORTEN) fell from 2.0 at admission to 1.0 and the median body surface area detached fell from 32.0% at admission to 9.5%. Patients in the cyclosporine group had a higher rate of re-epithelialized area than patients in the non-cyclosporine group (p < 0.05). Cyclosporine significantly reduced the length of stay (19.0 vs. 13.0 days, p=0.019) and the rate of systemic infection (71.4% vs. 36.0%, p=0.017) compared with the non-cyclosporine group. SCORTEN was the only significant risk factor for death and the risk ratio was 1.96 (1.17-3.31, p=0.011). Conclusively, the combined use of cyclosporine could reduce the occurrence of systemic infection and accelerate the re-epithelialization.

Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome.

Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome.

Assessment and Comparison of Performance of ABCD-10 and SCORTEN in Prognostication of Epidermal Necrolysis

Epidermal necrolysis is a rare severe cutaneous drug reaction associated with high mortality. The ABCD-10 score (age, bicarbonate, cancer, dialysis, 10% body surface area), a new prognostic score for mortality in epidermal necrolysis, was recently developed and validated in the US. However, to our knowledge, it remains to be externally validated in other cohorts. To assess ABCD-10 among patients in a contemporary Asian cohort and compare its performance with the Score of Toxic Epidermal Necrosis (SCORTEN) and study the associations of time and immunomodulatory therapy with the performance of ABCD-10 and SCORTEN. This retrospective cohort study was conducted over a 17-year period from January 2003 to March 2019 and included 196 patients with epidermal necrolysis who were recruited from Singapore General Hospital, the national referral center for epidermal necrolysis. In-hospital mortality. Discrimination and calibration of each risk score were assessed and compared using the area under the receiver operating characteristic curve and calibration plot, respectively. Among 196 patients (median [interquartile range] age, 56 [42-70] years; 116 women [59.2%]), 45 (23.0%) did not survive to discharge. All risk factors in ABCD-10 were significantly associated with in-hospital mortality. However, dialysis before admission, the most heavily weighted factor in ABCD-10, performed weaker in this cohort (odds ratio, 3.7; 95% CI, 1.0-13.2, P = .04). Although the discrimination of ABCD-10 and SCORTEN did not differ (area under the curve: ABCD-10, 0.78; 95% CI, 0.72-0.85; vs SCORTEN, 0.77; 95% CI, 0.69-0.84; P = .53), the calibration of ABCD-10 was poorer compared with SCORTEN. From graphical analysis of the calibration plots, ABCD-10 showed mortality underestimation at lower score ranges and overestimation at higher score ranges. By contrast, SCORTEN was generally well calibrated, although at higher score ranges mortality may be overestimated. Assessment of calibration plots showed that there was increasing overestimation of mortality by SCORTEN during the later period or when immunomodulatory therapy was used compared with patients treated with supportive care alone. Calibration of ABCD-10 remained poor even during the later period or among patients treated with immunomodulatory therapy. In this cohort of patients, the performance of SCORTEN was superior to ABCD-10 in mortality prognostication in epidermal necrolysis. However, it did display time-associated deterioration in calibration leading to overestimation of mortality risk. Future studies may consider revising the existing SCORTEN given its current good discrimination.

Metabolite of Carbamazepine Activates NLRP3 Inflammasome in Keratinocytes and Regulates CD8+ T-Cell Skin Trafficking in SJS/TEN

