SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02

Magnetic resonance imaging in enterovirus-71, myelin oligodendrocyte glycoprotein antibody, aquaporin-4 antibody, and multiple sclerosis-associated myelitis in children.

Aim: We used magnetic resonance imaging (MRI) to compare the neuroimaging of children with their first episode of clinical enterovirus 71-associated transverse myelitis (EV71-TM), myelin oligodendrocyte glycoprotein antibody positive transverse myelitis (MOG-TM), aquaporin-4 antibody positive transverse myelitis (AQP4-TM), transverse myelitis in multiple sclerosis (MS-TM), and unclassified transverse myelitis (UNC-TM). Method: We performed a retrospective blinded radiological assessment and compared the neuroimaging of 52 children (32 females, 20 males; mean age 9y 8mo, SD 5y 5mo, range 5mo-17y) presenting with their first episode of myelitis caused by EV71-TM (n=11), MOG-TM (n=10), AQP4-TM (n=9), MS-TM (n=13), and UNC-TM (n=9). Results: In the EV71-TM group, lesions were distributed throughout the cord and enhancement of nerve roots (ventral and dorsal) was common. The MOG-TM group had lesions distributed throughout the cord and most commonly longitudinally extensive transverse myelitis and lesions involving the grey matter alone on axial scans. The AQP4-TM group had lesions distributed in the cervicothoracic spine, cavitation, and contrast enhancing lesions. All patients with AQP4-TM had an abnormal brain MRI scan. The MS-TM group characteristically had multiple short segment lesions of the cord involving the cervicothoracic spine. The UNC-TM group did not have distinctive spinal MRI findings but had a relative paucity of lesions on their brain MRI scans. Interpretation: There are neuroimaging findings that are helpful in differentiating between myelitis associated with EV71, MOG, AQP4, and multiple sclerosis in children. These features may be useful early in the presentation of transverse myelitis while awaiting infectious/immunological testing, and/or further demyelinating events. What this paper adds: Magnetic resonance imaging can help identify aetiologies for children presenting with a first episode of myelitis. Entervirus-71-associated myelitis lesions are distributed throughout the cord and enhancement of nerve roots is common. Lesions distributed throughout the cord are commonly seen in myelin oligodendrocyte-associated myelitis. Aquaporin-4-associated myelitis lesions are distributed in the cervicothoracic spine, cavitation and contrast enhancing lesions are common. Short segment lesions in the cervicothoracic spine are commonly seen in multiple sclerosis-associated myelitis

Recommendations for imaging tumor response in neurofibromatosis clinical trials

Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NFrelated tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enablemeaningful comparison of results across studies. Conclusions: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors

Frontal fibrosing alopecia:a descriptive cross-sectional study of 711 cases in female patients from the UK

Frontal fibrosing alopecia (FFA) is an inflammatory primary scarring alopecia of uncertain aetiology that represents a variant of lichen planopilaris. It predominantly, although not exclusively, affects post-menopausal women. Its pathogenesis is characterised by immune-mediated follicular destruction at the level of the hair bulge, which leads to a clinical phenotype of progressive fronto-temporal hair and eyebrow loss that is often preceded by widespread body hair loss

SJS/TEN 2017: Building multidisciplinary networks to drive science and translation

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN