Stevens-Johnson Syndrome/toxic Epidermal Necrolysis Research Articles

Greater mechanistic understanding of the cutaneous pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis can shed light on novel therapeutic strategies: a comprehensive review.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (SCARs) characterized by widespread epithelial detachment and blistering, which affects the skin and mucocutaneous membranes. To date, therapeutic interventions for SJS/TEN have focused on systematic suppression of the inflammatory response using high-dose corticosteroids or intravenous immunoglobulin G (IgG), for example. No targeted therapies for SJS/TEN currently exist. Though our understanding of the pathogenesis of SJS/TEN has advanced from both an immunological and dermatological perspective, this knowledge is yet to translate into the development of new targeted therapies. Greater mechanistic insight into SJS/TEN would potentially unlock new opportunities for identifying or repurposing targeted therapies to limit or even prevent epidermal injury and blistering.

Risk factors for the development of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, following drug administration: a systematic review and meta-analysis.

Risk factors for the development of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, following drug administration: a systematic review and meta-analysis.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study

PurposeTo compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis...

British Association of Dermatologists national clinical audit on the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards. To audit current management of SJS/TEN in adults against standards in the BAD guidelines. BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022. Thirty-nine (29%) dermatology centres in the UK participated and data for 147 adults with SJS/TEN were collected. Within 24 hours of the diagnosis being made or suspected, the following were documented: SCORTEN for 52% (76/147) of submitted cases, list of medications for 77% (113/147) and timelines for commencement/alterations of medications for 71% (104/147). Initial assessment was documented of the eyes by an ophthalmologist for 48% (71/147) of cases, mouth in 88% (130/147), genital skin in 70% (103/147) and the urinary tract in 63% (93/147). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 18% (26/147) of cases, eyes in 8% (12/147) and urinary tract and genital skin in 10% (14/147). Documentation regarding advice on i) avoidance of the culprit drug was present for 58% (76/130) and ii) requesting a MedicAlert® bracelet/amulet in 6% (9/147). This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and request for a MedicAlert® bracelet/amulet.

Updates in SJS/TEN: collaboration, innovation, and community.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Correlations between histopathologic findings, serum biomarker levels, and clinical outcomes in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.

Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA-B*1502 genotyping in Taiwan, 2000-2017: A nationwide longitudinal study.

The HLA-B*1502 allele is strongly associated with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA-B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA-B*1502 genotyping before prescribing CBZ was reimbursed in June 2010. Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score-based stabilized weighting (PSSW) ensured well-balanced covariates. The difference in 3-month SCAR and SJS/TEN rates between phase 2 (2011-2017) and phase 1 (2000-2009) was examined using a one-sample Z-test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA-B*1502 genotyping. CBZ prescriptions reduced from 7% (2000-2003) to 6% (2004-2010) and 4% (2011-2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3-month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = -.38, p = .0342) and nonusers (r = -.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates. Recognizing HLA-B*1502 allele and avoiding CBZ therapy in HLA-B*1502-positive patients is critical for preventing CBZ-induced severe adverse events.

Cost-effectiveness of HLA-B*58:01 testing to prevent Stevens-Johnson syndrome/toxic epidermal necrolysis in Vietnam.

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND)14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

Insights into Stevens-Johnson syndrome/toxic epidermal necrolysis lifetime burden: assessing life expectancy, healthcare costs and quality of life.

This study highlights the need for further exploration of factors that influence the declining incidence rate of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), interventions to mitigate loss-of-life expectancy and healthcare costs, and impact on quality of life. The findings emphasize the importance of ongoing efforts to minimize the burden of SJS/TEN and optimize patient care.

Lamotrigine-induced Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (SJS/TEN) overlap with transaminitis in an Asian female: a case report

