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Purpose Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are severe and potentially lethal adverse drug reactions characterized by acute inflammation of the skin, mucous membranes, and ocular surface that typically occurs within weeks of a culprit drug ingestion. The purpose of this study is to report a retrospective trend analysis of SJS spectrum diagnoses and associated culprit drugs in patients admitted to the Loyola University Medical Center (LUMC) Burn Unit, the major referral center in the Chicagoland region for patients with SJS disease spectrum. Methods The electronic medical records (EMR) of 163 patients with a diagnosis of SJS/TENS admitted to the LUMC Burn Unit from 2000 to 2019 were reviewed. Clinical data in addition to the well-established algorithm of drug causality for epidermal necrolysis (ALDEN) allowed us to identify the single most probable culprit drug in 131 cases. Results From 2000 to 2019, the most common spectrum classification was TENS (48.1%), followed by SJS (33.6%) and SJS-TEN Overlap Syndrome (18.3%). Anticonvulsants were found to be the most probable culprit class in 30% of cases followed by Trimethoprim-Sulfamethoxazole in 19% of cases. Beta-lactams were the most probable culprit class in 11% of cases while NSAIDs and allopurinol were each the most probable culprit class/drug in 8.4% of cases. Conclusions This is one of the largest single center series of SJS/TENS cases in the United States. Further study into culprit drug distribution by region as well as continuous monitoring of trends is crucial in order to advise prescribing practices.

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile non-follicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug specific T-cells that mediate neutrophilic intracorneal, subcorneal, and/or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathological features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies such as cyclosporine, and intravenous immunoglobulin.

Background/purpose Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. Methods Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. Results A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. Conclusions The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.

Background Mycoplasma pneumoniae (MP) infection is associated with extrapulmonary complications such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective We evaluated the differences in epidemiology, clinical characteristics, and disease outcomes between drug-induced and Mycoplasma-related SJS/TEN. Methods All patients with SJS/TEN admitted to our center between 2003 and 2016 inclusive were treated under a standardized protocol. Comparative analysis was made between patients who tested positive for MP versus a control group with negative MP serology in the presence of high-notoriety drugs defined by an algorithm for assessment of drug causality in epidermal necrolysis >5. Results Of 180 cases of SJS/TEN patients treated in our institution, 6 had positive MP serologies and were compared to a control group of 71 cases of drug-induced SJS/TEN with an algorithm for assessment of drug causality in epidermal necrolysis score of >5. There were no significant differences in baseline characteristics, disease classification, body surface area involved, and extent of mucosal involvement. We found significant differences in mortality rates between the Mycoplasma and control groups on discharge (0% vs 22.5%, P Limitations Retrospective design, small sample size. Conclusion Although recent studies have shown that MP-induced SJS/TEN is morphologically different and deserves a separate classification system, this would need to be borne out in larger prospective studies.

The objective of this study was to investigate the clinical manifestations and pathologic appearances of the submandibular gland (SMG) in Stevens-Johnson syndrome (SJS).Patients with autologous transplantation of SMG for treatment of severe dry eye between March 1998 and May 2018 were divided into the SJS group (70 cases) and non-SJS group (50 cases) according to the history of SJS. The SMG weight and computed tomography volume and salivary flow rate were measured. The concentration index and secretion index were estimated using scintigraphy with technetium-99m-pertechnetate. Histopathology studies of SMG tissues were conducted, and the acini parameters were measured using a digital image analyzer.A decreased computed tomography volume and weight was observed in 48.57% the SJS group and 2% in the non-SJS group (P.01). The rest whole, acid-stimulated whole, and SMG rest salivary flow rates decreased in the SJS group (P.05). The normal SMG concentration index (37.5% vs 96.67%, P.001) and secretion index (35% vs 96.67%, P.001) rates were lower in the SJS group than in the non-SJS group. The glandular parenchyma was reduced, the acinar space was widened, and the fat content was increased in the SJS group.SMG atrophic and degenerative changes occurred in the SJS group, with a decrease in salivary secretion function in more than half of the patients.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious adverse cutaneous drug reactions, characterized by epidermal detachment and mucous membrane involvement. SJS/TEN is more common in female patients, with unique findings in the ocular and vulvar regions. Early recognition and intervention, as well as long-term follow-up, are crucial to prevent devastating scarring and sequelae. This review examines the vulvar and ocular manifestations of SJS/TEN and describes the current treatment recommendations for female patients, requiring close consultation and collaboration among dermatology, ophthalmology, and gynecology.

