A Prospective Observational Study of Disease Severity and Mortality in Hispanic American Patients With Systemic Sclerosis.

OBJECTIVE: To characterize disease manifestations in Hispanic American patients with systemic sclerosis (SSc) in comparison with non-Hispanic White and Black patients. METHODS: Longitudinal clinical characteristics were collected prospectively in the Genetics versus Environment in Scleroderma Outcome Study cohort. All patients fulfilled the classification criteria for SSc and had a disease duration less than five years at enrollment. RESULTS: A cohort of 427 patients, consisting of 124 Hispanic, 220 non-Hispanic White, and 83 non-Hispanic Black participants were examined. At enrollment, Hispanic patients were significantly younger but had longer disease duration, higher frequency of U1-RNP positivity as well as concurrent systemic lupus erythematosus (SLE) diagnosis, and lower income and educational levels in comparison to non-Hispanic White patients. Compared with non-Hispanic Black patients, Hispanic patients had more frequently limited cutaneous involvement and anticentromere antibodies. In the longitudinal analysis, Hispanic patients had significantly lower forced vital capacity percents predicted (point estimate, -9.3%; P < 0.001) than non-Hispanic White but not Black patients. Hispanic patients had similar longitudinal modified Rodnan Skin Scores like non-Hispanic White patients but lower measurements than non-Hispanic Black patients (point estimate, -3.2; P = 0.029). Hispanic patients had significantly higher serially obtained perceived functional disability scores than White patients (point estimate, 0.29; P < 0.001). Hispanic patients also had higher mortality rates than White Americans even after adjustment for age, gender, and socioeconomic statuses. CONCLUSION: Hispanic patients have higher likelihood of having U1-RNP positivity and SLE overlap, more severe restrictive lung disease, as well as higher rate of mortality than non-Hispanic White patients.

False positive anti-Topoisomerase I (Scl-70) antibody results in clinical practice: A case series from a scleroderma referral center.

PURPOSE: To determine if some patients who tested positive for anti-Scl-70 antibody in clinical practice, but did not have classifiable systemic sclerosis, were negative for anti-Scl-70 antibody by the more specific immunodiffusion method of testing. METHODS: Patients evaluated by a rheumatologist at a Scleroderma referral center who had tested positive for anti-Scl-70 antibody prior to referral, but did not have classifiable SSc based on clinical criteria, were invited to undergo testing for anti-Scl-70 antibody by immunodiffusion. Patient demographics and clinical features were recorded at the time of their evaluation, and diagnostic testing results were reviewed using the medical records. RESULTS: 52 patients were enrolled over an 8-year period, with 48 (92.3%) testing negative and 4 (7.7%) testing positive for anti-Scl-70 antibody by immunodiffusion. Of the 48 patients who tested negative, 18 (37.5%) tested negative for ANA by indirect immunofluorescence, 33 (68.8%) did not have Raynaud's phenomenon, and 43 (89.6%) had ≤1 clinical criteria items based on the 2013 ACR/EULAR SSc classification criteria. Nevertheless, 21 (43.8%) patients who were negative for anti-Scl-70 antibody by immunodiffusion had undergone a chest CT and 14 (29.2%) had undergone an echocardiogram. A total of 23 patients had at least one follow up clinic visit. 3 out of 4 patients who were positive for anti-Scl-70 antibody by immunodiffusion, but none of the 19 patients who tested negative by immunodiffusion, developed sufficient criteria during follow up to be classified as SSc. CONCLUSION: Assays for anti-Scl-70 antibody in commercial laboratories that are commonly utilized in clinical practice can produce false positive results. These results can lead to angst for patients, as well as unnecessary referrals and diagnostic evaluations.

The Effect of Anti-Scl-70 Antibody Determination Method on Its Predictive Significance for Interstitial Lung Disease Progression in Systemic Sclerosis.

OBJECTIVE: The objective of this study was to assess the predictive significance of anti-Scl-70 (anti-topoisomerase I) antibodies, as determined by three different methods, for decline in forced vital capacity (FVC) within the first year of follow-up in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: Patients in the Genetics Versus Environment in Scleroderma Outcome Study cohort who had ILD (verified by imaging) and available FVC% at enrollment, plus 12 to 18 months thereafter, were examined. All patients had a disease duration of 5 years or less at enrollment. The annualized percentage change in FVC% at 1 year follow-up was the outcome variable. Anti-Scl-70 antibodies were determined by passive immunodiffusion (ID) against calf thymus extract, chemiluminescent immunoassay (CIA), and line blot immunoassay (LIA). RESULTS: Ninety-one patients with a mean disease duration of 2.36 years were included. Anti-Scl-70 antibodies by ID predicted a faster rate of FVC% decline (b = -0.06, P = 0.04). None of the other clinical or serological variables significantly predicted ILD progression. Interestingly, anti-Scl-70 antibodies as determined by CIA and LIA were not significant predictors of FVC decline (P = 0.26 and 0.64, respectively). The observed level of agreement between ID and LIA was moderate (κ = 0.568), whereas it was good between ID and CIA (κ = 0.66). CONCLUSION: Anti-Scl-70 antibodies determined by ID predicted faster FVC decline in patients with SSc-related ILD. Notably, both CIA and LIA for the same antibody did not predict rate of FVC decline at their current cutoffs of positivity. The discrepancy observed between anti-Scl-70 antibody assays can have relevant implications for clinical care and trial enrichment strategies in SSc-ILD.

Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BACKGROUND: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. METHODS AND FINDINGS: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. CONCLUSIONS: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02319525.

Incidence and risk of heart failure in systemic lupus erythematosus.

BACKGROUND: Although case series suggest a higher burden of cardiovascular risk factors in patients with systemic lupus erythematosus (SLE) compared with the general population, the association between SLE and heart failure (HF) remains undefined. We sought to investigate the incidence and risk of HF in patients with SLE. METHODS: In April 2016, we performed a retrospective cohort analysis using the Explorys platform, which provides aggregated electronic medical record data from 26 major integrated healthcare systems across the USA from 1999 to present. Demographic and regression analyses were performed to assess the impact of SLE on HF incidence. RESULTS: Among 45 284 540 individuals in the database, we identified 95 400 (0.21%) with SLE and 98 900 (0.22%) with a new diagnosis of HF between May 2015 and April 2016. HF incidence was markedly higher in the SLE group compared with controls (0.97% vs 0.22%, relative risk (RR): 4.6 (95% CI 4.3 to 4.9)), as were other cardiovascular risk factors. In regression analysis, SLE was an independent predictor of HF (adjusted OR: 3.17 (2.63 to 3.83), p<0.0001). RR of HF was highest in young males with SLE (65.2 (35.3 to 120.5) for age 20-24), with an overall trend of increasing absolute risk but decreasing RR with advancing age in both sexes. Renal involvement in SLE correlated with earlier and higher incidence of HF. CONCLUSIONS: The findings of this study suggest that patients with SLE have significantly higher risk of developing HF and a worse cardiovascular risk profile compared with the general population. These results need to be confirmed by prospective studies.