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.

Characterizing drug-induced epidermal necrolysis in a pediatric cohort.

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug-induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti-epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window.

Toxic epidermal necrolysis-like cutaneous toxicity following chimeric antigen receptor T-cell therapy in recurrent large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.

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.

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.

A nationwide study of Stevens-Johnson syndrome and toxic epidermal necrolysis in hospitalized pregnant women in the United States, 2009-2020.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rarely described in the pregnant population, and knowledge of their impact on the mother/fetus is limited. Objective: To describe SJS/TEN in pregnant women and to investigate the risk factors for developing SJS/TEN in pregnancy. Methods: We utilized hospitalization data from the 2009-2020 National Inpatient Sample. Pregnancy hospitalizations and SJS/TEN involvement were identified by ICD-9/10 codes and analyzed by chi-square and logistic regression. Results: We identified 650 pregnancies complicated by SJS/TEN requiring hospitalization. The median age was 28 years, and most were non-Hispanic White (55.2%). There were ≤10 cases associated with mortality. Most SJS/TEN cases (73.9%) occurred during the third trimester. HIV infection (OR = 9.49; P = .030), herpes simplex virus infection (OR = 2.49; P = .021), genitourinary tract infections (OR = 3.80; P < .001), malignant neoplasm (OR = 8.67; P = .031), and lupus erythematosus (OR = 41.94; P < .001) were associated with increased odds of developing SJS/TEN in pregnancy. Rates of preterm births were higher in the SJS/TEN cohort, 16.9% versus 8.2% (P < .001). Rates of pre-eclampsia, stillbirths, and post-term births were similar between the SJS/TEN versus non-SJS/TEN pregnancy cohorts. Limitations: Limited cohort size. Conclusions: SJS/TEN in pregnancy appears to be mild and is associated with favorable maternal-fetal outcomes, except for increased preterm birth.

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.

Paraneoplastic dermatomyositis and Stevens-Johnson syndrome related to immunotherapy.

Paraneoplastic syndromes such as dermatomyositis, often emerge as the initial clinical manifestation across various cancer types and are characterized by the development of B-cell responses targeting cancer-cell antigens that cross-react with normal skin and muscle cells. While these syndromes may alleviate following antineoplastic intervention, their response to immunotherapy remains elusive due to the exclusion of patients with autoimmune phenomena from clinical trials. In this report, we present the case of a female patient with advanced urothelial cancer presenting with dermatomyositis, who subsequently underwent treatment with anti-PD1 immunotherapy and experienced the onset of Stevens-Johnson syndrome. We discuss these two autoimmune entities and provide a comprehensive review of the existing literature to elucidate similar associations.

Dermatomyositis, an inflammatory disorder that causes a skin rash, might be the first sign that someone has cancer. But when scientists test new cancer treatments, they often don't include people with this skin problem. So, we do not know much about how safe or effective these treatments are for them. Here's a story about someone who had bladder cancer and dermatomyositis. They received a treatment called immunotherapy, but it caused a serious problem called Stevens-Johnson syndrome. We also found similar cases in medical papers.

A systematic review of case-control studies of cytokines in blister fluid and skin tissue of patients with Stevens Johnson syndrome and toxic epidermal necrolysis.

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)-alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case-control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)-8 and B-cell lymphoma (Bcl)-2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL-2, IL-6, TNF-alpha, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon-gamma and matrix metalloproteinase-2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL-33, TGF-beta-1 and IL-13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL-13, IFN-gamma, IL-2 and IL-5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed.

Pembrolizumab-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis in a Vietnamese patient with nonsmall-cell lung cancer.

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

Effect of Early Cyclosporine Treatment on Survival in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

INTRODUCTION: Early cyclosporine administration is a potentially useful treatment in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, previous studies have reported conflicting results regarding the survival benefits. Therefore, in this study, we evaluated the survival of patients with SJS/TEN according to whether they received early cyclosporine administration. METHODS: This retrospective cohort study was conducted using a Japanese national administrative claims database. Data on patients admitted to the hospital with SJS/TEN between April 1, 2016, and March 31, 2021, were extracted. Patients with missing data, those discharged within two days of admission, pregnant women, and children aged <16 years were excluded. Patients who received cyclosporine on the day of admission (early cyclosporine group) were compared with those who did not (comparison group). The primary endpoint was in-hospital mortality. Secondary endpoints were 30- and 50-day mortality and length of hospital stay. The effect of early cyclosporine treatment was evaluated after baseline adjustment using doubly robust estimation. RESULTS: Among 3807 enrolled patients (mean age, 65.5 years; 53.8% women), the early cyclosporine and comparison groups included 115 and 3692 patients, respectively. After adjustment, cyclosporine treatment decreased in-hospital mortality by 6.03% (95% confidence interval (CI), 5.27-6.82%), 30-day mortality by 2.94% (95% CI, 2.43-3.50%), and 50-day mortality by 4.38% (95% CI, 3.70-5.04%), but increased the length of hospital stay by 9.45 days (95% CI, 1.00-20.23 days). CONCLUSION: Early cyclosporine administration can improve the survival of patients with SJS/TEN but is associated with a longer hospital stay.

