RARE DISEASE
Stevens-Johnson syndrome
Stevens-Johnson syndrome
Stevens-Johnson syndrome
Synonyms: Dermatostomatitis, Stevens Johnson type
Synonyms: Dermatostomatitis, Stevens Johnson type
Synonyms: Dermatostomatitis, Stevens Johnson type
Drug discovery
0
drugs
With orphan designations
Overview
Stevens-Johnson syndrome (SJS) is a rare, life-threatening mucocutaneous disorder characterized by widespread epidermal necrosis and detachment triggered primarily by medications (≥80% of cases). It progresses from flu-like symptoms to painful blistering of skin/mucous membranes (>2 mucosal sites in 85-95% of cases), with mortality increasing proportionally to affected body surface area (BSA). SJS (<10% BSA), TEN (>30% BSA), and overlap syndromes are managed with immediate culprit drug cessation, intensive supportive care, and immunomodulatory therapies [1][6][12].
Therapies
▲ First-line: Cyclosporine (3–5 mg/kg/day, reduces mortality) ± early corticosteroids (prednisolone 1–2 mg/kg ≤72h from onset) [3][18]
▲ Advanced care: IVIG (2.7 g/kg over 3 days) or TNF-α inhibitors (etanercept) [3][8]
▲ Critical support: Burn unit admission, ophthalmic/enteral nutrition intervention, infection prophylaxis [1][16]
Categories: rare skin diseases
Research Papers
1,330 drug discovery papers about Stevens-Johnson syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,330 drug discovery papers about Stevens-Johnson syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-02-09 | Treatment of toxic epidermal necrosis lesions with ovine forestomach matrix.
Stevens-Johnson syndrome and toxic epidermal necrosis (TEN) are used to describe a spectrum of acute mucocutaneous reactions primarily affecting the skin and mucous membranes, resulting in painful blisters and epidermal detachment. Swift diagnosis followed by management of the damaged epidermis is vital to prevent further infection, which if left untreated can become life-threatening. We report a case of TEN in a 42-year-old female who presented with 55% epidermal loss. Over the course of 41 days, the affected regions were treated with ovine forestomach matrix (OFM) grafts, which led to epithelial restoration of the lesions in 1-2 weeks with good functional and cosmetic outcomes. This case is the first documented use of OFM in the treatment of TEN lesions.
2025-12-04 | Evaluation of umbilical cord blood serum eye drops for severe dry eye in two distinct populations-Sjögren's syndrome and mustard gas-induced ocular injury: Protocol for a pilot randomized clinical trial.
Human umbilical cord blood (HUCB) serum eye drops contain growth factors, neurotrophic agents, and antimicrobial compounds that may promote ocular surface healing and regeneration. Sjögren's syndrome is a chronic autoimmune condition characterized by reduced tear production and ocular surface damage, often resulting in severe dry eye symptoms. Mustard gas chemical veterans also suffer from similar debilitating ocular complications due to chronic inflammation and meibomian gland dysfunction. While conventional treatments offer symptomatic relief, they lack essential components of natural tears. This pilot randomized controlled trial will evaluate the efficacy of HUCB eye drops in three patient groups: (A) Sjögren's patients treated with HUCB drops, (B) Sjögren's patients receiving conventional treatment, and (C) mustard gas veterans receiving conventional treatment in the right eye and HUCB drops in the left eye. Patients will be assessed using subjective and objective tools, including the Ocular Surface Disease Index (OSDI), visual acuity, tear film breakup time (TBUT), SM tube test, and fluorescein staining based on SICCA criteria. Group allocation will follow a blocked randomization sequence for groups A and B; group C will follow a within-subject paired-eye design. Follow-up will occur at 30 and 60 days. This study aims to assess the regenerative potential of HUCB serum in patients with autoimmune and chemically induced dry eye. Its results may support broader clinical use of HUCB drops in treating severe ocular surface disorders, including conditions like Stevens-Johnson syndrome and industrial chemical exposures. This trial was registered at the Iranian Registry of Clinical Trials (Registration number: IRCT20230925059512N1, Registration date: 2024-08-11).
2025-12-01 | A Novel Case of Biktarvy-Associated Stevens-Johnson Syndrome With Severe Ocular Involvement
Purpose: The purpose of this study was to describe the first reported case of Stevens-Johnson syndrome (SJS) associated with bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), highlighting a rare presentation with severe ocular and oral involvement in the absence of cutaneous findings. Case report: A 59-year-old woman developed mucosal-limited SJS 2 weeks after initiating Biktarvy as postexposure prophylaxis. She presented with severe bilateral ocular involvement—characterized by extensive conjunctival and corneal epithelial defects, pseudomembranes, and symblepharon—as well as painful oral ulcerations, but no skin rash. She was treated with topical corticosteroids, antibiotics, and immunomodulators, in addition to multiple amniotic membrane transplants and supportive measures. Persistent corneal epithelial defects were ultimately resolved with cenegermin-bkbj 0.002% therapy. At final follow-up, her visual acuity was 20/20 in both eyes with minimal residual ocular surface damage. Conclusions: This case illustrates an atypical presentation of medication-associated SJS without skin involvement, triggered by a previously unreported agent. Clinicians should recognize that antiretroviral drugs such as Biktarvy may induce SJS and that mucosal-limited disease can cause profound ocular morbidity. Prompt ophthalmologic assessment and early surgical intervention with amniotic membrane transplants are crucial to preserving vision.
2025-08-25 | Ocular Complications in stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comprehensive Review.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are rare but life-threatening mucocutaneous disorders, primarily triggered by adverse drug reactions. Although systemic manifestations have been extensively studied, ocular involvement remains a major cause of morbidity, often resulting in severe visual impairment or blindness. This narrative review synthesizes current evidence regarding the clinical presentation, pathophysiology, and management strategies for ocular complications in SJS/TEN. A comprehensive literature search was conducted to highlight both acute and chronic ophthalmic manifestations and therapeutic interventions. Ocular involvement is reported in up to 75% of SJS/TEN patients during the acute phase, manifesting as conjunctivitis, pseudomembrane formation, corneal erosions, and eyelid abnormalities. Early interventions such as lubrication, topical corticosteroids, and amniotic membrane transplantation (AMT) have shown efficacy in mitigating long-term damage. Nonetheless, a substantial number of patients develop chronic complications including symblepharon, limbal stem cell deficiency, and severe dry eye syndrome. Long-term management involves scleral lenses and surgical procedures such as limbal stem cell transplantation, mucous membrane grafting (MMG), and keratoprosthesis. Innovations like ProKera® have improved epithelial healing, yet irreversible damage from the acute phase remains a persistent challenge. Ocular complications of SJS/TEN are multifaceted and necessitate early and sustained multidisciplinary management. Timely ophthalmologic intervention is crucial in the acute phase, while chronic care aims to restore ocular surface stability and preserve vision. Further research is needed to develop standardized treatment protocols and explore emerging therapies that may enhance long-term outcomes and quality of life.
2025-04-28 | A Case-Based Approach to the Management of Corneal Melts and Perforations in Ocular Surface Disorders.
Corneal perforations caused by chronic ocular surface disorders present significant management challenges and can lead to blindness if untreated. This case series reviews the pathophysiology of corneal melts and examines treatment strategies tailored to the size, location, and etiology of perforations in conditions such as Stevens-Johnson syndrome, graft-versus-host disease, and chemical injuries. Through detailed case analyses, various interventions, including cyanoacrylate glue, Tenon's patch grafting, mucous membrane grafts, scleral patch grafts, and conjunctival flaps, were evaluated, along with emerging therapies like biosynthetic hydrogels and collagen-like peptides. Findings highlight the role of chronic inflammation and adnexal abnormalities in disrupting ocular surface integrity, affecting treatment outcomes. This case series underscores the importance of a comprehensive approach that not only repairs corneal defects but also addresses underlying systemic and ocular conditions, with advancements in biosynthetic materials showing promise for improving patient outcomes.
small molecules
2026-08-12 | RUCAM-ascertained immunology and autoimmunity specifics of six idiosyncratic drug-induced liver injury types with refined classification: their individual complex molecular interplay.