Background: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) is a dermatologic emergency characterized by extensive epidermal detachments. The most frequent etiology is drug reaction within an interval of the last 8 weeks. SJS/TEN may occur in any age, race, and gender; however, there is an increased risk in patients over 65. SJS and TEN are differentiated based on the extent of epidermal detachments, which is &lt;10% in SJS, 10-30% in SJS-TEN overlap, and &gt;30% in TEN. This case study aims to evaluate the Lamotrigine-induced Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (SJS/TEN) overlap with transaminitis in an Asian female. Case Presentation: A 34-year-old woman presented with a pruritic and burning rash on almost all body parts. The suspected causative drug was lamotrigine, which she consumed within the last 2 weeks. Mucosal involvement was also found on the lips and genital mucosal. The affected body surface area was approximately 20%, with a positive Nikolsky sign. Laboratory studies showed elevated liver function tests. Based on the history, physical examination, and biopsy, the patient was diagnosed with SJS/TEN overlap. The suspected causative drug was immediately stopped, and supportive and systemic corticosteroid treatments were provided. The SCORTEN was 2, with a mortality rate of 12.1%. After a few days, the patient's condition had improved, the liver function test was normal, and there was no significant complication. Conclusion: SJS-TEN is a part of epidermal necrolysis, characterized by an extensive epidermal detachment. The management of SJS/TEN includes early detection, immediately stopping the suspected drugs, administering systemic corticosteroids, and other supportive treatments.

Neutrophil-to-lymphocyte ratio (NLR) in dermatology perspective: a review

The neutrophil-to-lymphocyte ratio (NLR) is the ratio between the number of neutrophils and lymphocytes in the peripheral blood. Neutrophils are responsible for an initial immune response to pathogens that enter the body through the mechanisms of chemotaxis, phagocytosis, the release of reactive oxygen species (ROS), granular proteins, production and release of cytokines. Neutrophils also have an important role in the occurrence of the systemic inflammatory response (SIRS). There are several types of diseases in the field of dermatology that are also related to NLR. It is associated with the presence of an inflammatory process. In addition, NLR is considered an easy, inexpensive, and reproducible parameter associated with clinical outcomes and disease severity. Several diseases in the field of dermatology found to be associated with NLR include leprosy, Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), psoriasis, vitiligo, atopic dermatitis, systemic sclerosis, and skin cancer. In recent years, its role as an independent prognostic factor for neoplasms and as an inflammatory biomarker in various acute and chronic diseases has been increasingly established in the dermatology field. However, not all studies have found significant results. One of them is vitiligo which still finds controversial results. For this reason, this literature review will discuss specifics related to several diseases in dermatology associated with NLR.

Assessment of Need for Improved Identification of a Culprit Drug in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug. To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification. This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women's Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN. This study descriptively analyzed potential culprits to SJS/TEN, patients' allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes. Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians' approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited. The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.

Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01

Allopurinol, widely used in gout treatment, is the most common cause of severe cutaneous adverse drug reactions. The risk of developing such life-threatening reactions is increased particularly for HLA-B*58:01 positive individuals. However the mechanism of action between allopurinol and HLA remains unknown. We demonstrate here that a Lamin A/C peptide KAGQVVTI which is unable to bind HLA-B*58:01 on its own, is enabled to form a stable peptide-HLA complex only in the presence of allopurinol. Crystal structure analysis reveal that allopurinol non-covalently facilitated KAGQVVTI to adopt an unusual binding conformation, whereby the C-terminal isoleucine does not engage as a PΩ that typically fit deeply in the binding F-pocket. A similar observation, though to a lesser degree was seen with oxypurinol. Presentation of unconventional peptides by HLA-B*58:01 aided by allopurinol contributes to our fundamental understanding of drug-HLA interactions. The binding of peptides from endogenously available proteins such as self-protein lamin A/C and viral protein EBNA3B suggest that aberrant loading of unconventional peptides in the presence of allopurinol or oxypurinol may be able to trigger anti-self reactions that can lead to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

TNF-α induced extracellular release of keratinocyte high-mobility group box 1 in Stevens-Johnson syndrome/toxic epidermal necrolysis: Biomarker and putative mechanism of pathogenesis.

Decreased epidermal high-mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Etanercept, an anti-tumor necrosis factor therapeutic, is effective in the treatment of SJS/TEN. The objective was to characterize antitumor necrosis factor-alpha (TNF-α)-mediated HMGB1 keratinocyte/epidermal release and etanercept modulation. HMGB1 release from TNF-α treated (± etanercept), or doxycycline-inducible RIPK3 or Bak-expressing human keratinocyte cells (HaCaTs) was determined by western blot/ELISA. Healthy skin explants were treated with TNF-α or serum (1:10 dilution) from immune checkpoint inhibitor-tolerant, lichenoid dermatitis or SJS/TEN patients ± etanercept. Histological and immunohistochemical analysis of HMGB1 was undertaken. TNF-α induced HMGB1 release in vitro via both necroptosis and apoptosis. Exposure of skin explants to TNF-α or SJS/TEN serum resulted in significant epidermal toxicity/detachment with substantial HMGB1 release which was attenuated by etanercept. Whole-slide image analysis of biopsies demonstrated significantly lower epidermal HMGB1 in pre-blistered SJS/TEN versus control (P < 0.05). Keratinocyte HMGB1 release, predominantly caused by necroptosis, can be attenuated by etanercept. Although TNF-α is a key mediator of epidermal HMGB1 release, other cytokines/cytotoxic proteins also contribute. Skin explant models represent a potential model of SJS/TEN that could be utilized for further mechanistic studies and targeted therapy screening.

