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Objective: Dietary intake is a complex exposure and a potential risk factor for systemic lupus erythematosus (SLE) due to its impact on lipid and glucose metabolism, oxidative stress, and the intestinal microbiome. We aimed to test whether a prudent dietary pattern is associated with a lower risk of SLE, and whether a Western dietary pattern is associated with a higher risk of SLE. Methods: We prospectively investigated two dietary patterns and SLE risk among women in the Nurses' Health Study (NHS, 1984–2014) and Nurses' Health Study II (NHSII, 1991–2015). Food frequency questionnaires were completed every four years. Congruent with prior work in NHS and NHSII, we derived two separate dietary patterns (prudent and Western) using principal component analysis within each cohort. Incident SLE was confirmed by the American College of Rheumatology's 1997 criteria. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for SLE by dietary pattern quartiles using Cox models adjusted for time-varying covariates. Models were performed separately in each cohort and results were meta-analyzed. Stratified analyses tested the association of dietary patterns with anti-dsDNA positive SLE and anti-dsDNA negative SLE. Results: We confirmed 82 NHS incident SLE cases and 98 NHSII SLE cases during 3,833,054 person-years of follow-up. A higher (healthier) prudent dietary pattern score was not associated with SLE risk (meta-analyzed HRQ4 versus Q1 0.84 [95% CI 0.51, 1.38]). Women with higher (less healthy) Western dietary pattern scores did not have a significantly increased risk for SLE (meta-analyzed HRQ4 versus Q1 1.35 [95% CI 0.77, 2.35]). Results were similar after further adjustment for body mass index. Incident anti-dsDNA positive SLE and anti-dsDNA negative SLE were not associated with either dietary pattern. Conclusion: We did not observe a relationship between prudent or Western dietary pattern score and risk of SLE. [ABSTRACT FROM AUTHOR]

Objective: Non-infectious myelitis in systemic lupus erythematosus (SLE) may be due to SLE myelitis, comorbid multiple sclerosis (MS), or neuromyelitis optica (NMO). We compared characteristics of these three conditions in SLE patients at a large academic institution. Methods: We searched for neurologic diagnoses of SLE myelitis, NMO myelitis, and MS myelitis among 2297 patients with at least four 1997 American College of Rheumatology revised criteria for SLE between 2000 and 2015. Each subject was reviewed by a neurologist to confirm the underlying neurologic diagnosis. Demographic, clinical, laboratory, and radiographic data were extracted and compared using Fisher's exact test, analysis of variance, and Wilcoxon rank-sum test. Results: Fifteen of the 2297 subjects with SLE (0.7%) met criteria for a spinal cord syndrome: seven had SLE myelitis, three had AQP4 seropositive NMO, and five had MS. The median SLE Disease Activity Index 2000 score at time of neurologic syndrome presentation was higher in SLE myelitis subjects (8, interquartile range (IQR) 7–16) compared with subjects with NMO (6, IQR 0–14) or MS (2, IQR 0–4), p = 0.02. Subjects with SLE myelitis were also more likely to have elevated anti-dsDNA antibodies at presentation (86%) compared with subjects with NMO (33%) or MS (0%), p = 0.03. Conclusion: Myelitis occurs rarely among patients with SLE. Compared with subjects with SLE + NMO and subjects with SLE + MS, subjects with SLE myelitis had higher SLE disease activity at presentation. [ABSTRACT FROM AUTHOR]