Idiosyncratic drug-induced liver injury (iDILI) is not a uniform disease but rather includes a variety of types based on immune, autoimmune, and clinical considerations. This review attempts to close information gaps regarding the role of immunity and autoimmunity involved in the different iDILI disease types. The analysis of the current literature focusing on iDILI reveals compelling evidence of a pivotal role of immunity or autoimmunity in various types of iDILI. Among the autoimmune-triggered ones are the drug-induced autoimmune hepatitis (DIAIH) and the idiosyncratic drug-induced anti-CYP autoimmune hepatitis. In contrast, clearly immune-triggered are the human leukocyte antigen (HLA)-based immune iDILI, the immune iDILI with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and the immune iDILI induced by immune checkpoint inhibitors (ICIs), but immune-triggered mechanisms account for only a part of the classic iDILI cases. For all these iDILI types, the use of the original or updated Roussel Uclaf Causality Assessment Method (RUCAM) allowed for confirming causality of the implicated drug, assisted by the simplified autoimmune hepatitis (AIH) score in the DIAIH cases and the Algorithm of Drug Causality for Epidermal Necrolysis (ALDEN) score in the cases of immune-based iDILI with SJS/TEN. All these diagnostic causality assessment algorithms are validated methods and have helped define clinical features of the different iDILI types. The first treatment goal is the cessation of the suspected drug, which alone may lead to clinical and laboratory improvement and restoration of health. However, therapy with immunosuppressive agents is often needed to treat the injury caused by immune and autoimmune processes and can lead to complete remission in all iDILI types with the exception of the classic iDILI, where only a subset of the patients achieve remission. At the molecular pathomechanistic level, there is a complex interplay mostly related to the adaptive immune system activated by the innate system. In sum, immunology and autoimmunity specifics in cases of RUCAM-ascertained iDILI types, as part of a refined classification, remain a challenging topic that can be deepened by future cases if validated diagnostic algorithms are applied.
2026-08-06 | Carbamazepine-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Spectrum: A Life-threatening Cutaneous Reaction in Epilepsy Management.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions, most commonly triggered by medications such as aromatic antiepileptics. We report the case of SJS/TEN overlap in an adolescent female with epilepsy following initiation of carbamazepine. The patient developed prodromal fever, sore throat, and mucocutaneous lesions within 1 week of therapy, progressing to widespread erythematous rash, blistering, and epidermal detachment involving >10% body surface area. All suspected drugs were promptly discontinued, and the patient was managed with supportive care, systemic corticosteroids, and cyclosporine, leading to gradual clinical improvement and complete recovery. Causality assessment using the Naranjo algorithm for drug causality for epidermal necrolysis scores suggested a probable association with carbamazepine. This case highlights the importance of early recognition, prompt drug withdrawal, and timely initiation of immunomodulatory therapy in improving outcomes. It also underscores the need for careful drug selection and consideration of genetic susceptibility in high-risk populations.
2026-07-22 | A clinical case of successful treatment of Stevens-Johnson syndrome in combination with disseminated intravascular coagulation syndrome
The article describes the case of a 45-year-old male patient who developed Stevens-Johnson syndrome (SJS), likely drug-induced (NSAIDs, metronidazole, ceftriaxone), prescribed for a traumatic tibia fracture and infected abrasions. The condition progressed rapidly with skin involvement of less than 10% of the body surface area but with severe mucosal lesions, consistent with SJS. The disease course was further complicated by the development of DIC, manifesting as critical hypocoagulation. Other complications included nosocomial pneumonia and deep vein thrombosis. Key interventions involved a complex balance of simultaneous treatment for both conditions: high-dose intravenous dexamethasone (12 mg twice daily) for SJS and transfusions of fresh frozen plasma (FFP) to correct the coagulopathy, alongside broad-spectrum antibiotics and anticoagulant therapy. Despite the high risk of exacerbating SJS with FFP administration, this intervention was vitally necessary and successfully resolved DIC within 48 hours. Treatment required a multidisciplinary approach and meticulous wound care. Although SJS and DIC were successfully controlled, the patient subsequently developed a localized wound infection, necessitating transfer to a specialized surgical department. This case demonstrates the importance of early DIC diagnosis in SJS patients, cautious yet decisive correction of coagulopathy, and continuous collaboration between intensivists, internists, pulmonologists, dermatologists, hematologists, and surgeons.
2026-07-22 | Proportion of Antiepileptic Drug-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Meta-Analysis.
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. To evaluate the proportion of AED-associated SJS/TEN. The MEDLINE and Embase databases were searched from inception through March 17, 2026, with results limited to English-language publications and human participants. All experimental and observational studies that reported patient-level triggers of SJS/TEN were included. 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. To estimate the proportion of AED-associated SJS/TEN. 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). 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.
2026-07-16 | Successful management of pembrolizumab-associated Stevens-Johnson syndrome/toxic epidermal necrolysis in a patient with uterine serous carcinoma: a case report.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening cutaneous adverse reactions associated with immune checkpoint inhibitors (ICIs). Evidence guiding optimal management remains limited. We report the case of a 75-year-old woman with stage IV endometrial carcinoma who developed extensive epidermal necrosis three weeks after the second cycle of maintenance pembrolizumab. Skin biopsy confirmed full-thickness epidermal necrosis, and the SCORTEN score was 3, predicting a high risk of mortality. There was no significant ocular or mucosal involvement. The patient was treated with etanercept, cyclosporine, and pulse methylprednisolone, followed by tapering oral corticosteroids alongside meticulous supportive care. Epidermal detachment stabilized rapidly after therapy and early re-epithelialization occurred within 10 days. The case highlights the importance of early recognition and judicious use of combination immunomodulatory therapy leading to improved outcomes. Multidisciplinary management is essential.
cell therapies
2026-07-21 | Route-Dependent Therapeutic Effects and Tissue Retention of Mesenchymal Stem Cell-Derived Exosomes in a Murine Model of Stevens-Johnson Syndrome.
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). 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. 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. 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.
2026-02-06 | Efficacy of Cultivated Oral Mucosal Epithelial Transplantation for Limbal Stem Cell Deficiency in Stevens-Johnson Syndrome Versus Other Etiologies.
The aim of this study was to compare the efficacy and outcomes of cultivated oral mucosal epithelial transplantation (COMET) in limbal stem cell deficiency (LSCD) between patients with Stevens-Johnson syndrome (SJS) and those with other etiologies (non-SJS), evaluated by clinical manifestations and epithelial phenotypes. This prospective, comparative study enrolled patients with LSCD who were scheduled for COMET. Preoperative and postoperative assessments were performed using slit-lamp microscopy, in vivo confocal microscopy (IVCM), and impression cytology with immunofluorescence staining. Successful outcomes were defined as an intact ocular surface without conjunctivalization and the presence of cornea-like epithelium detected by IVCM and/or immunofluorescence staining at the central cornea. Otherwise, the outcomes were interpreted as failure. Visual improvement and risk factors of COMET failure were analyzed. Eighteen eyes of 18 patients (7 with SJS, 11 non-SJS) were included. The median follow-up time was 15.5 months (range: 13-35 months). The overall success rate was 72.2% (13 eyes: 2 with SJS and 11 non-SJS), which was significantly lower in patients with SJS (28.6%) than in non-SJS patients (100%) (P = 0.002). Among successful cases, 60.2% showed visual improvement while the others (30.8%) remained unchanged. The risk of COMET failure was significantly associated with SJS (P = 0.002), lid margin keratinization (P = 0.023), preoperative symblepharon (P = 0.036), postoperative epithelial defects lasting more than 2 weeks (P = 0.022), and the absence of multilayered cornea-like epithelium detected by IVCM at 6 months postoperatively (P = 0.017). COMET demonstrates good efficacy and favorable outcomes for LSCD, particularly in non-SJS eyes. While the success rate was excellent in non-SJS patients, the outcomes were significantly limited in those with SJS.
2026-01-10 | Outcome of sutureless amniotic membrane dressing ring for acute Stevens-Johnson syndrome with severe ocular involvement: A case report of 5 patients.
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis can lead to severe ocular damage and long-term vision complications. Our self-made sutureless amniotic membrane dressing (AMD) ring leverages the anti-inflammatory and regenerative properties of the amniotic membrane (AM), promoting healing, reducing scarring, and enhancing patient comfort. Five consecutive patients (3 females, 2 males; aged from 18 to 53 years) with acute SJS/TEN were at immediate risk of significant ocular surface damage, including corneal and conjunctival epithelial defects and eyelid margin erosions, which can progress to chronic dry eye, scarring, or permanent vision loss without timely intervention. All patients were diagnosed with SJS/TEN based on their clinical presentations, including acute onset of mucocutaneous eruptions and extensive epidermal detachment, and comprehensive histories, confirmed by a dermatologist. Ocular involvement was assessed through detailed ophthalmologic examination and classified using the Sotozono grading system. A self-made AMD ring, inspired by commercially available products such as Prokera, was used to cover the ocular surface. Constructed from readily available materials, this ring provides therapeutic benefits similar to Prokera without the need for suturing. High epithelial healing rates and stable follow-up visual acuity underscore this technique's potential efficacy in selected SJS/TEN cases with severe ocular involvement. Early and accessible interventions are essential for managing SJS/TEN-related ocular complications. The self-made AMD ring is a cost-effective and minimally invasive option that shows potential as an alternative to commercial AM devices, particularly in settings where availability or affordability is limited. Further research with larger cohorts is warranted to confirm its efficacy.
