Search

Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions. However, only a few studies have investigated the clinicodemographic and laboratory parameters predicting SJS and TEN outcomes other than mortality, such as severe complications or increased length of hospital stays. Our objectives are to identify admission risk factors predictive of severe complications and the accompanying clinical or biochemical markers associated with prolonged hospitalization., Methods: A retrospective cohort study over a 9-year period (2013-2022)., Results: The study included 216 patients with SJS (n = 122), SJS/TEN overlap (n = 71), and TEN (n = 23). On multivariate analysis, the clinical factor on admission that was predictive of severe complications was blood urea nitrogen (BUN) >8.3 mmol/L (p = 0.007). Furthermore, BSA epidermal detachment >10% (p < 0.001), Severity-of-illness score for TEN (SCORTEN-1) ≥2 (p = 0.04), and positive skin culture (p = 0.04), from which the Prolonged Hospitalization Risk Score was created, were predictive of length of hospital stays >10 days. Using systemic methylprednisolone at a mean dose ≥1 mg/kg/day for a median duration of 10.5 days was not shown to increase or reduce complication rates of SJS/TEN and shorten hospital stays., Conclusion: BUN >8.3 mmol/L present at admission is a risk factor for severe complications of SJS/TEN. BSA involvement >10%, SCORTEN-1 ≥2, and positive skin culture on admission are useful markers to predict extended hospitalization., (© 2024 S. Karger AG, Basel.)

