Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially fatal mucocutaneous emergencies that exist on a spectrum and are most commonly caused by a medication reaction. Although data guiding diagnosis and management remain limited, early recognition, prompt identification and discontinuation of the causative agent, symptomatic management, and multidisciplinary involvement are essential to improving patient outcomes. Validated prognostic tools can further guide management decisions. This review provides an evidence-based approach to the recognition and management of SJS/TEN in the emergency department.

Adverse drug reactions (ADRs) can lead to severe consequences and increased morbidity and mortality rates. Phenobarbital is one of the most common anti-epileptic drugs that has numerous adverse drug reactions, including toxic epidermal necrolysis. The event is rare and a medical emergency. A six-year-old female epileptic child with phenobarbital-induced toxic epidermal necrolysis was referred for the management of diffuse exfoliative lesions involving her eyes and buccal mucosa. Associated with the skin lesions, the patient reported high-grade fever, reddish eye discoloration, dysphagia and dry cough. The exfoliative skin lesion involved 90% of her total body surface area. The patient was managed with withdrawal of phenobarbital, IV antibiotics, systemic corticosteroid, twice daily wound care, analgesic, and nutritional support. Early recognition, discontinuation of offending medications and prompt intervention are crucial to mitigate harm. Raising awareness about ADRs and their management is vital for enhancing patient safety and outcomes.

In patients with severe ocular surface disease (OSD) and cornea and cataract-related vision impairment, where the risk of allograft rejection after allogeneic corneal transplantation is unacceptably high and cataract surgery impossible because of corneal opacity, cataract extraction may still offer meaningful improvement in vision-related quality of life. We describe ipsilateral, nonrotational autokeratoplasty (INRA) as option to perform open-sky cataract surgery after removal of the central cornea and prevent immune responses by placing back the original host cornea. This report presents 2 patients with only 1 functional eye, cataract and severe OSD (Lyell syndrome, chemical burn) undergoing INRA to enable cataract surgery as an alternative approach to visual rehabilitation, aiming to avoid high-risk corneal transplantation. Both patients had a small central zone of relative corneal clarity. This is the first report of INRA for concomitant cataract surgery. Postoperatively, both visual acuity and patient-reported visual satisfaction improved. In 1 case, delayed wound healing was noted and successfully managed with standard treatments. No other severe complications, adverse events, or rejection episodes were observed. Although INRA does not address corneal vision impairment, it allows effective cataract management in patients with relative central corneal clarity and otherwise very high risk for corneal allograft failure.

Mycoplasma-induced rash and mucositis (MIRM) is a recently recognized mucocutaneous disorder, often misdiagnosed as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or erythema multiforme (EM). We report a 6-year-old boy presenting with fever, cough, and cold, followed by painful oral ulcerations, conjunctivitis, genital mucositis, and generalized vesiculobullous rash. He was on levetiracetam for a prior unprovoked seizure, raising suspicion of drug reaction. Initial differentials included SJS, TEN, EM, and Drug reaction with eosinophilia and systemic symptoms. Laboratory findings showed leukocytosis, thrombocytosis, and positive Mycoplasma pneumoniae Immunoglobulin M, while Herpes simplex virus polymerase chain reaction was negative. Histopathology revealed liquefactive necrosis with lymphohistiocytic infiltrates. Despite intravenous antibiotics, antivirals, and immunoglobulin, there was no improvement until pulse methylprednisolone was initiated. He was discharged on tapering oral steroids and doxycycline, with complete mucosal healing on follow-up. As there is no clear-cut distinction between histopathological findings of EM and MIRM, reporting biopsy changes whenever feasible is essential. Early recognition, targeted antibiotics, and timely immunomodulation are key to favorable outcomes.

Evaluating Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Associated With Newer Antiseizure Medications Using FAERS and JADER Combined With Bioinformatics Exploration.

Two cases of toxic epidermal necrolysis with severe ocular involvement treated with adjunctive tofacitinib.