2025-12-29 | Case Report: Successful weaning after 113 days of VV-ECMO in a pediatric patient with severe ARDS following Stevens-Johnson syndrome.
Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an established rescue therapy for severe pediatric acute respiratory distress syndrome (ARDS), but prolonged support is rarely reported. We describe the case of a previously healthy 6-year-old boy who developed Stevens-Johnson syndrome (SJS), complicated by progressive respiratory failure and severe ARDS. Despite maximal ventilation, oxygenation remained insufficient, and VV-ECMO was initiated on day 11 of illness. Cannulation was performed via jugular and femoral access, followed by lung-protective ventilation, repeated surfactant administration, corticosteroid therapy according to the Meduri protocol, and angiotensin-converting enzyme inhibitor therapy. ECMO support was complicated by pulmonary fibrosis, cholestatic liver dysfunction with secondary hemochromatosis, and prolonged sedation-associated delirium with subsequent critical illness polyneuropathy. The first attempt to discontinue ECMO after 90 days failed due to presumed pulmonary embolism, requiring recannulation. Ultimately, successful weaning was achieved after 113 days of VV-ECMO. The patient was transferred to a specialized pulmonary and neurological rehabilitation center and discharged home after 6 months, still dependent on a tracheostomy cannula. At the 18-month follow-up, he required only nocturnal mechanical ventilation through the tracheostomy, was attending school, and led an otherwise normal life. A trial removal of the cannula with closure of the stoma is scheduled for spring 2026. This case illustrates that prolonged VV-ECMO can allow lung recovery in pediatric patients with ARDS secondary to SJS, despite complications. Careful multidisciplinary management and preserved neurological function were key factors supporting long-term survival.
2025-12-11 | Long-Term Outcomes of Boston Type I Keratoprosthesis After Minor Salivary Gland Transplantation and Labial Mucous Membrane Grafting as an Alternative Treatment for Stevens-Johnson Syndrome.
Total limbal stem cell deficiency (LSCD), severe dry eye disease (DED), and ocular surface keratinization are severe ocular complications of Stevens-Johnson syndrome (SJS) that can be difficult to manage, resulting in poor visual outcomes. Several ocular surface reconstruction and visual rehabilitation techniques have been attempted with no satisfactory outcomes to date. Our purpose is to assess the functional and anatomical outcomes of Boston keratoprosthesis type I (Kpro-I) after minor salivary glands transplantation (mSG) and labial mucous membrane (MMG) grafting in patients with SJS suffering from total LSCD, DED, and ocular surface keratinization. This is a retrospective multicenter case series from 2 tertiary referral centers (New England Eye Center, Tufts Medical Center, Boston, Massachusetts and Federal University of Sao Paulo) assessing long-term outcomes of patients with SJS with severe ocular complications who received mSG/MMG grafting before Kpro-I implantation, including best-corrected visual acuity, Kpro-I device retention, and postoperative complications. Three patients with SJS with severe ocular complications (total LSCD, symblepharon, DED, and ocular surface keratinization) were treated with mSG/MMG grafting, followed by Kpro-I. Ocular surface keratinization was ameliorated in all patients after mSG. At the end of the long-term follow-up period, all patients retained the Kpro-I (33-63 months) and achieved improved visual acuity (20/40, 20/80, 20/100). Complications included glaucoma (n = 1), requiring a glaucoma drainage device; peripheral corneal thinning (n = 2), which was treated with a corneal patch graft; postoperative infectious keratitis (n = 1); cystoid macular edema (n = 1); and retroprosthetic membrane (n = 1), which was successfully treated. mSG/MMG grafting can optimize the ocular surface to allow for successful Kpro-I in patients with severe SJS, providing an alternative approach to Boston type II Kpro.
antibodies
2026-07-31 | Clinical Heterogeneity in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Case Series
Abstract Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening mucocutaneous disorders, characterised by extensive epidermal necrosis and severe mucosal involvement. Although drugs remain the most frequent triggers, infectious and autoimmune aetiologies may closely mimic classical SJS/TEN, leading to diagnostic delay and inappropriate management. We report three clinically heterogeneous cases of epidermal necrolysis with differing underlying aetiologies, emphasising detailed clinical presentation, serial severity-of-illness score for toxic epidermal necrolysis-based prognostic assessment, management strategies and outcomes. All patients demonstrated clinical improvement following aetiological differentiation, meticulous supportive care and individualised immunomodulatory therapy. This case series highlights the importance of comprehensive clinical evaluation, dynamic prognostication and tailored management in epidermal necrolysis.
2026-07-16 | Life-threatening multiorgan immune-related toxicities complicated by sepsis after anti-PD-1 therapy with complete tumor regression: a case report and literature review.
Immune checkpoint inhibitors (ICIs) enhance antitumor immunity but can disrupt immune tolerance, leading to immune-related adverse events (irAEs) affecting multiple organs. Simultaneous life-threatening multiorgan irAEs remain rare and poorly characterized, particularly in head and neck cancer. A 73-year-old man with sinonasal squamous cell carcinoma developed fulminant multisystem immune toxicity after a single dose of pembrolizumab combined with nab-paclitaxel. The clinical course was marked by Stevens-Johnson syndrome, hematologic and renal failure, pneumonitis, metabolic dysregulation, and recurrent sepsis requiring intensive care. A multidisciplinary strategy, including team discussion, intensive care, corticosteroids and two courses of intravenous immunoglobulin (IVIG), was employed. Dose-escalated corticosteroids may cause potent immunosuppression and potentially raise the risk of opportunistic infections. IVIG serves as an immunomodulator which can balance immune control with infection risk. His organ function recovered despite concurrent catheter-related systemic infection. Remarkably, the patient achieved complete tumor regression after one treatment cycle and disease-free duration was 6 months. This case illustrates the extreme spectrum of immunologic dysregulation associated with PD-1 blockade and highlights the importance of rapid and early diagnosis, multidisciplinary management, and risk-adapted immunomodulation. IVIG may represent a pragmatic therapeutic strategy when escalation of immunosuppression is limited by infection risk. Further investigation is needed to optimize prediction and management of life-threatening multiorgan irAEs.
2026-06-24 | Biologics and Small Molecule Inhibitors: Novel Therapeutic Strategies for Cutaneous Adverse Drug Reactions.
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.
2026-06-22 | A Systematic Review of Literature: TNF-α Blockers and JAK Inhibitors for the Treatment of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Severe Forms of Erythema Multiforme.
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.
2026-06-15 | Immunological Interplay at the Ocular Surface of Stevens-Johnson Syndrome, Ocular Cicatricial Pemphigoid, and Ocular Graft Versus Host Disease.
Rare ocular surface inflammatory disorders (OSIDs), such as ocular cicatricial pemphigoid (OCP; 1.3-2/million), Stevens-Johnson Syndrome (SJS; 1-5/million), and ocular graft versus host disease (oGVHD; occurring in >50% of chronic GVHD cases) share overlapping clinical phenotypes. Their defining features include conjunctival cicatrization and chronic inflammation. An incomplete understanding of the underlying immunopathogenesis of these conditions has hindered the development of targeted therapies, leaving patients at risk of permanent vision loss and highlighting the need to define distinct ocular immune profiles. Existing literature indicates elevated levels of neutrophils and macrophages/monocytes, along with major increases in their related secretory factors, IL-8 (P < 0.05) and TNF-α (P < 0.05), at the ocular surface across all three groups. Whereas both B cells and cytotoxic T cells are elevated in oGVHD, OCP is characterized by elevated B cells and a concomitant reduction in cytotoxic T cells. Apart from neutrophils and macrophages/monocytes, the local immune landscape-especially in SJS-has been underexplored. At the molecular level, extensive studies of tears have reported elevated levels of IL-17, CXCR1 (P < 0.01), CTGF (P < 0.05) in OCP; IFN-α and IFN-γ (P < 0.05) in oGVHD; and MCP-1, MIP-1β (P < 0.05) in SJS. These studies also indicate that sampling methods and patients' medication status may influence immune profile outcomes. Comprehensive immunophenotyping studies, coupled with the establishment of pathological links to respective molecular profiles, could advance understanding of condition-specific disease biology.
other
2026-05-17 | Sulfamethoxazole-trimethoprim-induced Stevens-Johnson syndrome in a NAT2 slow acetylator: A case for pre-emptive pharmacogenomic screening?