Inflammatory markers such as neutrophil-lymphocyte ratio (NLR) and eosinophil count are known prognostic indicators for the severity of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). This study explores the correlation of systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR) and NLR with Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) and patient outcomes. A retrospective audit of 34 patients with SJS/TEN (25 SJS, 3 SJS/TEN overlap, 6 TEN) was conducted from 2018 to 2022. Mean admission values were SII 1597 (SD 1904), NLR 6.52 (SD 5.99) and PLR 202 (SD 135). Cut-off values for predicting mortality were SII 1238 [area under receiver operating characteristic curve (AUROC) 0.82], NLR 8.32 (AUROC 0.80) and PLR 285 (AUROC 0.78). Multiple logistic regression using a backward stepwise method identified SCORTEN as a significant factor associated with mortality (P = 0.03) after adjusting for SII, NLR and PLR. None of the inflammatory markers significantly predicted mortality, although PLR at admission may be a potential risk factor (P = 0.05)., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, usually to drugs, characterized by blistering and epithelial sloughing. SCORTEN is an established prognosticator index employed in SJS/TEN patients to evaluate their severity degree and mortality risk. Many studies done in the recent past have indicated that neutrophil-lymphocyte ratio (NLR) is related to disease activity in several dermatological diseases. Hence, this study has been performed to correlate the NLR of each patient with their respective SCORTEN values and assess whether NLR can be used as a prognostic marker in SJS/TEN. A single centre, retrospective, 4 year study was conducted at a tertiary care hospital. The required clinical and laboratory data were obtained from existing IP records of all cases of SJS/TEN disorders admitted in the last 4 years in our hospital between May 1st 2019 and April 30th 2023. The correlation coefficient and p value were analysed using the Spearman's rank correlation. The total sample size of the study was 22 patients. A female preponderance (59.1%) with an age range between 10 to 74 years was noted. Drugs were the main triggering factor in all the patients and antiepileptics were the most commonly implicated drug group. On statistical analysis a weak positive correlation (r = 0.182) between NLR and SCORTEN was noted, however p value was insignificant (p = 0.417). Further, mean ± SD of NLR was found to be higher in group II (patients with SCORTEN ≥ 3) as compared to group I (patients with SCORTEN < 3). On correlating NLR with each group separately, p value still remained insignificant. Elevation in NLR value reflects the systemic inflammation, but its role in predicting the severity of the disease needs further research involving larger sample size., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aromatic antiepileptic drugs (AEDs) are common causes of cutaneous adverse drug reactions, which range from morbilliform drug eruption to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens‒Johnson syndrome, and toxic epidermal necrolysis. Different in vitro methods for identifying the culprit drugs have been developed; however, it is particularly challenging for Stevens‒Johnson syndrome-toxic epidermal necrolysis. In this study, we enrolled 63 patients (39 with Stevens‒Johnson syndrome-toxic epidermal necrolysis, 13 with drug reaction with eosinophilia and systemic symptoms, and 11 with morbilliform drug eruption) and 30 tolerant controls to examine the performance of lymphocyte activation tests by measuring the expression of granulysin, granzyme B, and IFN-γ. Granulysin-based lymphocyte activation tests displayed the best sensitivity and specificity to identify the causality: 73.9% sensitivity and 96.7% specificity for carbamazepine and 68.2% sensitivity and 96.7% specificity for phenytoin. Oxcarbazepine and lamotrigine show weak antigenicity. Granulysin-based lymphocyte activation tests expanded predominantly memory cytotoxic T lymphocytes with characteristics of drug-specific T-cell receptor, major histocompatibility complex I dependence, and cross reactivity to different aromatic AEDs. Among 29 follow-up patients, 28 alternatively used nonaromatic AEDs, and none developed cutaneous adverse drug reactions. Our data suggest that granulysin-based lymphocyte activation tests represent in vitro cytotoxic T-lymphocyte memory response to offending drugs and are useful to confirm drug causality of AED-induced severe cutaneous adverse reactions. Implementing these tests will improve the AED-induced severe cutaneous adverse reactions prevention and clinical care., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Antiseizure medications (ASMs) are frequently implicated in T cell-mediated drug hypersensitivity reactions and cause skin tropic pathologies that range in severity from mild rashes to life-threatening systemic syndromes. During the acute stages of the more severe manifestations of these reactions, drug responsive proinflammatory CD8 + T cells display classical features of Th1 cytokine production ( e.g. IFNγ) and cytolysis ( e.g. granzyme B, perforin). These T cells may be found locally at the site of pathology ( e.g. blister cells/fluid), as well as systemically ( e.g. blood, organs). What is less understood are the long-lived immunological effects of the memory T cell pool following T cell-mediated drug hypersensitivity reactions. In this study, we examine the ASM carbamazepine (CBZ) and the CBZ-reactive memory T cell pool in patients who have a history of either Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from 3-to-20 years following their initial adverse reaction. We show that in vitro drug restimulation of CBZ-reactive CD8 + T cells results in a proinflammatory profile and produces a mainly focused, yet private, T cell receptor (TCR) usage amongst human leukocyte antigen (HLA)-B*15:02-positive SJS or TEN patients. Additionally, we show that expression of these CBZ-reactive TCRs in a reporter cell line, lacking endogenous αβTCR, recapitulates the features of TCR activation reported for ASM-treated T cell lines/clones, providing a useful tool for further functional validations. Finally, we conduct a comprehensive evaluation of the HLA-B*15:02 immunopeptidome following ASM (or a metabolite) treatment of a HLA-B*15:02-positive B-lymphoblastoid cell line (C1R.B*15:02) and minor perturbation of the peptide repertoire. Collectively, this study shows that the CBZ-reactive T cells characterized require both the drug and HLA-B*15:02 for activation and that reactivation of memory T cells from blood results in a focused private TCR profile in patients with resolved disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mifsud, Illing, Lai, Fettke, Hensen, Huang, Rossjohn, Vivian, Kwan and Purcell.)

Background: Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied., Objective: To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms., Methods: Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor α, interleukin (IL) 6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including 3 with acute pancreatic injuries., Results: Acute pancreatic injury was diagnosed in 7.3% of patients (9/124) in the SJS/TEN cohort. Elevation of serum transaminase level and hypoalbuminemia occurred more frequently in patients with acute pancreatic injuries compared with those without pancreatic symptoms (P = .004 and <.001, respectively). Although acute pancreatic injury did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = .008). Within the serum cytokines whose levels were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with acute pancreatic injuries compared with those without them (P = .03)., Limitations: Cohort was small., Conclusion: Acute pancreatic injury is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are Severe Cutaneous Adverse Reactions (SCARS) characterized by fever and mucocutaneous lesions leading to necrosis and sloughing of the epidermis. Conjunctival lesions are reported in 85% of patients. The pathogenesis of SJS/TEN/SCARS is not completely understood. It is hypothesized that IL-13, IL-15 and Granulysin expressed in plasma and skin may play a role. We measured the circulating levels of these cytokines in the plasma using ELISA and their expression in the skin using immunofluorescence microscopy. A total of 12 SJS/TEN skin biopsy samples (8 SJS, 2 SJS/TEN overlap and 2 TEN) were analyzed. Biopsy samples from patients with Lichen Planus (an inflammatory condition of the skin and mucous membranes) served as controls. Studies were also performed in human corneal epithelial cells where expression of these cytokines were measured following a challenge with TNF-α (0, 1, 10 and 100 ng/ml). The intensity of immunofluorescence was measured Using Imaris® software. The results showed significantly increased expression of these cytokines in the skin biopsy samples as measured by the average intensities of IL-13 (6.1 x 133.0 ± 4.231 x 10^8), and Granulysin (4.2 x 123.0 ± 4.231 x 10^8) compared to Lichen planus control (3.0 x 123.0 ±1.62 x 10^5). Increased expression of IL-13 and IL-15 were noted in cell culture studies and in the plasma samples when compared to Normal Human Plasma as controls. It is concluded that IL-13, IL-15 and Granulysin play a role in the pathogenesis of SJS/TEN.

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., (© 2019 Japanese Dermatological Association.)

Background: Sepsis is the main cause of death in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)., Objectives: Our aim was to identify admission risk factors predictive of bacteremia and the accompanying clinical or biochemical markers associated with positive blood cultures., Methods: A retrospective cohort study over a 14-year period (2003-2016) was performed., Results: The study included 176 patients with SJS (n = 59), SJS-TEN overlap (n = 51), and TEN (n = 66). During hospitalization, bacteremia developed in 52 patients (29.5%), who experienced poorer outcomes, including higher intensive care unit admission (P < .0005), longer length of stay (P < .0005), and higher mortality (P < .0005). There were 112 episodes of bacteremia, and isolates included Acinetobacter baumannii (27.7%, n = 31) and Staphylococcus aureus (21.4%, n = 24). On multivariate analysis, clinical factors present at admission that were predictive of bacteremia included hemoglobin ≤10 g/dL (odds ratio [OR] 2.4, confidence interval [CI] 2.2-2.6), existing cardiovascular disease (OR 2.10, CI 2.0-2.3), and body surface area involvement ≥10% (OR 14.3, CI 13.4-15.2). The Bacteremia Risk Score was constructed with good calibration. Hypothermia (P = .03) and procalcitonin ≥1 μg/L (P = .02) concurrent with blood culture sampling were predictive of blood culture positivity., Limitations: This is a retrospective study performed in a reference center., Conclusion: Hemoglobin ≤10 g/dL, cardiovascular disease, and body surface area involvement ≥10% on admission were risk factors for bacteremia. Hypothermia and elevated procalcitonin are useful markers for the timely detection of bacteremia., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: High-mobility group box 1 (HMGB1) is a damage-associated molecular-pattern protein. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are serious, immune-mediated skin-blistering conditions., Objectives: To determine serum and/or blister-fluid total HMGB1 levels in SJS/TEN cohorts, and HMGB1 expression in formalin-fixed, paraffin-embedded (FFPE) SJS/TEN skin vs. healthy and maculopapular exanthema (MPE) skin. Methods Serum HMGB1 was quantified in Malawian nevirapine-induced hypersensitivity, Taiwanese SJS/TEN and Spanish SJS/TEN cohorts. FFPE skin (healthy skin, MPE, SJS/TEN) was stained and assessed for HMGB1 expression., Results: Serum total HMGB1 was not significantly elevated in patients with nevirapine-induced SJS/TEN (3·98 ± 2·17 ng mL -1 ), MPE (3·92 ± 2·75 ng mL -1 ) or drug reaction with eosinophilia and systemic symptoms (4·73 ± 3·00 ng mL -1 ) vs. tolerant controls (2·97 ± 3·00 ng mL -1 ). HMGB1 was significantly elevated in Taiwanese patients with SJS/TEN, highest during the acute phase (32·6 ± 26·6 ng mL -1 ) vs. the maximal (19·7 ± 23·2 ng mL -1 ; P = 0·007) and recovery (24·6 ± 25·3 ng mL -1 ; P = 0·027) phases. In blister fluid from Spanish patients with SJS/TEN, HMGB1 (486·8 ± 687·9 ng mL -1 ) was significantly higher than in serum (8·8 ± 7·6 ng mL -1 ; P <0·001). Preblistered SJS/TEN skin showed decreased epidermal nuclear HMGB1 expression in upper epidermis vs. healthy or MPE skin but retained basal/suprabasal expression., Conclusions: Epidermal HMGB1 expression was decreased in SJS/TEN skin. Retained basal/suprabasal epidermal HMGB1 expression may exacerbate localized injury in SJS/TEN., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Severe cutaneous adverse reactions (SCARs) are frequent in inpatient oncology. Early intervention might reduce morbidity, mortality, and hospitalization costs; however, current clinical and histologic features are unreliable SCAR predictors. There is a need to identify rational markers of SCARs that could lead to effective therapeutic interventions., Objective: To characterize the clinical and serologic features of hospitalized patients with cancer who developed SCARs., Methods: Retrospective review of 49 hospitalized cancer patients with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL] 6, IL-10, and tumor necrosis factor [TNF] α) or elafin, and a prior dermatology consultation. Patients were categorized as having a simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement., Results: Fifteen out of 49 patients (30.6%) were deceased at 6 months from time of dermatologic consultation. Elafin, IL-6, and TNF-α were significantly higher in patients who died compared with patients who were still alive at 6 months. IL-6 and IL-10 were significantly higher in patients with a drug-related complex rash., Limitations: Retrospective design, limited sample size, and high-risk patient population., Conclusion: In cancer patients with SCARs, elafin, IL-6, and TNF-α levels might predict a poor outcome. Agents directed against these targets might represent rational treatments for the prevention of fatal SCARs., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2018 Japanese Dermatological Association.)