Severe Cutaneous Adverse Drug Reactions at a Tertiary Care Center in Saudi Arabia.

Severe cutaneous adverse drug reactions (SCARs), although rare, are known to be associated with significant morbidity and mortality. SCARs include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and acute generalized exanthematous pustulosis (AGEP). Studies on SCARs are limited in Saudi Arabia. This study aims to characterize SCARs at a tertiary care center in Saudi Arabia. A cross-sectional study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia. All inpatient and emergency department consultations to dermatology were electronically reviewed during the period from January 2016 to December 2020. All patients who developed an adverse cutaneous drug reaction were enrolled. Detailed analysis was performed only for SCARs. The culprit medication was determined based on the latency period, history of previous intake of the medication, and drug notoriety. There were 3050 hospital consultations to dermatology during the study period. Cutaneous adverse drug reactions constituted 253 (8.3%) cases. A total of 41 patients with SCARs were identified, accounting for 16.2% of all cutaneous drug reactions. Antibiotics and anticonvulsants were the most common causative drug groups accounting for 28 (68.3%) and 9 (22%) cases, respectively. DRESS was the most common SCAR. The latency period was the longest for DRESS and shortest for AGEP. Vancomycin was responsible for approximately a third of DRESS cases. Piperacillin/tazobactam was the most common cause for SJS/TEN and AGEP. The majority of drugs causing AGEP were antibiotics. The mortality rate was the highest in SJS/TEN (5/11 (45.5%)), followed by DRESS (1/23 (4.4%)) and AGEP (1/7 (14.3%)). SCARs are rare in Saudis. DRESS appears to be the most common SCAR in our region. Vancomycin is responsible for most cases of DRESS. SJS/TEN had the highest mortality rate. More studies are required to further characterize SCARs in Saudi Arabia and Arabian Gulf countries. More importantly, thorough studies of HLA associations and lymphocyte transformation tests among Arabs with SCARs are likely to further improve patient care in the Arabian Gulf region.

Nutritional and metabolic characteristics of critically ill patients admitted for severe toxidermia

Drug-induced toxidermia is an idiosyncratic adverse skin reaction that may become life-threatening in a small portion of patients, requiring intensive care unit (ICU) admission. The treatment recommendations are extrapolated from those of major burns, while prospective data remain sparse. The objective was to observe the application of these recommendations in patients treated in a burn ICU. Retrospective cohort study including patients requiring ICU between 2006 and 2020 in a tertiary university hospital. Age >18 years. Patients were categorized as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), or other toxidermia. severity scores, body surface area (BSA) involvement, nutritional and metabolic variables, trace element status, outcome variables. Descriptive statistics: median [IQR]. Altogether 35 patients were included (27 SJS/TEN and 8 "other"), aged 58 [48; 69] years. Skin involvement was 45% [30; 60] of body surface, 17 patients required mechanical ventilation, and length of ICU stay was 16 [6.5; 26] days. Hospital mortality was 23%. Fluid resuscitation requirements were moderate, despite intense inflammation (admission CRP (144 [89; 218] mg/L). The first 2 weeks' energy and protein intakes were below recommendations (p<0.0001), lowest with oral feeding. Indirect calorimetry showed high energy expenditure in 11 patients (30.4 [23.9; 35.5] kcal/kg) resulting in negative energy balances (mean-245 kcal/day). Copper and zinc levels were below reference range during the first week, the low copper values being a novel finding. Trace elements should be monitored. The cohort was underfed with intakes lower than our ICU protocols, partly explained by short intubation times, and mucocutaneous involvement complicating the management and placement of feeding tubes. Oral feeding was least efficient and may become an indication for supplemental parenteral nutrition in the absence of an enteral feeding tube. gov Identifier: NCT05320653.