Severe Cutaneous Adverse Reactions (SCAR), such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), are serious complications associated with several high-risk medications and can result in significant morbidity and mortality. While HLA-mediated SCARs have been well-characterized-particularly involving drugs like carbamazepine, abacavir, and allopurinol-there is limited data on the role of N-acetyltransferase 2 (NAT2) polymorphisms in SCAR pathogenesis. We present a case of sulfamethoxazole-trimethoprim-(SMX-TMP)- induced SJS (Naranjo probability score: seven), hypothesized to be linked to NAT2 slow acetylator (SA) status. This case underscores the potential utility of pre-emptive pharmacogenomic screening to reduce the incidence of SCARs. NAT2 SA status has also been strongly associated with isoniazid-induced liver injury; Clinical Pharmacogenetics Implementation Consortium (CPIC) recently published a guideline that NAT2 SA predicted for hydralazine-induced systemic lupus erythematosus (SLE) and were at higher risk of side effects, suggesting broader clinical implications for routine NAT2 genotyping.1 Aside from G6PD testing, there is an emergent role to test for NAT2 genotype in preparation for SMX-TMP therapy. Clinically relevant NAT2 alleles include *4, *5, *6, and *7. Given that multiple single nucleotide variant (SNV) must be tested, multiplex pharmacogenomic panels may offer a more cost-effective and comprehensive approach than reactive testing. Some multiplex panels that may be employed include: GeneXpert NAT2-PGx Assay--a rapid assay targeting 5 key polymorphisms to predict isoniazid-acetylation, nanopore sequencing-based panels --a scalable targeted sequencing panel useful for NAT2 and other antitubercular genes (rifampicin, linezolid and bedaquiline), Fulgent genetics pharmacogenomics comprehensive panel, CleanPlex® pharmacogenomics kit and GenoPharm®.
2024-10-15 | Implementation of HLA-related genotype-guided prescribing in Singapore.
To describe the implementation of human leukocyte antigen (HLA)-related genotype-guided prescribing in Singapore. Various HLA alleles have been implicated in drug hypersensitivity syndromes (DHS). These include HLA-B*15:02, which has been associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, HLA-B*58:01, which has been associated with increased risk of severe cutaneous adverse reactions with allopurinol use, and HLA-B*57:01, which has been associated with increased risk of hypersensitivity reactions with abacavir use. Integrating pharmacogenomics into patient care through genotype-guided prescribing potentially optimizes use of these drugs by reducing DHS-related and healthcare costs. We describe the prevalence of HLA-related DHS in Singapore, the cost-effectiveness of genotype-guided prescribing, and local policies and guidelines, as well as the impact of genotype-guided prescribing where available. HLA-related genotype-guided prescribing has the potential to reduce the incidence of DHS and decrease healthcare costs, as seen in the success with carbamazepine. However, not all genotype-guided prescribing is cost-effective when implemented across the population, as was evident from local studies for allopurinol and abacavir. The cost-effectiveness of such measures may change over time with new data (eg, allele frequencies, test costs, drug prices, genotyping approach) and should be evaluated periodically and locally. Implementation of preemptive pharmacogenomics panel testing as part of routine clinical care may shift the threshold for cost-effectiveness and brings promise of further optimization of pharmacotherapy through precision medicine.
2024-09-20 | A case of Stevens–Johnson syndrome after influenza a virus infection
Stevens–Johnson syndrome (SJS) is characterized by widespread erythema, erosions, blisters, and epidermal necrosis. While drugs are a common cause, infections such as mycoplasma and herpes simplex virus can also induce SJS. We present a case of SJS triggered by an influenza infection. A 17-year-old male with a history of SJS at age 12 during an influenza B infection developed symptoms again after contracting influenza A identified by rapid antigen test. He took Kakkonto twice on the first day of the fever and the next day, and the fever was resolved within 2 days. However, 9 days post-onset, he relapsed with a 38°C fever, lip swelling, oral erosions, and eyelid edema, prompting a visit to our department. On admission, examination revealed swollen lips with yellow crusts, oral erosions, conjunctival hyperemia of the eyelids, and erosions on the glans (Figure 1a–c). Tests for streptococcal antigens and mycoplasma (LAMP method) were negative. An antibody test for herpes simplex virus indicated a previous infection. A lip skin biopsy showing lymphocytic infiltration and necrosis of the squamous epithelium confirmed SJS without skin lesions (Figure 1d). The timing between Kakkonto administration and symptom onset negated drug-induced SJS, leading us to conclude that the SJS was triggered by the influenza infection. He received prednisolone 50 mg on day 1. However, due to the development of pseudomembranous conjunctivitis, glucocorticoid pulse therapy was performed on days 2–4. Prednisolone 55 mg was restarted on day 5, and intravenous immunoglobulin therapy was conducted from day 8. The conjunctivitis and mucosal eruptions were improved, and he was discharged without relapse. Seven months later, cytotoxic T lymphocyte populations in peripheral blood mononuclear cells (PBMC) were analyzed using HLA-matched influenza tetramers and flow cytometry; we detected 2.3% tetramer-positive cells in the CD8+ T cell population (Figure 1e). Mycoplasma and herpes simplex virus infections are known infectious causes of SJS, although other contagious agents are rarely implicated.1 The pathogenesis of infection-induced SJS remains unclear. However, some cases of SJS following influenza infection occurred without prior drug exposure, suggesting a direct causal relationship between the influenza infection and SJS onset.2, 3 This patient, having experienced SJS at age 12, had been regularly vaccinated against influenza every year, except this year, and did not develop SJS subsequently. The influenza vaccine, being an inactivated formulation, does not contain live virus and thus lacks infectivity.4 Although there is a theoretical risk that the influenza vaccine itself could trigger SJS, there is no definitive evidence suggesting that vaccination increases the risk of developing SJS.5 We recommend annual influenza vaccination for this patient to prevent SJS triggered by influenza infection. Although no clear association between the onset of SJS and the presence of influenza-specific CD8-positive cells has been demonstrated, clear positive cells were still evident in the peripheral blood 7 months after the onset of influenza, and accumulating case studies may shed light on the potential links between viral infections and SJS. Infection-triggered SJS, while rare, underscores the need to consider a variety of viral infections as possible causes. None of the authors received any financial support for the present study. The authors received no financial support for the present case. Keiichi Yamanaka is an Editorial Board member of the Journal of Dermatology and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Other authors have declared no conflicting interests.
2022-07-05 | Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand
Objective: This study aimed to investigate the clinical impact of HLA-B*15:02 pharmacogenomics (PGx) testing before carbamazepine (CBZ)/oxcarbazepine (OXC) prescriptions and to determine whether this PGx testing was associated with the reduction of CBZ/OXC-induced cutaneous adverse drug reactions (CADRs) in Thailand. Methods: This retrospective observational cohort study was conducted by obtaining relevant HLA-B*15:02 PGx-testing and clinical data from electronic medical records during 2011–2020. 384 patient data were included in this study to investigate the clinical decision on CBZ/OXC usage before and after the HLA-B*15:02 PGx testing, and 1,539 patient data were included in this study to demonstrate the incidence of CBZ/OXC-induced SCARs and SJS between HLA-B*15:02 tested and non-tested patients. To analyze and summarize the results, descriptive statistics were employed, and Fisher exact test was used to compare the clinical difference between the HLA-B*15:02 positive and negative groups and to compare the differences of SCARs incidence. Results: 384 patients were included in this study as per the inclusion criteria. Of these, 70 patients carried HLA-B*15:02, of which 63 and 65 patients were not prescribed with CBZ/OXC before and after the availability of genotyping results, respectively. In the remaining HLA-B*15:02 non-carriers, 48, and 189 patients were prescribed CBZ/OXC before and after genotyping results were available, respectively. The findings of this study showed that the incidence of SCARs of CBZ/OXC was significantly lower ( p < 0.001) in the HLA-B*15:02 screening arm than in the non-screening arm. Conclusion: HLA-B pharmacogenetics testing influenced the selection of appropriate AEDs. The presence of mild rash in the HLA-B*15:02 negative group indicates that other genetic biomarker ( HLA-A*31:01 ) and/or non-genetic variables are involved in CBZ/OXC-induced CADRs, emphasizing that CBZ/OXC prescriptions necessitate CADR monitoring. The hospital policy and clinical decision support (CDS) alert system is essential to overcome the barriers associated with the utilization of PGx guidelines into clinical practice.
2022-04-14 | Allopurinol-induced severe cutaneous adverse reactions in Vietnamese: the role of HLA alleles and other risk factors.