Based on a representative case, which was treated in our center for severe burn injuries, the severity of the Waterhouse-Friderichsen syndrome and the complexity of the prolonged course of treatment are illustrated. Special attention is focused on the new treatment paradigm using the CytoSorb® adsorber.

Background: 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., Aim: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2017 British Association of Dermatologists.)

Background/objectives: Keratinocyte death is a hallmark of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). Apoptotic signal-associated cytokines, such as TNF-α, sFasL, granulysin, sTRAIL and IFN-γ have been reported to participate in keratinocyte apoptosis. However, their levels are variable, which hampers the elucidation of the role of these cytokines. We sought to determine whether cytokine levels vary with disease course., Methods: The serum cytokine levels of 24 patients and blister fluid of 10 were analysed by enzyme-linked immunosorbent assay on the first day of their admission to hospital and were evaluated at different time points in the disease course. Meanwhile, surface markers (CD3, CD4, CD8, CD1a, CD14, CD16+56 and CD68) of blister fluid cells were measured by flow cytometry., Results: The concentrations of all cytokines in the serum and blister fluid were higher than those in the controls and were more elevated in the blister fluid than in the serum. Moreover, sTRAIL, IFN-γ and TNF-α quantities were relatively stable, while those of sFasL and granulysin decreased rapidly in the disease course. On the first day, CD8+ T and natural killer cells were predominant in the blister fluid but their relative percentage diminished gradually, while that of CD14+ cells increased., Conclusion: Our study confirmed there are high but variable levels of these cytokines in SJS/TEN, especially in the early phase and different tendencies are manifested in the disease course., (© 2016 The Australasian College of Dermatologists.)

Early diagnosis and prognosis monitoring for Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN) still remain a challenge. This study aims to explore any cytokine/chemokine with prognostic potential in Stevens-Johnson syndrome/TEN. Through screening a panel of 28 serological factors, IL-6, IL-8, IL-15, tumor necrosis factor-α, and granulysin were upregulated in patients with Stevens-Johnson syndrome/TEN and selected for the further validation in total 155 patients with Stevens-Johnson syndrome/TEN, including 77 from Taiwan and 78 from the Registry of Severe Cutaneous Adverse Reactions. Among these factors evaluated, the levels of IL-15 (r = 0.401; P < 0.001) and granulysin (r = 0.223; P = 0.026) were significantly correlated with the disease severity in 112 samples after excluding patients with insufficient data to calculate the score of TEN. In addition, IL-15 was also associated with mortality (P = 0.002; odds ratio, 1.09; 95% confidence interval, 1.03-1.14; P = 0.001; adjusted odds ratio, 1.10; 95% confidence interval, 1.04-1.16). Consistent results were obtained after the exclusion of Taiwanese patients with sepsis to rule out possible confounders. Moreover, IL-15 was shown to enhance cytotoxicity of cultured natural killer cells and blister cells from patients with TEN. Our findings highlight a usefulness of IL-15 in prognosis monitoring and therapeutic intervention of this devastating condition., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe mucocutaneous reactions that incur high mortality, and in which the systemic application of corticosteroids remains controversial., Objective: This study aimed to determine the optimal protocols for the use of corticosteroids and treatment measures., Methods: We performed a retrospective analysis of 70 patients with SJS/TEN who were hospitalized between January 2008 and May 2015 in the Department of Dermatology, Shandong Provincial Hospital, and treated with corticosteroids. Expected and actual mortality rates in patients treated with different doses of corticosteroids, according to SCORTEN, were compared., Results: The diagnoses associated with initial corticosteroid use differed significantly between the low- and high-dose groups (P = 0.041). There were significant differences between expected and actual mortality rates according to the use of corticosteroid therapy (P = 0.0168, standardized mortality ratio [SMR] = 0.30). There was a statistical difference between expected and actual mortality rates in the low-dose group (P = 0.0145, SMR = 0.20). Serum albumin levels were significantly lower in patients administered corticosteroids additive therapy (31.12 ± 8.32 g/l vs. 35.54 ± 5.82 g/l; P = 0.016), and the rate of use of antibiotics was higher among patients in the additive therapy group than in the non-additive group (94.7% vs. 60.8%)., Conclusions: Our research supports the use of corticosteroids for the systemic treatment of SJS/TEN. Corticosteroids should be used in a timely manner and in accordance with disease severity, age, underlying diseases, serum albumin level, and concurrent treatment with antimicrobial therapy., (© 2016 The International Society of Dermatology.)

Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can be challenging to treat due to pain with wound care and ongoing fluid loss. The purpose of this study is to determine the role of porcine xenograft as a modality for wound coverage., Material and Methods: A retrospective review from 2006 to 2014 was performed at a regional burn center on all patients admitted with the diagnosis of SJS (<10% TBSA involvement), SJS/TEN overlap (10-30% TBSA involvement), and TEN (>30% TBSA involvement). Patients who received porcine xenograft had physiologic and biochemical parameters compared in the 24h before and after graft placement. In addition, xenograft patients were compared to historical controls that received traditional wound care which included silver impregnated dressings. Outcomes and variables collected included intravenous fluid given, urine output, pain scores (1-10), pain medication for wound care, biochemical markers, skin infections, hospital length of stay, and mortality., Results: Eight patients had placement of a porcine xenograft. Median age was 50 years (IQR 41, 66) and 2 were male. Median % TBSA affected was 76 (IQR 64, 80). The median amount of fluid (ml/kg/day/%TBSA) administered decreased from 1.45 (IQR 1.03, 1.78) to 0.9 (IQR 0.65, 1.08) after xenograft placement (p=0.02). The median amount of intravenous fluid (ml/kg/day/%TBSA) administered in the treatment group and historical control group was 0.9 (IQR 0.65, 1.08) and 0.8 (IQR 0.7, 1.47) respectively (p=0.72). The median amount of urine output (ml/kg/day) in the treatment group and historical control group was 34.2 (IQR 22, 44.38) and 22 (IQR 11.25, 38.13) respectively (p=0.17). Pain scores significantly decreased from 5.5 (IQR 2.5, 8.25) pre-xenograft to 2.8 (IQR 0.75, 4) post-xenograft placement (p=0.03). There was a significant difference in pain scores between the treatment group and historical control group, 2.8 (IQR 0.75, 4) and 6 (IQR 5, 8) respectively (p=0.02). Each study patient underwent moderate sedation for wound care prior to xenograft placement and one study patient required one moderate sedation for wound care after xenograft placement. One patient in the xenograft placement group was diagnosed with a cutaneous infection compared to 4 patients in the historical control group (p=0.63). The mortality was 12.5% in each group., Conclusions: Placement of a porcine xenograft in patients with SJS, SJS/TEN overlap, or TEN is associated with a significant reduction in intravenous fluid use, pain scores, and pain medication. Further study with larger sample sizes is warranted to evaluate for statistically significant differences in outcomes after porcine xenograft placement for SJS, SJS/TEN overlap or TEN., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs., Competing Interests: The authors have declared that no competing interests exist.

Objective: To describe a case of a possible incipient Stevens-Johnson reaction while a patient had been on a stable dose of lamotrigine for several months and to consider the likely cause., Methods: The history is recounted., Results: One likely cause implicates differing effective doses of lamotrigine across differing brands and raises quality control issues., Conclusion: The patient's severe reaction may reflect changing to a brand of lamotrigine that precipitously generated a higher serum level of lamotrigine., (© The Royal Australian and New Zealand College of Psychiatrists 2015.)

