Stevens-Johnson Syndrome/toxic Epidermal Necrolysis Research Articles

Dysregulation of Regulatory T Cells and Autoimmune Sequelae in DRESS: Insights From Flow Cytometry and NanoString Analysis.

Drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse hypersensitivity reactions with distinct clinical manifestations. Regulatory T (Treg) cells may behave differently in these syndromes, contributing to their diverse clinical features and outcomes. This study compared Treg dynamics between DRESS and SJS/TEN patients during the acute and recovery phases. Flow cytometry quantitatively analysed and defined the immunophenotype of CD4+CD25+CD127-FoxP3+ Tregs in blood from DRESS and SJS/TEN patients indicated that Treg percentages were lowest in DRESS patients during the acute phase compared to those in the recovery phase in DRESS patients and the acute phase in SJS/TEN patients. During the acute phase, CTLA-4 expression in Tregs in both DRESS patients with and without autoimmune sequelae was significantly increased, while only DRESS patients without autoimmune sequelae had elevated OX40 expression compared to the healthy controls. High IL-10 expression in Tregs during the acute phase in SJS/TEN patients was also observed. The suppressive function of Tregs was lower in DRESS compared to SJS/TEN, which was determined using a suppression assay by co-culturing autologous Treg and effector T cells. Furthermore, NanoString technology explored mRNA profiles in Tregs. Genes associated with the JAK/STAT pathway were found to be downregulated during the acute phase in DRESS patients who later developed autoimmune sequelae. Our findings evidenced impaired Treg function in DRESS compared to SJS/TEN. The early disturbance of the JAK/STAT pathway may serve as a prognostic marker for autoimmune development in DRESS patients.

Suture-Less and Glue-Less Amniotic Membrane Graft for Keratopathy and Early Keratinization in Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome

Purpose: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome can cause significant keratopathy and lead to lasting visual effects. The main objective of this study was to describe an ocular presentation of DRESS treated with a modified suture-less and glue-less amniotic membrane graft technique. This study also provides a literature review of ocular DRESS manifestations and ocular management of the other severe cutaneous adverse reactions. Methods: This is a case review about an 82-year-old man with sepsis due to recent Mycobacterium tuberculosis, who presented with DRESS based on clinical findings. Results: The patient was treated with a modified suture-less and glue-less amniotic membrane graft technique along with a Prokera corneal bandage placement. The patient had significant improvement of visual acuity and symptoms with this technique. Conclusions: Patients with significant corneal and conjunctival involvement associated with DRESS, similar to Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), may benefit from more aggressive treatment with amniotic membrane transplantation and Prokera corneal bandage placement to prevent scarring and subsequent vision loss. The modified technique described in this article can be used for patients who may be poor candidates for the operating room.

P25 Pharmacovigilance assessment of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with antibacterial drugs using FDA adverse event reporting system data

P25 Pharmacovigilance assessment of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with antibacterial drugs using FDA adverse event reporting system data

Antibiotic-induced severe cutaneous adverse reactions: a single-center retrospective study over ten years.

Severe cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs. We analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out. Among 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups. The identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

Utility of the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) in Pediatric Stevens-Johnson Syndrome Patients.

The Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) is a system that predicts in-hospital mortality for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). The system is widely utilized in adults but not pediatrics. We aim to determine the accuracy of the SCORTEN in pediatrics. A retrospective review of pediatric patients admitted to a verified pediatric burn center with SJS/TEN from 2008 to 2022 was performed. Twenty-four patients were analyzed. Ten patients had 0-1 SCORTEN risk factor, thirteen had 2 risk factors, and one had three risk factors. There was no relationship between initial BUN, bicarbonate, glucose, or initial heart rate on the length of intensive care unit (ICU) stay or ventilator days. Hospital length of stay and feeding tube days were positively related (p<0.001) along with length of stay and maximum total body surface areas (TBSA) (p<0.05 Hospital length of stay, ICU length of stay, and ventilator days were not statistically significant between those having 0-1 and 2 risk factors. This study suggests that the SCORTEN system is not useful for pediatrics and a different scoring system is needed, as SCORTEN overestimates mortality and does not have a relationship to outcome measures.

