Coronavirus-disease-2019-associated Stevens-Johnsons syndrome in a 15-year-old boy: a case report and review of the literature.

BACKGROUND: Stevens-Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens-Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens-Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature. CASE PRESENTATION: A previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens-Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient's condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae. CONCLUSION: We should be aware that coronavirus disease 2019 infection is associated with the development of Stevens-Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens-Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Route of Delivery in a Patient with Vaginal Stenosis from Stevens-Johnson Syndrome and Review of the Management of Genital Complications.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological conditions, predominantly affecting women with mortality rates of 4.8-48%. Antibiotics are common triggers. They cause painful mucous membrane erosions in various body parts. Treatment involves steroids, creams, and therapy. Pregnant women with SJS-related vaginal stenosis face challenges of delivery route. Case Report: A 34-year-old primigravida woman presented at term with vaginal stenosis consequent to a 10-year-history of Stevens-Johnson syndrome triggered by cephalosporin. On pediatric Pederson speculum examination, vaginal stenosis, adhesion, scarred cervix, telangiectasis of the vaginal mucosa, and moderate bleeding after examination were noted. The risks of severe genital tract laceration and excessive bleeding from vaginal birth was discussed with the couple. Shared clinical decision making was reached to undergo a cesarean delivery. Conclusion: SJS and TEN can result in severe genital complications in women, sometimes requiring cesarean sections due to genital scarring.

Toxic Epidermal Necrolysis Observed in a Patient With the HLA-B*1502 Treated With Levofloxacin.

PURPOSE: To determine the relationship between HLA-B gene mutations and levofloxacin-induced toxic epidermal necrolysis (TEN). METHODS: A 71-year-old Chinese woman developed TEN after oral administration of solifenacin (5 mg) and levofloxacin (0.5 g) for cystitis. HLA-B*5801 and HLA-B*1502 alleles were detected using real-time PCR. FINDINGS: After supportive therapy (antiallergic treatments, plasma exchange, etc) and withdrawal of the culprit medication levofloxacin, the patient was discharged with re-epithelialization of the exfoliated skin. The patient was HLA-B*1502 allele positive and HLA-B*5801 allele negative. IMPLICATIONS: This is the first report of levofloxacin-induced TEN suspected to be caused by mutations in the HLA-B*1502 allele.

Long-term outcomes of eyelash-sparing surgical technique for severe segmental cicatricial entropion.

PURPOSE: To assess the long-term outcomes of segmental entropion correction using anterior lamellar recession (ALR) with mucous membrane graft (MMG). METHODS: Prospective interventional study of 16 patients (mean age, 35.3 ± 16.3 years; 10 females) with severe segmental cicatricial entropion, managed using ALR and MMG. Outcome measures include eyelid and eyelash status, changes in the ocular surface, visual acuity, and cosmetic appearance at a minimum nine months of follow-up. RESULTS: Of 16 patients (16 eyelids), 11 had Stevens-Johnson Syndrome (SJS) and five had chemical injury. The most common location of entropion was medial (87.5%) followed by central and lateral. All patients had severe entropion with trichiatic eyelashes. Anatomical success was 87.5% (14/16) at six weeks of follow-up. Residual trichiasis was managed with a repeat ALR with MMG in one and eyelash resection in the other eyelid. The etiology-wise success rates were 90% in SJS and 80% in chemical injury. At the final mean follow-up of 14.8 months, entropion was corrected in 100% of eyelids. None of the patients had cosmetic concerns. Ocular surface symptomatology and visual acuity improved in 87.5% of patients and 40% of eyes, respectively. CONCLUSION: Anterior lamellar recession with lid margin mucous membrane grafting successfully repairs the severe segmental cicatricial entropion without raising any cosmetic concerns.

S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 1: Diagnosis, initial management, and immunomodulating systemic therapy.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute, life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical speciallved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. This first part focuses on the diagnostic aspects, the initial management as well as the immunomodulating systemic therapy.

Stevens-Johnson Syndrome/Toxic epidermal necrolysis complicated with fulminant type 1 diabetes mellitus: a case report and literature review.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed ß-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. CASE PRESENTATION: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. CONCLUSIONS: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis.

Acute and chronic ocular outcomes in SJS/TEN patients treated with oral ciclosporin vs intravenous immunoglobulin.