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Purpose To investigate the long-term effects of corticosteroid pulse therapy (CPT) for the treatment of acute-stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients with severe ocular involvement. Design Retrospective, comparative case series. Methods This study retrospectively reviewed the medical records of 116 SJS/TEN patients who developed the disease between 2002 and 2018. Patients with severe ocular disorders (ie, ocular surface epithelial defect, pseudomembranous formation, or both) at the acute stage and who were followed for >1 year post SJS/TEN onset were enrolled. In those patients, the treatments administered for acute-stage SJS/TEN and associated ocular sequelae were examined, including the best-corrected visual acuity (BCVA) in the patient's worse eye and the incidence of the ocular complications at the final follow-up examination. Results A total of 85 patients were enrolled. Of those, 36 received CPT within 4 days post disease onset (group A) and 49 patients did not receive CPT within 4 days post disease onset (group B). The percentage of eyes with a BCVA in the worse eye of ≥ 1.0 were 52.8% in group A and 14.3% in group B. Severe ocular sequelae (ie, a worsening of BCVA and corneal and conjunctival complications) were significantly less in group A than in group B. Conclusions In SJS/TEN patients with acute ocular involvement, CPT initiated within 4 days from disease onset may help reduce severe ocular sequelae.

Background Stevens-Johnson syndrome is a rare medical condition with severe mucocutaneous lesions due to adverse drug reactions characterized by exudative multiform erythema, stomatitis, and conjunctivitis. Long-term oral consequences of such cases include xerostomia, caries, impactions, and multiple dental developmental aberrations as short root anomalies. Aim and objective To highlight the role of pedodontist in early diagnosis and treatment planning of dental abnormalities due to Stevens-Johnson syndrome (SJS) using a cone-beam computed tomography (CBCT). Case description A 16-year-old male reported a chief complaint of decayed posterior teeth. Past medical history revealed adverse reactions to an unknown drug at the age of 4 to 5 years. In addition to carious teeth, clinical examination revealed that all canines were missing along with mandibular incisors. On CBCT examination, abnormal short, plump roots with normal crown were seen in all permanent first molars and incisors along with impacted canines and mandibular incisors. This condition was diagnosed as a "Short root anomaly" (SRA) due to SJS. He was found positive to allergy tests for NSAIDs such as ibuprofen and paracetamol. Conclusion NSAIDs can cause a severe adverse reaction resulting in SJS. If this hypersensitivity reaction occurs early during the development of a permanent tooth it may cause dental anomalies such as short roots, root dysmorphia, agenesis, and multiple impacted teeth. Clinical significance This report highlights a unique case of multiple dental aberrations due to SJS and the role of a pedodontist in the early diagnosis and treatment planning of such cases with the help of CBCT. Short root anomalies can be misdiagnosed as root resorption or immature apex. Medical history, clinical and CBCT findings are essential for diagnosis and treatment in SJS patients. Careful orthodontic treatment planning is required in cases of short root anomalies. How to cite this article Katyal S, Yadav V. Diagnostic and Treatment Approach in the Management of Dental Anomalies Associated with Stevens-Johnson Syndrome: A Case Report. Int J Clin Pediatr Dent 2021;14(4):569-574.

Diverse ethnic genetic populations display variability in the risk regarding anti-seizure medicine (ASM)-induced severe cutaneous adverse reactions (SCARs). However, clinical and epidemiological data on ASM-induced SCARs in Asians is limited.We conducted a retrospective, post-market study until April 30, 2020 using VigiBase® for demographic characteristics, causative ASMs, complications and mortality. The study included adverse events as classified by Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries of SCARs, mainly Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and SJS/TEN overlap reported for ASMs.A total of 694,811 adverse events were reported across the world while using ASMs. Of this, skin and subcutaneous tissue adverse events were 122,885 (17.6%). Among ASM-induced skin and subcutaneous tissue adverse events, SJS, TEN, DRESS and SJS/TEN overlap represented 11,181 (9.1%), 3,645 (3.0%), 5,106 (4.1%) and 6 (0.004%) cases, respectively. Female SJS/TEN/DRESS patients were 54.1%, and 75% of them were adults (18Y). Nearly 64% of the ASM-induced SCARs were serious and culminated in death (3.5%), life-threatening conditions (11.5%), and hospitalization/prolonged hospitalization (43.5%) of patients on ASM therapy. Carbamazepine (31.6%), phenytoin (29.6%), lamotrigine (24.3%), valproic acid (6.4%) and phenobarbital (5.7%) are the most commonly used ASMs linked with SCARs. ASMs associated with significantly higher risk of SCARs in Asians were carbamazepine [n = 3265, ROR 3.55 (95% CI 3.38-3.72, P 0.0001)], lamotrigine [n = 1253, ROR 3.90 (95% CI 3.63-4.18, P 0.0001)], gabapentin [n = 85, ROR 3.58 (95% CI 2.79-4.60, P 0.0001)], pregabalin [n = 68, ROR 3.16 (95% CI 2.40-4.16, P 0.0001)], clonazepam [n = 53, ROR 3.19 (95% CI 2.31-4.41, P 0.0001)], lorazepam [n = 31, ROR 3.07 (95% CI 2.06-4.59, P 0.0001)] and acetazolamide [n = 28, ROR 3.90 (95% CI 2.45-6.21, P 0.0001)].Based on our study, carbamazepine, lamotrigine, gabapentin, pregabalin, clonazepam, lorazepam, and acetazolamide are the most common causative ASMs for SCARs in the Asian population.