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute cutaneous adverse drug reactions involving keratinocyte death and CD8+ T lymphocyte-mediated immune response. Drugs, especially anti-epileptic drugs such as carbamazepine (CBZ) are the most important etiologic agents in patients with SJS/TEN. Carbamazepine-10,11-epoxide (CBZE), a pharmacologically active metabolite of CBZ, oxidated by cytochrome P450 enzyme 3A4 (CYP3A4) in the liver, and is also distributed in the epidermis of skin. Why do patients of SJS/TEN develop a violent CD8+ T cells immune response to the epidermis of skin is unknown. Methods: Sera and blister fluid of six patients with SJS and four patients with TEN were obtained from Xijing Hospital. The levels of interleukin-1β (IL-1β), IL-18, Granzyme B, and granulysin were assessed by ELISA and quantitative real-time PCR. The mechanism results were confirmed with transient transfection of small interfering RNAs into cultured keratinocytes, western blot, migration assay, flow cytometry, and immunohistochemistry. Findings: Increased expression of NLRP3 inflammasome in lesions of patients with SJS/TEN. Increased levels of interleukin-1β (IL-1β) and IL-18 significantly correlated with body surface area (BSA), SCORe of Toxic Epidermal Necrosis (SCORTEN), and levels of Granzyme B in sera, blister fluid and lesions of patients with SJS/TEN. CBZE induces NLRP3 inflammasome activation in SJS/TEN keratinocytes. Activation of NLRP3 inflammasome in SJS/TEN keratinocytes upregulates the expression of CXCL9/CXCL10, activates CD8+ T lymphocytes, and increases the expression of cytotoxic markers via signaling of IL-1β/IL-1R or IL-18/IL-18R. This promotes chemotactic ability in CD8+ T lymphocytes of patients with SJS/TEN. Interpretation: To our knowledge, this study shows for the first time that CBZE induces activation of NLRP3 inflammasome and increases activation, migration and cytotoxic functions of CD8+ T lymphocytes in skin, thereby contributing to the dysregulated response in patients with SJS/TEN. Funding: This work was supported by the National Natural Science Foundation of China (81371738, 31400782, 81573038, 81472885). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The investigational protocol was approved by the Ethics Committee of the Fourth Military Medical University, according to the guidelines of Declaration of Helsinki.

Toxic epidermal necrolysis data from the CELESTE multinational registry. Part II: Specific systemic and local risk factors for the development of infectious complications

The aim of the study was to identify the most important systemic and local risk factors for the development of infectious complications in patients with toxic epidermal necrolysis (TEN). Material and methodologyThis is a multicentric study that included all patients with TEN who were hospitalized between 2000–2015 in specialized centres in the Czech Republic and Slovakia. The total catchment area included a population of over 12.5 million inhabitants.The actual implementation of the project was carried out using data obtained from the CELESTE (Central European LyEll Syndrome: Therapeutic Evaluation) registry, wherein specific parameters related to epidemiological indicators and infectious complications in patients with TEN were evaluated as a retrospective analysis. ResultsA total of 38 patients (97%) of the group were treated with corticosteroids. The comparison of patients with different doses of corticosteroids did not exhibit a statistically significant effect of corticosteroid administration on the development of infectious complications (p=0.421).There was no effect of the extent of the exfoliated area on the development of infectious complications in this area. The average extent of the exfoliated area was 66% TBSA (total body surface area) in patients with reported infectious complications and 71% TBSA (p=0.675) in patients without infectious complications.In the case of the development of an infectious complication in the bloodstream (BSI), the increasing effect of the SCORTEN (SCORe of Toxic Epidermal Necrosis) value was monitored during hospitalization. Within 5days from the beginning of the hospitalization, the average SCORTEN value was 2.7 in 6 patients with BSI and 3.0 in 32 patients without BSI (p=0.588). In the period after the 15th day of hospitalization, 7 patients with BSI had an average SCORTEN value of 3.4, and 16 patients without BSI had an average SCORTEN value of 2.5 (p=0.079).In the case of low respiratory tract infection (LRTI), the effects of the necessity for artificial pulmonary ventilation and the presence of tracheostomy were monitored. The statistically significant effect of mechanical ventilation on the development of LRTI occurred only during the period of 11–15days from the beginning of the hospitalization (p=0.016). The effect of the tracheostomy on the development of LRTI was proven to be more significant. ConclusionWe did not find any statistically significant correlation between the nature of immunosuppressive therapy and the risk of developing infectious complications. We failed to identify statistically significant risk factors for the development of BSI. Mechanical ventilation and tracheostomy increase the likelihood of developing LRTIs in patients with TEN.

Serum IL-17 in patients with erythema multiforme or Stevens-Johnson syndrome/toxic epidermal necrolysis drug reaction, and correlation with disease severity.