Objective: Past studies have reported associations between pesticide exposure and the risk of systemic lupus erythematosus (SLE). Residential pesticide exposure has been less well studied than agricultural exposure. The purpose of this study was to assess SLE risk associated with residential pesticide exposure in an urban population of predominantly African-American women. Methods: Adult women with SLE were identified from six hospital databases and community screening in three neighborhoods in Boston, Massachusetts, USA. Controls were adult women volunteers from the same neighborhoods who were screened for the absence of connective tissue disease and anti-nuclear antibodies. Subjects were considered exposed to pesticides if they had ever had an exterminator for an ant, cockroach, or termite problem prior to SLE diagnosis or corresponding reference age in controls. Risks associated with pesticide exposure were analyzed using multivariable logistic regression models, adjusted for sociodemographic factors. Results: We identified 93 SLE subjects and 170 controls with similar baseline characteristics. Eighty-three per cent were African-American. Pesticide exposure was associated with SLE, after controlling for potential confounders (odds ratio 2.24, 95% confidence interval 1.28–3.93). Conclusion: Residential exposure to pesticides in an urban population of predominantly African-American women was associated with increased SLE risk. Additional studies are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Summary: Determining the risk of progression to systemic lupus erythematosus (SLE) among patients diagnosed with discoid lupus erythematosus (DLE), and the time frame of this risk, are important clinical questions. Past reports have demonstrated a wide time frame of progression from DLE to SLE, with mean time to progression of approximately 8 years. Using data obtained from an academic lupus centre, we identified 32 patients who progressed from DLE to SLE. In our cohort, we found that the median time to progression from DLE to SLE was 453 days, much sooner than previously reported. We believe this information can help inform clinicians on monitoring visit intervals and how best to counsel patients on SLE progression. [ABSTRACT FROM AUTHOR]

Background: Macrophage activation syndrome (MAS) is an uncommon but serious complication of systemic lupus erythematosus (SLE). We aimed to identify factors associated with MAS among adult hospitalized SLE patients. Methods: Within the Brigham and Women's Hospital (BWH) Lupus Center Registry, we identified adult SLE patients>age 17 who had been hospitalized from 1970 to 2016, with either ferritin>5000 ng/ml during admission or "macrophage activation syndrome" or "MAS" in discharge summary. We confirmed MAS by physician diagnosis in medical record review. We matched each hospitalized SLE patient with MAS to four SLE patients hospitalized without MAS (by SLE diagnosis date ±1 year). We employed conditional logistic regression models to identify clinical factors associated with MAS among hospitalized SLE patients. Results: Among 2094 patients with confirmed SLE, we identified 23 who had a hospitalization with MAS and compared them to 92 hospitalized without MAS. Cases and controls had similar age at SLE diagnosis (29.0 vs. 30.5, p=0.60), and hospital admission (43.0 vs. 38.3, p=0.80), proportion female (78% vs. 84%, p=0.55), and time between SLE diagnosis and hospitalization (1971 vs. 1732 days, p=0.84). Arthritis (OR 0.04 (95% CI 0.004-0.35)) and hydroxychloroquine use (OR 0.18 (95% CI 0.04-0.72)) on admission were associated with decreased MAS risk. Admission Systemic Lupus Erythematosus Disease Activity Index scores (30 vs. 19, p=0.002) and lengths of stay (16 days vs. 3 days, p<0.0001) were much higher among cases. Death during hospitalization was 19% among cases and 3% among controls (p=0.03). Conclusions: In this case-control study of hospitalized adult SLE patients, arthritis and hydroxychloroquine use at hospital admission were associated with decreased MAS risk. Further studies are needed to validate these factors associated with lowered MAS risk. [ABSTRACT FROM AUTHOR]