Importance Immune checkpoint inhibitors (ICIs) have emerged as active therapies for a variety of cancers. Cutaneous toxicities are common immune-related adverse events and patients will often be referred to dermatologists for evaluation. Observations Cutaneous adverse events to ICIs can have a variety of clinical presentations. Among the more common are eczematous, morbilliform, and lichenoid dermatoses, as well as vitiligo and pruritus. Less common adverse events include psoriasiform dermatoses, bullous disorders, and severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Because of the immunologic mechanism of ICIs, there are also a variety of rheumatologic adverse reactions with cutaneous manifestations, such as scleroderma, dermatomyositis, cutaneous lupus erythematosus, and various vasculitides. These cutaneous reactions often respond to topical or systemic steroids, although specific toxicities may have alternative treatments available. Conclusions and relevance As they become more widely prescribed, dermatologists will see an increasing number of patients with cutaneous adverse events caused by ICI therapies. Accurately diagnosing and treating these toxicities is paramount to achieving the most favorable outcomes for patients.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient’s attacks are crucial to accurate diagnosis and treatment in PKD patients.

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

AIMS Carbamazepine (CBZ) is one of the most common causative drugs of severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms. Although genetic polymorphisms of the human leucocyte antigens (HLA) are well recognized key elements for the susceptibility to CBZ-induced SCARs, some evidence suggest that polymorphisms of microsomal epoxide hydrolase 1 (EPHX1) may also contribute to the risk of these SCARs. This study investigated the association between the HLA and EPHX1 polymorphisms on CBZ-induced SCARs in large sample sizes and well-defined SCARs patients. METHODS Ninety-one CBZ-induced SCARs Thai patients and 144 CBZ-tolerant patients were enrolled in the study. The genotypes of HLA-A, HLA-B and EPHX1 were determined. RESULTS Only 2 HLA alleles including HLA-B*15:02 and HLA-A*24:07 were statistically significant association with CBZ-induced SJS/TEN. The highest risk was observed in patients with HLA-B*15:02 allele (OR = 44.33, 95% confidence interval = 20.24-97.09, corrected P-value = 6.80 × 10-29 ). Moreover, HLA-B75 serotypes were significantly associated with CBZ-induced SJS/TEN groups with an odds ratio of 81.00 (95% confidence interval = 32.39-202.56, corrected P-value = 3.84 × 10-34 ). There is no association between EPHX1 c.337 T > C polymorphism and all phenotypes of CBZ-induced SCARs. CONCLUSION The HLA-B*15:02 allele is the strongest genetic marker for the prediction of SJS/TEN induced by CBZ in Thai population. Screening for other alleles in the HLA-B75 serotype increases sensitivity for prediction of a life-threatening SCARs caused by CBZ.

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are life-threatening conditions best approached with multidisciplinary burn-equivalent care. There is a lack of consensus on wound management, in particular, whether to debride detached epidermis. Our center instituted “antishear” wound therapy 35 years ago, where detached skin is left in situ as a biologic dressing and a standardized protocol avoids shear forces to prevent further desquamation. Our center’s initial results showed outcomes comparable to SCORTEN predictions, but advancements in burn critical care necessitate a reevaluation of the antishear approach. A retrospective chart review was conducted for all patients admitted between June 2004 and May 2020 with a dermatologist-confirmed diagnosis of SJS/TEN (N = 51). All patients were treated with burn-equivalent critical care and antishear wound therapy. Standardized mortality ratios were calculated using the established SCORTEN, and newly developed ABCD-10, prediction models. Mean SCORTEN, ABCD-10, and %TBSA were 2.6, 2.0, and 28%. Overall mortality was 22%; SCORTEN score (P < .001), ABCD-10 score (P < .01), %TBSA involved (P = .02), and development of multisystem organ failure (P < .001) correlated with increased mortality. Cohort-wide standardized mortality based on ABCD-10 was 1.18 (P = .79). Standardized mortality based on SCORTEN was 0.62 (P = .20) and 0.77 (P = .15) for patients with scores ≤3 and >3; across the cohort it was 0.71 (P = .11), representing a 29% mortality reduction. Incorporating the antishear approach as part of burn-equivalent care for SJS/TENs led to outcomes comparable to those predicted for surgical debridement via SCORTEN. However, the antishear approach has the advantage of avoiding painful dressing changes, sedation, and general anesthesia required for surgical debridement.

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

INTRODUCTION The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P

Adverse drug reactions involving the skin are commonly known as drug eruptions. Severe drug eruption may cause severe cutaneous adverse drug reactions (SCARs), which are considered to be fatal and life-threatening, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Although cases are relatively rare, approximately 2% of hospitalized patients are affected by SCARs. There is an incidence of 2 to 7 cases/million per year of SJS/TEN and 1/1000 to 1/10,000 exposures to offending agents result in DRESS. However, the mortality rate of severe drug eruptions can reach up to 50%. SCARs represent a real medical emergency, and early identification and proper management are critical to survival. The common pathogenesis of severe drug eruptions includes genetic linkage with HLA- and non-HLA-genes, drug-specific T cell-mediated cytotoxicity, T cell receptor restriction, and cytotoxicity mechanisms. A multidisciplinary approach is required for acute management. Immediate withdrawal of potentially causative drugs and specific supportive treatment is of great importance. Immunoglobulins, systemic corticosteroids, and cyclosporine A are the most frequently used treatments for SCARs; additionally, new biologics and plasma exchange are reasonable strategies to reduce mortality. Although there are many treatment methods for severe drug eruption, controversies remain regarding the timing and dosage of drug eruption. Types, dosages, and indications of new biological agents, such as tumor necrosis factor antagonists, mepolizumab, and omalizumab, are still under exploration. This review summarizes the clinical characteristics, risk factors, pathogenesis, and treatment strategies of severe drug eruption to guide clinical management.

BACKGROUND & AIMS Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR. METHODS We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020. RESULTS A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P

Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD; n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; n = 27), maculopapular drug eruption (MDE; n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (MΦ, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4+ and CD8+ T cells. The majority of CD4+ T-helper cells were localized in the upper dermis, whereas cytotoxic CD8+ T cells were found in the epidermis. Increased numbers of CD56+ natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE.

BACKGROUND Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2 - positive metastatic breast cancer. The most frequently reported adverse events attributed to capecitabine include diarrhea, hyperbilirubinemia, and hand-foot syndrome (HFS). A number of cutaneous adverse events have been attributed to capecitabine, including Stevens-Johnson syndrome (SJS) as a rare and potentially life-threatening mucocutaneous condition. We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment. CASE SUMMARY A 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions. Six weeks earlier, she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer. She subsequently developed worsening erythema and bullae on her palms and soles, as well as reddish macules on her back and chest wall. Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis. The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids. This treatment resolved most lesions, although the lesions on her palms and soles required Vaseline gauze dressings, which resulted in re-epithelialization. Therefore, we determined that the patient had concurrent SJS and HFS. Although the dermatological problems resolved, the patient ultimately died because of multiple organ failure. CONCLUSION Oral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions, such as SJS.

OBJECTIVE To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history. METHODS We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls. RESULTS The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p

The neutrophil : lymphocyte ratio (NLR), platelet : lymphocyte ratio (PLR), C-reactive protein : albumin ratio (CAR), and albumin : fibrinogen ratio (AFR) have been considered as useful inflammatory biomarkers. However, their roles in Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) still remain unclear. This study aimed to test whether NLR, PLR, CAR, and AFR serve as predictive markers of disease severity and systemic inflammation in patients with SJS/TEN. This retrospective study included 40 patients with SJS/TEN and 60 healthy controls. The correlation between these markers and severity-of-illness score for toxic epidermal necrolysis (SCORTEN), ABCD-10, procalcitonin (PCT), C-reactive protein (CRP) were analyzed and compared. Univariable and multivariable analysis were used to assess associations of variables with mortality. The receiver-operator curves (ROC) were used to evaluate the predictive value of variables for mortality in SJS/TEN patients. The results demonstrated that the NLR and PLR of SJS/TEN patients were significantly higher and the AFR was significantly lower when compared with healthy controls (p 0.05). The NLR and CAR were positively correlated with SCORTEN, ABCD-10, PCT, and CRP. The NLR in SCORTEN of ≥3 group was significantly higher than that in SCORTEN3 group (p 0.05) and there were no significant differences between PLR, CAR, and AFR between the two groups. The univariate analysis suggested that NLR of5.79 was a risk factor for mortality (odds ratio, 10.5; p 0.05), but the association was no longer statistically significant in multivariable analysis. The ROC showed that NLR had a sensitivity of 85.7% and specificity of 63.6% for predicting death with a cut-off value of 5.79 (p 0.05) in SJS/TEN patients. In conclusion, among the four markers, NLR and CAR can partially reflect severity and inflammatory status in patients with SJS/TEN. NLR was also a predictor of death.

Stevens-Johnson syndrome (SJS) is a rare but severe mucocutaneous epidermolysis commonly triggered by medications. SJS is characterized by mucocutaneous lesions of the trunk, face, and limbs, as well as the oral cavity, gastrointestinal tract, and respiratory tract. Although uncommon, laryngeal involvement in SJS can lead to severe respiratory, phonatory and deglutitive complications. Providers caring for patients with SJS should maintain a high index of suspicion for laryngeal involvement and low threshold to solicit Otolaryngology consultation. Laryngeal complications can be more expediently managed when anticipated early in the course of disease. Laryngoscope, 131:2519-2522, 2021.

Introduction Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening, allergic reactions affecting the skin and mucous membranes. SJS is considered to be a milder form with less than 10% of body surface area (BSA) involvement. We report successful management of two cases of SJS and TEN. Firstly, a case of a 24-year-old female who presented with rashes over face, chest, and upper limbs after the oral intake of ciprofloxacin and local application of moxifloxacin eye drops. She developed high-grade fever and difficulty in breathing requiring intubation and lung-protective mechanical ventilation and was treated with high-dose methylprednisolone, azithromycin, soframycin skin dressings, and topical ocular antibiotics. Secondly, another case of a 16-year-old female who developed bullous eruptions over the trunk, arms, hands, face, and sole involving 60% of BSA, after oral intake of albendazole. She was diagnosed as TEN and successfully managed with sterile silver nitrate, soframycin dressings, and antibiotics. Key message Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, allergic reactions affecting the skin and mucous membranes. Early identification, withdrawal of the suspected drug, and early transfer to a specialized center decrease mortality. How to cite this article Arora R, Pande RK, Panwar S, Gupta V. Drug-related Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Review. Indian J Crit Care Med 2021;25(5):575–579.

Background: Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). Aims: To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. Methods: Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. Results: Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on “surface under the cumulative ranking curves” (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. Limitations: Evidence is mainly based on retrospective studies. Conclusion: The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.

Analysis of lacrimal glands in eyes with severe dryness following Stevens-Johnson syndrome (SJS) showed normal acinar morphology, secretory activity and myoepithelial cells; indicating that ocular dryness in SJS is not because of primary glandular destruction.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. Methods: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. Results: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. Conclusions: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.

The Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) spectrum of diseases are devastating blistering disorders involving mucosal surfaces with ocular sequelae that manifest particularly profound long-term morbidity. Advances in deoxyribonucleic acid (DNA) sequencing, genome-wide association studies, and both molecular and pharmacogenetics have helped clarify genetic susceptibility and characterize the iatrogenic risk of SJS for a given patient.A review of peer reviewed publications featured on PubMed pertaining to the clinical, pathologic, pharmacogenetic and molecular genetic features of SJS/TEN was conducted. Propose: To provide an in-depth clinicopathologic description of the ocular, ocular adnexal, and cutaneous findings in SJS/TEN, summarize pathogenesis and related conditions, and provide an update on the molecular genetic modifications that contribute to the phenotypic variations and genetic susceptibilities of SJS.HLA subtyping and other genetic testing may eventually be valuable in the appropriate context to prevent the debilitating ocular sequelae of SJS, particularly as it relates to medication use.

Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied.To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms.Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor α, interleukin (IL) 6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including 3 with acute pancreatic injuries.Acute pancreatic injury was diagnosed in 7.3% of patients (9/124) in the SJS/TEN cohort. Elevation of serum transaminase level and hypoalbuminemia occurred more frequently in patients with acute pancreatic injuries compared with those without pancreatic symptoms (P = .004 and .001, respectively). Although acute pancreatic injury did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = .008). Within the serum cytokines whose levels were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with acute pancreatic injuries compared with those without them (P = .03).Cohort was small.Acute pancreatic injury is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe diseases. This study aimed to validate the predictive ability of risk models in patients with SJS/TEN and propose possible refinement in China. Patients in the Department of Dermatology of Huashan Hospital from January 2008 to January 2019 were included. Results showed that the severity-of-illness score for TEN (SCORTEN) had a good discrimination (area under the receiver operating characteristic curve (AUC), 0.78), and it was superior to auxiliary score (AS) and ABCD-10, which indicates age, bicarbonate level, cancer, dialysis, and 10% involved body surface area (AUC, 0.69 and 0.68, respectively). The calibration of SCORTEN (Hosmer-Lemeshow goodness-of-fit test, P = 0.69) was also better than that of AS (P = 0.25) and ABCD-10 (P = 0.55). SCORTEN and ABCD-10 were similar (Brier score (BS), 0.04 and 0.04) in terms of accuracy of predictions. In addition, the imaging appearance of pulmonary consolidation on computed tomography was associated with high mortality. Refined models were formed using the variables and this imaging appearance. The refined AS and ABCD-10 models were similar in discrimination compared with the original SCORTEN (0.74 vs. 0.78, P = 0.23; 0.74 vs. 0.78, P = 0.30, respectively). Therefore, SCORTEN showed good discrimination performance, calibration, and accuracy, and refined AS or ABCD-10 model may be an option when SCORTEN variables are not available.

