Unraveling the genetic link: an umbrella review on HLA-B*15:02 and antiepileptic drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

PURPOSE: This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957). RESULTS: Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin. CONCLUSION: In summary, although HLA-B*1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.

Pharmacogenetics to prevent hypersensitivity reactions to antiepileptic drugs: is testing performed when indicated?

Extensive scientific evidence consistently demonstrates the clinical validity and utility of HLA-B*15:02 pre-screening in averting severe cutaneous adverse reactions (SCARs), namely Stevens-Johnson syndrome and toxic epidermal necrolysis, associated with carbamazepine or oxcarbazepine usage. Current practice guidelines and drug labeling actively advocate for pharmacogenetic pre-screening before initiating these antiepileptic drugs (AED), with particular emphasis on patients of Asian descent. However, there is a potential need to strengthen compliance with these recommendations. This retrospective study aimed to describe the pharmacogenetic pre-screening, documentation, and SCARs incidence for patients of Asian ancestry initiated on carbamazepine or oxcarbazepine at a large Northeastern USA healthcare system. Between 1 July 2016 and August 1, 2021, 27 patients with documented Asian heritage in the electronic health record (EHR) were included. The overall rate of HLA-B*15:02 pre-screening before carbamazepine or oxcarbazepine initiation was 4%. None who underwent pharmacogenetic pre-screening carried the associated HLA-B risk allele, and no SCARs were reported. Notably, pharmacogenetic results were not discretely entered into the EHR, and the results were only found as attached documents in the miscellaneous section of the EHR. There remains a significant opportunity for improving HLA-B*15:02 pre-screening for patients starting carbamazepine and oxcarbazepine to prevent SCARs in the USA.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Uncommon toxic epidermal necrolysis -like presentation of cutaneous lupus erythematosus: A series of 6 cases.

TEN like Lupus erythematosus is an uncommon life-threatening variant of Lupus erythematosus. It is usually associated with flares of systemic lupus erythematosus and also because of widespread skin erosions, it can cause acute skin failure. It is often confused with drug induced TEN, however the management of both the diseases is different and hence correct diagnosis becomes crucial. In this study we aimed to assess the clinical characteristics and outcome of TEN like LE in the Indian population. All patients satisfying ACR/EULAR 2019 criteria for SLE and clinically diagnosed with TEN like LE were retrospectively reviewed. A total of 6 patients were identified. All patients were female. Except 1 patient who presented de-novo, the others had pre-existing symptoms of connective tissue disease. Half of the patients had palmoplantar involvement. Mucosal involvement was only mild. Majority had systemic involvement in the form of nephritis followed by arthralgia, autoimmune hepatitis and autoimmune hemolytic anemia.

Afatinib-induced toxic epidermal necrolysis: A case report with a literature review.

We present a 70-year-old female patient diagnosed with epidermal growth factor receptor-mutated metastatic non-small cell lung cancer (T4N2M1a), who developed afatinib-induced toxic epidermal necrolysis (TEN). We have also performed a PubMed/Medline literature review to detect other possible cases of TEN/Stevens-Johnson syndrome associated with afatinib treatment and found only 5 other cases reported. To our best knowledge, this is the first case of afatinib-induced TEN successfully treated with cyclosporine.

Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis spectrum disorders.

Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD.

Clinical Profiles of Japanese Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Collected by a Nationwide System from 2006 to 2023.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening severe cutaneous adverse drug reactions. These diseases are rare, and their onset is difficult to predict because of their idiosyncratic reactivity. The Japan Severe Adverse Reactions Research Group, led by the National Institute of Health Sciences, has operated a nationwide to collect clinical information and genomic samples from patients with SJS/TEN since 2006. This study evaluated the associations of clinical symptoms with sequelae and specific causative drugs/drug groups in Japanese patients with SJS/TEN to identify clinical clues for SJS/TEN treatment and prognosis. Acetaminophen, antibiotics, and carbocisteine were linked to high frequencies of severe ocular symptoms and ocular sequelae (p < 0.05). For erythema and erosion areas, antipyretic analgesics had higher rates of skin symptom affecting <10% of the skin than the other drugs, suggesting narrower lesions (p < 0.004). Hepatic dysfunction, was common in both SJS and TEN, and antiepileptic drugs carried higher risks of hepatic dysfunction than the other drug groups (p = 0.0032). This study revealed that the clinical manifestations of SJS/TEN vary according to the causative drugs.