Cutaneous adverse drug reactions (cADRs) are unintended and harmful skin responses to medications that impose significant clinical and economic burdens worldwide. The increasing use of novel agents, particularly immune checkpoint inhibitors, has further compounded this challenge. While most cADRs are mild and resolve upon drug discontinuation, approximately 2-6.7% progress to severe, potentially fatal conditions. The most common severe forms include acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, and drug-associated bullous pemphigoid. Current therapeutic options for refractory cADRs remain limited, primarily relying on systemic corticosteroids, conventional immunosuppressants, and intravenous immunoglobulin. Growing insights into disease pathogenesis and the subsequent repurposing of novel targeted therapies offer promising solutions to the persistent challenges of cADRs. Emerging agents, such as biologics targeting tumor necrosis factor-α, interleukins (IL-4/IL-13, IL-5, IL-6, IL-17, IL-36), immunoglobulin E, and CD20, along with small molecule inhibitors of Janus kinases and phosphodiesterase 4, hold the potential to revolutionize management paradigms, though their long-term efficacy and safety profiles await robust clinical validation.

Mycoplasma pneumoniae is a common cause of respiratory infections, which in some cases leads to extrapulmonary complications, including mucocutaneous eruptions. The authors describe a clinical case of a 5-year-old Polish boy presenting with symptoms consistent with the diagnostic criteria of Mycoplasma pneumoniae-induced rash and mucositis (MIRM), a relatively new clinical entity distinguished from the spectrum of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The patient was initially admitted to the acute admissions unit of the Children's Health Centre in Poznan, Poland, due to prolonged fever, erosive-ulcerative lesions of the oral mucosa and lips, and slightly elevated, pink, rash-like skin eruptions. After 2months, he was followed up in the University outpatient department. The treatment included systemic and local steroids (hydrocortisone, prednisolone), antibiotics (gentamicin), mucolytics (ambroxol), analgesics (paracetamol), and local antifungal agents (nystatin). This report discusses the clinical presentation, diagnostic procedures, differential diagnosis, and treatment. We recommend that pneumonia accompanied by mucocutaneous eruptions, especially in young patients, should raise clinical suspicion of MIRM. Differential diagnosis should include EM, SJS, TEN, and Kawasaki disease.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening mucocutaneous reactions most commonly triggered by medications. While cytotoxic T-cell-mediated keratinocyte death is considered central to disease pathogenesis, the contribution of innate immune pathways, particularly NLRP1-mediated inflammasome activation, remains insufficiently characterized. In this retrospective study, we analyzed skin biopsy specimens from 22 patients with histopathologically confirmed SJS/TEN and 18 controls with normal skin. Immunohistochemical staining for NLRP1 and IL-1β was semiquantitatively assessed using H-scores, and clinical features including suspected triggers, SCORTEN, and outcomes were recorded. NLRP1 and IL-1β expression in both epidermal keratinocytes and dermal lymphocytes was significantly elevated in SJS/TEN compared with controls (all p < 0.05), and NLRP1 levels demonstrated a strong positive correlation with SCORTEN (p < 0.001). No significant differences in expression were observed between survivors and non-survivors. These findings support a role for inflammasome activation in SJS/TEN pathogenesis and suggest that NLRP1 may serve as a potential biomarker of disease severity. Larger, prospective studies are warranted to confirm these observations.

Data on the incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Thailand, where high-risk HLA alleles are prevalent, remain limited. Existing prognostic scores, including SCORTEN, may not capture all mortality determinants. To estimate the incidence and identify factors associated with in-hospital mortality in adult patients with SJS/TEN in Thailand. We conducted a retrospective cohort study using the nationwide Thai National Health Security Office database. Adults hospitalized with SJS/TEN were identified by International Statistical Classification of Diseases, 10th Revision codes between 2017 and 2024. Cox regression with time-varying coefficients was used to examine mortality risk factors. A total of 7237 incident cases were identified (83.9% SJS). Median age was 57 years (interquartile range 42-69), and 50.5% were female. The estimated incidence was 17.3/million (95% confidence interval [CI], 16.9-17.7), with a decline over time. In-hospital mortality was 4.1% for SJS and 15.5% for TEN. Independent factors associated with mortality beyond SCORTEN included invasive ventilation (hazard ratio [HR], 14.99; 95% CI, 7.08-31.75), liver disease (HR, 2.49; 95% CI, 1.13-5.46), renal disease (HR, 2.46; 95% CI, 1.96-3.04), and myocardial infarction (HR, 1.90; 95% CI, 1.19-3.04). Mortality risk also increased progressively with age (≥60 years) and varied by hospital type. Time-varying analysis showed that TEN, liver disease, and ventilation had the strongest early impact, whereas infections, particularly skin and soft tissue infections, emerged later (HR at day 28, 2.64; 95% CI, 1.37-5.09). The incidence of SJS/TEN in Thailand is high. Mortality is influenced by factors beyond established scoring systems, with effects that evolve over time.