Exosomal microRNAs from PBMCs stimulated with culprit drugs enhanced keratinocyte cell death in Stevens-Johnson syndrome/toxic epidermal necrolysis.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are both severe cutaneous adverse reactions. Keratinocyte death is much more prominent in SJS/TEN compared to DRESS. This study aimed to investigate the role of exosomal miRNAs on keratinocyte death in SJS/TEN. Peripheral blood mononuclear cells (PBMCs) from SJS/TEN and DRESS patients were stimulated with the culprit drugs. The exosomes released in cell supernatants were co-incubated with HaCaT cells to study the cytotoxic effects on keratinocytes. Exosomal miRNA sequencing analysis was performed to compare the expression patterns between SJS/TEN and DRESS subjects. HaCaT cells were then transfected with miRNA mimics and inhibitors to explore the functions of miRNAs on keratinocyte cell death. Cytotoxic effects of PBMC-derived exosomes on keratinocytes were demonstrated in SJS/TEN and could be neutralized with exosome inhibitors. Cytotoxic effects of PBMC-derived exosomes from SJS/TEN subjects were higher after incubating PBMCs with the culprit drugs than those incubating with irrelevant drugs and unstimulated controls. The sequencing data revealed differential expressions of 61 exosomal miRNAs between SJS/TEN and DRESS. Exosomal miR-4488 was upregulated while miR-486-5p, miR-96-5p and miR-132-3p were downregulated in SJS/TEN compared to DRESS as determined by quantitative real-time PCR. The increased percentage of apoptotic cells upon transfection of HaCat cells was 36.3% and 34.9% with miR-4488 mimic and miR-96-5p inhibitor, respectively. This study illustrated the regulatory functions of exosomal miRNAs in controlling keratinocyte death in SJS/TEN. Exosome inhibitors might have a therapeutic role in SJS/TEN.

Sutureless Amniotic Membrane Transplantation Using Pediatric Nasogastric Tube for Patients With Acute Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Evaluation of the results of sutureless amniotic membrane transplantation (AMT) using a pediatric nasogastric tube (NGT) for patients with acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) was aimed. Twenty-six eyes of 13 patients with SJS/TEN with ocular involvement at a single tertiary care hospital between May 2020 and January 2022 were included in the study. An amniotic membrane was implanted to the ocular surface and conjunctival fornix using a modified symblepharon ring (MR) created by inserting NGT end-to-end. Patients were followed for at least 6 months. The mean duration of the surgery was recorded. The presence of corneal epithelial defect and vascularization, meibomian gland dysfunction (MGD) grade, conjunctival scarring, eyelid margin keratinization, symblepharon, and trichiasis were recorded. The mean age of the patients was 38.4±17.6 years. Amniotic membrane transplantation was performed only once for eight patients and twice for five patients. The mean duration of the surgery was 3.2±0.4 min. The modified symblepharon ring was removed 28 days after its application. At the first examination, 20 eyes (76.9%) had a corneal epithelial defect and 6 (23.1%) had early symblepharon. At the postoperative 6 months, although seven eyes (26.9%) had conjunctival scarring and 5 (19.2%) had eyelid margin keratinization, all patients were without any corneal defect, corneal vascularization, or symblepharon. Only 11 eyes (42.3%) showed MGD, and 1 eye (3.8%) showed trichiasis. This study showed that sutureless AMT using pediatric NGT could be a potentially fast and inexpensive treatment option for the treatment of SJS/TEN with ocular involvement at the bedside without the need for general anesthesia.

Drug-Induced Reaction With Eosinophilia and Systemic Symptoms: A Review.

Drug-induced reaction with eosinophilia and systemic symptoms (DRESS) is a part of severe cutaneous adverse reactions (SCAR), often a life-threatening condition. DRESS is an uncommon reaction; however, it is more prevalent than Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and is left undiagnosed due to its atypical clinical presentation. So far, no standard criteria or investigational tool assists in early and accurate diagnosis. The administration of systemic corticosteroids remains the widely used first line of management. However, new studies have revealed other potential treatment armamentariums. Because of the potential life-threatening outcome, every physician who deals with acute cases should be familiar with the clinical presentation and be able to start the necessary measurements.Recent studies revealed important information in the pathogenesis and management of the disorder were summarized in this review.