Epidermal necrolysis (EN, including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN)) is mostly induced by drugs. Prevalence of lupus erythematosus (LE) is higher in EN than in general population (1.2 to 2%).1,2 Furthermore, flares of LE may present as EN (TEN-like LE).3-5 We aimed to describe EN in patients with clinical or biological LE to better characterize the relation between both diseases.

BackgroundBiologic drugs have the potential to halt the progression of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by decreasing concentrations of tumor necrosis factor-α, a cytokine implicated in epithelial cell death. The objective of this systematic review is to investigate the efficacy and safety of biologic monotherapy and combination therapy for SJS/TEN.MethodsMEDLINE and EMBASE in OVID were searched on October 28, 2020. Inclusion criteria were original studies containing human participants diagnosed with SJS/TEN and treated with biologics. Studies were excluded if they were literature reviews, systematic reviews, letters to the editor, or conference abstracts.ResultsThe 38 articles reviewed included 27 (71.1%) case reports, 6 (15.8%) case series, 3 (7.9%) retrospective reviews, and 2 (5.3%) RCTs. The age range of the included studies was 2 to 85 years, the mean age was 46.4 years. The mean body surface (BSA) across the 38 included articles was 31.0%. The average actual mortality reported within the 38 included articles was 9.2%. Both biologic monotherapy and combination therapy were associated with improved outcomes in SJS/TEN. Furthermore, anti TNF-alpha therapy, specifically etanercept, showed improved outcomes as monotherapy.ConclusionsOverall, reviewed studies presented a strong case for biologic treatment, both monotherapy and combination use, in SJS/TEN treatment. Based on the number of fatal adverse events observed, biologic monotherapy may be safer compared to combination therapy. Further research with a larger sample size and a randomized control trial design is required.

Stevens‐Johnson syndrome (SJS) is an acute, exfoliative disease that causes severe blistering of the skin and mucosal membranes.1 SJS is often caused by an extreme allergic reaction to a medication...

Purpose To study the outcomes of cultivated oral mucosal epithelial transplantation (COMET) in eyes with chronic Stevens-Johnson syndrome (SJS) sequelae. Design Prospective interventional case series. Methods Forty-five eyes of 41 patients with chronic SJS sequelae were recruited and evaluated from 2013 to 2017 in an institutional setting. All patients underwent COMET, with an aim of fornix reconstruction and visual rehabilitation. Change in corrected distance visual acuity (CDVA), severity scores of various ocular surface parameters, and the occurrence of complications were documented during a follow up period of 2 years. Attainment and maintenance of a stable ocular surface, as assessed by change in the ocular surface severity scores was the primary outcome measure, while change in CDVA was the secondary outcome measure. Results The mean preoperative CDVA was 2.7± 0.5 logMAR, which improved to 1.5± 0.7 logMAR and 1.49± 0.98 postoperatively, at 1- and 2-year follow-up visit. Overall, 82.2% eyes (37/45) had improvement in visual acuity, 13.3% (6/45) experienced no change, whereas 2 eyes (4.4%) had worsening of visual acuity. The total ocular surface severity scores improved from a mean preoperative value of 29.1± 9.7 to 18.7± 7.2 postoperatively, at 2-year follow-up. Two eyes developed persistent epithelial defects, with progression to corneal melting requiring keratoplasty. Conclusions COMET allows successful and sustained restoration of ocular surface anatomy with functional improvement, in eyes with chronic sequelae of SJS.