ABSTRACTBackgroundSevere cutaneous adverse reactions (SCARs) are rare but potentially fatal immune‐mediated toxicities associated with antiseizure medications (ASMs). Phenotype‐resolved post‐marketing safety profiles for newer‐generation ASMs have not been comprehensively characterized across pharmacovigilance systems.MethodsA cross‐database disproportionality analysis was conducted using FAERS and JADER (January 2004–September 2025). Twenty‐two newer‐generation ASMs coded as primary‐suspect drugs were included; outcomes were the four SCAR phenotypes (Stevens–Johnson syndrome, SJS; toxic epidermal necrolysis, TEN; drug reaction with eosinophilia and systemic symptoms, DRESS; acute generalized exanthematous pustulosis, AGEP) defined using MedDRA preferred terms. Signals were evaluated using reporting odds ratios (RORs) and Bayesian information component metrics. Time‐to‐onset (TTO) was characterized by Weibull modeling with confidence‐interval–based failure‐pattern classification and Kaplan–Meier analysis. Pre‐specified sensitivity analyses excluded reports with concomitant valproic acid or other SCAR‐inducing co‐medications, applied multivariate logistic regression, and restricted FAERS reports to healthcare professionals.ResultsIn total, 10,073 SCAR reports were included (SJS, 3776; TEN, 1762; DRESS, 4298; AGEP, 237). Lamotrigine and zonisamide showed the strongest, most reproducible associations across SJS/TEN/DRESS (FAERS RORs for lamotrigine, 35.60/22.35/27.30; zonisamide, 28.08/25.05/40.78), with concordant directions in JADER. Sensitivity analyses attenuated but did not abolish the principal lamotrigine, zonisamide, levetiracetam, and eslicarbazepine signals, whereas the gabapentin–TEN signal in JADER lost statistical significance after exclusion of high‐risk co‐medications. Median TTO was 22 days overall; SJS/TEN occurred earlier, while DRESS showed delayed and more dispersed onset (median, 28 days), with eslicarbazepine–DRESS uniquely exhibiting a wear‐out pattern. TEN carried the highest reported fatality proportion (FAERS, 17.7%; JADER, 17.5%). Key signals remained robust under healthcare‐professional restriction, with eslicarbazepine–DRESS further enhanced.ConclusionsAcross FAERS and JADER, reporting associations between newer‐generation ASMs and SCARs were highly concentrated in a limited set of agents and exhibited phenotype‐specific latency patterns. After accounting for polytherapy confounding, levetiracetam and eslicarbazepine emerged as the most consistent under‐recognized signals, warranting heightened vigilance during initiation—particularly when co‐administered with aromatic ASMs. Drug–phenotype combinations with both high disproportionality and a high reported fatality proportion (notably lamotrigine–TEN and zonisamide–TEN) warrant intensified early monitoring for SJS/TEN and sustained vigilance into maintenance therapy for DRESS, although population‐level absolute risk cannot be inferred from spontaneous‐report data.

Epidermal necrolysis sequelae: A cohort study on prevalence and risk factors.

Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme major (EM major) are severe dermatologic conditions characterized by varying degrees of skin detachment and involvement of mucosal membranes, often triggered by drug reactions or infections. The management of these conditions poses a significant challenge due to the potential for rapid progression to life-threatening complications. Recently, emerging therapeutic approaches such as Tumor Necrosis Factor-alpha (TNF-α) blockers and Janus Kinase (JAK) inhibitors have shown promise in regulating the dysregulated immune response implicated in these disorders. A comprehensive literature review was conducted to evaluate the efficacy and safety of TNF-α blockers and JAK inhibitors in treating SJS, TEN, and EM. A systematic review was conducted according to PRISMA guidelines. A comprehensive literature search was performed in PubMed, Scopus, Embase, Web of Science, and Google Scholar, up to September 5, 2025, on JAK inhibitors and TNF inhibitors in treating SJS, TEN, or EM major. The current review studies 82 articles (748 patients), including case reports, cohort studies, and clinical trials. Various JAK inhibitors and TNF inhibitors, such as tofacitinib, etanercept, adalimumab, and infliximab, were assessed regarding effectiveness in treating SJS/TEN and EM. Notably, some cases demonstrated a rapid response to these inhibitors, resulting in faster re-epithelialization and a reduction in the severity of lesions. TNF-α blockers like infliximab and etanercept show promise for patients unresponsive to standard treatments, shortening acute phases, reducing hospitalization, and mortality rates, and enhancing healing. Further research, especially registry-based studies, is crucial. Healthcare practitioners are advised to exercise caution and reserve novel drugs for managing hypersensitivity reactions.

