Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

The SLICC/ACR Damage Index (SDI) may predict adverse obstetric events in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this study was to evaluate the potential impact of irreversible damage accrual in women with systemic lupus erythematosus (SLE) and adverse maternal and/or fetal/neonatal outcomes. METHODS: Retrospective cohort study with SLE pregnant patients was carried out from January 2011 to January 2020 at the Hospital University Pedro Ernesto (HUPE) of the State University of Rio de Janeiro, Brazil. Irreversible damage was defined according to SLICC/ACR damage index (SDI). The association of SDI on pregnancy outcomes was established by univariate and multivariate regression models and included demographic and clinical variables. RESULTS: This study included data from 260 patients in their first pregnancies after SLE diagnosis, with a quarter of them (67/260) scoring one or more points on SDI at the beginning of prenatal care. These patients presented more frequently adverse maternal events, namely, disease activity during pregnancy (p = 0.004) and puerperium (p = 0.001), active lupus nephritis (p = 0.04), and hospitalizations (p = 0.004), than those with no SDI score. Similarly, the risks of adverse fetal and neonatal outcomes were also higher among the patients with SDI ≥ 1 (59.7% vs 38.3% p = 0.001) even after controlling data for disease activity (SLEPDAI > 4). Patients with SDI ≥ 1 presented more frequently preterm deliveries (46.3% vs 31.6%; p = 0.01), small for gestational age infants (28.3% vs 18.1%; p = 0.04), and neonatal intensive care unit admission (26.9% vs 1.5%; p < 0.001). The multivariate analyses showed that SDI ≥ 1 is an independent risk factor for hospitalization due to obstetric complications (p = 0.0008) and preterm delivery (p = 0.009). CONCLUSION: Pregnant SLE patients who present irreversible damage accrual may have higher risk of maternal and fetal adverse outcomes, independently of disease activity. These results should be validated in further prospective studies.

Damage index for antiphospholipid syndrome during long term follow-up: Correlation between organ damage accrual and quality of life.

BACKGROUND: Consequences of organ damage in primary antiphospholipid syndrome (PAPS) are diverse, our aim was to determine organ damage over time and the correlation of organ damage accrual with health-related quality of life (HRQoL) in PAPS. METHODS: First phase: retrospective cohort applying Damage Index for Antiphospholipid Syndrome (DIAPS) at 1, 5, 10, 20 years, or longer since diagnosis. Second phase: cross-sectional study, assessing HRQoL by the Medical Outcomes Study Short Form 36 (SF-36), and organ damage accrual. Descriptive statistics and Spearman correlation coefficient were used. RESULTS: Sixty-seven patients were included, mean follow-up:15 years. Deep vein thrombosis prevailed (71.6%), pulmonary embolism (35.8%) and stroke (32.8%). Organ damage was found in 98.5%, with a cumulative DIAPS value of 3, with greater involvement in the neuropsychiatric and peripheral vascular domains. Regarding HRQoL, deterioration in the physical component summary (PCS) was found in 89.6%. Organ damage accrual correlated inversely and significantly with all the SF-36 domains, mainly with the total score and PCS. Body pain and PCS correlated the most (rho = -0.503, rho = -0.475). CONCLUSIONS: Organ damage accrual impaired HRQoL in PAPS. Secondary thromboprophylxis through adequate systemic management and control of cardiovascular risk factors are necessary to prevent further impairment.

Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort.

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

Predictors of damage accrual in systemic lupus erythematosus: a longitudinal observational study with focus on neuropsychological factors and anti-neuronal antibodies.