Background Therapeutic plasma exchange (TPE) is an effective means of treating systemic lupus erythematosus in children and is safe for most pediatric patients with systemic lupus erythematosus, but severe complications such as toxic epidermal necrolysis (TEN) may occur, which is a life-threatening condition. Methods In this study, three systemic lupus erythematosus (SLE) children developed toxic epidermal necrolysis after TPE. We analyzed their medical history, clinical manifestations, SLEDAI scores, and immunological characteristics, compared to 117 cases of SLE patients without TEN after TPE, trying to find the possible risk factors. Results The three children with TEN after plasma exchange appeared to have a higher proportion of male (male: female = 2:1), fever (100% Vs 32.5%), erythema on the cheek (100% Vs 54.7%), itching rash (100% Vs 54.7%), ruptured rash (100% Vs 54.7%), oral ulcer (100% Vs 54.7%) and higher LDH level (1826.0 ± 1113.1 Vs 721.1 ± 799.5 U/L), but lower white blood cell count (5.5 ± 3.3 Vs 7.2 ± 4.2 × 109/L), neutrophil count (4.7 ± 3.7 Vs 5.2 ± 3.6 × 109/L), lymphocyte count (0.6 ± 0.5 Vs 1.5 ± 0.8 × 109/L), platelet count (133.7 ± 58.1 Vs 178.5 ± 103.1 × 109/L) and C-reactive protein (all normal Vs 47.9% elevated). Autoantibody spectrum revealed that positive anti-SSA seemed more common (100% Vs 42.7%) in the three children. Relative risk analysis revealed that male (OR 21.4, 95%CI 1.78–257.186), ruptured skin rash (OR 56.5, 95%CI 4.199–760.196) and rash with itching (OR 24, 95%CI 1.98–290.896) are the risk factors of SLE patients developing TEN after plasma exchange. Conclusions We should pay particular attention to TEN after plasma exchange in SLE patients (3/120, 2.5%). This condition may be related to male, ruptured skin rash and rash with itching. For SLE patients with risk factors. We should arrange plasmapheresis more carefully.

Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are adverse drug reactions. Objectives To learn about the clinical characteristics of patients with SJS/TEN including treatments provided, outcomes, and mortality. Methods We conducted a retrospective chart review of patients who were hospitalized with the diagnosis of SJS/TEN at the Ross Tilley Burn Center between the years 1999 and 2015. Results A total of 43 patients were identified with a mean age of 54 ± 19 (58, 18-85). The most common offending medications were allopurinol and carbamazepine. The overall mortality rate in our study is 21% with the most common causes of death being multiorgan failure and sepsis. The majority of our patients had oral (84%), ocular (79%), and genital (60%) involvement during hospitalization. Our data revealed that combination treatment involving oral corticosteroids with intravenous immunoglobulin (IVIG) had the highest mortality rate in our study since 55% (6/11) of patients who were treated in this manner passed away compared to 11% (2/18) of patients passing away who were treated with solely IVIG and 33% (1/3) who were treated with only supportive care. Our study also demonstrates the addition of etanercept and cyclosporine treatment in the second time period we studied: 2008-2015 versus the earlier time period of 1999-2007. None of the patients in our study who were treated with therapies including cyclosporine and/or etanercept passed away. Conclusions Our study sheds light on a possible beneficial role of cyclosporine and etanercept for the treatment of SJS and TEN and reinforces the necessity of a multidisciplinary care team for patients.

Purpose: To describe a new technique of intracorneal scleral patch (ICSP) supported cyanoacrylate tissue adhesive (CTA) application in corneal perforations, greater than 3.0 mm secondary to rheumatoid arthritis (RA). Methods: This Prospective, non-randomized, non-comparative, interventional series included 14 eyes (14 patients). All patients had corneal perforations sized 3.5 to 4.5 mm due to RA, which were treated with ICSP supported CTA application. A partial thickness scleral patch 1.0 mm larger than diameter of corneal perforation was prepared. A lamellar corneal pocket 0.5 mm all around the corneal perforation was created. The partial thickness scleral patch was placed in the corneal perforation site and the edge was fitted into the lamellar intracorneal pocket. A minimum quantity of CTA was applied on the scleral patch to seal the perforation. Results: The corneal perforations healed in 14 eyes (100%) in a mean 7.71 ± 1.14 (range, 6–9) weeks. One eye (7.14%) had inadvertent extrusion of ICSP due to premature removal of CTA but, Seidel's test was negative, and the corneal epithelial defect healed with BCL alone. One eye each (7.14%) developed steroid induced cataract and glaucoma. None of eyes developed infective keratitis, re-opening of corneal perforation (necessitating repeat procedure) or enlargement of corneal perforation requiring penetrating keratoplasty (PKP). Conclusion: ICSP supported CTA application is a successful alternative option to emergency PKP in treating corneal perforations sized 3.5 to 4.5 mm with associated RA.

