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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: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients.Design: Retrospective study.Setting: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository.Population: Women with Ob-APS.Methods: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM).Main Outcome Measures: Risk factors for thrombosis and aGAPSS.Results: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089].Conclusion: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women.Tweetable Abstract: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity. [ABSTRACT FROM AUTHOR]

The association between antiphospholipid antibodies (aPL) and clinical events is stronger with a positive lupus anticoagulant (LA) test, higher anticardiolipin antibody (aCL) titers, and/or higher anti-β2-glycoprotein-I antibody (aβ2GPI) titers. The objective of this study was to determine the clinical characteristics of persistently high-titer (≥80 U) aCL-positive patients compared with those with persistent moderate aCL titers (40-79 U). Second, we analyzed whether high-titer ab2GPI test adds predictive information in persistently moderate-to-high titer aCL-positive patients. In this cross-sectional study, the primary analysis compared the clinical and aPL characteristics of 58 patients with at least two moderate-titer aCL results to another 85 patients with at least two high-titer aCL results. In the secondary analysis of patients with at least two aβ2GPI test results, we compared 29 patients with 'aCL 40-79 U and aβ2GPI<80 U' profiles with 8 patients with 'aCL 40-79U and aβ2GPI≥80 U', and also compared 27 patients with 'aCL>80 U and aβ2GPI<80 U' with 32 patients with 'aCL>80 U and aβ2GPI≥80 U'. Although aPL-related vascular and pregnancy events were similar between the moderate- and high-titer aCL groups, the number of patients with positive LA tests (RR 2.06, CI 1.38-3.08, p<0.01) and with at least one non-criteria aPL manifestation (RR 1.66, CI 1.20-2.30, p=0.0005) were significantly higher in the high-titer aCL group. While magnetic resonance imaging (MRI) white matter changes were statistically more common in the high-titer aCL group (RR 2.03, CI 1.04-3.94, p=0.02), there was a trend towards increased prevalence of livedo reticularis, cardiac valve disease, and cognitive dysfunction occurring in the high-titer aCL group. The secondary analysis showed that MRI white matter changes, cardiac valve disease, and cognitive dysfunction were proportionally more common in the high-titer aβ2GPI groups, suggesting a linear relationship between non-criteria aPL manifestations and aPL titers. Our results suggest that patients with high aCL titers, compared with those with moderate titers, are more likely to have a positive LA test and a higher prevalence of non-criteria aPL manifestations. Furthermore, high-titer aβ2GPI positivity may further increase the prevalence of non-criteria aPL manifestations in moderate- or high-titer aCL-positive patients. [ABSTRACT FROM AUTHOR]

This narrative review summarizes current evidence on the risk of systemic autoimmune rheumatic disease (SARD) flare following coronavirus disease 2019 vaccination. The authors detail key studies in the literature employing diverse methodologies, including cross-sectional surveys, prospective and retrospective cohorts, case-crossover designs, self-controlled case series, and systematic reviews. Data are reassuring, suggesting that vaccination is unlikely to increase the risk of flares across a range of SARD. When postvaccination flares do occur, individuals with high disease activity and frequent flares at baseline may be at higher risk. Rheumatologists may consider discussing these findings with patients during collaborative conversations about risks and benefits of vaccination., Competing Interests: Disclosure G. Braverman and M. Nong have no disclosures. M. Barbhaiya is supported by the Rheumatology Research Foundation, United States Investigator Award. L.A. Mandl receives research support from Regeneron Pharmaceuticals, United States and payments from UpToDate, unrelated to this work. L.A. Mandl works as an associate editor for Annals of Internal Medicine., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Objective: We assessed ultraprocessed food (UPF) intake and systemic lupus erythematosus (SLE) incidence within the prospective Nurses' Health Study (NHS) cohorts., Methods: A total of 204,175 women were observed (NHS 1984-2016; NHSII 1991-2017). Semiquantitative food frequency questionnaires were completed every two to four years. UPF intake was determined as per the Nova classification. Nurses self-reported new doctor-diagnosed SLE, confirmed by medical records. Time-varying Cox regressions estimated hazard ratios (HRs; 95% confidence intervals [CIs]) for patients with incident SLE and SLE by anti-double-stranded DNA (dsDNA) antibody at diagnosis, according to cumulatively updated daily (a) UPF servings, (b) total intake (in grams and milliliters), and (c) percentage of total intake. Analyses adjusted for age, race, cohort, caloric and alcohol intakes, household income, smoking, body mass index (BMI), physical activity, menarchal age, and oral contraceptive use. We tested for interaction with BMI and examined UPF categories., Results: Mean baseline age was ~50 years (NHS) and ~36 years (NHSII); 93% self-reported White race. A total of 212 patients with incident SLE were identified. SLE risk was higher in the third versus first UPF tertile (servings per day pooled multivariable [MV] HR 1.56, 95% CI 1.04-2.32; P = 0.03). Results were stronger for dsDNA antibody in patients with SLE (servings per day pooled MV HR 2.05, 95% CI 1.15-3.65; P = 0.01) and for absolute (servings or total) than percentage of total intake. Sugar-sweetened/artificially sweetened beverages were associated with SLE risk (third vs first tertile MV HR 1.45, 95% CI 1.01-2.09). No BMI interactions were observed., Conclusion: Higher cumulative average daily UPF intake was associated with >50% increased SLE risk and with doubled risk for anti-dsDNA antibody in patients with SLE. Many deleterious effects on systemic inflammation and immunity are postulated., (© 2024 American College of Rheumatology.)

Objective: We aimed to determine the association of COVID-19 vaccination with flares of systemic rheumatic disease (SRD)., Methods: Adults with systemic rheumatic disease (SRD) in a single-center COVID-19 Rheumatology Registry were invited to enroll in a study of flares. COVID-19 vaccine information from March 5, 2021, to September 6, 2022, was obtained from chart review and self-report. Participants self-reported periods of SRD flare and periods without SRD flare. "Hazard periods" were defined as the time before a self-report of flare and "control periods" as the time before a self-report of no flare. The association between flare and COVID-19 vaccination was evaluated during hazard and control periods through univariate conditional logistic regression stratified by participant, using lookback windows of 2, 7, and 14 days., Results: A total of 434 participants (mean ± SD age 59 ± 13 years, 84.1% female, 81.8% White, 64.5% with inflammatory arthritis, and 27.0% with connective tissue diseases) contributed to both the hazard and control periods and were included in analysis. A total of 1,316 COVID-19 vaccinations were identified (58.5% Pfizer-BioNTech, 39.5% Moderna, and 1.4% Johnson & Johnson); 96.1% of participants received at least one dose and 93.1% at least two doses. There was no association between COVID-19 vaccination and flares in the subsequent 2, 7, or 14 days (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.86-2.46; OR 1.09, 95% CI 0.76-1.55; and OR 0.85, 95% CI 0.64-1.13, respectively). Analyses stratified on sex, age, SRD subtype, and vaccine manufacturer similarly showed no association between vaccination and flare., Conclusion: COVID-19 vaccination was not associated with flares in this cohort of participants with SRD. These data are reassuring and can inform shared decision-making on COVID-19 immunization., (© 2024 American College of Rheumatology.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Objective: Antiphospholipid antibody (aPL) nephropathy (-N) can be challenging to recognize due to a lack of established classification or diagnostic criteria. As part of efforts to develop new antiphospholipid syndrome (APS) classification criteria (CC), the APS CC Renal Pathology Subcommittee aimed to better characterize the entity of aPL-N., Methods: We used a 4-pronged approach that included (1) administering Delphi surveys to worldwide APS physicians to generate aPL-N terminology; (2) conducting a literature review to demonstrate the association of nephropathy with aPL and identify published aPL-N histopathological terminology and descriptions; (3) evaluating aPL-N terminology used in renal biopsy reports from an international patient registry; and (4) evaluating proposed kidney pathologic features for aPL-N by assessment of international Renal Pathology Society (RPS) members., Results: After completing our metaanalysis demonstrating an association between nephropathy and aPL, we used Delphi surveys, a literature review, and international renal biopsy reports to develop