A Review of the Use of Intravenous Immunoglobulin Therapy in Dermatology.

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.

Evaluation of the Factors Influencing Mortality in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Study of 166 Patients.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute mucocutaneous disorders usually triggered by drugs. In this study, we aimed to evaluate the factors affecting mortality in patients with SJS-TEN. METHODS: Our study is a retrospective cohort study, analyzing data collected from a total of 12 tertiary care centers between April 2012 and April 2022. RESULTS: The study included 59 males and 107 females, a total of 166 patients, with an average age of 50.91 ± 21.25 years. Disease classification was TEN in 50% of cases, SJS in 33.1%, and SJS-TEN overlap in 16.9%. The average SCORTEN within the first 24 h was 2.44 ± 1.42. Supportive care was provided to 99.4% of patients. The most commonly used systemic immunomodulatory treatments were systemic steroids (84.3%), IVIG (intravenous immunoglobulin) (49.3%), and cyclosporine (38.6%). Plasmapheresis was administered to five patients. While 66.3% of patients were discharged, 24.1% resulted in exitus. Our comparative analysis of survivors and deceased patients found no effect of systemic steroids, IVIG, and cyclosporine treatments on mortality. Univariate analysis revealed that the SCORTEN scores on days 1 and 3 as well as the rates of detachment at the onset and during follow-up were significantly higher in deceased patients compared to survivors. The rates of fever, positive blood cultures, and systemic antibiotic use were higher in deceased patients compared to survivors. The presence of comorbidities, diabetes, and malignancy were significantly more common in deceased patients. Multivariate regression analysis indicated that over SCORTEN 2, the mortality risk exponentially rose with each SCORTEN increment, culminating in an 84-fold increase in mortality at SCORTEN 5-6 (odds ratio [95% confidence interval]: 13.902-507.537, p < 0.001) compared to SCORTEN 0-1. Additionally, the utilization of plasmapheresis was associated with a 22-fold increase in mortality (odds ratio [95% confidence interval]: 1.96-247.2, p = 0.012). CONCLUSION: Our study found that a high SCORTEN score within the first 24 h and the use of plasmapheresis were related to increased mortality, while systemic steroids, IVIG, and cyclosporine treatments had no impact on mortality. We believe that data gathered from one of the most comprehensive studies which we conducted on SJS-TEN will enrich the literature, although additional research is warranted.

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.

Empowering advanced clinical practitioners in managing acute dermatological emergencies.

Advanced clinical practitioners (ACPs) encounter patients with acute dermatological presentations ranging from minor to life-threatening conditions in both primary and secondary care settings. However, ACPs often feel unprepared to assess and treat patients with dermatological emergencies. This article aims to provide guidance to trainee and qualified ACPs, whether in acute hospital settings or primary care, in understanding the essential aspects to consider when consulting with patients presenting with acute dermatological emergencies. It also emphasises appropriate referrals to relevant specialties for necessary inpatient or outpatient investigations and ensure prompt treatment.

Trichiasis in cicatricial ocular surface disease: a multi-center comparison of electroepilation versus eyelash resection outcomes.

PURPOSE: To evaluate the outcomes of trichiasis (excluding entropion) management in non-trachomatous cicatricial ocular surface diseases. METHODS: This is a multicenter, retrospective study of 59 patients with trichiasis who were managed using two different techniques: electroepilation using radiofrequency (RF) cautery and eyelash resection. The assessed outcomes were residual trichiasis at 6 weeks, 6, and 12 months of follow-up and the number of procedures needed. RESULTS: 41 patients (90 eyelids) underwent electroepilation, and 18 (41 eyelids) were managed with eyelash resection. All patients belonged to either Indian or Japanese ethnicity. Most patients in both groups had Stevens-Johnson Syndrome (63.4% vs. 88.9%). The mean age (43.2 vs. 46 years), disease duration (122 vs. 192.4 months), median trichiasis grade (2 vs. 2), and involvement of upper eyelids (53/90 vs. 23/41) were similar in the two groups. At six weeks, 48.9% of eyelids that underwent electroepilation had no trichiasis, and recurrences were managed with repeat electroepilation (6 eyelids) and mucous membrane grafting (10 eyelids), and 35 eyelids opted for manual epilation, giving 67.8% success at a mean follow-up of 20 months. The eyelash resection group had 75.6% success at 6 months, and recurrences were managed using lid splitting and eyelash resection, resulting in 100% success at a mean follow-up of 79 months. More interventions were needed in the electroepilation group compared to eyelash resection. CONCLUSION: Eyelash resection of the trichiatic eyelashes achieves a better success rate than electroepilation in cicatricial ocular surface disorders. Following electroepilation, one needs multiple interventions to resolve trichiasis.