Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

Effectiveness of early treatment with plasma exchange in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially fatal medical conditions that lack established treatment. Therapeutic plasma exchange (PE) is a potential treatment option; however, its effectiveness is unclear. We aimed to evaluate the effectiveness of PE in patients with SJS/TEN. A retrospective cohort study was conducted using data from the Japanese National Administrative Claims database from 2016 to 2021. The analysis included 256 patients diagnosed with SJS/TEN who were admitted to the intensive care unit, of whom 38 received PE and 218 did not. The outcomes of patients who did and did not receive PE within the first 24 h of admission were compared. The risk ratios and 95% confidence intervals of the PE group compared with those of the no-PE group were as follows: in-hospital mortality, 0.983 (0.870-1.155); 30-day mortality rate, 1.057 (0.954-1.217); 50-day mortality rate, 1.023 (0.916-1.186); and length of hospital stay, 1.163 (0.762-1.365). This study does not provide evidence of a benefit of PE in reducing mortality or length of hospital stay in patients with severe SJS/TEN.

Immune checkpoint inhibitor-induced epidermal necrolysis: A narrative review evaluating demographics, clinical features, and culprit medications.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but can cause immune-related adverse events (irAEs). Severe cutaneous irAEs, including epidermal necrolysis, are rare but potentially life-threatening. There is limited understanding of the clinical features and management of ICI-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), so we aimed to analyze 95 cases of ICI-induced SJS/TEN (35 cases of SJS, 26 cases of TEN, two cases of SJS/TEN overlap, and 32 cases of unspecified) to increase knowledge of this condition among oncologists and dermatologists. We conducted a comprehensive search of PubMed for all relevant case reports published until the end of December 2022, and collected data on patient demographics, cancer type, ICI regimen, time to onset of SJS/TEN, clinical presentation, management strategies, and outcomes. PD-1 inhibitors were the most common ICIs associated with SJS/TEN (58.9%), followed by the combination of PD-1 and CTLA-4 inhibitors (11.6%), and PD-L1 inhibitors (6.3%). Lung cancer and melanoma were the most frequent malignancies treated (35.8% and 25.4%, respectively). SJS/TEN occurred most frequently within the first 4 weeks (51.7%), and corticosteroid monotherapy was the most commonly chosen systemic treatment (56.4%). The overall mortality rate of ICI-induced SJS/TEN was 30.8%. Our findings highlight the frequency and severity of ICI-induced SJS/TEN and the urgent need for predictive molecular biomarkers aimed at preventive measures and early intervention.

Outcomes in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Patients Treated With a Medicine-Led Multidisciplinary Approach.

Patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have traditionally been treated in burn centers. Our burn center's approach differs by admitting these patients to a medicine service, with support from the burn team. The aim of this study was to determine whether SJS/TEN patients cared for with our system, with burn involvement but not burn admission, demonstrate equivalent outcomes. We conducted a retrospective review of all SJS/TEN patients admitted to the medicine service at a single academic medical center from 2009 to 2021. Outcome measures such as mortality, length of ICU stay, and total length of hospitalization were collected. The Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) was used to calculate expected mortality rates within the cohort. The observed mortality rates were then compared to the expected mortality rates. One hundred and twenty-six patients who were admitted for SJS/TEN were included (70 SJS, 40 SJS/TEN overlap, 16 TEN). The mortality rate for the entire cohort was 10.32% as compared to a 22.33% expected mortality rate (P = .010). The observed and expected mortality rates for SJS, SJS/TEN overlap, and TEN subgroups were 1.43% observed versus 10.22% expected (P = .029), 20.00% observed versus 35.83% expected (P = .133), and 25.00% observed version 44.06% expected (P = .264), respectively. Mortality rates in SJS/TEN patients admitted to medicine units are equivalent or decreased as compared to SCORTEN-predicted mortality rates. Admission of SJS/TEN patients to a medicine unit is appropriate providing there is burn team involvement in their care.

Anesthesia management in a child with mucopolysaccharidosis and toxic epidermal necrolysis: A case report.

Toxic epidermal necrolysis and mucopolysaccharidosis are both rare diseases that pose significant airway maintenance challenges to anesthesiologists. In this report, we describe the anesthesia management in a 4-year-old male with mucopolysaccharidosis type II who developed toxic epidermal necrolysis and presented for ophthalmic surgical procedures. Combined use of propofol and ketamine with the support of high-flow nasal oxygen enabled adequate analgesia and sedation while maintaining spontaneous ventilation and airway patency. The strategy presented in this report may contribute to enhancing the safety of sedation in spontaneously breathing children with abnormal airways.

Stevens-Johnson syndrome and toxic epidermal necrolysis: 11-year retrospective experience in a high-complexity tertiary hospital in Milan, Italy.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced hypersensitivity reactions characterized by widespread epidermal necrosis, mucous membrane erosions, and systemic findings. We have provided our 11-year experience from a Milan, Italy tertiary hospital managing SJS/TEN, evaluating the clinical and histopathologic features plus the impact on mortality. We retrospectively analyzed 28 patients diagnosed with SJS/TEN based on the clinical and histopathologic findings, according to the classification criteria of multiple studies. We assessed the dermatographics, comorbidities, drug history, lesion characteristics, clinical findings, treatments, blood tests, and outcomes. Severity scores (SCORTEN, Re-SCORTEN, ABCD-10) were used for treatment evaluation and mortality prediction. Data were statistically analyzed, and significant factors associated with mortality were identified. We found that among the 28 patients, 89.2% had comorbidities, mainly cardiovascular diseases, and 21.4% had autoimmune disorders. All patients had received systemic therapy (46.6% monotherapy, 53.6% combination therapy), with systemic steroids (71.4%) and intravenous immunoglobulins (67.8%) being common treatments. There were complications, including systemic infections (67.9%) and septic shock (10.7%). The overall mortality rate was 17.8%. The statistical analysis indicated that malignancy, a high ABCD-10 score, and a high neutrophil-to-lymphocyte ratio were significantly associated with mortality. The extent of affected body surface area did not correlate significantly with mortality. This study provides insights into SJS/TEN management, revealing factors influencing mortality in a high-complexity tertiary hospital setting.

Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment.

New insights into the diagnosis and management of Stevens-Johnson syndrome and toxic epidermal necrolysis.

PURPOSE OF REVIEW: Recent studies have been clarifying the pathogenesis and early diagnostic markers of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Additionally, the efficacy of tumor necrosis factor alpha inhibitors is attracting attention. This review provides) recent evidence for the diagnosis and management of SJS/TEN. RECENT FINDINGS: Risk factors for the development of SJS/TEN have been identified, particularly the association between HLA and the onset of SJS/TEN with specific drugs, which has been intensively studied. Research on the pathogenesis of keratinocyte cell death in SJS/TEN has also progressed, revealing the involvement of necroptosis, an inflammatory cell death, in addition to apoptosis. Diagnostic biomarkers associated with these studies have also been identified. SUMMARY: The pathogenesis of SJS/TEN remains unclear and effective therapeutic agents have not yet been established. As the involvement of innate immunity, such as monocytes and neutrophils, in addition to T cells, has become clear, a more complex pathogenesis is predicted. Further elucidation of the pathogenesis of SJS/TEN is expected to lead to the development of new diagnostic and therapeutic agents.

Deadly drug rashes: Early recognition and multidisciplinary care.

Potentially deadly drug rashes include Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, and drug-induced vasculitis. Differentiating them can be a challenge. Factors to consider include timing of rash to drug exposure, rash distribution and clinical appearance, and the presence of systemic features such as mucosal involvement, organ failure, or eosinophilia. Various scoring systems aid in the diagnosis, but skin biopsy is the gold standard. Prompt identification and withdrawal of the suspected offending agent are the crucial first steps in management.

Long-Term Benefits of Tear Exchangeable Limbal-Rigid Contact Lens Wear Therapy in Stevens-Johnson Syndrome Cases.

OBJECTIVES: To evaluate the long-term benefits of tear-exchangeable, limbal-rigid contact lens (CL) wear therapy in patients with Stevens-Johnson syndrome (SJS)-associated ocular sequelae. METHODS: This retrospective study evaluated 50 eyes of 41 SJS patients (15 men and 26 women) who underwent limbal-rigid CL wear therapy for more than 2 years post fitting. Ocular sequelae (i.e., conjunctival hyperemia, corneal neovascularization, and upper tarsus scarring) before fitting and at 3 months, 6 months, 12 months, and annually after initiating CL wear therapy were evaluated and then graded on a severity score (range: 0-3, maximum score: 3). Moreover, visual acuity (VA) at immediately post initiating CL wear therapy was evaluated. RESULTS: The mean follow-up period was 4.3±1.1 years. Compared with before fitting, the mean conjunctival hyperemia score improved from 1.14 to 0.86 at 3 months of CL wear therapy ( P <0.01) and was maintained thereafter; the mean corneal neovascularization score improved from 2.10 to 1.98 at 3 months of CL wear therapy, with no deterioration of the score observed in all cases at the final follow-up examination, and mean VA (log of minimum angle of resolution) improved from 1.60 to 1.04 at immediately post initiating CL wear therapy ( P <0.01). CONCLUSIONS: Limbal-rigid CL wear therapy can provide long-term ocular surface stabilization and improved VA in SJS patients.

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

BACKGROUND: 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. OBJECTIVE: This study aimed to investigate the role of exosomal miRNAs on keratinocyte death in SJS/TEN. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Multidisciplinary Treatment in Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis, Leyll's syndrome (TEN), is a rare mucocutaneous blistering disease burdened with high mortality rates. The diagnosis of TEN is based on clinical symptoms and histopathological findings. In approximately 90% of cases, it is a severe adverse reaction to drugs. In TEN, not only is the skin affected, but also mucosa and organs' epithelium. There are no unequivocal recommendations in regard to systemic and topical treatment of the patients. The aim of this paper is to review available literature and propose unified protocols to be discussed. Early management and multidisciplinary treatment are necessary to improve patients' outcome. Treatment of patients with TEN suspicions should be initiated with early drug withdrawal. TEN patients, like patients with burns, require intensive care and multidisciplinary management. Each patient with TEN should be provided with adequate fluid resuscitation, respiratory support, nutritional treatment, pain control, infection prophylaxis, anticoagulant therapy, and gastric ulcer prophylaxis. The key to local treatment of patients with TEN is the use of nonadherent dressings that do not damage the epidermis during the change. The aim of the systemic treatment is purification of the blood stream from the causative agent. The most efficient way to clarify serum of TEN patients' is the combination of plasmapheresis and IVIG. Immunomodulatory therapy can reduce the mortality five times in comparison with the patients with immunosuppression or lack of full protocol.

TEN mimics: Classification and practical approach to toxic epidermal necrolysis-like dermatoses.

Toxic epidermal necrolysis (TEN) is an acute life-threatening dermatologic emergency. However, many dermatoses can present with a TEN-like eruption. Those "TEN-mimics" are a true diagnostic challenge and an alarming differential diagnosis to such a serious condition. Herein, we will expose and classify the landscape of TEN-mimics. Also, the key differentiating clinical and/or laboratory points will be highlighted to help an accurate diagnosis of either a TEN or a TEN-like presentation.