a preliminary definition of aPL-N. The preliminary definition included include specific terms associated with acute (ie, thrombotic microangiopathy in glomeruli or arterioles/arteries) and chronic (ie, organized arterial or arteriolar microthrombi with or without recanalization, organized glomerular thrombi, fibrous and fibrocellular [arterial or arteriolar] occlusions, focal cortical atrophy with or without thyroidization, and fibrous intimal hyperplasia) lesions. Most RPS survey respondents agreed with this terminology and the importance of knowing aPL results for histopathological diagnosis., Conclusion: Our results support the inclusion of aPL-N in the 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology APS CC, and provide the most widely accepted terminology to date for both acute and chronic pathologic lesions of aPL-N., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: The aim of this study was to measure COVID-19 vaccine hesitancy among rheumatology outpatients from an early COVID-19 "hotspot" during the initial period of vaccine availability., Methods: In March 2021, a Web-based survey was sent to 7505 adults seen at a Rheumatology Division in New York City. We evaluated characteristics associated with 3 categories of COVID-19 vaccination status: declined, undecided, and willing/already received. We used multinomial logistic regression models to calculate relative risk ratios assessing predictors of vaccination status., Results: Among 2384 (32%) respondents (80% female, 87% White, 59% with systemic rheumatic disease), 2240 (94.0%) were willing/already received COVID-19 vaccination, 88 (3.7%) were undecided, and 56 (2.3%) declined. Compared with those willing/already vaccinated, those declining or undecided were younger, more likely identified as Black or Hispanic/Latinx, and had lower household income and educational attainment. Immunosuppressive medication use did not differ among groups. After multivariable adjustment, every 1-year increase in age was associated with a 0.96 lower relative risk of declining or being undecided versus willing/already vaccinated. Respondents identifying as Black versus White had a higher relative risk ratio of being undecided (4.29 [95% confidence interval, 1.96-9.36]), as did those identifying as Hispanic/Latinx versus non-Hispanic/non-Latinx (2.81 [95% confidence interval, 1.29-6.09]). Those declining vaccination were least likely to believe in general vaccine importance or the safety and efficacy of the COVID-19 vaccine., Conclusions: Among rheumatology patients in New York City with and without systemic rheumatic disease, COVID-19 vaccine uptake was high after its initial availability. Sociodemographic but not medication-related factors were associated with vaccine hesitancy; these findings can inform future rheumatology vaccination programs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Objective: Ultraviolet (UV) radiation exposure is associated with photosensitivity, rashes, and flares in systemic lupus erythematosus (SLE). However, it is not known whether UV exposure increases risk of developing SLE. We examined UV exposure and SLE risk in a large prospective cohort., Methods: The Nurses' Health Study (NHS) enrolled 121,700 US female nurses in 1976; in 1989, 116,429 nurses were enrolled in NHS II. Biennial questionnaires collected lifestyle and medical data. Self-reported incident SLE by American College of Rheumatology classification criteria was confirmed by medical record review. Ambient UV exposure was estimated by linking geocoded residential addresses with a spatiotemporal UV exposure model. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) across tertiles of time-varying cumulative average UV. We examined SLE risk overall and stratified by anti-Ro/La antibodies and by cutaneous manifestations from 1976 through 2014 (NHS)/2015 (NHS II), adjusting for confounders., Results: With 6,054,665 person-years of exposure, we identified 297 incident SLE cases; the mean ± SD age at diagnosis was 49.8 ± 10.6 years. At diagnosis, 16.8% of women had +anti-Ro/La, and 80% had either +anti-Ro/La or ≥1 cutaneous manifestation. Compared with the lowest UV exposure tertile, risk of overall SLE was increased, but not significantly (HR 1.28 [95%CI 0.96-1.70]). Women in the highest tertile had increased risk of malar rash (HR 1.62 [95% CI 1.04-2.52])., Conclusion: Cumulative UV exposure was not associated with SLE risk. Higher UV exposure, however, was associated with increased risk of malar rash at presentation. UV exposure may trigger SLE onset with malar rash among susceptible women., (© 2022 American College of Rheumatology.)

