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.

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.

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.

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.

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.

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.

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.

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

The Occurrence of Etoricoxib-Induced Stevens-Johnson Syndrome With Oral Manifestations in a Female Patient: A Case Study.

Stevens-Johnson Syndrome (SJS) constitutes a rather uncommon, and rarely fatal hypersensitivity reaction that primarily impacts the skin and mucous membranes and in certain cases may be attributed to drug administration. The aim of this article is to present a case of etoricoxib-induced SJS in a 46-year-old, female patient. The patient presented herself, as a medical emergency, to the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, reporting pain, especially acute pain while eating certain foods, discomfort, dysphagia, and a wound in the left half of the hard palate. The clinical examination revealed a broad ulcer, in the left half of the hard palate as well as multiple ulcerations and erosions in the upper and lower lip. Her medical history was clear; however, the patient mentioned to have received etoricoxib, due to severe back pain, one day prior to our clinical examination. The patient received methylprednisolone 16 mg, twice per day, for two days, followed by methylprednisolone 8 mg, twice per day, for two more days. Her symptoms resigned and since the connection between etoricoxib and SJS was established, the patient was advised to avoid etoricoxib and be wary of adverse effects, when taking drugs especially non-steroidal anti-inflammatory medication. This is one of the first case reports in the literature, linking etoricoxib administration with the emergence of SJS, highlighting the importance of pharmacovigilance. The up-to-date registration of drug-induced adverse effects is of immense importance to protect future patients. SJS does not have a defined treatment strategy. Therefore, most patients are given supportive care and symptomatic treatment, which most commonly involves corticosteroids and antivirals such as acyclovir.

Stevens-Johnson syndrome-toxic epidermal necrolysis overlap in a patient taking quetiapine and famotidine: a case report.

BACKGROUND: Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky's sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens-Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy. CASE PRESENTATION: An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky's sign was positive. A diagnosis of Steven-Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission. CONCLUSION: Stevens-Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted.

Stevens-Johnson syndrome and toxic epidermal necrolysis associated with immune checkpoint inhibitors: a systematic review.

Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare yet life-threatening adverse events associated with immune checkpoint inhibitors (ICIs). This systematic review synthesizes the current literature to elucidate the clinical characteristics and outcomes of patients with ICI-related SJS/TEN. Methods: We conducted a thorough search across databases including Embase, Web of Science, Cochrane, MEDLINE, Scopus, and PubMed. Selection criteria focused on reports of SJS/TEN among cancer patients treated with ICIs, analyzing clinical manifestations, therapeutic interventions, and outcomes. Results: Our analysis included 47 articles involving 50 patients with ICI-related SJS/TEN. The cohort had a mean age of 63 years, with a slight male predominance (54%). Most patients had melanoma or non-small cell lung cancer. SJS/TEN typically occurred early, with a median onset of 23 days post-ICI initiation. Treatment primarily involved systemic corticosteroids and intravenous immunoglobulins. The overall mortality rate was 20%, higher for TEN at 32%, with infections and tumor progression as leading causes. Median time from onset to death was 28 days. Survivors experienced a median re-epithelization time of 30 days, positively correlated with the extent of epidermal detachment (rs = 0.639, p = 0.009). Deceased patients exhibited a significantly higher proportion of TEN (90% vs. 48%, p = 0.029) and a larger epidermal detachment area (90% vs. 30% of the body surface area [BSA], p = 0.005) compared to survivors. The combination therapy group showed a higher proportion of TEN compared to corticosteroid monotherapy or non-corticosteroid therapy groups (72% vs. 29% and 50%, p = 0.01), with no significant differences in mortality or re-epithelization time. Dual ICI therapy resulted in a higher TEN rate than single therapy (100% vs. 50%, p = 0.028). Among single ICI therapies, the sintilimab-treated group trended towards a higher TEN rate (75% vs. 40-50%, p = 0.417), a larger detachment area (90% vs. 30-48% of BSA, p = 0.172), and a longer re-epithelization time (44 vs. 14-28 days, p = 0.036) compared to other ICI groups, while mortality rates remained similar. Conclusion: ICI-related SJS/TEN substantially impacts patient outcomes. Prospective clinical trials are critically needed to further clarify the pathogenesis and optimize therapeutic regimens.

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.

Stevens-Johnson syndrome associated with pancytopenia: a case report.

Introduction and importance: Stevens-Johnson syndrome (SJS) is a rare and unusual hypersensitivity reaction to certain drugs like allopurinol, commonly used for treating gout. SJS is recognized by extensive necrosis and detachment of skin and mucus membranes. Pancytopenia, characterized by decreased levels of red blood cells, white blood cells and platelets, is an exceedingly rare occurrence in the rare disorder SJS. Case presentation: The authors present a 61-year-old male who exhibited symptoms of fever and rash for 5 days accompanied by pancytopenia and liver injury. Clinical discussion: The abdomen and bilateral lower extremities exhibited several well-defined dusky-colored hyperpigmented macular lesions. Initially, these lesions were small, tender, erythematous, and raised, later transitioning to a dark red. Multiple distinct ulcerations were present on the lips and buccal cavity. Additionally, there was denudation of the skin with bleeding observed between the toes of both legs. The causality was assessed as a definite adverse drug reaction according to the Naranjo and ALDEN algorithm. The patient received treatment consisting of intravenous steroid along with prophylactics antibiotics. The individual's pancytopenia was resolved without requiring any blood cells or plasma or platelet concentrate transfusion. Conclusion: The exact pathophysiology of SJS associated with pancytopenia has not yet been fully elucidated. The authors' study hypothesized that the cause of pancytopenia in SJS could be either the direct cytotoxicity of drugs or immune-mediated damage to the bone marrow cells. Additional studies are necessary to establish the precise pathophysiology of the condition. Moreover, our study also indicates that pancytopenia can resolve in SJS without the need for blood cells or plasma or platelet concentrate transfusion. Once more, further studies are required to establish precise management strategies for managing SJS associated with pancytopenia.

Prevalence of limbal stem cell deficiency at an academic referral center over a two-year period.

Aim: To evaluate the prevalence and clinical characteristics of limbal stem cell deficiency (LSCD) in the setting of a tertiary referral cornea practice at an academic center. Patient and methods: A retrospective chart review was performed to identify all unique medical record numbers (MRNs) presenting to a single cornea specialist (JHH) at the University of Minnesota during calendar years 2019 and 2020. Records were queried and confirmed for a diagnosis of LSCD. Clinical characteristics of identified patients, including demographics, etiology of LSCD, severity of LSCD, treatment, and best corrected visual acuity (BCVA) at final follow-up, were documented. Results: In total 1436 unique MRNs were identified over the study period. There were 61 individuals (91 eyes) diagnosed with LSCD, resulting in a prevalence of 4.25% (95% CI, 3.33-5.42). Of 91 eyes, 60 eyes were bilateral (65.9%). Among all eyes, ocular surface burns were the most common etiology (18.7%) followed by iatrogenic or medicamentosa (15.4%). There were 51 eyes (56.0%) that underwent some form of transplantation. The median BCVA at final follow-up was Snellen 20/80 (range 20/20 to no light perception). Conclusions: The prevalence of LSCD found at a cornea subspecialty tertiary referral center in our study was much higher than previously reported prevalence rates. This may reflect referral bias and potential underdiagnosis of LSCD in practices outside of subspecialty referral centers. The high prevalence rate in our study also suggests that LSCD patients are concentrated in subspecialty referral practices, with many having high morbidity disease. This constitutes a major health burden for these practices.