OBJECTIVE:The 2023 American College of Rheumatology (ACR)/EULAR antiphospholipid syndrome (APS) classification criteria aim to identify patients with a high likelihood of APS for research. Phases I/II of our four-phase methodologic approach resulted in 27 candidate criteria organized in clinical and laboratory domains. Here, we summarize phase III efforts to reduce and refine criteria using patient scenarios. METHODS:Using standardized definitions for candidate criteria, the Steering Committee collected antiphospholipid antibody (aPL)-positive cases referred for "suspected APS." Treating physicians assessed APS case likelihood using a Likert scale. Poisson regression calculated risk ratios (RRs) and 95% confidence intervals (CIs) to quantify the direction and size of the association of candidate criteria with "highly likely" versus "equivocal or unlikely" APS, which guided Steering Committee candidate criteria refinement and organization. RESULTS:We collected 314 suspected APS cases (137 [44%] highly likely and 177 [56%] equivocal/unlikely APS). Provoking venous thromboembolism (VTE) or arterial thrombosis (AT) risk factors reduced the size of the association with highly likely APS (RR 4.31 [95% CI 2.11-8.78] to RR 1.56 [95% CI 0.89-2.75] for VTE and RR 3.48 [95% CI 1.91-6.32] to RR 1.64 [95% CI 0.77-3.51] for AT). Persistent lupus anticoagulant, anticardiolipin IgG antibody ≥40 U, and anti-β2-glycoprotein-I IgG antibody ≥40 U were positively associated with highly likely APS (all P < 0.05). Eventually, items within eight additive and independent clinical and laboratory domains were refined. CONCLUSION:Referred suspected APS cases provided insight into associations of individual candidate criteria with APS likelihood. RR analyses helped refine items and organize the draft classification system into eight additive and independent clinical and laboratory domains.

An international multi-disciplinary initiative resulted in the development of 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria to identify patients with high likelihood of APS for research. Phase I/II resulted in 27 candidate criteria organized into six clinical and laboratory domains. Here, we summarize early Phase III efforts to better define and structure candidate criteria within clinical and laboratory domains. Using comprehensive literature reviews and expert consensus, domain subcommittees developed definitions for candidate criteria. Prevalence information was incorporated when available. Definitions were finalized and approved by the Steering Committee for future use during real-world case collection (derivation cohort), multi-criteria decision analysis, and validation. Clinical domain items defined were: (a) macrovascular thrombosis (venous thromboembolism including superficial venous thrombosis, arterial thrombosis, and transient ischemic attack) and associated provoking risk factors; (b) microvascular disease (livedo racemosa, livedoid vasculopathy, antiphospholipid-antibody-nephropathy, diffuse alveolar hemorrhage, cardiac microthrombosis, adrenal hemorrhage, and acute ischemic encephalopathy); (c) pregnancy morbidity (pre-fetal death, fetal death, and pre-eclampsia and placental insufficiency with severe features); (d) cardiac valve disease (thickening or vegetation); and (e) thrombocytopenia. Laboratory domain items defined were coagulation-based functional assay (lupus anticoagulant) and solid phase-based assays (anticardiolipin antibody IgG/M and anti-β2-Glycoportein-I antibody IgG/M). Based on comprehensive literature review and Steering Committee consensus, we defined and structured APS clinical and laboratory domains. Preliminary definitions were subsequently evaluated and confirmed in late Phase III using the derivation cohort and multicriteria decision analysis prior to validation the 2023 ACR/EULAR APS Classification Criteria.

Background/ObjectiveAlthough breastfeeding is safe in women with systemic lupus erythematosus (SLE) who take breastfeeding-compatible medications, rates of breastfeeding are inconsistent, and little is known about the lived experiences surrounding infant feeding among women with SLE. In this qualitative study, we identified factors that influence infant feeding practices of these women.MethodsUsing a phenomenological approach, we conducted and thematically analyzed semi-structured interviews on infant feeding practices with adult women with SLE evaluated at a single tertiary care musculoskeletal center who had given birth within the last 6 years. We collected and summarized maternal, SLE disease, and pregnancy characteristics using descriptive statistics.ResultsSemi-structured interviews were conducted among 19 women with SLE with mean age of 36.1 years at delivery. We identified four overarching themes: general considerations related to infant feeding, medical considerations related to infant feeding, perspectives on infant feeding, and messages to peers with SLE and healthcare providers.ConclusionsWe identified both SLE-specific and disease-agnostic factors impacting infant feeding behaviors in women with SLE. SLE-specific factors influencing infant feeding practices should be viewed holistically within the context of individuals' personal preferences, which in turn may be shaped by interpersonal and cultural factors. Our findings can inform shared decision-making related to infant feeding practices in women with SLE, as well as tailored educational strategies to meet their unique needs.

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.

Objective To evaluate and quantify the indicators of fetal and maternal morbidity in deliveries for patients with systemic lupus erythematosus (SLE) compared with deliveries in patients without SLE. Methods We used retrospective data from the National Inpatient Sample (NIS) to identify all delivery related hospital admissions of patients with and without SLE from 2008 to 2017 using ICD-9/10 codes. Fetal morbidity indicators included pre-term delivery and intrauterine growth restriction (IUGR). 21 indicators of severe maternal morbidity were identified using standard Centers for Disease Control and Prevention (CDC) definitions. Descriptive statistics, including 95% confidence intervals, were calculated using sample weights from the NIS dataset. Results Among the 40 million delivery-related admissions, 51 161 patients were reported to have SLE. Patients with SLE had a higher risk of fetal morbidity, including IUGR (8.0% vs 2.7%) and pre-term delivery (14.5% vs 7.3%), than patients without SLE. During delivery, mothers with SLE were nearly four times as likely to require a blood transfusion or develop a cerebrovascular disorder, and 15 times as likely to develop acute renal failure than those without SLE. Conclusion Our study demonstrates that fetal morbidity and severe maternal morbidity occur at a higher rate in patients with SLE compared with those without. This quantitative work can help inform and counsel patients with SLE during pregnancy and planning.

ObjectiveTo 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.MethodsThis 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.ResultsThe 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–β2-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%.ConclusionThese 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.

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.

Background/Objective Despite increased awareness of the diagnosis and treatment of undifferentiated connective tissue disease (UCTD), there is little research on related psychosocial factors. This cross-sectional study qualitatively assesses the psychosocial impact of UCTD on patient health and well-being. 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.