Ocular involvement in Steven-Johnson syndrome/toxic epidermal necrolysis: recent insights into pathophysiology, biomarkers, and therapeutic strategies.

PURPOSE OF REVIEW: To review the pathophysiology, recent biomarkers related to the ocular aspects of Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and to highlight notable evidence published in recent years. RECENT FINDINGS: Several studies reveal the relationship between tear cytokines and the pathological components in eyes of SJS/TEN patients. Specific clinical features and associated risk factors in the acute stage have shown significant correlations with chronic ocular sequelae. Recent treatment protocols, including early pulse systemic and topical steroids, as well as tumor necrosis factor-α inhibitors, have demonstrated positive effects on ocular outcomes. In addition to conventional surgical treatment, a new surgical technique, simple oral mucosal epithelial transplantation (SOMET), has been introduced as a simple ocular surface reconstruction for patient with SJS. SUMMARY: Advancements in knowledge and management strategies have notably enhanced ocular outcomes for SJS/TEN eyes. A deeper understanding of the biomarker changes in these eyes could facilitate the development of future targeted treatment options.

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.

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art.

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests.Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Toxic epidermal necrolysis in a patient on atorvastatin therapy expressing human leukocyte antigen alleles: A case report.

RATIONALE: Toxic epidermal necrolysis (TEN) is a rare, severe mucosal response of the skin associated with a high mortality rate. TEN is most commonly caused by drugs, and is characterized by extensive skin epidermal exfoliation. PATIENT CONCERNS: A 68-year-old woman presented with a rash that had persisted for four days. The patient who had undergone a mitral valve replacement 1 month prior and was taking atorvastatin at the time of admission. DIAGNOSES: The patient exhibited more than 30% exfoliation surfaces and the severe drug eruption was considered to be TEN. According to human leukocyte antigen (HLA) allele detection and ALDEN score, HLA alleles which found in this case report may be an cause of TEN induced by atorvastatin. INTERVENTIONS: All drugs used prior to admission were discontinued and the patient was given antiallergic drugs. OUTCOMES: After 3 weeks following Antiallergic treatment, the rash on patient's calf had subsided, the edema was relieved, and the patient was no longer experiencing pain. After 60 days following discharge, the patient's skin has regrown. LESSONS: This is the first report describing the induction of TEN by atorvastatin in a HLA alleles carrier. For HLA alleles carrier, atorvastatin may need to be used with caution to avoid TEN. Future systematic research is also required to confirm this finding and avoid similar serious skin adverse reactions.

Oral Mucosal Epithelial Transplantation and Limbal-Rigid Contact Lens: A Therapeutic Modality for the Treatment of Severe Ocular Surface Disorders.

Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and severe thermal or chemical injury are considered severe ocular surface disorders (OSDs) because they affect the entire ocular surface, including corneal and conjunctival epithelial stem cells. In patients with severe OSDs, the long-term prognosis for limbal transplantation is poor, and the related corneal opacity and cicatrization lead to devastating visual impairment. To date, there is no standardized treatment to improve vision in cases with severe OSD. Investigating novel treatment methods for severe OSDs, our group began cultivated oral mucosal epithelial transplantation in 2002 and developed a limbal-supported rigid-type contact lens that can be applied as a nonsurgical treatment. When used in combination, these treatment methods make it possible to successfully restore vision in cases with severe OSDs.

Acute generalized exanthematous pustulosis and Stevens-Johnson syndrome overlap due to hydroxychloroquine: a case report.