Background: Toxic epidermal necrolysis (TEN) is a lethal complication of drugs, thus early diagnosis and treatment are important. However, there are no satisfactory clinical biomarkers of TEN., Objectives: We investigated miR-124 and miR-214 expressions in serum and skin tissues of severe drug eruptions to evaluate the possibility of biomarkers of TEN., Materials & Methods: microRNAs were extracted from serum and skin tissues. Serum samples were obtained from 7 TEN patients, 5 Stevens-Johnson syndrome (SJS) patients, 11 erythema multiforme (EM) minor patients and 21 healthy volunteers. Skin tissues were obtained from 4 TEN patients, 3 SJS patients, 8 EM minor patients, 3 psoriasis and 3 atopic dermatitis patients. Six control skin samples were obtained. MicroRNA concentrations were determined by PCR array and real-time PCR., Results: The concentrations of miR-124 in sera from TEN were significantly higher than those from healthy controls. In the characteristics curve analysis of serum miR-124 for differentiating TEN patients from normal subjects, the area under curve was 0.94. The serum miR-124 concentration was strongly correlated with the erosion area and the SCORTEN scale. The expression of miR-214 was significantly increased in the skin of TEN., Conclusion: The serum miR-124 concentration can be used as a disease activity marker for severe drug eruptions, reflecting the severity of keratinocyte apoptosis.

Background: Skin infiltration of different types of T lymphocytes is responsible for inflammatory profiles of nonimmediate drug hypersensitivity reactions (niDHRs). Important chemokines attracting skin-specific homing T cells include thymus activation-regulated chemokine (TARC) and cutaneous T-cell-attracting chemokine (CTACK). Interleukin-10 (IL-10) is a potent chemokine attracting CD8(+) T cells., Objective: To investigate serum levels of TARC, CTACK, and IL-10 in patients with niDHRs and evaluate the correlation among these 3 chemokines., Methods: Forty patients, including 19 patients with Stevens-Johnson syndrome and toxic epidermal necrolysis and 21 patients with maculopapular exanthema, and 21 healthy donors were recruited into the study. Clinical data of patients were obtained. Serum TARC, CTACK, and IL-10 levels were determined by enzyme-linked immunosorbent assay., Results: Serum levels of TARC, CTACK, and IL-10 were significantly elevated in patients with niDHRs compared with those in normal controls (P < .05, P < .001, P < .001, respectively). The CTACK and IL-10 levels were significantly higher (P < .05, P < .001) in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis than in normal controls. Patients with maculopapular exanthema exhibited higher levels of TARC, CTACK, and IL-10 compared with normal controls (P < .001, P < .001, P < .05). Serum CTACK levels were positively correlated with TARC levels in all 40 patients (rs = 0.3422, P < .05). Serum CTACK levels positively correlated with detachment of body surface area in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (rs = 0.510, P < .05)., Conclusion: These results support a role for TARC, CTACK, and IL-10 in the pathogenesis of niDHRs for their chemotactic ability to attract different T-cell subtypes and different functional severities in niDHRs., (Copyright © 2014. Published by Elsevier Inc.)

Background: Here, we report the first case of patient with intracranial tumors (ICT) who developed a cutaneous adverse drug reaction during lansoprazole and prophylactic anticonvulsant treatment. SCORTEN is a scoring system used to predict mortality in TEN patients. If SCORTEN index is 5 or more, mortality rate is more than 90%. SCORTEN of our patient was calculated as 5., Methods: Our patient is a 64 year-old white female, who had glioma and had been on post-op prophylactic anticonvulsant therapy. On the 3rd day post operation, lansoprazole was added to the therapy. After the first lansoprazole dose, erythematous dusky red macules occurred on extremities and trunk and on the following day confluent purpuric lesions tended to run together in 95% of the whole body including scalp, oral and genital mucosa. Nikolsky's Sign was positive on the skin. Physical examination; body temperature was 38.4 degrees C with a heart rate of 146 beats/minute and 80/50 mm Hg arterial blood pressure, Glascow Coma Scale was E1 M1e, pupillary light reflex was 2/2 +/+ and she was confused. Her biopsy resulted as toxic epidermal necrolysis. Moreover, sTRAIL and sCD200 levels of serum and blister fluid were investigated as an apoptotic marker and a negative marker for inflammation., Results and Conclusions: sTRAIL and sCD200 were evaluated both in the sera and blister fluid. sTRAIL level was lower than for healthy individuals with high levels in blister fluid; and sCD200 level was depressed by up to 10% of the normal values of healthy individuals but with high levels in the blister fluid during the active phase of the disease. After our successful treatment with human albumin, prednisolone pulse therapy, and IVIG at a dose of 400 mg/kg, she was discharged from the hospital on the 23rd day and followed up after 2 months. The increase in sTRAIL (up to two-fold) and sCD200 (up to six-fold) levels may provide useful information in understanding disease pathogenesis and monitoring treatment efficacy.