Aim: To reveal the association of three class I HLA alleles, including HLA-A*33:03, HLA-B*58:01 and HLA-C*03:02, and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. Methods: A case-control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The HLA-A*33:03 and HLA-C*03:02 alleles were detected with the nested allele-specific PCR method; the HLA-B*58:01 allele was detected with the sequence-specific primer PCR method. Results: There were strong associations between HLA-B*58:01 and HLA-C*03:02 and allopurinol-induced SCARs. Specific associations were found between HLA-B*58:01 and Stevens-Johnson syndrome/toxic epidermal necrolysis and between HLA-C*03:02 and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: HLA-B*58:01/HLA-C*03:02 and estimated glomerular filtration rate <60 ml/min/1.73 m2. The specificity, positive predictive value and negative predictive value of HLA-B*58:01 testing were higher than the HLA-C*03:02 or the multiplex testing, especially in patients with impaired renal function. Conclusion: The results supported pre-treatment HLA-B*58:01 testing in Vietnamese patients with declined renal function to prevent SCARs.
proteins
2026-02-09 | Treatment of toxic epidermal necrosis lesions with ovine forestomach matrix.
Stevens-Johnson syndrome and toxic epidermal necrosis (TEN) are used to describe a spectrum of acute mucocutaneous reactions primarily affecting the skin and mucous membranes, resulting in painful blisters and epidermal detachment. Swift diagnosis followed by management of the damaged epidermis is vital to prevent further infection, which if left untreated can become life-threatening. We report a case of TEN in a 42-year-old female who presented with 55% epidermal loss. Over the course of 41 days, the affected regions were treated with ovine forestomach matrix (OFM) grafts, which led to epithelial restoration of the lesions in 1-2 weeks with good functional and cosmetic outcomes. This case is the first documented use of OFM in the treatment of TEN lesions.
2025-12-04 | Evaluation of umbilical cord blood serum eye drops for severe dry eye in two distinct populations-Sjögren's syndrome and mustard gas-induced ocular injury: Protocol for a pilot randomized clinical trial.
Human umbilical cord blood (HUCB) serum eye drops contain growth factors, neurotrophic agents, and antimicrobial compounds that may promote ocular surface healing and regeneration. Sjögren's syndrome is a chronic autoimmune condition characterized by reduced tear production and ocular surface damage, often resulting in severe dry eye symptoms. Mustard gas chemical veterans also suffer from similar debilitating ocular complications due to chronic inflammation and meibomian gland dysfunction. While conventional treatments offer symptomatic relief, they lack essential components of natural tears. This pilot randomized controlled trial will evaluate the efficacy of HUCB eye drops in three patient groups: (A) Sjögren's patients treated with HUCB drops, (B) Sjögren's patients receiving conventional treatment, and (C) mustard gas veterans receiving conventional treatment in the right eye and HUCB drops in the left eye. Patients will be assessed using subjective and objective tools, including the Ocular Surface Disease Index (OSDI), visual acuity, tear film breakup time (TBUT), SM tube test, and fluorescein staining based on SICCA criteria. Group allocation will follow a blocked randomization sequence for groups A and B; group C will follow a within-subject paired-eye design. Follow-up will occur at 30 and 60 days. This study aims to assess the regenerative potential of HUCB serum in patients with autoimmune and chemically induced dry eye. Its results may support broader clinical use of HUCB drops in treating severe ocular surface disorders, including conditions like Stevens-Johnson syndrome and industrial chemical exposures. This trial was registered at the Iranian Registry of Clinical Trials (Registration number: IRCT20230925059512N1, Registration date: 2024-08-11).
2025-12-01 | A Novel Case of Biktarvy-Associated Stevens-Johnson Syndrome With Severe Ocular Involvement
Purpose: The purpose of this study was to describe the first reported case of Stevens-Johnson syndrome (SJS) associated with bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), highlighting a rare presentation with severe ocular and oral involvement in the absence of cutaneous findings. Case report: A 59-year-old woman developed mucosal-limited SJS 2 weeks after initiating Biktarvy as postexposure prophylaxis. She presented with severe bilateral ocular involvement—characterized by extensive conjunctival and corneal epithelial defects, pseudomembranes, and symblepharon—as well as painful oral ulcerations, but no skin rash. She was treated with topical corticosteroids, antibiotics, and immunomodulators, in addition to multiple amniotic membrane transplants and supportive measures. Persistent corneal epithelial defects were ultimately resolved with cenegermin-bkbj 0.002% therapy. At final follow-up, her visual acuity was 20/20 in both eyes with minimal residual ocular surface damage. Conclusions: This case illustrates an atypical presentation of medication-associated SJS without skin involvement, triggered by a previously unreported agent. Clinicians should recognize that antiretroviral drugs such as Biktarvy may induce SJS and that mucosal-limited disease can cause profound ocular morbidity. Prompt ophthalmologic assessment and early surgical intervention with amniotic membrane transplants are crucial to preserving vision.
2025-08-25 | Ocular Complications in stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comprehensive Review.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are rare but life-threatening mucocutaneous disorders, primarily triggered by adverse drug reactions. Although systemic manifestations have been extensively studied, ocular involvement remains a major cause of morbidity, often resulting in severe visual impairment or blindness. This narrative review synthesizes current evidence regarding the clinical presentation, pathophysiology, and management strategies for ocular complications in SJS/TEN. A comprehensive literature search was conducted to highlight both acute and chronic ophthalmic manifestations and therapeutic interventions. Ocular involvement is reported in up to 75% of SJS/TEN patients during the acute phase, manifesting as conjunctivitis, pseudomembrane formation, corneal erosions, and eyelid abnormalities. Early interventions such as lubrication, topical corticosteroids, and amniotic membrane transplantation (AMT) have shown efficacy in mitigating long-term damage. Nonetheless, a substantial number of patients develop chronic complications including symblepharon, limbal stem cell deficiency, and severe dry eye syndrome. Long-term management involves scleral lenses and surgical procedures such as limbal stem cell transplantation, mucous membrane grafting (MMG), and keratoprosthesis. Innovations like ProKera® have improved epithelial healing, yet irreversible damage from the acute phase remains a persistent challenge. Ocular complications of SJS/TEN are multifaceted and necessitate early and sustained multidisciplinary management. Timely ophthalmologic intervention is crucial in the acute phase, while chronic care aims to restore ocular surface stability and preserve vision. Further research is needed to develop standardized treatment protocols and explore emerging therapies that may enhance long-term outcomes and quality of life.
2025-04-28 | A Case-Based Approach to the Management of Corneal Melts and Perforations in Ocular Surface Disorders.
Corneal perforations caused by chronic ocular surface disorders present significant management challenges and can lead to blindness if untreated. This case series reviews the pathophysiology of corneal melts and examines treatment strategies tailored to the size, location, and etiology of perforations in conditions such as Stevens-Johnson syndrome, graft-versus-host disease, and chemical injuries. Through detailed case analyses, various interventions, including cyanoacrylate glue, Tenon's patch grafting, mucous membrane grafts, scleral patch grafts, and conjunctival flaps, were evaluated, along with emerging therapies like biosynthetic hydrogels and collagen-like peptides. Findings highlight the role of chronic inflammation and adnexal abnormalities in disrupting ocular surface integrity, affecting treatment outcomes. This case series underscores the importance of a comprehensive approach that not only repairs corneal defects but also addresses underlying systemic and ocular conditions, with advancements in biosynthetic materials showing promise for improving patient outcomes.
small molecules
2026-08-12 | RUCAM-ascertained immunology and autoimmunity specifics of six idiosyncratic drug-induced liver injury types with refined classification: their individual complex molecular interplay.
Idiosyncratic drug-induced liver injury (iDILI) is not a uniform disease but rather includes a variety of types based on immune, autoimmune, and clinical considerations. This review attempts to close information gaps regarding the role of immunity and autoimmunity involved in the different iDILI disease types. The analysis of the current literature focusing on iDILI reveals compelling evidence of a pivotal role of immunity or autoimmunity in various types of iDILI. Among the autoimmune-triggered ones are the drug-induced autoimmune hepatitis (DIAIH) and the idiosyncratic drug-induced anti-CYP autoimmune hepatitis. In contrast, clearly immune-triggered are the human leukocyte antigen (HLA)-based immune iDILI, the immune iDILI with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and the immune iDILI induced by immune checkpoint inhibitors (ICIs), but immune-triggered mechanisms account for only a part of the classic iDILI cases. For all these iDILI types, the use of the original or updated Roussel Uclaf Causality Assessment Method (RUCAM) allowed for confirming causality of the implicated drug, assisted by the simplified autoimmune hepatitis (AIH) score in the DIAIH cases and the Algorithm of Drug Causality for Epidermal Necrolysis (ALDEN) score in the cases of immune-based iDILI with SJS/TEN. All these diagnostic causality assessment algorithms are validated methods and have helped define clinical features of the different iDILI types. The first treatment goal is the cessation of the suspected drug, which alone may lead to clinical and laboratory improvement and restoration of health. However, therapy with immunosuppressive agents is often needed to treat the injury caused by immune and autoimmune processes and can lead to complete remission in all iDILI types with the exception of the classic iDILI, where only a subset of the patients achieve remission. At the molecular pathomechanistic level, there is a complex interplay mostly related to the adaptive immune system activated by the innate system. In sum, immunology and autoimmunity specifics in cases of RUCAM-ascertained iDILI types, as part of a refined classification, remain a challenging topic that can be deepened by future cases if validated diagnostic algorithms are applied.
