The outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome: case series.

PURPOSE: To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS). METHODS: This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed. RESULTS: A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed. CONCLUSIONS: Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.

Unique cytokine signature in ocular Stevens-Johnson syndrome non-responders.

PURPOSE: To clinically define a subset of patients with chronic ocular Stevens-Johnson syndrome non-responders (SJS-NR) and analyze their cytokine profile compared to clinical responders (SJS-CR). METHODS: A total of 32 SJS cases (n = 32, 64 eyes) managed over a period of three years were segregated into clinical responders (n = 24, 48 eyes) and non-responders (n = 8, 16 eyes). Cases were determined as non-responders based on persistent, refractory, and non-mechanical inflammation of the conjunctiva. Age- and sex-matched healthy controls (n = 25, 50 eyes) were recruited. Tear specimens collected using Schirmer's strip were profiled for 27 cytokines using an immunoassay-based 27-bioplex array. RESULTS: Tear cytokine profiling revealed 18 cytokines to be differentially expressed in SJS-NR compared to SJS-CR. While PDGF-BB, IL-4, IL-1ß, VEGF, IL-12p70, IFN-γ, IL-9, and IL-1RA were upregulated, GM-CSF, eotaxin, IP-10, IL-10, MCP-1, G-CSF, IL-6, IL-13, and bFGF were downregulated in SJS-NR compared to SJS-CR. The cytokines IL-13, IL-10, and IP-10 were decreased in both SJS-NR and SJS-CR compared to controls. CONCLUSION: The inflammation in SJS-NR continues to worsen despite the correction of mechanical causes, resulting in progressive deterioration of the cornea. The cytokine profile of SJS-NR was remarkably different from that of SJS-CR, indicating a T helper 2-type protective proliferative response and an impaired migratory potential of the conjunctival epithelium. These factors could possibly lead to poor healing of the corneal epithelium in a markedly pro-inflammatory and pro-angiogenic milieu. The top four differentially expressed cytokines, PDGF-BB, IL-4, IL-10, and IL-6, are proposed as potential biomarkers of SJS-NR.

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

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

Steven-Jonhson Syndrome in a Patient With Dengue Infection in Peru: A Case Report.

Stevens-Johnson syndrome is an infrequent condition affecting the skin and mucous membranes, it involves cutaneous detachment with high mortality without adequate treatment. We present the case of a 40-year-old male with a history of epilepsy treated with valproic acid and lamotrigine, previously diagnosed with dengue. Evaluation showed erythematous blisters on skin and mucosa with bleeding and desquamation, covering 10% of the body surface. The patient progressed favorably with the medical care received. Stevens-Johnson syndrome should be studied in association with arboviral diseases.

A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence. Methods: We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study. Results: CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS. Conclusion: Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.

Drug-induced Stevens-Johnson syndrome in Post traumatic facial injury.

Stevens-Johnson syndrome is a severe adverse drug reaction affecting the skin and mucous membrane. The causes include Sulfonamides, Anticonvulsants, etc. A patient developed ulcerations in the lips and oral cavity with difficulty in swallowing and rashes over the back, abdomen, and genitalia following administration of injection ceftriaxone 1 g intravenous (IV) b.i.d, injection pantoprazole 40 mg IV b.i.d, tablet aceclofenac + paracetamol 325 mg b.i.d, tablet cetirizine 10 mg b.i.d, chlorhexidine mouth wash, and injection metronidazole 500 mg IV t.i.d for the treatment of traumatic facial injury after 4 days of treatment. Injection ceftriaxone and tablet aceclofenac + paracetamol were suspected as the cause of this reaction. The two drugs were stopped. The patient was treated with corticosteroids, other antimicrobials, and oral topical anesthetics. Health-care providers should be careful about the possible adverse drug reactions even to commonly used drugs.

Cutaneous Hypersensitivity Reactions to Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread application of ICIs has unveiled a spectrum of immune-related adverse events (irAEs), most often affecting the skin. Cutaneous irAEs (cirAEs) encompass a range from common morbilliform and lichenoid rashes to more severe conditions such as bullous dermatoses and psoriasiform eruptions, each presenting distinct clinical challenges. Moreover, less common but clinically severe cutaneous reactions like toxic epidermal necrolysis have also been observed. cirAEs are frequently observed, with an incidence ranging from 37% to 70% for anti-cytotoxic T lymphocyte-associated antigen-4 antibodies and 17% to 40% for anti- programmed death-1/anti-programmed death ligand-1 antibodies. Recognizing the critical need for effective therapeutic strategies, this review carefully examines current approaches and guidelines for managing cirAEs.

Pharmacogenetics and Oxcarbazepine in Children and Adolescents: Beyond HLA-B*15:02.

Background: Oxcarbazepine is thought to be better-tolerated and less susceptible to drug-drug interactions than its predecessor, carbamazepine. Genetic testing for HLA-B*15:02 is recommended in specific populations to identify those at high risk of severe hypersensitivity reactions; however, other pharmacologic and pharmacogenetic factors that can impact drug disposition may be involved. Methods: We present a case of an 8-year-old boy treated with oxcarbazepine who developed drug reaction with eosinophilia and systemic symptoms (DRESS) with Stevens-Johnsons syndrome overlap and was negative for HLA-B*15:02. We review the extant literature related to oxcarbazepine disposition, and potential pharmacogenetic variants in aldoketoreductase 1C (AKR1C)2-4 that may contribute to this risk. Results: Genetic variability in oxcarbazepine disposition pathways may contribute to tolerability and toxicity, including the development of hypersensitivity reactions. Conclusions: While preemptive genetic testing for HLA-B*15:02 in individuals of Asian ancestry is recommended to prevent severe hypersensitivity reactions to oxcarbazepine, oxcarbazepine concentrations and AKR1C variation may contribute to the risk of severe adverse reactions. We provide recommendations for future study to elucidate whether these individual factors are important for reducing the risk of severe adverse events.

Etanercept treatment for pediatric toxic epidermal necrolysis induced by deflazacort: a case report and literature review.

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-α antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe.

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

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