Solid lipid nanoparticles in skin cancer: A comprehensive review of mechanism, formulation, and therapeutic advances.

Update on dermatological toxicities of immune checkpoint inhibitors.

Hydroxychloroquine (HCQ) is pivotal in rheumatology and dermatology for its potent anti-malarial and immunomodulatory properties. Though generally safe, HCQ causes cutaneous adverse reactions (CARs) ranging from mild pigmentation to life-threatening severe cutaneous adverse reactions (SCARs). This review synthesizes data from studies indexed PubMed, Web of Science, Embase, and the Cochrane Library up to December 2025. Search keywords included "hydroxychloroquine," "adverse reactions," "skin lesions" (e.g., pigmentation, maculopapular rash, psoriasiform eruption), and "mechanisms." We included original studies, reviews, and case reports, excluding duplicates and studies focused solely on non-cutaneous reactions. Two reviewers independently screened the literature, and any discrepancies were resolved via discussion. Study quality was assessed based on methodological rigor and data completeness, with priority given to high‑impact literature published in the last decade.Common adverse reactions include pigmentation, maculopapular rash, and pruritus; rare but severe reactions include acute generalized exanthematous pustulosis (AGEP), drug hypersensitivity syndrome (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Underlying mechanisms may involve alteration of pigment metabolism, lysosomal ion trapping, and T-cell-mediated hypersensitivity. Management depends on early recognition, dose adjustment, or drug discontinuation. For select mild cases, desensitization may be appropriate. Ongoing monitoring of pharmacovigilance databases is crucial for proactive surveillance and early warning.

4579 Background: SYS6002 is a next-generation Nectin-4-targeting antibody-drug conjugate (ADC) utilizing a novel site-specific enzymatic conjugation technology to link monomethyl auristatin E (MMAE) with a uniform drug-antibody ratio of 2. This design aims to enhance linker stability, minimize free payload release, and improve the therapeutic window. Methods: This phase 1 study (ChiCTR2200066256) included dose escalation (0.2–4.5 mg/kg Q3W; 2.4–2.7 mg/kg Q2W), pharmacokinetic (PK) expansion, and cohort expansion phases. Eligible patients had advanced solid tumors refractory to standard therapies. The primary endpoints were safety and recommended phase 2 dose (RP2D). Secondary endpoints included PK profile and efficacy, with the latter reported herein were specific to the pretreated advanced urothelial carcinoma (aUC) cohort. Results: As of Dec 19, 2025, 150 patients were enrolled (dose escalation n=32; PK expansion n=70; cohort expansion n=48). The maximum tolerated dose was not reached up to 4.5 mg/kg. The RP2D in aUC patients was determined as 3.6 mg/kg Q3W. SYS6002 exhibited a manageable safety profile in all 150 patients. With a median follow-up of 11.5 months (IQR 6.5-15.5), 2 (1.3%) patients discontinued treatment due to treatment-related adverse events (TRAEs) and no TRAE led to death. The most common TRAEs were ocular disorders (e.g., corneal disorder, dry eye), which were predominantly Grade 1-2. While ocular events were frequent (consistent with on-target effects), they were reversible and effectively managed with prophylaxis, resulting in no treatment discontinuations due to ocular toxicity. Notably, TRAEs typically associated with payload shedding were characterized by low incidence, with peripheral neuropathy reported in 11.3% of patients (no Grade ≥3) and rash in 20.7% (2.0% Grade ≥3), which compared favorably to historical data of other MMAE-based ADCs. Furthermore, no Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis reported. In 85 efficacy-evaluable aUC patients across all tested doses, the objective response rate (ORR) was 37.6% (95%CI 27.4-48.8) and disease control rate (DCR) was 77.6% (95%CI 67.3-86.0), with a median duration of response of 6.2 months (95%CI 4.3-10.4) and median overall survival of 13.2 months (95%CI 10.6-14.9). At the RP2D (n=39), the ORR reached 41.0% (95%CI 25.6-57.9). Encouragingly, in heavily pretreated patients with prior MMAE-based ADC exposure (n=25), SYS6002 maintained activity with an ORR of 24.0% (95%CI 9.4-45.1) and DCR of 72.0% (95%CI 50.6-87.9), suggesting potential to overcome resistance. Conclusions: SYS6002 demonstrated a distinct safety profile from other Nectin-4 ADCs. Its promising efficacy in aUC patients, extending to those progressing on prior MMAE-based ADCs, supports further phase 3 trials. Clinical trial information: ChiCTR2200066256.