Reactive Infectious Mucocutaneous Eruption with Extensive Cutaneous Involvement

Abstract Recently, there has been discussion to reclassify pediatric Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) as drug-induced epidermal necrolysis (DEN), separating it from infectious etiologies and redefining pediatric mucocutaneous eruptions as either reactive infectious mucocutaneous eruption (RIME) or DEN. In this report, we describe a previously healthy 4-year-old girl with rapidly progressive mucocutaneous blistering involving four mucosal membranes and 37.5% of total body surface area (BSA) following a prodromal rhinovirus and enterovirus infection. The symptoms occurred in the absence of an inciting medication and improved with only supportive care. This case illustrates a rare occurrence of RIME with TEN-like BSA involvement, prompting a review of the literature exploring the relationship between BSA involvement in RIME and its influence on patient outcomes. Findings support the proposed reclassification of SJS/TEN as DEN and postinfectious mucocutaneous eruptions as RIME.

Life-threatening Rash Due to Lamotrigine and a Failure to Understand Its Pharmacology: How Forensic Detective Work Uses Medical Knowledge and Clinical Pharmacology to Solve Cases.

This column is the second of a 3-part series describing cases where general medical knowledge, including psychiatric and clinical pharmacology, were instrumental in determining dereliction and direct cause in a malpractice suit. This case summarizes how lamotrigine can cause dangerous consequences if its pharmacology is not properly understood. The case also illustrates how the 4 Ds of a forensic malpractice suit were met in this case. First, there was duty on the part of the prescriber which, if followed, would have prevented or minimized the damages experienced by the patient. Dereliction in the performance of a patient-physician treatment contract was a direct cause of the development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in this patient. An immune-mediated reaction to lamotrigine or one of its metabolites has been extensively reported in the literature, with the risk of this reaction increasing at higher doses and with more rapid titration, fulfilling the elements of direct cause. Dereliction implies a deviation from the standard of care. On the basis of the clinical information from the package insert, more likely than not a deviation from the standard of care occurred in this case when lamotrigine was titrated faster than recommended by the package insert.

Greater mechanistic understanding of the cutaneous pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis can shed light on novel therapeutic strategies: a comprehensive review.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (SCARs) characterized by widespread epithelial detachment and blistering, which affects the skin and mucocutaneous membranes. To date, therapeutic interventions for SJS/TEN have focused on systematic suppression of the inflammatory response using high-dose corticosteroids or intravenous immunoglobulin G (IgG), for example. No targeted therapies for SJS/TEN currently exist. Though our understanding of the pathogenesis of SJS/TEN has advanced from both an immunological and dermatological perspective, this knowledge is yet to translate into the development of new targeted therapies. Greater mechanistic insight into SJS/TEN would potentially unlock new opportunities for identifying or repurposing targeted therapies to limit or even prevent epidermal injury and blistering.

Risk factors for the development of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, following drug administration: a systematic review and meta-analysis.

The aim of this systematic review was to determine risk factors for the development of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) following drug administration. The study protocol was registered on PROSPERO. The PRISMA guidelines were followed. On 17 October 2022, a search, advised by a librarian, was conducted in MEDLINE and Embase. Five studies were pooled. We report that HIV and male gender may be risk factors for SJS/TEN; however, this review was limited by a low number and quality of included studies. We conclude that a well-designed, large population-based case–control study with an appropriate control group is required to assess risk factors for the development of drug-induced SJS/TEN.

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

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). 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. 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. 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.

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study

PurposeTo compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis...

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

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. To audit current management of SJS/TEN in adults against standards in the BAD guidelines. BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022. 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%). 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.

Updates in SJS/TEN: collaboration, innovation, and community.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Correlations between histopathologic findings, serum biomarker levels, and clinical outcomes in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.

Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA-B*1502 genotyping in Taiwan, 2000-2017: A nationwide longitudinal study.

