スティーヴンス・ジョンソン症候群

IMPORTANCE: Antiepileptic drugs (AEDs) are frequently implicated in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are the most severe type of drug hypersensitivity reaction, with a mortality rate up to 50%. However, the overall proportion of these cases attributed to AEDs has not been systematically reviewed. OBJECTIVE: To evaluate the proportion of AED-associated SJS/TEN. DATA SOURCES: The MEDLINE and Embase databases were searched from inception through March 17, 2026, with results limited to English-language publications and human participants. STUDY SELECTION: All experimental and observational studies that reported patient-level triggers of SJS/TEN were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies and extracted data using a predefined template. To estimate the proportion of AED-associated SJS/TEN, a random-effects meta-analysis was performed, calculating the pooled proportions with 95% CIs. Subgroup analyses by age group (children vs adults) and geographic region were performed to explore heterogeneity. MAIN OUTCOMES AND MEASURES: To estimate the proportion of AED-associated SJS/TEN. RESULTS: This systematic review and meta-analysis included 50 studies with 4403 patients that reported patient-level triggers of SJS/TEN. Single-drug triggers accounted for 88% (95% CI, 83-92) of cases. The pooled proportion of SJS/TEN cases attributed to AEDs was 23% (95% CI, 19-26). Nearly all AED-associated cases were due to aromatic AEDs (96%; 95% CI, 92-99), most commonly carbamazepine (39%; 95% CI, 29-50), followed by phenytoin (19%; 95% CI, 11-28), and lamotrigine (15%; 95% CI, 8-22). Nonaromatic AEDs were rarely implicated (2%; 95% CI, 0-4). Significant geographic variation was observed in the proportion of AED-associated SJS/TEN, ranging from 42% (95% CI, 26-59) in West Asia to 10% (95% CI, 0-33) in Africa (P < .001). The proportion of AED-associated SJS/TEN cases was significantly higher in children (35%; 95% CI, 22-48) than in adults (23%; 95% CI, 20-27). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of observational studies, AEDs accounted for nearly one-quarter of SJS/TEN cases reported worldwide, predominantly involving aromatic AEDs, such as carbamazepine, phenytoin, and lamotrigine. These findings suggest aromatic AEDs as leading contributors to SJS/TEN and support the preferential use of nonaromatic AEDs when clinically appropriate.

Polypharmacology is dedicated to the development of compounds acting on at least two targets (multi-target-directed ligands, MTDLs). In 2025, the European Medicines Agency (EMA) approved 38 drugs, and 11 out of them were MTDLs. Most of them are antibody-drug conjugates, bispecific antibodies, or kinase inhibitors, all of which are indicated for tumor treatment, including datopotamab deruxtecan (hormone receptor-positive, HER2-negative breast cancer), tisotumab vedotin (advanced cervical carcinoma), linvoseltamab (fourth-line treatment of multiple myeloma), and erdafitinib (advanced urothelial carcinoma). The small molecule tiratricol is an orphan drug, which is indicated for the treatment of the very rare Allan-Herndon-Dudley syndrome. The second part of the present review is dedicated to the post-marketing safety surveillance of MTDLs approved by the EMA in 2022-2024. For 19 out of the 27 MTDLs, which are still available on the European market, comprehensive pharmacovigilance studies, mainly based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), were found. New safety signals have been identified, including Stevens-Johnson syndrome and progressive multifocal leukoencephalopathy. The analysis also revealed a more favorable safety profile of the MTDL tirzepatide (a dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide analogue) compared to the single-targeted drug semaglutide (glucagon-like peptide-1 analogue), including lower reporting rates of acute kidney injury and no significant suicidality signal.

Hypertension, a major global health burden affecting over one billion people worldwide, is primarily managed with pharmacological therapy. While effective for cardiovascular protection, antihypertensive drugs can cause under-recognized cutaneous adverse drug reactions (CADRs). This review summarizes CADRs associated with antihypertensive medications, including pathophysiology, clinical presentation, diagnosis, management, and prevention. A narrative review of PubMed (January 2001-August 2025) was conducted to identify studies on CADRs linked to antihypertensive therapy, and observational studies, case reports, case series, and clinical trials were included. CADRs arise through immunologic (Types I-IV hypersensitivity, most often Type IV) and non-immunologic mechanisms. Clinical presentations range from mild eruptions (maculopapular rash, photosensitivity, urticaria) to severe reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Symptoms usually occur within weeks of initiation, though delayed reactions are possible. Diagnosis relies on detailed medication history, examination, and, in selected cases, histopathology, and resolution after drug withdrawal is a key diagnostic clue. Management involves discontinuing the offending agent, supportive care, and pharmacological interventions (e.g. corticosteroids, antihistamines). Preventive strategies include avoidance of reexposure, substitution with safer alternatives, and strict photoprotection. Antihypertensive medications can cause diverse CADRs with variable severity and clinical impact, and early recognition and prompt management are essential to minimize morbidity. Prospective studies with standardized definitions and pharmacogenomic approaches are needed to improve risk prediction and guide safer, individualized prescribing.