BACKGROUND: Since the World Health Organization declared a global pandemic due to the novel coronavirus disease2019, there have been targeted efforts to establish management modalities. Hydroxychloroquine has been suggested as a possible treatment; however, it is associated with multiple adverse reactions. We report a rare case of a patient with acute generalized exanthematous pustulosis with Stevens-Johnson syndrome due to hydroxychloroquine. Acute generalized exanthematous pustulosis is characterized by acute onset of a generalized rash that is pustular and erosive in nature, affecting limbs; trunk; face; and, less often, mucosal membranes. Although rare, it is important to be mindful of this side effect because the diagnosis is often delayed, and the disease has the potential to be life-threatening. CASE PRESENTATION: A 68-year-old American woman presented to our hospital with a painful, rapidly spreading rash. Its morphologic features included erythema multiforme-like lesions with extensive skin sloughing in various regions of the head, neck, and trunk and mucosal involvement. Her Nikolsky sign was negative, and she had no evidence of lesions on areas of skin trauma. Four weeks prior, she had been initiated on hydroxychloroquine for a presumed diagnosis of cutaneous sarcoidosis. Three punch biopsies of the head and neck area revealed subcorneal pustules consistent with acute generalized exanthematous pustulosis. Treatment began with high doses of methylprednisolone, leading to only minimal improvement of existing areas and ongoing spread to new areas. Treatment with intravenous immunoglobulin was initiated, at which point disease stability was achieved. The patient's rash ultimately resolved, as did her cutaneous pain and pruritus. CONCLUSIONS: Among many potential adverse reactions involving hydroxychloroquine, cutaneous side effects are varied and can lead to significant morbidity or even death. The drug is currently being investigated in a multitude of trials for coronavirus disease2019 treatment, prevention, and prophylaxis after exposure to severe acute respiratory syndrome coronavirus 2. Acute generalized exanthematous pustulosis is a rare side effect of hydroxychloroquine, and even fewer cases demonstrate histologic evidence of acute generalized exanthematous pustulosis while clinically presenting with Stevens-Johnson syndrome. Patients who develop Stevens-Johnson syndrome/toxic epidermal necrolysis require best supportive care with aggressive fluid and electrolyte replacement and prevention of further breakdown of the skin barrier. With the potential of widespread hydroxychloroquine use, it is important that providers be aware of its potential severe adverse drug reactions.

A new case series on etanercept treatment for toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe, potentially lethal drug reaction for which no standard treatment is available. OBJECTIVE: To describe 17 consecutive TEN patients treated with a single dose of etanercept, a TNF-alpha inhibitor. MATERIALS & METHODS: Comorbidities and any drug treatment initiated within the previous month were recorded on admission. Patients received 50 mg etanercept in a single subcutaneous injection. The clinical severity of the disease was computed using the SCORTEN scale. The expected number of deaths was calculated based on the probability of death associated with each SCORTEN score level. Healing was defined as complete re-epithelialization. Time to healing was analysed using the Kaplan-Meier estimator. RESULTS: The lowest SCORTEN score was 2, and seven patients scored in the most severe risk category (i.e., =>5). A comparison between observed (2/17) vs. expected deaths (10/17) was statistically significant (p=0.012). Fifteen patients promptly responded to treatment and achieved complete re-epithelization (median time to healing: 8.5 days), without complications or side effects. The two observed deaths were due to other causes, although re-epithelization had initiated in both patients. CONCLUSION: These preliminary results add to our initial observations indicating that etanercept may effectively control TEN, a potentially lethal skin condition for which there is currently no effective cure. Where funding is available, randomized controlled trials on etanercept for TEN should be conducted.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Guide for Nurses.

Nurses are central to the care of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Patients with these conditions present with nuanced symptoms and have complex nursing care needs. Although much of the exact pathophysiology of these diseases is not known, all nurses benefit from a fundamental understanding of the genesis of skin manifestations, associated pharmacology, and prognosis. The care of patients hospitalized with Stevens-Johnson syndrome and toxic epidermal necrolysis consists of wound care, infection prevention, comfort management, hydration and nutrition, psychosocial support, and the prevention of long-term complications. This article provides an overview of these diseases, including clinical diagnosis, history and physical assessment, related pharmacology, and nursing care priorities. A description of the current state of the science in clinical management for nurses at all levels is provided, with an emphasis on nursing's contribution to the best possible patient outcomes.

Burns vs. toxic epidermal necrolysis: A medico-legal dilemma.