Objective The chronicity and severity of childhood-onset systemic lupus erythematosus (cSLE) necessitate effective transition from pediatric to adult providers. We studied transition outcomes in a cSLE cohort. Methods We identified patients at an adult lupus clinic diagnosed with SLE ≤ 18 years who had been followed by a pediatric rheumatologist. Data extracted from the first three years in adult care (“post-transition period”) included: sociodemographics, depression, anxiety, SLE manifestations, SLE Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index for SLE (SLICC) scores, non-adherence, and gaps in care (no appointments in the recommended time frame). Multivariable logistic regression analyses for predictors of: (1) time between pediatric and adult providers, (2) gaps in care, (3) unscheduled utilization (emergency department visits and admissions) (4) depression and/or anxiety were performed, as was a multivariable Poisson regression analysis for number of missed appointments. Results In 50 patients, SLEDAI scores were stable (mean 5.7 ± 5.0 at start vs. 4.7 ± 4.8 at year 3, p = 0.2), but SLICC scores increased (0.46 ± 0.84, vs. 0.78 ± 1.25, p = 0.01). Depression and anxiety increased significantly (10% vs. 26%, p = 0.02). Mean time from last pediatric to first adult provider visit was almost nine months (253 ± 392 days). Nearly 75% of patients had ≥ 1 gap in care. White race, low education level and non-adherence were significantly associated with missed appointments. Conclusion Despite moderate disease activity in this cSLE transition cohort, prolonged time between pediatric and adult providers and gaps in care in the post-transition period occurred. Anxiety and depression were frequently reported. Future work should identify methods to improve transition. [ABSTRACT FROM AUTHOR]

Past studies have focused on aggregate lupus disease activity during pregnancy and have produced conflicting results. Our study evaluated lupus activity based on involvement of five specific organ systems during the six months prior to conception and during pregnancy. We assessed 147 pregnancies among 113 women followed at Brigham and Women’s Lupus Center, 1990–2013. Organ-specific activity included hematologic disorder, nephritis, skin disease, arthritis, and serositis. We hypothesized that the presence of organ-specific activity six months prior to conception would increase the risk for that same type of activity during pregnancy. Our study population was 68% white; 100% had a positive ANA and 30% had a history of nephritis. Among women with organ-specific lupus activity during the six months before conception, the crude odds for the same type of activity during pregnancy was 7.7- to 32.5-fold higher compared to women without that type of activity immediately before conception. An adjusted logistic regression model also indicated significantly higher odds of organ-specific activity during pregnancy if that type of activity were present six months before conception. Approaching lupus based on specific organ systems may be a useful way for women and their physicians to consider the potential risk for disease activity during pregnancy. [ABSTRACT FROM AUTHOR]

Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE).We present the case of a 24-year-old Cambodian woman with SLE followed in the Brigham and Women's Hospital Lupus Center in Boston,Massachusetts. She presented with dyspnoea and chest pain and was found to have DAH that required a prolonged hospitalization that was complicated by recurrentDAHepisodes andmultiple infections.We discuss the diagnostic approach and management of patients with SLE-associated DAH as well as treatment options for refractory disease. Emerging therapies include plasmapheresis, the anti-CD20 monoclonal antibody rituximab and recombinant activated Factor VII therapy. In addition, we review the literature to date and compile what is known about the epidemiology, presenting features, diagnostic findings, management and outcomes in this condition.We found that DAH has been reported in 1.9% of patients with SLE. These patients were mostly female (88%) and young (mean age 30.2 years). Common presenting features included dyspnoea (94%), anaemia (97%) and new radiographic chest infiltrate (99%). Bronchoscopy, when performed, identified DAH in 90% of cases. Corticosteroids were the mainstay of care, and usage of cyclophosphamide varied by report. Despite recent advances in therapy, mortality has not improved substantially (48% overall survival versus 53% survival in reports published since 1993). [ABSTRACT FROM AUTHOR]

Current cigarette smoking is a risk factor for SLE, and recent work has demonstrated that early-life smoke exposure was related to the risk of related rheumatic conditions in female children. Therefore, we sought to investigate whether early-life cigarette smoke exposure might be associated with incidence of SLE in adult women. We studied 93,054 Nurses' Health Study (NHS) and 95,554 NHSII participants free of SLE at baseline who provided information on perinatal exposures. By medical record review, 236 incident SLE cases were confirmed (142 NHS and 94 NHSII) among these women using American College of Rheumatology criteria. We used stratified Cox models to estimate the association of smoke exposure with SLE adjusting for race, birth weight, preterm birth and parents' occupation. Combined estimates were computed using random effects meta-analytic techniques. Maternal cigarette smoking did not increase the risk of SLE (relative risk (RR) = 0.9, 95%CI: 0.6 to 1.4) nor did paternal smoking during the participant's childhood (RR = 1.0, 95% CI: 0.8 to 1.3) in combined analyses. Early-life exposure to cigarette smoke due to mothers' or fathers' smoking was not associated with increased risk of adult-onset SLE in women. [ABSTRACT FROM AUTHOR]