Stevens‐Johnson syndrome (SJS) is serious conditions that happen as a result of infection, side effects to medications, or unknown etiology. Carbamazepine is one of the common medications that can cause SJS. Good history taking is crucial if treatment with carbamazepine is clinically indicated. We would like to alert all physicians that carbamazepine should be avoided in any patient with a previous history of drug reaction such as mast cell activation syndrome.

Background: Stevens Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) represent adverse drug reactions characterized by generalized rash, blisters, epidermal detachment, mucosal and systemic involvement presenting as dermatological emergencies. Drugs are the most common culprits implicated in the pathogenesis of SJS /TEN. The primary step in the management of SJS/TEN is identification and stopping the offending drug. Materials and methods: This was a multi-centric retrospective as well as prospective observational study conducted in 7 tertiary care hospitals including Father Muller Medical College Hospital , Mangalore, India. A detailed evaluation of the hospital in patient record for 10 years retrospective from September 2015 and all new cases of SJS/TEN as well as SJS-TEN overlap presenting to these centres for 1 year prospective was performed. Detailed history was taken and clinical examination was recorded and different modalities of treatment was noted and compared. Results: A total of 152 patients with clinical diagnosis of SJS ,TEN and SJS-TEN overlap were analysed. Males were more commonly affected than females and history of drug intake was present in 118 patients (77.6%). The most common drugs which caused SJS/ TEN in our study were antibiotics in 40 patients (26.3%) followed by anti epileptics in 35 patients (23%) and nevirapine in 10 patients (6.5%). In our study the most common finding on cutaneous examination was maculopapular rash (19.3%). Conclusion: SJS and TEN form part of a spectrum of severe cutaneous drug reactions that can lead to high morbidity which can be reduced by early withdrawal of the offending drug and timely intervention. Individuals with known drug allergies need to be educated and drug allergy card has to be carried.

Background There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. Objective To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. Methods We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. Results Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. Conclusions Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Objective Previous studies have found an association between HLA-B*1502 allele and lamotrigine-induced Stevens-Johnson syndrome (SJS)/ toxic epidermal necrosis (TEN) spectrum in Han Chinese populations. This study aims to investigate the association between HLA-B*1502 and lamotrigine- or phenytoin- induced SJS/TEN in an Iranian population. Methods The medical records of twenty-eight lamotrigine-induced SJS/TEN patients and twenty-five lamotrigine-tolerant controls as well as eight phenytoin-induced SJS/TEN and twelve phenytoin-tolerant controls were extracted between March 2013 to March 2019 from the university hospitals in Mashhad, Iran. The presence of HLA-B*1502 allele was determined using real-time polymerase chain reaction (PCR). Results Among lamotrigine-induced patients with SJS/TEN, 11 (39.3%) patients tested positive for the HLA-B*1502 while only 3 (12.0%) of the lamotrigine-tolerant controls tested positive for this allele. The risk of lamotrigine-induced SJS/TEN was significantly higher in patients with HLA-B*1502, with an odds ratio (OR) of 4.74 [95% confidence interval (CI) 1.14-19.73, p = 0.032]. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HLA-B*1502 for lamotrigine-induced SJS/TEN was 39.29%, 88.00%, 78.57% and 56.41%, respectively. The HLA-B*1502 allele was present in 2 (25.0%) of phenytoin-induced SJS/TEN cases and 5 (41.7%) of the phenytoin-tolerant controls tested positive for HLA-B*1502 allele. The risk of phenytoin-induced SJS/TEN was not higher in the patients with HLA-B*1502 (OR = 0.467 [95% confidence interval (CI) 0.065-3.34, p = 0.642]). Significance Lamotrigine-induced SJS/TEN is associated with HLA-B*1502 allele in an Iranian population but this is not the case for phenytoin-induced SJS/TEN.

This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.

Purpose To analyze the therapeutic benefits of limbal-supported contact lens (CL) wear in patients with ocular sequelae due to Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Methods This interventional study enrolled 10 chronic SJS/TEN eyes with a spectacle best-corrected visual acuity (BCVA) of between 0.01 and 0.7 that were fitted with a limbal-supported CL. At baseline and at after 3-months CL use, CL-wear BCVA and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores were measured, and then compared. Incidence rates and severities of adverse events were also analyzed. Results At after 3-months CL use, BCVA with the fitted CL significantly improved compared to that with spectacle correction at baseline (LogMAR: 0.76−0.15) (P = 0.0039), all NEI VFQ-25 scores improved, however, only in ocular pain and mental health showed statistically significant improvement (P = 0.0078 and 0.0039). No serious adverse events were observed during the follow-up. Conclusion Wearing of the limbal-supported CL improved vision compared to spectacles and reduced ocular pain in patients with ocular sequelae due to SJS/TEN.