2026-08-06 | Carbamazepine-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Spectrum: A Life-threatening Cutaneous Reaction in Epilepsy Management.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions, most commonly triggered by medications such as aromatic antiepileptics. We report the case of SJS/TEN overlap in an adolescent female with epilepsy following initiation of carbamazepine. The patient developed prodromal fever, sore throat, and mucocutaneous lesions within 1 week of therapy, progressing to widespread erythematous rash, blistering, and epidermal detachment involving >10% body surface area. All suspected drugs were promptly discontinued, and the patient was managed with supportive care, systemic corticosteroids, and cyclosporine, leading to gradual clinical improvement and complete recovery. Causality assessment using the Naranjo algorithm for drug causality for epidermal necrolysis scores suggested a probable association with carbamazepine. This case highlights the importance of early recognition, prompt drug withdrawal, and timely initiation of immunomodulatory therapy in improving outcomes. It also underscores the need for careful drug selection and consideration of genetic susceptibility in high-risk populations.
2026-07-22 | A clinical case of successful treatment of Stevens-Johnson syndrome in combination with disseminated intravascular coagulation syndrome
The article describes the case of a 45-year-old male patient who developed Stevens-Johnson syndrome (SJS), likely drug-induced (NSAIDs, metronidazole, ceftriaxone), prescribed for a traumatic tibia fracture and infected abrasions. The condition progressed rapidly with skin involvement of less than 10% of the body surface area but with severe mucosal lesions, consistent with SJS. The disease course was further complicated by the development of DIC, manifesting as critical hypocoagulation. Other complications included nosocomial pneumonia and deep vein thrombosis. Key interventions involved a complex balance of simultaneous treatment for both conditions: high-dose intravenous dexamethasone (12 mg twice daily) for SJS and transfusions of fresh frozen plasma (FFP) to correct the coagulopathy, alongside broad-spectrum antibiotics and anticoagulant therapy. Despite the high risk of exacerbating SJS with FFP administration, this intervention was vitally necessary and successfully resolved DIC within 48 hours. Treatment required a multidisciplinary approach and meticulous wound care. Although SJS and DIC were successfully controlled, the patient subsequently developed a localized wound infection, necessitating transfer to a specialized surgical department. This case demonstrates the importance of early DIC diagnosis in SJS patients, cautious yet decisive correction of coagulopathy, and continuous collaboration between intensivists, internists, pulmonologists, dermatologists, hematologists, and surgeons.
2026-07-22 | Proportion of Antiepileptic Drug-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Meta-Analysis.
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. To evaluate the proportion of AED-associated SJS/TEN. The MEDLINE and Embase databases were searched from inception through March 17, 2026, with results limited to English-language publications and human participants. All experimental and observational studies that reported patient-level triggers of SJS/TEN were included. 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. To estimate the proportion of AED-associated SJS/TEN. 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). 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.
2026-07-16 | Successful management of pembrolizumab-associated Stevens-Johnson syndrome/toxic epidermal necrolysis in a patient with uterine serous carcinoma: a case report.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening cutaneous adverse reactions associated with immune checkpoint inhibitors (ICIs). Evidence guiding optimal management remains limited. We report the case of a 75-year-old woman with stage IV endometrial carcinoma who developed extensive epidermal necrosis three weeks after the second cycle of maintenance pembrolizumab. Skin biopsy confirmed full-thickness epidermal necrosis, and the SCORTEN score was 3, predicting a high risk of mortality. There was no significant ocular or mucosal involvement. The patient was treated with etanercept, cyclosporine, and pulse methylprednisolone, followed by tapering oral corticosteroids alongside meticulous supportive care. Epidermal detachment stabilized rapidly after therapy and early re-epithelialization occurred within 10 days. The case highlights the importance of early recognition and judicious use of combination immunomodulatory therapy leading to improved outcomes. Multidisciplinary management is essential.
cell therapies
2026-07-21 | Route-Dependent Therapeutic Effects and Tissue Retention of Mesenchymal Stem Cell-Derived Exosomes in a Murine Model of Stevens-Johnson Syndrome.
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). 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. 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. 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.
2026-02-06 | Efficacy of Cultivated Oral Mucosal Epithelial Transplantation for Limbal Stem Cell Deficiency in Stevens-Johnson Syndrome Versus Other Etiologies.
The aim of this study was to compare the efficacy and outcomes of cultivated oral mucosal epithelial transplantation (COMET) in limbal stem cell deficiency (LSCD) between patients with Stevens-Johnson syndrome (SJS) and those with other etiologies (non-SJS), evaluated by clinical manifestations and epithelial phenotypes. This prospective, comparative study enrolled patients with LSCD who were scheduled for COMET. Preoperative and postoperative assessments were performed using slit-lamp microscopy, in vivo confocal microscopy (IVCM), and impression cytology with immunofluorescence staining. Successful outcomes were defined as an intact ocular surface without conjunctivalization and the presence of cornea-like epithelium detected by IVCM and/or immunofluorescence staining at the central cornea. Otherwise, the outcomes were interpreted as failure. Visual improvement and risk factors of COMET failure were analyzed. Eighteen eyes of 18 patients (7 with SJS, 11 non-SJS) were included. The median follow-up time was 15.5 months (range: 13-35 months). The overall success rate was 72.2% (13 eyes: 2 with SJS and 11 non-SJS), which was significantly lower in patients with SJS (28.6%) than in non-SJS patients (100%) (P = 0.002). Among successful cases, 60.2% showed visual improvement while the others (30.8%) remained unchanged. The risk of COMET failure was significantly associated with SJS (P = 0.002), lid margin keratinization (P = 0.023), preoperative symblepharon (P = 0.036), postoperative epithelial defects lasting more than 2 weeks (P = 0.022), and the absence of multilayered cornea-like epithelium detected by IVCM at 6 months postoperatively (P = 0.017). COMET demonstrates good efficacy and favorable outcomes for LSCD, particularly in non-SJS eyes. While the success rate was excellent in non-SJS patients, the outcomes were significantly limited in those with SJS.
2026-01-10 | Outcome of sutureless amniotic membrane dressing ring for acute Stevens-Johnson syndrome with severe ocular involvement: A case report of 5 patients.
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis can lead to severe ocular damage and long-term vision complications. Our self-made sutureless amniotic membrane dressing (AMD) ring leverages the anti-inflammatory and regenerative properties of the amniotic membrane (AM), promoting healing, reducing scarring, and enhancing patient comfort. Five consecutive patients (3 females, 2 males; aged from 18 to 53 years) with acute SJS/TEN were at immediate risk of significant ocular surface damage, including corneal and conjunctival epithelial defects and eyelid margin erosions, which can progress to chronic dry eye, scarring, or permanent vision loss without timely intervention. All patients were diagnosed with SJS/TEN based on their clinical presentations, including acute onset of mucocutaneous eruptions and extensive epidermal detachment, and comprehensive histories, confirmed by a dermatologist. Ocular involvement was assessed through detailed ophthalmologic examination and classified using the Sotozono grading system. A self-made AMD ring, inspired by commercially available products such as Prokera, was used to cover the ocular surface. Constructed from readily available materials, this ring provides therapeutic benefits similar to Prokera without the need for suturing. High epithelial healing rates and stable follow-up visual acuity underscore this technique's potential efficacy in selected SJS/TEN cases with severe ocular involvement. Early and accessible interventions are essential for managing SJS/TEN-related ocular complications. The self-made AMD ring is a cost-effective and minimally invasive option that shows potential as an alternative to commercial AM devices, particularly in settings where availability or affordability is limited. Further research with larger cohorts is warranted to confirm its efficacy.
2025-12-29 | Case Report: Successful weaning after 113 days of VV-ECMO in a pediatric patient with severe ARDS following Stevens-Johnson syndrome.
Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an established rescue therapy for severe pediatric acute respiratory distress syndrome (ARDS), but prolonged support is rarely reported. We describe the case of a previously healthy 6-year-old boy who developed Stevens-Johnson syndrome (SJS), complicated by progressive respiratory failure and severe ARDS. Despite maximal ventilation, oxygenation remained insufficient, and VV-ECMO was initiated on day 11 of illness. Cannulation was performed via jugular and femoral access, followed by lung-protective ventilation, repeated surfactant administration, corticosteroid therapy according to the Meduri protocol, and angiotensin-converting enzyme inhibitor therapy. ECMO support was complicated by pulmonary fibrosis, cholestatic liver dysfunction with secondary hemochromatosis, and prolonged sedation-associated delirium with subsequent critical illness polyneuropathy. The first attempt to discontinue ECMO after 90 days failed due to presumed pulmonary embolism, requiring recannulation. Ultimately, successful weaning was achieved after 113 days of VV-ECMO. The patient was transferred to a specialized pulmonary and neurological rehabilitation center and discharged home after 6 months, still dependent on a tracheostomy cannula. At the 18-month follow-up, he required only nocturnal mechanical ventilation through the tracheostomy, was attending school, and led an otherwise normal life. A trial removal of the cannula with closure of the stoma is scheduled for spring 2026. This case illustrates that prolonged VV-ECMO can allow lung recovery in pediatric patients with ARDS secondary to SJS, despite complications. Careful multidisciplinary management and preserved neurological function were key factors supporting long-term survival.
2025-12-11 | Long-Term Outcomes of Boston Type I Keratoprosthesis After Minor Salivary Gland Transplantation and Labial Mucous Membrane Grafting as an Alternative Treatment for Stevens-Johnson Syndrome.
Total limbal stem cell deficiency (LSCD), severe dry eye disease (DED), and ocular surface keratinization are severe ocular complications of Stevens-Johnson syndrome (SJS) that can be difficult to manage, resulting in poor visual outcomes. Several ocular surface reconstruction and visual rehabilitation techniques have been attempted with no satisfactory outcomes to date. Our purpose is to assess the functional and anatomical outcomes of Boston keratoprosthesis type I (Kpro-I) after minor salivary glands transplantation (mSG) and labial mucous membrane (MMG) grafting in patients with SJS suffering from total LSCD, DED, and ocular surface keratinization. This is a retrospective multicenter case series from 2 tertiary referral centers (New England Eye Center, Tufts Medical Center, Boston, Massachusetts and Federal University of Sao Paulo) assessing long-term outcomes of patients with SJS with severe ocular complications who received mSG/MMG grafting before Kpro-I implantation, including best-corrected visual acuity, Kpro-I device retention, and postoperative complications. Three patients with SJS with severe ocular complications (total LSCD, symblepharon, DED, and ocular surface keratinization) were treated with mSG/MMG grafting, followed by Kpro-I. Ocular surface keratinization was ameliorated in all patients after mSG. At the end of the long-term follow-up period, all patients retained the Kpro-I (33-63 months) and achieved improved visual acuity (20/40, 20/80, 20/100). Complications included glaucoma (n = 1), requiring a glaucoma drainage device; peripheral corneal thinning (n = 2), which was treated with a corneal patch graft; postoperative infectious keratitis (n = 1); cystoid macular edema (n = 1); and retroprosthetic membrane (n = 1), which was successfully treated. mSG/MMG grafting can optimize the ocular surface to allow for successful Kpro-I in patients with severe SJS, providing an alternative approach to Boston type II Kpro.
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2026-07-31 | Clinical Heterogeneity in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Case Series
Abstract Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening mucocutaneous disorders, characterised by extensive epidermal necrosis and severe mucosal involvement. Although drugs remain the most frequent triggers, infectious and autoimmune aetiologies may closely mimic classical SJS/TEN, leading to diagnostic delay and inappropriate management. We report three clinically heterogeneous cases of epidermal necrolysis with differing underlying aetiologies, emphasising detailed clinical presentation, serial severity-of-illness score for toxic epidermal necrolysis-based prognostic assessment, management strategies and outcomes. All patients demonstrated clinical improvement following aetiological differentiation, meticulous supportive care and individualised immunomodulatory therapy. This case series highlights the importance of comprehensive clinical evaluation, dynamic prognostication and tailored management in epidermal necrolysis.
2026-07-16 | Life-threatening multiorgan immune-related toxicities complicated by sepsis after anti-PD-1 therapy with complete tumor regression: a case report and literature review.
Immune checkpoint inhibitors (ICIs) enhance antitumor immunity but can disrupt immune tolerance, leading to immune-related adverse events (irAEs) affecting multiple organs. Simultaneous life-threatening multiorgan irAEs remain rare and poorly characterized, particularly in head and neck cancer. A 73-year-old man with sinonasal squamous cell carcinoma developed fulminant multisystem immune toxicity after a single dose of pembrolizumab combined with nab-paclitaxel. The clinical course was marked by Stevens-Johnson syndrome, hematologic and renal failure, pneumonitis, metabolic dysregulation, and recurrent sepsis requiring intensive care. A multidisciplinary strategy, including team discussion, intensive care, corticosteroids and two courses of intravenous immunoglobulin (IVIG), was employed. Dose-escalated corticosteroids may cause potent immunosuppression and potentially raise the risk of opportunistic infections. IVIG serves as an immunomodulator which can balance immune control with infection risk. His organ function recovered despite concurrent catheter-related systemic infection. Remarkably, the patient achieved complete tumor regression after one treatment cycle and disease-free duration was 6 months. This case illustrates the extreme spectrum of immunologic dysregulation associated with PD-1 blockade and highlights the importance of rapid and early diagnosis, multidisciplinary management, and risk-adapted immunomodulation. IVIG may represent a pragmatic therapeutic strategy when escalation of immunosuppression is limited by infection risk. Further investigation is needed to optimize prediction and management of life-threatening multiorgan irAEs.
2026-06-24 | Biologics and Small Molecule Inhibitors: Novel Therapeutic Strategies for Cutaneous Adverse Drug Reactions.
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.
2026-06-22 | A Systematic Review of Literature: TNF-α Blockers and JAK Inhibitors for the Treatment of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Severe Forms of Erythema Multiforme.
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.
2026-06-15 | Immunological Interplay at the Ocular Surface of Stevens-Johnson Syndrome, Ocular Cicatricial Pemphigoid, and Ocular Graft Versus Host Disease.
Rare ocular surface inflammatory disorders (OSIDs), such as ocular cicatricial pemphigoid (OCP; 1.3-2/million), Stevens-Johnson Syndrome (SJS; 1-5/million), and ocular graft versus host disease (oGVHD; occurring in >50% of chronic GVHD cases) share overlapping clinical phenotypes. Their defining features include conjunctival cicatrization and chronic inflammation. An incomplete understanding of the underlying immunopathogenesis of these conditions has hindered the development of targeted therapies, leaving patients at risk of permanent vision loss and highlighting the need to define distinct ocular immune profiles. Existing literature indicates elevated levels of neutrophils and macrophages/monocytes, along with major increases in their related secretory factors, IL-8 (P < 0.05) and TNF-α (P < 0.05), at the ocular surface across all three groups. Whereas both B cells and cytotoxic T cells are elevated in oGVHD, OCP is characterized by elevated B cells and a concomitant reduction in cytotoxic T cells. Apart from neutrophils and macrophages/monocytes, the local immune landscape-especially in SJS-has been underexplored. At the molecular level, extensive studies of tears have reported elevated levels of IL-17, CXCR1 (P < 0.01), CTGF (P < 0.05) in OCP; IFN-α and IFN-γ (P < 0.05) in oGVHD; and MCP-1, MIP-1β (P < 0.05) in SJS. These studies also indicate that sampling methods and patients' medication status may influence immune profile outcomes. Comprehensive immunophenotyping studies, coupled with the establishment of pathological links to respective molecular profiles, could advance understanding of condition-specific disease biology.
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2026-05-17 | Sulfamethoxazole-trimethoprim-induced Stevens-Johnson syndrome in a NAT2 slow acetylator: A case for pre-emptive pharmacogenomic screening?