Background/objective: Conflicting data exist regarding whether patients with systemic rheumatic disease (SRD) experience more severe outcomes related to COVID-19. Using data from adult patients hospitalized with COVID-19 in New York City during the first wave of the pandemic, we evaluated whether patients with SRD were at an increased risk for severe outcomes., Methods: We conducted a medical records review study including patients aged ≥18 years with confirmed SARS-CoV-2 infection hospitalized at 3 NewYork-Presbyterian sites, March 3-May 15, 2020. Inverse probability of treatment weighting was applied to a multivariable logistic regression model to assess the association between SRD status and the composite of mechanical ventilation, intensive care unit admission, or death., Results: Of 3710 patients hospitalized with COVID-19 (mean [SD] age, 63.7 [17.0] years; 41% female, 29% White, and 34% Hispanic/Latinx), 92 (2.5%) had SRD. Patients with SRD had similar age and body mass index but were more likely to be female, ever smokers, and White or Black, compared with those without SRD. A higher proportion of patients with versus without SRD had hypertension and pulmonary disease, and used hydroxychloroquine, corticosteroids, and immunomodulatory/immunosuppressive medications before admission. In the weighted multivariable analysis, patients with SRD had an odds ratio of 1.24 (95% confidence interval, 1.10-1.41; p < 0.01) for the composite of mechanical ventilation, intensive care unit admission, or death, compared with patients without SRD., Conclusions: During the initial peak of the pandemic in New York City, patients with versus without SRD hospitalized with COVID-19 had a 24% increased likelihood of having severe COVID-19 after multivariable adjustment., Competing Interests: Dr Barbhaiya is supported by the Rheumatology Research Foundation Investigator Award and the Barbara Volcker Center for Women and Rheumatic Diseases. Dr Siegel and Dr Christos are supported by the National Center for Advancing Translational Sciences grant #UL1TR002384 of the Clinical and Translational Science Center at Weill Cornell Medical College. Dr Navarro-Millan is supported by NIH/NIAMS grant #K23AR068449 and the Rheumatology Research Foundation Innovative Research Award. This study received support from NewYork-Presbyterian Hospital and Weill Cornell Medical College, including the Clinical and Translational Science Center (UL1 TR000457) and Joint Clinical Trials Office, and the Hospital for Special Surgery COVID-19 Special Pilot Grant. The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Fertility is often a concern for women with SLE. In addition to known indirect factors that influence the ability of a woman with SLE to become pregnant, such as cytotoxic agents, other medications, advanced age and psychosocial effects of the disease, direct disease-related factors are believed to influence fertility. These include diminished ovarian reserve, menstrual irregularities (a function of disease activity) and the presence of antiphospholipid antibodies. The question of whether SLE intrinsically affects fertility, however, remains unanswered. In this review, we address known factors affecting fertility, assess current data regarding a direct impact of SLE on fertility and evaluate potential disease-related risk factors. We focus primarily on studies measuring anti-Müllerian hormone and antral follicle count, the most widely measured markers of ovarian reserve. Our goal is to provide information to rheumatologists faced with counselling patients with SLE regarding their fertility, family planning and options for assisted reproductive technologies, which now include fertility preservation through oocyte cryopreservation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Microvascular renal lesions have been described in patients with antiphospholipid antibodies (aPL), however their association with aPL is inconsistent among studies. Therefore, our objective was to investigate associations between microvascular renal lesions and aPL among systemic lupus erythematosus (SLE) patients., Methods: Studies were selected if they included SLE patients with and without aPL positivity with a description of kidney biopsy identifying acute and/or chronic microvascular renal lesions as well as lupus nephritis. Data sources were Pubmed, Embase, Cochrane Library, hand search, congress abstracts, and reference lists of studies, without language restrictions. Risk estimates were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the Mantel-Haenszel method (random effects)., Results: Of 1860 identified records obtained between 1991 and 2021, 35 published studies (10 cohorts, 7 case-control, 18 cross-sectional) met inclusion criteria, including 3035 SLE patients according to American College of Rheumatology criteria and 454 cases of microvascular renal lesions. Frequency of microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 