BACKGROUND: Autoimmune bullous diseases (AIBD), Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) and erythema multiforme (EM) often present with clinically similar features in the oral mucosa: classically widespread mucosal erosions or ulceration. Despite this, there are no formalized guidelines for the specific management of the oral manifestations of these conditions. OBJECTIVES: We sought to establish an consensus on the management of oral involvement of AIBD, SJS-TEN and EM using the Delphi method. METHODS: Participants were sent a survey comprising 62 statements organized into 6 categories: general oral and dental recommendations; disease severity scoring; topical therapies for active oral involvement in AIBD; systemic therapies for active oral involvement in AIBD; additional considerations for inpatient care of AIBD, EM, SJS-TEN; specific considerations for EM and SJS-TEN. Participants rated the level of appropriateness of each statement. Results were analysed using the RAND/UCLA Appropriateness Method. RESULTS: 34 experts, primarily Oral Medicine clinicians and Dermatologists, completed the survey. Consensus was achieved for 58 (93.5%) statements after a single round. General recommendations included rigorous oral hygiene and regular dental/periodontal care. Disease-specific severity scoring was recommended to guide treatment and monitor response. For active oral AIBD, experts recommended moderate-to-super potent topical corticosteroids, guided by severity and site of oral disease. For inpatients, supported oral hygiene, regular topical anaesthetics and nutritional support for impaired intake were recommended. For acute EM and SJS-TEN, recommendations included regular lip care with gentle debridement of haemorrhagic crusts and application of soft paraffin. CONCLUSIONS: This Delphi sets out a broad framework for the management of oral involvement in AIBD, SJS-TEN and EM, to be adapted by a multidisciplinary team, for both acute and long-term management of these conditions. It may help to standardize the management of oral manifestations of these conditions in future multicentre studies.

PURPOSE: To test the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-exos) in ocular surface inflammation and to characterize immune responses in an IKAROS family zinc finger (IKZF) murine model of Stevens-Johnson syndrome (SJS) with allergic eye disease (AED). METHODS: Transgenic mice expressing IKZF1 were used as the SJS model. To induce ocular surface inflammation, the mice were immunized with intraperitoneal ovalbumin in aluminum hydroxide (alum) and pertussis toxin and challenged with topical ovalbumin. Conjunctival tissues and draining lymph nodes (LNs) were analyzed by flow cytometry to characterize immune responses. MSC-exos were prepared from immortalized human embryonic stem cell-derived MSCs. Clinical disease was evaluated daily. The pharmacokinetics of Alexa Fluor 488-labeled MSC-exos were tracked using in vivo multiphoton confocal microscopy. RESULTS: IKZF mice demonstrated increased conjunctival immune cell infiltration compared with wild-type controls, which was further amplified following allergic challenge. IKZF+AED mice exhibited expansion of innate and adaptive populations in the conjunctiva. Draining LNs showed increased frequencies of cytokine-producing CD4⁺ T cells. MSC-exo treatment significantly reduced clinical disease severity, with subconjunctival administration producing the greatest improvement, comparable to corticosteroid therapy. Pharmacokinetic imaging demonstrated rapid clearance of topically administered exosomes, whereas subconjunctival delivery resulted in retention within ocular tissues for up to 72 hours and localization within the conjunctival stroma. CONCLUSIONS: The IKZF+AED model demonstrates local conjunctival inflammation and systemic T-cell activation consistent with SJS-associated ocular disease. MSC-exos significantly improved clinical inflammation, and their therapeutic efficacy was strongly influenced by delivery route. Prolonged tissue retention following subconjunctival administration suggests that pharmacokinetic exposure within conjunctival tissues may be a key determinant of therapeutic effect.