Sarcoidosis, systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are chronic conditions of immune dysregulation whose aetiologies remain mysterious. Expression of sarcoidosis and SLE within individuals has been reported in a handful of cases in the last 60 years. In this study, we report two cases of sarcoidosis and SLE occurring together, and each case demonstrated complications associated with the presence of anticardiolipin antibodies. Clinical, serological and pathological findings confirmed the diagnoses in each case and both patients improved with therapy. The association of sarcoidosis, SLE and APS is unique and may present difficult therapeutic options, as well as to shed light on their immunopathogenesis. [ABSTRACT FROM AUTHOR]

The utility of flow mediated dilation (FMD) a measure of endothelial function is limited by operator dependence. Pulse amplitude tonometry (PAT) is a novel, less operator-dependent technique to assess endothelial function. This study compares PAT to FMD in SLE and controls. Thirty women with SLE and 31 controls were enrolled.Medications, cardiovascular disease and risk factors, SLE activity (SLAM-R) and damage (SLICC-DI) were recorded. FMD and PAT were performed simultaneously. Endothelium-independent function was assessed with nitroglycerin. Average age was 48.3 ± 10.1 years, SLE duration 16.2 years, SLAM-R 8.3 and SLICC-DI 1.0. Framingham Risk Scores were ≤2% in most subjects. There were no differences between SLE cases and controls in FMD, PAT or response to nitroglycerin. This study found no association between FMD and PAT in SLE or controls. In the 17 SLE cases with a history of Raynaud's, correlation between FMD and PAT was 0.50 (P = 0.04). There was no difference in endothelial function assessed by FMD or PAT in SLE cases versus controls. FMD did not correlate with PAT except in SLE cases with a history of Raynaud's. Correlation between FMD and PAT may be stronger in populations with greater variation in endothelial function and more cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Cigarette smoking has been causally linked to the development of multiple autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Graves' hyperthyroidism, and primary biliary cirrhosis, among others. We review the known biologic effects of cigarette smoke, in particular its actions on the immune system, and the epidemiologic evidence associating smoking with increased risk of each of these autoimmune diseases. Interactions between cigarette smoking and genetic and immunologic factors, such as the human leukocyte antigen (HLA)–shared epitope, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and anti-double stranded DNA antibodies, may point to mechanisms in disease pathogenesis. [ABSTRACT FROM AUTHOR]

The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen populations for SLE and other CTDs, has been validated in a predominantly Caucasian population with hospital-based controls. We aimed to test the performance characteristics of the CSQ in an urban, predominantly African–American population. The CSQ was administered by interview to women recruited for a study of environmental risk factors and SLE, including 99 cases with SLE validated by medical record review and 202 healthy controls recruited from the community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4% were non-Hispanic Caucasian. Controls were more likely to report African heritage than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and specificity was 91%. In this study, where the prevalence of SLE was 33%, predictive value of a positive CSQ was 82% and predictive value of a negative CSQ was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE in an urban, predominantly African–American population with community-based controls compared with a Caucasian population with hospital-based controls. These results suggest that the CSQ has adequate sensitivity and specificity and could be used in population studies to screen African–American women for SLE. [ABSTRACT FROM AUTHOR]