31.3% vs. 10.4%, respectively. The overall pooled odds ratios (OR) for microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 3.03 (95% confidence interval [CI], 2.25-4.09). The risk of microvascular renal lesions was the highest for lupus anticoagulant (OR = 4.84 [95% CI, 2.93 to 8.02]) and IgG anticardiolipin antibodies (OR = 3.12 [95% CI,1.08-9.02]) while the association with anti-β 2 -glycoprotein I antibodies (OR = 1.88 [95% CI, 0.25-14.14]) did not reach statistical significance. Furthermore, aPL were not associated with any classes of lupus nephritis., Conclusion: In SLE patients, aPL-positivity is associated with a significant 3- to 5-fold increased risk for specific microvascular renal lesions. This risk is mainly driven by lupus anticoagulant and IgG anticardiolipin antibodies. Our results support the inclusion of microvascular renal lesions as new criteria for definite antiphospholipid syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Methods: We identified 20 adult patients with UCTD enrolled in the UCTD and Overlap Registry at our tertiary care level hospital. A licensed clinical social worker administered a 30-minute semistructured interview by telephone. The standardized questionnaire consisted of 14 open-ended questions on UCTD. A team of physicians, research coordinators, and a social worker used grounded theory to analyze the qualitative data and identify themes., Results: Among 14/20 study participants (100% female; mean age, 53.6 ± 13.2 years [range, 27-74 years]), all had at least an associate's/bachelor's degree; 9 (64%) were White. The mean disease duration was 14.5 ± 13.5 years (range, 0.5-44 years). Nine study participants (64%) were engaged in counseling or mindfulness training. Ten specific psychosocial themes and categories emerged, including the need for professional guidance and peer and family support to increase awareness, reduce isolation, and promote self-efficacy., Conclusions: Emerging themes from semistructured interviews of women with UCTD at a major academic center suggest the need for psychosocial interventions (e.g., patient support groups, educational materials, peer counselors) to help UCTD patients manage and cope with their illness. Future studies evaluating the psychosocial impact of UCTD diagnosis on diverse cohorts are needed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Diagnostic uncertainty, commonly encountered in rheumatology and other fields of medicine, is an opportunity: Stakeholders who understand uncertainty's causes and quantitate its effects can reduce uncertainty and can use uncertainty to improve medical practice, science, and administration. To articulate, bring attention to, and offer recommendations for diagnostic uncertainty, the Barbara Volcker Center at the Hospital for Special Surgery sponsored, in April 2021, a virtual international workshop, "When a Diagnosis Has No Name." This paper summarizes the opinions of 72 stakeholders from the fields of medical research, industry, federal regulatory agencies, insurers, hospital management, medical philosophy, public media, health care law, clinical rheumatology, other specialty areas of medicine, and patients. Speakers addressed the effects of diagnostic uncertainty in their fields. The workshop addressed the following six questions: What is a diagnosis? What are the purposes of diagnoses? How do doctors assign diagnoses? What is uncertainty? What are its causes? How does understanding uncertainty offer opportunities to improve all fields of medicine? The workshop's conveners systematically reviewed video recordings of formal presentations, video recordings of open discussion periods, manuscripts, and slide files submitted by the speakers to develop consensus take-home messages, which were as follows: Diagnostic uncertainty causes harm when patients lack access to laboratory test and treatments, do not participate in research studies, are not counted in administrative and public health documents, and suffer humiliation in their interactions with others. Uncertainty offers opportunities, such as quantifying uncertainty, using statistical technologies and automated intelligence to stratify patient groups by level of uncertainty, using a common vocabulary, and considering the effects of time., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Competing Interests: LAM received grant support from Regeneron Pharmaceuticals. All other authors declare no competing interests. MB, JML, and LAM did the data collection, data analysis, formal analysis, and writing the original draft of the manuscript. MB and LAM did the data interpretation. VPB reviewed and edited the manuscript. MB is supported by the Rheumatology Research Foundation Investigator Award and the Barbara Volcker Center for Women and Rheumatic Diseases at Hospital for Special Surgery. We thank Deanna Jannat-Khah for her help in assembling the cohort for analysis.