OBJECTIVE: Central nervous system disease occurs in over 20% of patients with systemic lupus erythematosus (SLE) resulting in major morbidity and damage. Cognitive dysfunction is common in SLE, but the cause remains uncertain and treatment options are limited. This study explores the influence of clinical, neuropsychological factors and anti-neuronal antibodies on lupus damage accrual. METHOD: A prospective cohort with 99 SLE patients recruited between 2008 and 2013 and followed up in 2016 was established. Baseline evaluations were depression (MINI-Plus), cognitive function evaluating attention, visuospatial memory and executive functions, and anti-neuronal antibodies. Activity index (SLEDAI-2K) and SLICC/ACR Damage Index (SDI) were assessed at baseline and last follow-up. RESULTS: At baseline, median (interquartile range) age was 36.0 years (27.0-45.0), disease duration 3.7 years (0.4-12.4), SLEDAI-2K 6.0 (3.0-12.0), and SDI score 1.0 (0-1.0). Major depression was present in 23%, cognitive deficit in 18%, and received immunomodulators in 36%. Anti-dsDNA/N-methyl-D-aspartate receptor antibodies were present in 19%, anti-ribosomal P in 12%, and anti-neuronal surface P antigen (NSPA) in 5%. After a median follow-up of 55 months (interquartile range 39-78), 11% had damage accrual. In a multivariate analysis, baseline SDI, SLEDAI-2K, and immunomodulators use were associated with final damage, whereas SLEDAI-2K and immunomodulator use were also associated with accrual damage. Models including anti-NSPA showed impact on final and accrual damage. Cognitive deficit, depression, and other autoantibodies were not predictors. CONCLUSIONS: Disease activity and immunomodulator use associate with lupus damage. Of the anti-neuronal antibodies examined, anti-NSPA emerged as a potential poor prognostic factor, probably related to severe SLE onset requiring elevated corticosteroid doses. Key Points • Anti-NSPA may be a worse prognostic factor in SLE. • Other neuropsychological factors do not influence damage.

Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort.

OBJECTIVE: To determine the impact of homocysteine levels on damage accrual in systemic lupus erythematosus (SLE) patients. METHODS: This longitudinal study was conducted in consecutive patients seen every 6 months at our Rheumatology Department since 2012. Patients with available homocysteine levels and who had at least one subsequent visit were included. Univariable and multivariable Cox regression models were done to determine if homocysteine levels were predictive of damage accrual as per the SLICC Damage Index (SDI). The multivariable model was adjusted for pertinent variables (age at diagnosis, gender, socioeconomic status, disease duration, disease activity (SLEDAI), Framingham score, antimalarial and immunosuppressive drug use, average daily dose, and exposure time to prednisone (PDN)). RESULTS: One hundred forty-five patients were included; their mean (SD) age at diagnosis was 43.70 (12.09) years, 136 (93.8%) were female, and nearly all were Mestizo. At baseline, disease duration was 7.55 (6.73) years; patients were followed for 3.54 (1.27) years. The SLEDAI was 5.60 (4.34), and the SDI 0.97 (1.35). The average daily PDN dose was 7.30 (5.78) mg/day and the time of PDN exposure was 7.36 (6.73) years. Mean homocysteine levels were 10.07 (3.71) µmol/L. The highest tertile of homocysteine levels predicted new damage accrual in the univariable and multivariable models [HR 1.78 (95% CI, 1.042-3.039); p = 0.035 and HR 2.045 (95% CI, 1.077-3.883); p = 0.029, respectively]. Increased levels (> 15 µmol/L) were found in 12 (8.3%) patients; 75 (51.7%) patients increased ≥ 1 SDI point. CONCLUSION: In SLE patients, homocysteine levels predicted damage accrual independently of other well-known risk factors for such occurrence.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Damage accrual in systemic lupus erythematosus in Dominicans in New York City and the Dominican Republic.

Objectives Hispanics with systemic lupus erythematosus (SLE) in the United States have more severe disease and damage accrual compared with whites. Data on Hispanics of similar ancestry in geographically different locations is limited but essential in defining genetic and environmental factors for SLE. This study evaluates SLE disease burden in two Dominican communities, Washington Heights in New York City (NYC) and Santiago in the Dominican Republic (DR). Methods Disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)) and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) were cross-sectionally measured in 76 Dominican SLE patients from the Columbia University Lupus Cohort in NYC and compared with 75 Dominican SLE patients living in Santiago in the DR. Results Mean (±SD) age was 40 (±14) and 36 (±11) years for NYC and DR patients, respectively. Median disease duration was 8 years. Disease activity was mild in both groups (SLEDAI-2K of 3 in NYC versus 4 in the DR). NYC Dominicans had more discoid lesions, positive anti-dsDNA, and anti-SSB antibodies. Dominicans in the DR used more corticosteroids, had less medical insurance, lower educational level, and were more likely to be unemployed, whereas more Dominicans in NYC smoked. NYC patients had a higher SDI compared with SLE patients in the DR (0.96 versus 0.24, p < 0.0001). Statistical significance was maintained in adjusted analysis (1.26 versus 0.57, p < 0.0001). Conclusion SLE Dominican patients in NYC had a higher SDI than those in the DR. Longitudinal studies are needed to ascertain whether this difference is due to biological, environmental factors, immigration patterns or a survival bias.