Paediatric Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe mucocutaneous reaction requiring coordinated multidisciplinary care. Existing guidelines provide evidence-based recommendations, but implementation across tertiary paediatric hospitals requires practical consensus on local resources. To develop and evaluate multidisciplinary consensus-informed practical clinical guidance for assessment and management of paediatric SJS/TEN among clinicians from Australasian tertiary referral hospitals. A draft guidance document was developed after review of SJS/TEN guidelines, systematic reviews and other relevant literature. Clinicians from one tertiary paediatric centre (Group A) and other Australian and New Zealand tertiary centres (Group B) completed a 130-item questionnaire. Continuous items were scored on a 1-9 Likert scale. Categorical items addressed referral urgency and whether investigations should be routine, reasonable but not routine, or not ordered. Quantitative responses and free-text comments informed revision. Twenty-two multidisciplinary clinicians from the internal centre and nine clinicians from eight external centres participated. Agreement was high for history, examination, supportive care, multidisciplinary involvement, discharge planning and follow-up. Uncertainty remained regarding fluid requirements compared with burns patients, the scope of initial investigations and systemic immunomodulatory therapy. The guidance was revised to emphasise individualised fluid management, directed differential diagnosis and testing, and case-by-case systemic therapy. This practical multidisciplinary consensus-informed guidance supports paediatric SJS/TEN care in Australasian tertiary referral hospitals. Its contribution is the quantified consultative process and identification of consistent, variable and uncertain practice. It complements, rather than replaces, existing guidelines.

Long term multiorgan sequelae in a child with toxic epidermal necrolysis.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) are life-threatening adverse medication reactions, often with multiorgan involvement. Cardiac involvement in these conditions has not been well-characterised. To evaluate the prevalence, clinical spectrum, and outcomes of cardiac involvement in patients diagnosed with DRESS and SJS/TEN. A single-centre retrospective cohort study was conducted. DRESS and SJS/TEN patients between January 2014 and January 2024 were identified through the hospital adverse drug reaction database. Cardiac involvement was defined as the presence of cardiac symptoms accompanied by any new abnormality detected on electrocardiograms, cardiac biomarkers, and/or cardiac imaging during admission. 58 patients were included: 79 with DRESS and 79 with SJS/TEN. Cardiac involvement was identified in 15.2% of DRESS and 6.3% of SJS/TEN cases. Cardiovascular risk factors were prevalent across both conditions with hypertension being the most common. Cardiac symptoms were reported in up to 20% with dyspnoea being the most frequent. Of those who had cardiac investigations, new electrocardiographic abnormalities were detected in up to 42% of patients. ICU admissions and mortality were higher in SJS/TEN but there was no mortality attributable to cardiac involvement. Antibiotics were the most frequently implicated medications in both groups.In DRESS subgroup analysis, cardiac involvement was associated with higher rates of renal involvement (100% vs 64%, p = 0.014) and ICU admission (67% vs 34%, OR = 3.83, 95% CI 1.04-14.07, p = 0.043), but was less common with antibiotics exposure as a cause of DRESS (58% vs 84%, OR = 0.28, 95% CI 0.07- 1.03, p = 0.055). Cardiac involvement is an under-recognised but clinically important feature of DRESS and SJS/TEN. Findings highlight the contribution of cardiac dysfunction to morbidity and support routine cardiac assessment in patients with SCAR. Larger prospective studies and national drug reaction registries are needed to better define burden and guide care.