Background: Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes., Objective: We investigated the pathogenic role of TARC in patients with DIHS., Methods: Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab., Results: Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS., Conclusion: Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS., (Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Cutaneous adverse drug reactions (CADRs) may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants., Aims: (a) to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition (LMI) response in these patients in response to the suspected drug (s), and (c) to look for the association between oxidative stress parameters and LMI., Methods: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A) during the acute phase of reaction and healthy control subjects (group B). MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients' peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation., Results: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001), but GSH levels were significantly reduced in group A when compared with group B (P = <0.001). LMI response against drug(s) was performed in 33 cases (group A), out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25), exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25), vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to be significantly higher in the LMI positive CADRs (P < 0.001) when compared with LMI-negative ones, while no significant difference was seen for GSH (P = 0.100). Furthermore, there was a significant positive correlation between MDA levels and LMI response (r = 0.831, P < 0.001). On the other hand, a negative but statistically insignificant correlation was found between GSH and LMI response (r = -0.248, P = 0.271)., Conclusion: CADR patients were found to be under oxidative stress based on MDA and GSH levels in the peripheral blood. There is a significant positive correlation of LMI response (against the causative drug) with MDA levels, which strongly associates oxidative stress with the immunopathogenesis in CADRs.

Background: Toxic epidermal necrolysis (TEN) is a rare life-threatening disorder characterized by extensive epidermal necrolysis. Its mortality which varies from 20% to 60% is related to risk factors such as age, extent of epidermal detachment, and base deficit., Objectives: The purpose of this study is to investigate the risk factors of mortality in our patients with TEN., Patients and Methods: From the year 2000 to 2006, the patients with TEN admitted to the National Taiwan University Hospital Burn Center were studied retrospectively using chart review. Eleven potential risk factors including age, gender, underlying disease, malignancy, extent of epidermal detachment, tachycardia, serum urea, glucose, base deficit, leucopenia, and intravenous infusion of immunoglobulin (IVIG) were analyzed. Patients were grouped into survivors (n ¼ 11) and nonsurvivors (n ¼ 5) after intensive care treatment. Logistic regression was used in multivariate analysis for identifying important predictors of mortality., Results: The mean age of the patients with TEN was 58 years, while the mean total body surface area of epidermal necrolysis was 66.3%. The overall mortality rate was 31.3%. Among the potential risk factors, only serum bicarbonate <20 mmol/L was found to have significant association with mortality (P ¼ .0128) in our patients with TEN. The odds of mortality in the patients with TEN having serum bicarbonate <20 mmol/L was 40 times higher than those without., Conclusion: This study has shown that serum bicarbonate <20 mmol/L is the most important risk factor of mortality in our patients with TEN and it may be used as a marker to predict hospital mortality.

Background: Life-threatening adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) sometimes start with clinical features of ordinary drug-induced skin reactions (ODSRs) and it may be difficult to make a correct diagnosis before severe mucocutaneous erosions occur. We have reported that serum granulysin levels are elevated (cut off: 10 ng/mL) in patients with SJS/TEN before generalized blisters form., Objective: We sought to develop a rapid detection system for elevated serum granulysin to predict the progression from ODSRs., Methods: Serum samples from 5 patients with SJS/TEN at 2 to 4 days before mucocutaneous erosions formed were analyzed. Sera from 24 patients with ODSRs and 31 healthy volunteers were also investigated as control subjects. We developed a rapid immunochromatographic assay for the detection of high levels of serum granulysin using two different antigranulysin monoclonal antibodies., Results: The immunochromatographic test showed positive results for 4 of 5 patients with SJS/TEN but only one patient of 24 with ODSRs. The results correlated closely with those of enzyme-linked immunosorbent assays., Limitations: The validation of the long-time stability in this test strip has not been investigated., Conclusion: This novel test enables the prediction of SJS/TEN occurrence in patients even when only features of ODSRs are noted clinically., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Toxic epidermal necrolysis (TEN) is a life-threatening, drug-induced disorder characterized by severe epidermal injury. Although there is no standard therapeutic intervention in TEN, plasmapheresis (PP) is being used increasingly to treat extremely ill TEN patients. In addition to conventional PP, double-filtration PP (DFPP) has been recently used for severe and refractory TEN. In this review, we focus on the clinical usefulness of PP by both demonstrating three cases of TEN refractory to conventional therapies, who were successfully treated with conventional PP or DFPP, and evaluating its therapeutic efficiency. We also provide evidence to suggest the mechanisms of action of PP by investigating the correlation between disease intensity and serum cytokine levels before and after treatment with PP or DFPP in these patients with TEN. At present, PP is a much more effective option for treatment of severe and/or recalcitrant TEN than any other treatment, such as pulsed corticosteroids and i.v. immunoglobulin., (© 2011 Japanese Dermatological Association.)