Toxic epidermal necrolysis is a rapidly progressive exfoliating dermatosis which simulates second degree burns. The authors describe a fatal case reported as due to burns. Around 95% of the deceased's total body surface area was affected, with epidermolysis over face, chest, abdomen, limbs and associated with mucosal involvement. Histopathological findings revealed epidermal necrolysis and confirmed the autopsy suspicion. Because of its sudden onset and rapid progression, toxic epidermal necrolysis often arises suspicion of burns by investigators. We emphasise the differentiating features between toxic epidermal necrolysis and burns and its implications.

Fatal pediatric Stevens-Johnson syndrome/toxic epidermal necrolysis: Three case reports.

RATIONALE: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are extremely rare but potentially life-threatening disorders. We presented 3 fatal pediatric SJS/TEN cases. PATIENT CONCERNS: Our patients had some severe complications such as septic shock, respiratory failure and obliterans bronchiolitis (BO) etc. DIAGNOSIS:: Three patients diagnosed SJS/TEN with clinical symptoms that were triggered by antibiotics, nonsteroidal anti-inflammatory drugs, previous infection, or neoplasms. INTERVENTIONS: All of them accepted mechanical ventilation, intravenous immunoglobulin (IVIG), blood transfusion, glucocorticoid, and multi-anti-infectious therapy. OUTCOMES: They all died because of out-of-control severe infections. In Patient 1, he died 6 days after being admitted to the PICU on the 28th day from onset. In Patient 2, he died on the 211th day from the onset of illness during the third time of PICU admission. In Patient 3, she died 12 days after PICU admission on the 87th day from onset. LESSONS: We should be aware that mucosal damage occurs on the skin and within the mucosa of visceral organs, leading to the occurrence of bronchiectasia, BO, enterocolitis, acute renal failure, and severe secondary infections. Establish a clinically predictive score that includes severe infection for pediatric patients to evaluate the risk of mortality in children in order to improve poor outcomes.

Nursing problems in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome in a Dutch burn centre: A 30-year retrospective study.

OBJECTIVE: Multiple studies have been published on toxic epidermal necrolysis (TEN) and Stevens-Johnsen syndrome (SJS). Nursing care is an important part of the treatment of TEN patients. Unfortunately, limited information on nursing in TEN/SJS patients has been published in the current literature. Nursing research is needed to improve the complex nursing care required for these rare patients. Therefore, the objective was to assess nursing problems in TEN patients in a burn centre setting over a 30-year period. METHODS: The data for this study were gathered retrospectively from nursing records of all patients with TEN/SJS admitted to Burn Centre Rotterdam between January 1987 and December 2016. Dutch burn centres were recently accepted as expertise centres for TEN patients. Nursing problems were classified using the classification of nursing problems of the Dutch Nursing Society. RESULTS: A total of 69 patients were admitted with SJS/TEN. Fifty-nine patient files were available. The most frequently reported nursing problems (>20% of the patients) were wounds, threatened or disrupted vital functions, dehydration or fluid imbalance, pain, secretion problems and fever. Furthermore, TEN-specific nursing problems were documented, including oral mucosal lesions and ocular problems. The highest number of concomitant nursing problems occurred during the period between days three and 20 after onset of the disease and varied by nursing problem. CONCLUSIONS: The most frequently reported nursing problems involved physical functions, especially on days three to 20 after onset of the disease. With this knowledge, we can start nursing interventions early in the treatment, address problems at the first sign and inform patients and their families or relatives of these issues early in the disease process. A next step to improve nursing care for TEN patients is to acquire knowledge on the optimal interventions for nursing problems.

Characteristics of meibomian gland dysfunction in patients with Stevens-Johnson syndrome.