Severe Cutaneous Adverse Reactions (SCAR), such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), are serious complications associated with several high-risk medications and can result in significant morbidity and mortality. While HLA-mediated SCARs have been well-characterized-particularly involving drugs like carbamazepine, abacavir, and allopurinol-there is limited data on the role of N-acetyltransferase 2 (NAT2) polymorphisms in SCAR pathogenesis. We present a case of sulfamethoxazole-trimethoprim-(SMX-TMP)- induced SJS (Naranjo probability score: seven), hypothesized to be linked to NAT2 slow acetylator (SA) status. This case underscores the potential utility of pre-emptive pharmacogenomic screening to reduce the incidence of SCARs. NAT2 SA status has also been strongly associated with isoniazid-induced liver injury; Clinical Pharmacogenetics Implementation Consortium (CPIC) recently published a guideline that NAT2 SA predicted for hydralazine-induced systemic lupus erythematosus (SLE) and were at higher risk of side effects, suggesting broader clinical implications for routine NAT2 genotyping.1 Aside from G6PD testing, there is an emergent role to test for NAT2 genotype in preparation for SMX-TMP therapy. Clinically relevant NAT2 alleles include *4, *5, *6, and *7. Given that multiple single nucleotide variant (SNV) must be tested, multiplex pharmacogenomic panels may offer a more cost-effective and comprehensive approach than reactive testing. Some multiplex panels that may be employed include: GeneXpert NAT2-PGx Assay--a rapid assay targeting 5 key polymorphisms to predict isoniazid-acetylation, nanopore sequencing-based panels --a scalable targeted sequencing panel useful for NAT2 and other antitubercular genes (rifampicin, linezolid and bedaquiline), Fulgent genetics pharmacogenomics comprehensive panel, CleanPlex® pharmacogenomics kit and GenoPharm®.
2024-10-15 | Implementation of HLA-related genotype-guided prescribing in Singapore.
To describe the implementation of human leukocyte antigen (HLA)-related genotype-guided prescribing in Singapore. Various HLA alleles have been implicated in drug hypersensitivity syndromes (DHS). These include HLA-B*15:02, which has been associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, HLA-B*58:01, which has been associated with increased risk of severe cutaneous adverse reactions with allopurinol use, and HLA-B*57:01, which has been associated with increased risk of hypersensitivity reactions with abacavir use. Integrating pharmacogenomics into patient care through genotype-guided prescribing potentially optimizes use of these drugs by reducing DHS-related and healthcare costs. We describe the prevalence of HLA-related DHS in Singapore, the cost-effectiveness of genotype-guided prescribing, and local policies and guidelines, as well as the impact of genotype-guided prescribing where available. HLA-related genotype-guided prescribing has the potential to reduce the incidence of DHS and decrease healthcare costs, as seen in the success with carbamazepine. However, not all genotype-guided prescribing is cost-effective when implemented across the population, as was evident from local studies for allopurinol and abacavir. The cost-effectiveness of such measures may change over time with new data (eg, allele frequencies, test costs, drug prices, genotyping approach) and should be evaluated periodically and locally. Implementation of preemptive pharmacogenomics panel testing as part of routine clinical care may shift the threshold for cost-effectiveness and brings promise of further optimization of pharmacotherapy through precision medicine.
2024-09-20 | A case of Stevens–Johnson syndrome after influenza a virus infection
Stevens–Johnson syndrome (SJS) is characterized by widespread erythema, erosions, blisters, and epidermal necrosis. While drugs are a common cause, infections such as mycoplasma and herpes simplex virus can also induce SJS. We present a case of SJS triggered by an influenza infection. A 17-year-old male with a history of SJS at age 12 during an influenza B infection developed symptoms again after contracting influenza A identified by rapid antigen test. He took Kakkonto twice on the first day of the fever and the next day, and the fever was resolved within 2 days. However, 9 days post-onset, he relapsed with a 38°C fever, lip swelling, oral erosions, and eyelid edema, prompting a visit to our department. On admission, examination revealed swollen lips with yellow crusts, oral erosions, conjunctival hyperemia of the eyelids, and erosions on the glans (Figure 1a–c). Tests for streptococcal antigens and mycoplasma (LAMP method) were negative. An antibody test for herpes simplex virus indicated a previous infection. A lip skin biopsy showing lymphocytic infiltration and necrosis of the squamous epithelium confirmed SJS without skin lesions (Figure 1d). The timing between Kakkonto administration and symptom onset negated drug-induced SJS, leading us to conclude that the SJS was triggered by the influenza infection. He received prednisolone 50 mg on day 1. However, due to the development of pseudomembranous conjunctivitis, glucocorticoid pulse therapy was performed on days 2–4. Prednisolone 55 mg was restarted on day 5, and intravenous immunoglobulin therapy was conducted from day 8. The conjunctivitis and mucosal eruptions were improved, and he was discharged without relapse. Seven months later, cytotoxic T lymphocyte populations in peripheral blood mononuclear cells (PBMC) were analyzed using HLA-matched influenza tetramers and flow cytometry; we detected 2.3% tetramer-positive cells in the CD8+ T cell population (Figure 1e). Mycoplasma and herpes simplex virus infections are known infectious causes of SJS, although other contagious agents are rarely implicated.1 The pathogenesis of infection-induced SJS remains unclear. However, some cases of SJS following influenza infection occurred without prior drug exposure, suggesting a direct causal relationship between the influenza infection and SJS onset.2, 3 This patient, having experienced SJS at age 12, had been regularly vaccinated against influenza every year, except this year, and did not develop SJS subsequently. The influenza vaccine, being an inactivated formulation, does not contain live virus and thus lacks infectivity.4 Although there is a theoretical risk that the influenza vaccine itself could trigger SJS, there is no definitive evidence suggesting that vaccination increases the risk of developing SJS.5 We recommend annual influenza vaccination for this patient to prevent SJS triggered by influenza infection. Although no clear association between the onset of SJS and the presence of influenza-specific CD8-positive cells has been demonstrated, clear positive cells were still evident in the peripheral blood 7 months after the onset of influenza, and accumulating case studies may shed light on the potential links between viral infections and SJS. Infection-triggered SJS, while rare, underscores the need to consider a variety of viral infections as possible causes. None of the authors received any financial support for the present study. The authors received no financial support for the present case. Keiichi Yamanaka is an Editorial Board member of the Journal of Dermatology and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Other authors have declared no conflicting interests.
2022-07-05 | Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand
Objective: This study aimed to investigate the clinical impact of HLA-B*15:02 pharmacogenomics (PGx) testing before carbamazepine (CBZ)/oxcarbazepine (OXC) prescriptions and to determine whether this PGx testing was associated with the reduction of CBZ/OXC-induced cutaneous adverse drug reactions (CADRs) in Thailand. Methods: This retrospective observational cohort study was conducted by obtaining relevant HLA-B*15:02 PGx-testing and clinical data from electronic medical records during 2011–2020. 384 patient data were included in this study to investigate the clinical decision on CBZ/OXC usage before and after the HLA-B*15:02 PGx testing, and 1,539 patient data were included in this study to demonstrate the incidence of CBZ/OXC-induced SCARs and SJS between HLA-B*15:02 tested and non-tested patients. To analyze and summarize the results, descriptive statistics were employed, and Fisher exact test was used to compare the clinical difference between the HLA-B*15:02 positive and negative groups and to compare the differences of SCARs incidence. Results: 384 patients were included in this study as per the inclusion criteria. Of these, 70 patients carried HLA-B*15:02, of which 63 and 65 patients were not prescribed with CBZ/OXC before and after the availability of genotyping results, respectively. In the remaining HLA-B*15:02 non-carriers, 48, and 189 patients were prescribed CBZ/OXC before and after genotyping results were available, respectively. The findings of this study showed that the incidence of SCARs of CBZ/OXC was significantly lower ( p < 0.001) in the HLA-B*15:02 screening arm than in the non-screening arm. Conclusion: HLA-B pharmacogenetics testing influenced the selection of appropriate AEDs. The presence of mild rash in the HLA-B*15:02 negative group indicates that other genetic biomarker ( HLA-A*31:01 ) and/or non-genetic variables are involved in CBZ/OXC-induced CADRs, emphasizing that CBZ/OXC prescriptions necessitate CADR monitoring. The hospital policy and clinical decision support (CDS) alert system is essential to overcome the barriers associated with the utilization of PGx guidelines into clinical practice.
2022-04-14 | Allopurinol-induced severe cutaneous adverse reactions in Vietnamese: the role of HLA alleles and other risk factors.
Aim: To reveal the association of three class I HLA alleles, including HLA-A*33:03, HLA-B*58:01 and HLA-C*03:02, and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. Methods: A case-control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The HLA-A*33:03 and HLA-C*03:02 alleles were detected with the nested allele-specific PCR method; the HLA-B*58:01 allele was detected with the sequence-specific primer PCR method. Results: There were strong associations between HLA-B*58:01 and HLA-C*03:02 and allopurinol-induced SCARs. Specific associations were found between HLA-B*58:01 and Stevens-Johnson syndrome/toxic epidermal necrolysis and between HLA-C*03:02 and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: HLA-B*58:01/HLA-C*03:02 and estimated glomerular filtration rate <60 ml/min/1.73 m2. The specificity, positive predictive value and negative predictive value of HLA-B*58:01 testing were higher than the HLA-C*03:02 or the multiplex testing, especially in patients with impaired renal function. Conclusion: The results supported pre-treatment HLA-B*58:01 testing in Vietnamese patients with declined renal function to prevent SCARs.
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