British Association of Dermatologists national clinical audit on the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

BACKGROUND: UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards. OBJECTIVES: To audit current management of SJS/TEN in adults against standards in the BAD guidelines. METHODS: BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022. RESULTS: Thirty-nine dermatology centres in the UK (29%) participated, and data for 147 adults with SJS/TEN were collected. Within 24 h of the diagnosis being made or suspected, the following were documented, per 147 submitted cases: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for 76 (52%), list of medications for 113 (77%) and timelines for commencement/alterations of medications for 104 (71%). The initial assessment was documented of the eyes by an ophthalmologist in 71 (48%), of the mouth in 130 (88%), of the genital skin in 103 (70%) and of the urinary tract in 93 (63%). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 26 of 147 cases (18%), of the eyes in 12 (8%), and of the urinary tract and genital skin in 14 (10%). At discharge, a drug was declared to be the cause of SJS/TEN for 130 of 147 cases (88%), while 9 (6%) were thought to be secondary to infection. Eleven of 147 (8%) had no response to this question. Documentation regarding advice was present on avoidance of the culprit drug in 76 of 130 declared SJS/TEN cases (58%), and on requesting a MedicAlert® bracelet/amulet in 9 of the 147 cases (6%). CONCLUSIONS: This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and to request a MedicAlert® bracelet/amulet.

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.

High risk and low prevalence diseases: Stevens Johnson syndrome and toxic epidermal necrolysis.

INTRODUCTION: Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious conditions that carry a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of SJS/TEN, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: SJS/TEN is a rare, delayed hypersensitivity reaction resulting in de-epithelialization of the skin and mucous membranes. The majority of cases are associated with medication or infection. Clinicians should consider SJS/TEN in any patient presenting with a blistering mucocutaneous eruption. Evaluation of the skin, mucosal, pulmonary, renal, genital, and ocular systems are essential in the diagnosis of SJS/TEN, as well as in the identification of complications (e.g., sepsis). Laboratory and radiological testing cannot confirm the diagnosis in the ED setting, but they may assist in the identification of complications. ED management includes stabilization of airway and breathing, fluid resuscitation, and treatment of any superimposed infections with broad-spectrum antibiotic therapy. All patients with suspected SJS/TEN should be transferred and admitted to a center with burn surgery, critical care, dermatology, and broad specialist availability. CONCLUSIONS: An understanding of SJS/TEN can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Drugs associated with epidermal necrolysis in children: A World Health Organization pharmacovigilance database analysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening mucocutaneous reactions most often induced by drugs. To date, no large pharmacovigilance study has been conducted in the paediatric population. OBJECTIVES: To describe the spectrum of drugs associated with SJS-TEN in children through the analysis of cases reported in the WHO pharmacovigilance database (VigiBase). METHODS: Disproportionality study using data from VigiBase. All paediatric (age under 18 years) cases reported between January 1, 1967, and July 6, 2022, were included. For each molecule, a case-non-case study was performed to assess a potential pharmacovigilance signal by computing the lower end of the 95% credibility interval for the information component (IC025). We performed sensitivity analyses, (i) taking into account only cases reported by physicians and (ii) taking into account only cases reported in the last 10 years. RESULTS: Among 31,376,783 adverse drug reactions reported in VigiBase, 2,248,727 were paediatric cases and 7342 were encoded as paediatric SJS-TEN. Significant statistical pharmacovigilance signals were observed for 165 drugs. The two most represented drug classes were antiepileptics and anti-infectious drugs. The five drugs with the highest IC025 were lamotrigine (IC025 4.99), carbamazepine (IC025 4.88), phenobarbital (IC025 4.67), phenytoin (IC025 4.52) and nimesulide (IC025 4.23). Acetaminophen was significantly associated with paediatric SJS-TEN (IC025 2.85) and we also described various new suspected drugs. Vaccines had no significant pharmacovigilance signal. These results were confirmed with the sensitivity analyses. CONCLUSIONS: This study updates the spectrum of drugs potentially associated with paediatric SJS-TEN.

Anesthesia management in a child with mucopolysaccharidosis and toxic epidermal necrolysis: A case report.

Toxic epidermal necrolysis and mucopolysaccharidosis are both rare diseases that pose significant airway maintenance challenges to anesthesiologists. In this report, we describe the anesthesia management in a 4-year-old male with mucopolysaccharidosis type II who developed toxic epidermal necrolysis and presented for ophthalmic surgical procedures. Combined use of propofol and ketamine with the support of high-flow nasal oxygen enabled adequate analgesia and sedation while maintaining spontaneous ventilation and airway patency. The strategy presented in this report may contribute to enhancing the safety of sedation in spontaneously breathing children with abnormal airways.

Severe cutaneous adverse reactions associated with the immune checkpoint inhibitors: A case/non-case analysis using the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND/OBJECTIVES: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored. METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy. RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS). CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.