There is strong evidence that drug-induced cutaneous eruptions have an immunological component. Interleukin (IL)-17, a proinflammatory cytokine that is predominantly produced by T helper 17 cells, has been linked to various autoimmune and inflammatory diseases. To measure serum IL-17 levels in patients with cutaneous drug reactions [erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)] in order to study the associations between IL-17 and disease severity. In total, 32 patients (13 with EM and 19 with SJS/TEN) and 15 age- and sex-matched healthy controls (HCs) were enrolled. Patients with SJS/TEN were assessed clinically using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Serum IL-17 levels were determined by ELISA. Serum IL-17 levels were significantly higher compared with HCs (16.46 ± 5.21 pg/mL) in the EM (35.1 ± 23.89 pg/mL, P < 0.02) and SJS/TEN (68.19 ± 35.42 pg/mL, P = 0.001) groups. IL-17 levels were also significantly higher in the SJS/TEN group than in the EM group (P = 0.004). Mean affected body surface area percentage was 0.9 ± 0.21 in the EM group and 22.8 ± 10.67 in the SJS/TEN group. The SJS/TEN SCORTEN ranged from 1 to 5, with a mean of 2.5 ± 1. Serum IL-17 level correlated positively with both percentage surface area of detached skin and SCORTEN. Serum IL-17 levels may have prognostic and diagnostic value in patients with EM or SJS/TEN reactions, and can provide a valuable approach in managment.

Score of Toxic Epidermal Necrosis Predicts the Outcomes of Pediatric Epidermal Necrolysis.

Epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) includes immune-mediated, life-threatening inflammatory blistering disorders that can affect children. The Score of Toxic Epidermal Necrosis (SCORTEN) tool has accurately predicted the outcome of these disorders in adults but has not been tested in children. We performed a retrospective chart review to compare the accuracy of the adult SCORTEN tool with that of two modifications tailored to children in predicting disease outcome. The longer the patient's median length of hospital stay was, the higher the adult and two proposed pediatric SCORTENs were. In addition, all patients who died had SCORTENs greater than 4. The pediatric-modified tools were not superior to the adult SCORTEN, which accurately predicted outcome.

Stevens-Johnson syndrome and toxic epidermal necrolysis: ear, nose, and throat description at acute stage and after remission.

Ear, nose, and throat (ENT) lesions are frequently involved in Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), although a detailed description is lacking in the literature. To describe ENT lesions at the acute stage and follow-up in a large series of patients with SJS/TEN and identify factors associated with the severe ENT form. Retrospective study of 49 patients with SJS/TEN hospitalized in a referral care center from 2005 to 2010. Patients who underwent a full ENT workup including examination and a nasal fiberoptic endoscopy by an otorhinolaryngologist in the acute phase and during follow-up at 2 and 12 months were included in the study. Recorded variables included maximal body surface area (BSA) detachment, SCORTEN (Score of Toxic Epidermal Necrosis [a severity of illness score]), sites and type of ENT mucosal lesions, intensive care unit transfer, pulmonary infection, and mortality. "Severe ENT form" was defined by the occurrence of laryngeal lesions with the risk of airways obstruction. Clinical characteristics associated with severe ENT form were analyzed in univariate and multivariable analysis. Of the 49 patients who underwent a full ENT workup (female to male ratio, 1.1:1), ENT symptoms (eg, odynophagia, dysphagia, dysphonia, dyspnea, earache, nasal obstruction) occurred in 48 (98%). Dyspnea or dysphonia were significantly associated with severe ENT form (21% [P = .03] and 50% [P < .001], respectively). Topographic frequencies of lesions were as followed: lips and oral cavity (n = 46 [93%]) and pharynx and vestibule of the nose (n = 26 [53%]). Fourteen patients (29%) had severe ENT form. Findings for other recorded variables for those with vs without ENT examination are as follows: maximal BSA detachment (20% [0%-95%] vs 5.5% [0%-95%]; P = .004), SCORTEN (1 [0-5] vs 1 [0-5]; P = .54), intensive care unit transfer (10 [20%] vs 9 [19%]; P = .80), pulmonary infection (9 [18%] vs 6 [13%]; P = .10), and mortality (3 [6%] vs 5 [10%]; P = .70). In multivariable analysis, pulmonary infection was significantly associated with severe ENT form (odds ratio, 5.9 [95% CI, 1.1-32.8] [P = .04]). After remission of SJS/TEN, a complete ENT mucosal healing occurred in 36 patients (74%) at 2 months and in nearly all patients (n = 48 [98%]) at 1 year of follow-up. Severe ENT form is associated with pulmonary infection and is easily detected by nasal fiberoptic endoscopy. ENT evaluation should be suggested when dysphonia or dyspnea is observed at the acute stage of SJS/TEN.

Etanercept therapy for toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. To describe a case series of patients with TEN treated with a single dose of etanercept. We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan-Meier method. All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. This is a small, uncontrolled case series. These preliminary results suggest the possibility that tumor necrosis factor-alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found.