Large administrative databases such as Medicaid billing databases could be used to study care and outcomes of lupus nephritis if these patients could be correctly identified from claims data. We aimed to develop and validate an algorithm for the correct identification of cases of lupus nephritis using ICD-9 billing codes. We used the Research Patient Data Resource query tool at our institution to identify patients with potential lupus nephritis. We compared four ICD-9 code based strategies, identifying patients seen between 2000 and 2007 with Medicaid medical insurance with greater than two claims for a diagnosis of SLE (ICD-9 code 710.0) and a combination of greater than two nephrologist visits and/or renal ICD-9 codes. We assessed performance using the positive predictive value. Two hundred and thirty four subjects wereidentified and medical records reviewed. Our third strategy, based on a combination of lupus and renal ICD-9 codes and nephrologist encounter claims, had the highest positive predictive value (88%) for the identification of patients with lupus nephritis. This strategy may offer a sound method of identifying patients with lupus nephritis for health services research in addition to serving as a model for using claims data as a way to better understand rare diseases such as lupus. [ABSTRACT FROM AUTHOR]

An abstract of the article "Early life factors and adult-onset rheumatoid arthritis," by J.F. Simard and colleagues is presented.

Objective: The 2023 American College of Rheumatology/EULAR antiphospholipid syndrome (APS) classification criteria development, which aimed to identify patients with high likelihood of APS for research, employed a four-phase methodology. Phase I and II resulted in 27 proposed candidate criteria, which are organized into laboratory and clinical domains. Here, we summarize the last stage of phase III efforts, employing a consensus-based multicriteria decision analysis (MCDA) to weigh candidate criteria and identify an APS classification threshold score., Methods: We evaluated 192 unique, international real-world patients referred for "suspected APS" with a wide range of APS manifestations. Using proposed candidate criteria, subcommittee members rank ordered 20 representative patients from highly unlikely to highly likely to have APS. During an in-person meeting, the subcommittee refined definitions and participated in an MCDA exercise to identify relative weights of candidate criteria. Using consensus decisions and pairwise criteria comparisons, 1000Minds software assigned criteria weights, and we rank ordered 192 patients by their additive scores. A consensus-based threshold score for APS classification was set., Results: Premeeting evaluation of 20 representative patients demonstrated variability in APS assessment. MCDA resolved 81 pairwise decisions; relative weights identified domain item hierarchy. After assessing 192 patients by weights and additive scores, the Steering Committee reached consensus that APS classification should require separate clinical and laboratory scores, rather than a single-aggregate score, to ensure high specificity., Conclusion: Using MCDA, candidate criteria preliminary weights were determined. Unlike other disease classification systems using a single-aggregate threshold score, separate clinical and laboratory domain thresholds were incorporated into the new APS classification criteria., (© 2024 American College of Rheumatology.)

Background and Objectives: Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is most common, accounting for ∼15%-40% of adult encephalitis diagnoses. We aim to investigate the association between immune status and HSV encephalitis (HSVE). Using a US Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities., Methods: We used the US Medicaid Analytic eXtract data between 2007 and 2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age and sex-matched adult cases of HSVE with a sufficient enrollment period (12 months before HSVE diagnosis) to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson Comorbidity Index, and non-autoimmune comorbidities., Results: Incidence of HSVE was ∼3.01 per 10 5 person-years among adults. A total of 951 HSVE cases and 95,100 age and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong (adjusted odds ratio (OR) 2.6; 95% CI 2.2-3.2). The association of HSVE and immunomodulating medications had an OR of 2.2 (CI 1.9-2.6), also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: OR 2.3 (CI 1.9-2.7) for autoimmune disease and 2.0 (CI 1.7-2.3) for immunosuppressive and immunomodulatory medications., Discussion: In a large, national population, HSVE is strongly associated with preexisting autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date.

Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR., Methods: This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard., Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β 2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%., Conclusion: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research., (© 2023 American College of Rheumatology.)

Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR., Methods: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard., Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β 2 -glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%., Conclusion: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research., Competing Interests: Competing interests: RAL is an employee of GlaxoSmithKline., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk., Competing Interests: Declaration of interests J.B.R.’s institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline, and Biogen for projects unrelated to this research. He is the CEO of 5 Prime Sciences (www.5primesciences.com), which provides research services for biotech, pharma, and venture capital companies for projects unrelated to this research. J.L.-S. is a scientific advisor to Precion Inc. D.G.V. is a consultant for Sumitomo/Sunovion, Inhibikase, OLix Pharma, Twenty/Twenty, and Valitor., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics., Competing Interests: Competing interests: KC’s disclosures are as follows: editing/authoring/publishing: American College of Rheumatology; Elsevier, Inc.; UpToDate (Wolters Kluwer Health, Inc.); consulting/advising: Amgen, Inc.; AstraZeneca; GlaxoSmithKline; Hospital for Special Surgery; Neutrolis; faculty/instructing/speaking/lecturing: Harvard T. H. Chan School of Public Health; New York University—NYU Langone Hospitals; financial interest (<1%): Alkermes, PLC; governmental review process: National Institutes of Health; scientific advisory board: Lupus Foundation of America. All of KC’s financial interests were

Lupus is a complex disease that is often difficult to diagnose. Risks of diagnostic delays include non-specific signs and symptoms that mimic other diseases and a lack of diagnostic criteria and referral pathways for non-specialists. To address these issues, we convened a series of virtual meetings with members of our Addressing Lupus Pillars for Health Advancement clinical care team. Meeting participants included lupus physicians, treatment developers from biotechnology, patient advocacy group representatives from the Lupus Foundation of America and advocacy/government consultants. Causes and consequences of ambiguity in diagnosis and diagnostic delays were evaluated through historical, experiential and evidence-based accounts (survey data, literature reviews and patient testimonials). Discussions highlighted the need for a clearer understanding of the definition of lupus, the natural history of the disease and the need for advancements in biotechnology to support an accurate and timely diagnosis with the potential development of a lupus spectrum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This year, the American College of Rheumatology (ACR) 1982 classification criteria for systemic lupus erythematosus (SLE) celebrate their 40th anniversary. From this start, the quest for optimal SLE criteria has led to the 1997 ACR update, the 2012 publication of the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and, in 2019, the European League Against Rheumatism (EULAR)/ACR classification criteria. The latter have since been externally validated in more than two dozen studies and have become the gold standard inclusion criterion of SLE clinical trials. This comprehensive review attempts to follow the evolving success story of SLE classification, highlighting relevant decisions and their rationale, and discussing consequences for the way SLE is defined and managed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by disease flares which can require hospitalization. Our objective was to apply machine learning methods to predict hospitalizations for SLE from electronic health record (EHR) data., Methods: We identified patients with SLE in a longitudinal EHR-based cohort with ≥2 outpatient rheumatology visits between 2012 and 2019. We applied multiple machine learning methods to predict hospitalizations with a primary diagnosis code for SLE, including decision tree, random forest, naive Bayes, logistic regression, and an ensemble method. Candidate predictors were derived from structured EHR features, including demographics, laboratory tests, medications, ICD-9/10 codes for SLE manifestations, and healthcare utilization. We used two approaches to assess these variables over longitudinal follow-up, including the incorporation of lagged features to capture changes over time of clinical data. The performance of each model was evaluated by overall accuracy, the F statistic, and the area under the receiver operator curve (AUC)., Results: We identified 1996 patients with SLE. 4.6% were hospitalized for SLE in their most recent year of follow-up. Random forest models had highest performance in predicting SLE hospitalizations, with AUC 0.751 and AUC 0.772 for two approaches (averaging and progressive), respectively. The leading predictors of SLE hospitalizations included dsDNA positivity, C3 level, blood cell counts, and inflammatory markers as well as age and albumin., Conclusion: We have demonstrated that machine learning methods can predict SLE hospitalizations. We identified key predictors of these events including known markers of SLE disease activity; further validation in external cohorts is warranted.