The HLA-B*1502 allele is strongly associated with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA-B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA-B*1502 genotyping before prescribing CBZ was reimbursed in June 2010. Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score-based stabilized weighting (PSSW) ensured well-balanced covariates. The difference in 3-month SCAR and SJS/TEN rates between phase 2 (2011-2017) and phase 1 (2000-2009) was examined using a one-sample Z-test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA-B*1502 genotyping. CBZ prescriptions reduced from 7% (2000-2003) to 6% (2004-2010) and 4% (2011-2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3-month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = -.38, p = .0342) and nonusers (r = -.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates. Recognizing HLA-B*1502 allele and avoiding CBZ therapy in HLA-B*1502-positive patients is critical for preventing CBZ-induced severe adverse events.

Cost-effectiveness of HLA-B*58:01 testing to prevent Stevens-Johnson syndrome/toxic epidermal necrolysis in Vietnam.

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND)14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

Insights into Stevens-Johnson syndrome/toxic epidermal necrolysis lifetime burden: assessing life expectancy, healthcare costs and quality of life.

This study highlights the need for further exploration of factors that influence the declining incidence rate of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), interventions to mitigate loss-of-life expectancy and healthcare costs, and impact on quality of life. The findings emphasize the importance of ongoing efforts to minimize the burden of SJS/TEN and optimize patient care.

Lamotrigine-induced Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (SJS/TEN) overlap with transaminitis in an Asian female: a case report

Background: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) is a dermatologic emergency characterized by extensive epidermal detachments. The most frequent etiology is drug reaction within an interval of the last 8 weeks. SJS/TEN may occur in any age, race, and gender; however, there is an increased risk in patients over 65. SJS and TEN are differentiated based on the extent of epidermal detachments, which is &lt;10% in SJS, 10-30% in SJS-TEN overlap, and &gt;30% in TEN. This case study aims to evaluate the Lamotrigine-induced Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (SJS/TEN) overlap with transaminitis in an Asian female. Case Presentation: A 34-year-old woman presented with a pruritic and burning rash on almost all body parts. The suspected causative drug was lamotrigine, which she consumed within the last 2 weeks. Mucosal involvement was also found on the lips and genital mucosal. The affected body surface area was approximately 20%, with a positive Nikolsky sign. Laboratory studies showed elevated liver function tests. Based on the history, physical examination, and biopsy, the patient was diagnosed with SJS/TEN overlap. The suspected causative drug was immediately stopped, and supportive and systemic corticosteroid treatments were provided. The SCORTEN was 2, with a mortality rate of 12.1%. After a few days, the patient's condition had improved, the liver function test was normal, and there was no significant complication. Conclusion: SJS-TEN is a part of epidermal necrolysis, characterized by an extensive epidermal detachment. The management of SJS/TEN includes early detection, immediately stopping the suspected drugs, administering systemic corticosteroids, and other supportive treatments.

Neutrophil-to-lymphocyte ratio (NLR) in dermatology perspective: a review

The neutrophil-to-lymphocyte ratio (NLR) is the ratio between the number of neutrophils and lymphocytes in the peripheral blood. Neutrophils are responsible for an initial immune response to pathogens that enter the body through the mechanisms of chemotaxis, phagocytosis, the release of reactive oxygen species (ROS), granular proteins, production and release of cytokines. Neutrophils also have an important role in the occurrence of the systemic inflammatory response (SIRS). There are several types of diseases in the field of dermatology that are also related to NLR. It is associated with the presence of an inflammatory process. In addition, NLR is considered an easy, inexpensive, and reproducible parameter associated with clinical outcomes and disease severity. Several diseases in the field of dermatology found to be associated with NLR include leprosy, Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), psoriasis, vitiligo, atopic dermatitis, systemic sclerosis, and skin cancer. In recent years, its role as an independent prognostic factor for neoplasms and as an inflammatory biomarker in various acute and chronic diseases has been increasingly established in the dermatology field. However, not all studies have found significant results. One of them is vitiligo which still finds controversial results. For this reason, this literature review will discuss specifics related to several diseases in dermatology associated with NLR.

Assessment of Need for Improved Identification of a Culprit Drug in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug. To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification. This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women's Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN. This study descriptively analyzed potential culprits to SJS/TEN, patients' allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes. Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians' approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited. The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.