Background/Aim: To evaluate differences in ocular complications of Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) patients receiving either systemic IVIG or Ciclosporin (CsA) as initial treatments. Methods: Retrospective review of consecutive patients admitted for SJS/TEN at the Singapore General Hospital (SGH) from 2011 to 2017 who received either IVIG or Ciclosporin at the onset of the disease and had ophthalmological follow-up of at least 6 months were included. Acute ocular severity of SJS/TEN was graded using the Gregory grading score; chronic ocular complications were graded using the Sotozono system. Results: A total of 18 subjects were included for analysis, with eight in the IVIG group and 10 in the CsA group. There were no significant differences in acute Gregory severity grading between the two groups. The CsA group had a trend towards worse overall chronic Sotozono grading scores compared to the IVIG group (median [IQR]: 2 [0-3] vs. 1 [0-6.5], p = 0.27), with a higher incidence of acute severe cornea involvement (60% vs. 25%, p = 0.93) and chronic corneal and eyelid involvement in the former than the latter. SJS/TEN patients with worse acute ocular involvement were more likely to have TEN and perianal mucosal involvement (50% vs. 0, p = 0.01). Conclusion: Compared to those who received IVIG, SJS/TEN patients who received CsA at the acute disease stage, seemed to have worse acute corneal and chronic corneal and eyelid complications. Larger studies are needed to confirm this finding.

Development of Esophageal Epidermoid Metaplasia in a Pediatric Patient After Stevens-Johnson Syndrome.

Esophageal epidermoid metaplasia (EEM) is a rare condition that has not been described in Stevens-Johnson syndrome (SJS) and has only been described once in pediatrics. Neither the relationship, treatment, nor surveillance between SJS, esophageal strictures, and EEM has been established. We report the first case of EEM in an 8-year-old girl with esophageal stricture after SJS. Pediatric patients presenting with dysphagia after SJS should be evaluated for esophageal stricture and subsequent EEM development. Owing to EEM's, association with esophageal squamous cell cancer, close follow-up, biopsy surveillance for dysplasia, endoscopic treatment, and TP53 genetic sequencing should be considered.

Stevens-Johnson syndrome and toxic epidermal necrolysis-like eruptions in patients treated with immune checkpoint inhibitors: a systematic review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by targeting immune checkpoints such as PD-1, PDL-1, and CTLA-4, but concerns about severe immune-related adverse events persist. The scarcity of literature on dermatologic implications, especially severe reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), highlights the urgent need for investigation. OBJECTIVE: Our systematic review aims to address the gap in relevant literature by extensively examining the epidemiologic risk factors and management of SJS/TEN-like illnesses in ICI-treated patients to provide insights for risk assessment and clinical care. METHODS: We identified 158 case reports that detailed the incidence of SJS/TEN in patients being treated with ICIs, examining demographic patterns, type of malignancy, clinical characteristics, and treatments linked to onset. We assessed mortality rates, risk elements, and the effectiveness of interventions to help guide clinical care. RESULTS: Analysis of 158 case reports revealed that SJS/TEN in ICI users is typically seen on average at the age of 63 and is more common in males. PD1 inhibitors such as nivolumab and pembrolizumab are often associated with various mucocutaneous patterns and significant risks with ICI use, especially TEN, which is linked to high morbidity and mortality rates. LIMITATIONS: Our study notes limitations due to the inclusion of case reports or case series, such as potential publication and reporting biases, leading to skewed findings. Additionally, because of the heterogeneous reporting standards, the retrospective nature limits phenotypic precision, control for confounding variables, and data completeness. CONCLUSION: Our study provides valuable insights into the epidemiology, clinical features, management strategies, and outcomes of ICI-induced SJS/TEN, underscoring the importance of vigilant monitoring and personalized risk assessment in oncology practice. Continued research efforts are essential to optimize patient outcomes and enhance the safety profile of ICIs in cancer therapy.

Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Preceding Toxic Epidermal Necrolysis Secondary to Sildenafil: A Case Report.

Drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome and Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) are reactive entities of aberrant cytotoxic immunologic reactions to exogenous medications. While they are conventionally seen as distinct, separate conditions, we present a case of a rare evolution of DRESS syndrome into SJS-TEN in the setting of simultaneous amoxicillin-clavulanate initiation and long-term sildenafil use in a 66-year-old South Asian female with a known history of prior DRESS syndrome and pulmonary arterial hypertension. We discuss the conditions leading to her unique clinical presentation and provide considerations for future clinical encounters.