Objective: To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes., Methods: The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-β 2 -glycoprotein I [anti-β 2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity)., Results: The 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-β 2 GPI only., Conclusion: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification., (© 2020, American College of Rheumatology.)

Objective: Frailty is associated with mortality in systemic lupus erythematosus (SLE), but how best to measure frailty is unclear. We aimed to compare 2 frailty metrics, the self-reported Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight (FRAIL) scale (FS) and the Fried phenotype (FP), in SLE to evaluate differences between frail and nonfrail women and whether frailty is associated with self-reported disability., Methods: Adult women aged < 70 years with validated SLE and mild/moderate disease enrolled in this cross-sectional study between August 2018 and October 2019. Correlation and agreement between the FS and the FP were determined. Differences in sociodemographic and disease characteristics, patient-reported outcome measures (PROMs), and biomarkers between frail and nonfrail participants were evaluated, as well as the association of frailty with Valued Life Activities disability., Results: Of 67 participants, 27% and 18% were frail according to the FS and the FP, respectively. Correlation ( r = 0.51; P < 0.0001) and agreement (κ = 0.46; P = 0.0004) between the FS and the FP were significant. Frail women had greater disease damage, high-sensitivity C-reactive protein, and interleukin 6, and worse PROMs according to both frailty definitions. Both frailty measures were associated with self-reported disability after adjustment for age, comorbidity, and disease activity and damage; this relationship was attenuated for the FP., Conclusion: Frailty prevalence was high in this cohort of women with SLE using both frailty definitions, suggesting that frailty may be accelerated in women with SLE, particularly when based exclusively on self-report. Frailty remained associated with self-reported disability in adjusted analyses. The FS may be an informative point-of-care tool to identify frail women with SLE., (© 2022 The Journal of Rheumatology.)

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

Background: Systemic lupus erythematosus (SLE) affects African-American (AA) women disproportionately. The few prospective studies assessing dietary intake in relation to risk of SLE have been conducted in predominantly white populations and have been null., Objectives: The present study assessed associations of macronutrients and dietary patterns with risk of SLE in AA women., Methods: Data from the Black Women's Health Study was collected prospectively via biennial questionnaires starting in 1995. Participants completed a self-administered 68-item FFQ in 1995. Self-reported SLE was verified through medical record review. We used multivariable (MV) Cox regression models to estimate HRs and 95% CIs for macronutrients, carbohydrates, proteins, total fats, PUFAs, ω-3 fatty acids, ω-6 fatty acids, MUFAs, saturated fats, trans fatty acids, Alternative Healthy Eating Index score, vegetable/fruit and meat/fried food dietary patterns, and a reduced rank regression (RRR)-derived dietary pattern in relation to SLE risk., Results: We confirmed a total of 114 incident cases of SLE among 51,934 women during 1995-2015. MVHRs and 95% CIs for the highest quintile of intake versus the lowest were HR: 1.96, 95% CI: 1.02, 3.67 for carbohydrates; HR: 0.66, 95% CI: 0.37, 1.18 for protein; and HR: 0.54, 95% CI: 0.28, 1.01 for total fats. MUFAs, saturated fatty acids, and trans fatty acids were significantly associated with a lower risk of SLE. An RRR-derived factor, rich in fruits and sugar-sweetened drinks and low in margarines and butter, red and processed meats, fried chicken, poultry, and eggs, which explained 53.4% of the total variation of macronutrients, was the only food pattern associated with increased SLE risk (HR: 1.88, 95% CI: 1.06, 3.35)., Conclusion: These analyses suggest that a diet high in carbohydrates and low in fats is associated with increased SLE risk in AA women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: An international multidisciplinary initiative, jointly supported by the American College of Rheumatology and European Alliance of Associations for Rheumatology, is underway to develop new rigorous classification criteria to identify patients with high likelihood of antiphospholipid syndrome (APS) for research purposes. The present study was undertaken to apply an evidence- and consensus-based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains., Methods: During phase I, the APS classification criteria steering committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains., Results: Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in phase II, we initially reduced these items to 64 potential candidate criteria organized into 10 clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into 6 additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification., Conclusion: Using data- and consensus-driven methodology, we identified 27 APS candidate criteria in 6 clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real-world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification., (© 2020, American College of Rheumatology.)