Background: Similar drugs (e.g. anticonvulsants) have been implicated in the development of two distinct forms of severe cutaneous drug reactions, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS)., Aim: To investigate immunological alterations and underlying viral infections that could contribute to the variability in the clinical presentations of these diseases., Methods: We retrospectively analysed clinical variables, serum immunoglobulin levels, numbers of circulating white blood cells, lymphocytes and their subsets, serum levels of several cytokines, and underlying viral infections in both drug reactions, using samples obtained at onset from 9 patients with SJS/TEN and 19 patients with DIHS/DRESS., Results: There were significant differences between the two drug eruptions in the duration of drug intake before onset, the levels of IgG, IgA and IgM, the numbers of circulating white blood cell, lymphocyte, CD3+ T cell and CD8+ T cells, the serum levels of interferon-γ, and the titres of anti-herpes simplex virus IgG at onset., Conclusions: The difference in the pattern of immune responses shaped in part by previous and underlying viral infections at the time of drug exposure could cause a marked deviation in the pathological phenotype of severe drug eruptions. Elucidating these host factors may provide a basis for therapeutic approaches in patients with severe drug reactions., (© 2010 The Author(s). Journal compilation © 2010 British Association of Dermatologists.)

Background: There are no evidence-based guidelines for the treatment of neonatal sepsis although standard text books recommend 14 days of antibiotics for blood culture-proven neonatal sepsis., Objective: The present study compared the effectiveness of a 10-day course of antibiotic therapy with the conventional 14-day course in blood culture-proven neonatal sepsis., Methods: Infants ≥ 32 weeks and ≥ 1.5 kg weight with blood culture-proven sepsis were randomized to either 10-day (study group) or 14-day (control group) therapy on Day 7 of appropriate antibiotic therapy, if they were in clinical remission and were C-Reactive Protein (CRP) negative. The primary outcome was treatment failure within 28 days defined by either positive CRP or positive blood culture or clinical relapse., Results: The baseline characteristics were comparable between the two groups. There was one treatment failure in each group. The duration of hospital stay was significantly shorter in the 10-day treatment group., Conclusion: Ten-day antibiotic therapy is as effective as 14-day therapy in blood culture-proven neonatal sepsis, if the infant has achieved clinical remission by Day 7 of therapy.

The coagulation system protects the body from uncontrolled blood loss by means of highly regulated processes. In case of an injury the coagulation system instantly switches from controlled blood flow to acute coagulation and thrombus formation with the goal of stopping the blood loss. Minor changes in this well-maintained equilibrium of coagulation and blood flow tip the balance towards uncontrolled blood loss or even fatal thromboembolic events. Iatrogenic manipulation of this highly regulated system is possible with a variety of therapeutic agents. We review the basics of coagulation physiology and then discuss dermatologically relevant aspects of thrombosis prevention, as well as the use of anticoagulants to treat dermatologic diseases.

We describe a patient originally suffering from a depressive syndrome who developed Stevens-Johnson syndrome after 12 days of treatment with lamotrigine. The clinical symptoms and the inflammation parameters neopterin and C-reactive protein were documented. Neopterin values showed a good correlation with the course of the disease, which, to the best of our knowledge, has not been reported previously. C-reactive protein followed the neopterin curve with a delay of 4 days. Since neopterin is a widely available parameter it should be considered as a routine measurement in this type of hyperergic reaction. It might help to identify the beginning, the maximum and the regression of the disease in order to support therapeutic decisions.