Methotrexate might become the sole treatment option for leukemia following the occurrence of Stevens-Johnson syndrome.

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) arising from drug interactions can carry life-threatening implications and result in lasting effects. SCARs can be triggered by various factors, with trimethoprim/sulfamethoxazole identified as a primary culprit. Anticonvulsants and antineoplastic agents have been noted as secondary triggers. Notably, antineoplastics linked to SCARs include immunomodulatory agents. The higher mortality rates among cancer patients with SCARs underscore the significance of comprehending cancer--specific risk factors. Our objective is to present the case of a boy with acute lymphocytic leukemia (ALL) who developed Stevens-Johnson syndrome (SJS) following MTX treatment. CASE REPORT: We present the case of a three-year-old male patient diagnosed with ALL who developed Stevens-Johnson syndrome (SJS) subsequent to the administration of MTX, following the "BFM 2009" protocol. He had undergone intrathecal MTX administration on six previous occasions. Our patient received IVIG at a dose of 2g/kg along with steroids, resulting in partial clinical improvement after 21 days. An innovative protocol was developed, involving IVIG before MTX infusion and dexamethasone before MTXi, with folinic acid rescue. Intravenous immunoglobulin (IVIG) mitigates SJS/TEN via type IV hypersensitivity down-regulation and apoptosis curbing. CONCLUSION: As far as we know, the prophylactic use of IVIG to counteract SCARs in a pediatric leukemia patient represents uncharted territory. Moreover, research into the immune system dynamics within these patients and the preservation of indispensable treatments should involve allergist-immunologists as part of the multidisciplinary team attending to neoplastic conditions.

Medication Associations With Severe Cutaneous Adverse Reactions: A Case/Non-Case Analysis Using the FDA Adverse Event Reporting System.

BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications. OBJECTIVE: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. METHODS: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. RESULTS: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds. CONCLUSION: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.

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.

Stevens-Johnson syndrome/toxic epidermal necrolysis associated with natural thyroid medication.

Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immunologic hypersensitivity reaction to stimuli that presents as widespread eruption with mucocutaneous detachment and involvement of other organs. Multiple causes have been noted in literature, including numerous medications. In this report, we present a 52-year-old woman who arrived at the emergency department with a complaint of rash, malaise, and pruritus. She subsequently developed diffuse cutaneous and mucosal detachment. Work-up supported a diagnosis of SJS/TEN secondary to her thyroid replacement therapy, derived from desiccated pig thyroid glands. The patient's natural thyroid medication was discontinued and she responded well to appropriate treatment. This case is unique in that thyroid replacement therapy is not a commonly reported trigger of SJS/TEN. Providers should be aware of the potential for natural thyroid and other animal-derived natural medications to cause adverse reactions such as SJS/TEN.

[Chinese expert consensus on diagnosis and treatment of immune checkpoint inhibitor-related skin adverse reactions (2024 edition)].

Immune checkpoint inhibitors (ICIs) have emerged as crucial therapeutic agents for various malignancies by activating the host immune system against tumor cells. However, many different types of skin adverse reactions may occur during its use, including eruption, pruritus, blistering, hypopigmentation, alopecia, and even severe cases, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These cutaneous immune-related adverse events (cirAEs) had a high incidence, which seriously affected patients' quality of life and antitumor treatment decisions. Some severe cutaneous adverse reactions (SCARs) even endanger patients' lives. Therefore, the Chinese Society of Dermatology, the Chinese Dermatologist Association of the Chinese Medical Doctor Association, the Dermatology Division of the Chinese Geriatrics Society, and other relevant experts jointly discussed and formulated the 'Chinese Expert Consensus on the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Related Cutaneous Adverse Reactions'. This consensus covers the name, epidemiology, pathogenesis, clinical features, classification and grading of cirAEs, principles of management and the re-initiation of ICIs. It aims to provide a more scientific and authoritative reference for the diagnosis and treatment of cirAEs in China in the future.

Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis: Macules, Papules, and Bullae.

OBJECTIVE: The objective of this discussion paper is to illuminate the importance of early identification and treatment of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS/TEN may occur as quickly as 4 days, more commonly 4 to 8 weeks after starting a new medication and early identification is essential. METHODS: A review of literature revealed there is a lack of diagnostic awareness related to the clinical presentation and diverse populations at risk for this devastating syndrome. RESULTS: A Boolean search was conducted, and six quantitative and qualitative research articles were discovered that indicate a knowledge disparity between "rash" versus SJS/TEN. Research indicates evidence-based best clinical practices for nurses and health care practitioners for assessment of risks, clinical presentation, and treatment. CONCLUSIONS: Prompt diagnosis and discontinuation of the suspected medication will reduce potential life-threatening sequelae.