Lamotrigine Emerging as a Driver of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An 8-Year Retrospective Study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent severe manifestations of a potentially life-threatening spectrum defined by a desquamating rash of the skin and mucous membranes. This study was prompted by the observed increase in the off-label use of lamotrigine as a causal agent in SJS/TEN in our regional burn center. METHODS: A retrospective cohort of 48 patients presenting to the Connecticut Burn Center from 2015-2022 with suspicion for SJS/TEN were reviewed for age, sex, causative drug, presenting symptoms, hospital course, biopsy confirmation, length of stay, comorbidities, and 30-day mortality. Descriptive statistical analysis was conducted to identify trends in causative agent, clinical presentation, and mortality. RESULTS: Thirty patients in our cohort received a final diagnosis of SJS/TEN. While antibiotics remain the most frequent cause of SJS/TEN across the study period (33.3 %, n = 10), the incidence of cases attributable to lamotrigine increased from 1 case between 2015 and 2018 (6.7 %) to 6 cases between 2019 and 2022 (40 %). In 2020 alone, 50 % of all cases were attributable to lamotrigine (n = 4). Of the patients where lamotrigine was implicated, 71.4 % (n = 5) were prescribed lamotrigine for off-label use in the treatment of non-bipolar mood disorders. The average lamotrigine-associated SJS/TEN patient was younger (p < 0.001), had fewer comorbidities, and was more likely to be female than the general SJS/TEN population. CONCLUSION: Off-label use of lamotrigine is emerging as a major driver of SJS/TEN with notable changes in patient demographics. Further research is necessary to understand how changing trends in the patient population will impact clinical course and optimal management.

Topical imiquimod adverse event: Beyond the local skin reaction-A case report.

Imiquimod is a well-known topical treatment for its efficacy against various skin conditions. While generally well-tolerated, adverse reactions like local skin irritation are common. However, severe systemic effects such as Stevens-Johnson syndrome (SJS) are rare, but possible. We present the case of an 82-year-old male who developed SJS following topical Imiquimod therapy for basal cell carcinoma. Despite minimal systemic absorption, serious reactions can occur, warranting caution. Prompt recognition and discontinuation of treatment are crucial for managing such rare but severe adverse events. This case underscores the importance of informed consent and vigilant monitoring for adverse reactions associated with Imiquimod therapy.

Tumor necrosis factor inhibitors enhance corticosteroid therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis linked to immune checkpoint inhibitors: a prospective study.

Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.

Allopurinol: Clinical Considerations in the Development and Treatment of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Other Associated Drug Reactions.

Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, requiring cessation of the medication with initial signs of rash or other early manifestations of SJS/TEN. One major consideration in the increased risk of allopurinol-mediated or modulated SJS/TEN is the need to have a lower dose in the setting of renal disease. The purpose of this review is not only to examine the involvement of allopurinol in SJS/TEN but also to provide detailed information about the drug, allopurinol, and general features and characteristics of SJS/TEN and other associated drug reactions.

Role of neutrophil-lymphocyte ratio as a prognostic marker in SJS/TEN patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, usually to drugs, characterized by blistering and epithelial sloughing. SCORTEN is an established prognosticator index employed in SJS/TEN patients to evaluate their severity degree and mortality risk. Many studies done in the recent past have indicated that neutrophil-lymphocyte ratio (NLR) is related to disease activity in several dermatological diseases. Hence, this study has been performed to correlate the NLR of each patient with their respective SCORTEN values and assess whether NLR can be used as a prognostic marker in SJS/TEN. A single centre, retrospective, 4 year study was conducted at a tertiary care hospital. The required clinical and laboratory data were obtained from existing IP records of all cases of SJS/TEN disorders admitted in the last 4 years in our hospital between May 1st 2019 and April 30th 2023. The correlation coefficient and p value were analysed using the Spearman's rank correlation. The total sample size of the study was 22 patients. A female preponderance (59.1%) with an age range between 10 to 74 years was noted. Drugs were the main triggering factor in all the patients and antiepileptics were the most commonly implicated drug group. On statistical analysis a weak positive correlation (r = 0.182) between NLR and SCORTEN was noted, however p value was insignificant (p = 0.417). Further, mean ± SD of NLR was found to be higher in group II (patients with SCORTEN ≥ 3) as compared to group I (patients with SCORTEN < 3). On correlating NLR with each group separately, p value still remained insignificant. Elevation in NLR value reflects the systemic inflammation, but its role in predicting the severity of the disease needs further research involving larger sample size.