Objective: Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti-double-stranded DNA (anti-dsDNA) positive versus negative subtypes., Methods: We studied 79,568 women in the Nurses' Health Study (1984-2014) and 93,554 in the Nurses' Health Study II (1991-2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI-2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time-varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti-dsDNA, for cumulative average dietary quality score tertiles and individual AHEI-2010 components., Results: We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI-2010 HR 0.78 [95% CI 0.54-1.14], aMed HR 0.82 [95% CI 0.56-1.18], DASH HR 1.16 [95% CI 0.81-1.66], EDIP HR 0.83 [95% CI 0.57-1.21]). No association was demonstrated for anti-dsDNA+ or anti-dsDNA- SLE risk. Women in the highest (versus lowest) AHEI-2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40-0.87]). No association was demonstrated for other AHEI-2010 components and SLE risk., Conclusion: We observed no association between long-term adherence to the AHEI-2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation., (© 2020, American College of Rheumatology.)

Objective: The present study was undertaken to evaluate the pregnancy experiences of women receiving care in the division of rheumatology at a major academic center in New York City during the COVID-19 pandemic., Methods: A web-based COVID-19 survey was emailed to 26,045 patients who were followed in the division of rheumatology at a single center in New York City. Women ages 18-50 years were asked about their pregnancy. We compared the COVID-19 experience between pregnant and nonpregnant women and also explored the impact of the pandemic on prenatal care and perinatal outcomes., Results: Among 7,094 of the 26,045 respondents, 1,547 were women ages 18-50 years, with 61 (4%) reporting being pregnant during the pandemic. The prevalence of self-reported COVID-19 was similar in pregnant and nonpregnant women (8% versus 9%, respectively; P = 0.76). Among women with COVID-19, pregnant women had a shorter duration of symptoms (P < 0.01) and were more likely to experience loss of smell or taste (P = 0.02) than nonpregnant women. Approximately three-fourths of women had a systemic rheumatic disease, with no differences when stratified by pregnancy or COVID-19 status. In all, 67% of pregnant women noted changes to prenatal care during the pandemic, and 23% of postpartum women stated that the pandemic affected delivery., Conclusion: Among women followed in the division of rheumatology at a major center in New York City, pregnancy was not associated with increased self-reported COVID-19. Pregnancy was associated with a shorter duration of COVID-19 symptoms and a higher prevalence of loss of smell or taste. The COVID-19 pandemic impacted prenatal care for the majority of pregnant patients., (© 2020, American College of Rheumatology.)

Objective: Concerns about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have led to changes or discontinuation of immunosuppressive medications among patients with systemic rheumatic disease. Our goal was to assess patients' perspectives regarding medication modifications and deviations from planned uses during the height of the pandemic., Methods: Adult patients of 13 rheumatologists at an academic center with physician-diagnosed rheumatic disease and prescribed disease-modifying medications were interviewed by telephone and asked open-ended questions about the impact of SARS-CoV-2 on their medications. Responses were analyzed using content and thematic analyses to generate categories that described patterns of medication modification., Results: A total of 112 patients (mean age 50 years, 86% women, 34% non-White race or Latino ethnicity) with diverse diagnoses (30% lupus, 26% rheumatoid arthritis, 44% other) who were taking various medications were enrolled. Patients reported clinically relevant issues that were iteratively reviewed to generate unique categories of medication modification: medications and increased or decreased risk of SARS-CoV-2 infection; role of hydroxychloroquine; maintaining medication status quo; role of glucocorticoids; increasing or decreasing existing medications in relation to clinical disease activity; postponing infusions; and medication plan if infected by SARS-CoV-2. Some modifications were suboptimal for disease control but were made to mitigate infection risk and to minimize potential harm when patients were unable to obtain laboratory tests and physical examinations due to cessation of in-person office visits., Conclusion: During the height of the pandemic, substantial medication modifications were made that, in some cases, were temporizing measures and deviations from planned regimens. Future studies will assess short- and long-term sequelae of these medication modifications., (© 2020, American College of Rheumatology.)