To evaluate the characteristics of meibomian gland dysfunction (MGD) in patients with Stevens-Johnson Syndrome (SJS) and investigate the risk factors for severe MGD.Sixteen patients with a history of SJS were evaluated for MGD. To assess the SJS severity acute ocular involvement score (AOS), acute systemic involvement score (ASS), and chronic ocular manifestation score (COMS) were measured. Meibomian gland parameters were evaluated using meibomian gland dropout score (meiboscore - using a Keratograph 5 M), meibum expression score (MES), meibum quality score (MQS), and lid margin abnormality score (LMAS). Correlations between severity of meibomian gland parameters and degree of ocular and systemic involvement of SJS were analyzed. Risk factors for development of severe MGD were identified.The patients' mean age was 32.0 ±â€Š14.3 years. Four patients were men and 12 were women. MGD had developed in 14 patients (87.5%). The meibomian gland parameters were significantly correlated with ocular and systemic degree of SJS as evaluated using AOS (P < .01), ASS (P < .01), and COMS (P < .01). Patients with severe MGD had a higher AOS (P < .01) and COMS (P = .02) values than those without severe MGD. On multivariate analysis, AOS higher than 2 was a significant risk factor for developing severe MGD (P = .03).MGD was a common ocular manifestation with SJS patients. Severity of meibomian gland parameters was correlated with AOS, ASS, and COMS, and the presence of acute ocular complications was a risk factor for severe MGD in patients with SJS.

Long-Term Effect of a Treatment Protocol for Acute Ocular Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

PURPOSE: To describe the long-term effect of a treatment protocol for ocular involvement in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), including focused ocular examination and pathology-appropriate use of lubrication, topical corticosteroids, topical antibiotics, and amniotic membrane transplantation (AMT). DESIGN: Retrospective, comparative case series. METHODS: A total of 48 patients (96 eyes) were included in this study. Nine of 48 patients (18 eyes) had acute SJS/TEN from 2000 to 2007 and did not receive protocol care (Group I). Thirty-nine of 48 patients (78 eyes) had acute SJS/TEN from 2008 to 2017 and received protocol care (Group II). The main outcome measures were best-corrected visual acuity (BCVA) at final follow-up visit and incidence of complications in the chronic phase. RESULTS: No eyes in Group I received AMT for SJS/TEN, compared to 87% of qualifying eyes in Group II (P < .0001) There was a significant difference in the proportion of eyes with BCVA ≥20/40 at last follow-up between Group I and Group II (33% vs 92%, P < .001). The proportion of eyes with vision-threatening complications in the chronic phase was significantly higher in Group I versus Group II (67% vs 17%, P = .002), with most complications occurring in the first 2 years after disease onset in both groups. CONCLUSIONS: A specific protocol for acute ocular care in SJS/TEN, including aggressive use of AMT, was highly successful in reducing corneal blindness and severe vision-threatening complications of the disorder.

Evaluating Dry Eye and Meibomian Gland Dysfunction With Meibography in Patients With Stevens-Johnson Syndrome.

PURPOSE: To investigate ocular surface and meibomian gland characteristics using infrared meibography in patients with Stevens-Johnson syndrome (SJS). METHODS: This is a single-center, prospective, noncontrolled, observational study. Thirty-two Thai patients (64 eyes) with SJS for 1 year or longer (1-44 years) were enrolled in the study. All participants underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy, tear meniscus height, fluorescein tear breakup time, ocular surface fluorescein staining, eyelid morphology, Schirmer 1 test, meibomian gland expressibility, and upper and lower eyelid meibography using a noncontact infrared meibograph mounted on a slit-lamp biomicroscope. RESULTS: The mean age was 42.2 ± 17.7 years (range, 4-68 years). Twenty-nine patients (90.6%) had a history of severe ocular complications in the acute stage of the disease. Medications were the most common cause of SJS (93.8%). Meibum quality could not be assessed in 23 patients (71.9%) due to no glands expressible. Partial or complete loss of the meibomian glands in either the upper or lower eyelid was found in all patients. The degree of meibomian gland dropout significantly correlated with tear breakup time (P < 0.001), meibum quality (P < 0.001), meibum expressibility (P < 0.001), ocular surface staining (P < 0.001), and presence of long-term ocular sequelae including symblepharon (P = 0.027) and limbal stem cell deficiency (P = 0.003). CONCLUSIONS: SJS is associated with obstructive meibomian gland dysfunction. The severity of meibomian gland dropout has a relationship with abnormal dry eye tests, subjective meibomian gland evaluation, and other ocular sequelae of SJS.