Factors associated with development and mortality of pulmonary hypertension in systemic lupus erythematosus patients.

Objectives This study aims to identify the factors associated with the development and mortality of pulmonary hypertension (PH) in systemic lupus erythematosus (SLE) patients. Methods We conducted a prospective study of SLE patients in a single tertiary center. PH was defined as a systolic pulmonary arterial pressure ≥30 mmHg on transthoracic echocardiography. We assessed potential associated factors contributing to the development and mortality of PH in SLE patients. Results Of 1110 patients with SLE, 48 patients were identified to have PH. Multivariable analysis indicated that pleuritis or pericarditis (odds ratio (OR) = 4.62), anti-RNP antibody (OR = 2.42), interstitial lung disease (ILD) (OR = 8.34) and cerebro-cardiovascular disease (OR = 13.37) were independently associated with the development of PH in SLE. Subgroup analysis among patients with PH demonstrated that there were no statistically significant factors associated with PH mortality in SLE. Conclusions The prevalence of PH was 4.3% in our cohort. There were significant associations with pleuritis or pericarditis, anti-RNP antibody, ILD, and cerebro-cardiovascular disease in SLE, which may contribute to the development of PH. However, there were no statistically significant factors associated with PH mortality in SLE.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study.

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01-1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03-2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24-0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85-1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03-9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12-28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.

Late-onset systemic lupus erythematosus: Is it "mild lupus"?

Objective The objective of this paper is to investigate the clinical characteristics and prognosis of patients with late-onset systemic lupus erythematosus (SLE) using a prospective observational cohort. Methods Late-onset SLE (≥50 years old) was compared with adult-onset SLE (≥18 and <50 years old) using 1997 ACR classification criteria for SLE, autoantibodies, disease activity measured by Adjusted Mean SLE Disease Activity Index (AMS), and damage measured by Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI). The standardized mortality ratio (SMR) was calculated. Results A total of 917 patients with SLE were enrolled. The mean number of cumulative ACR criteria in late-onset SLE ( n = 32, 3.5%) was lower than that in adult-onset SLE (4.6 ± 1.2 vs. 5.5 ± 1.4, p < 0.05). The percentage of patients with low complement was lower in late-onset SLE than adult-onset SLE ( p < 0.05). AMS was also lower in late-onset SLE (2.7 ± 2.1 vs. 4.3 ± 2.6, p < 0.01), but SDI was similar between the two groups (50% vs. 43.4%, p = 0.58). The SMR of late-onset SLE was 1.58 (95% CI 0.58-3.43), while the SMR of adult-onset SLE was 3.34 (2.34-4.63). Conclusion Compared with adult-onset SLE, late-onset SLE has a lower number of ACR criteria and lower disease activity. Organ damage is not different, but prognosis and mortality are more favorable.

Lupus nephritis is associated with more corticosteroid-associated organ damage but less corticosteroid non-associated organ damage.

Objective The objective of this study was to investigate the association of lupus nephritis on organ damage and mortality in patients with systemic lupus erythematosus (SLE). Methods A total of 1112 patients with SLE were investigated. Lupus nephritis was defined as a proteinuria based on the 1997 American College of Rheumatology criteria. Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The associations of lupus nephritis with overall, non-renal, corticosteroid-associated, and non-associated damage were analyzed using logistic regression. The age-adjusted and sex-adjusted standardized mortality ratio was evaluated in patients with and without lupus nephritis. Results The prevalence of lupus nephritis in patients with SLE was 46.3%. Patients with lupus nephritis had a higher percentage of overall cumulative damage than patients without lupus nephritis (51.5% vs. 35.7%, p < 0.001). The odds ratio was 1.40 after adjusting for age at SLE diagnosis, sex, disease duration, anti-malarial agents, immunosuppressive agents and cumulative corticosteroid dose. Among non-renal damage, the odds of corticosteroid-associated damage were higher (2.06, 95% confidence interval (CI) 1.43-2.96) whereas the odds of non-associated damage were lower (0.50, 95% CI 0.35-0.75) in patients with lupus nephritis. The standardized mortality ratios of patients with and without lupus nephritis were 5.17 (95% CI 3.49-7.38) and 2.32 (95% CI 1.47-3.48), respectively. Conclusion In patients with SLE, the presence of lupus nephritis is associated with increased corticosteroid-associated damage but less corticosteroid non-associated damage. Also, mortality is significantly higher in patients with lupus nephritis than in those without lupus nephritis.

A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations characterized by the development of pathogenic autoantibodies manifesting in inflammation of target organs such as the kidneys, skin and joints. Genome-wide association studies have identified genetic variants in the UBE2L3 region that are associated with SLE in subjects of European and Asian ancestry. UBE2L3 encodes an ubiquitin-conjugating enzyme, UBCH7, involved in cell proliferation and immune function. In this study, we sought to further characterize the genetic association in the region of UBE2L3 and use molecular methods to determine the functional effect of the risk haplotype. We identified significant associations between variants in the region of UBE2L3 and SLE in individuals of European and Asian ancestry that exceeded a Bonferroni-corrected threshold (P<1 × 10(-4)). A single risk haplotype was observed in all associated populations. Individuals harboring the risk haplotype display a significant increase in both UBE2L3 mRNA expression (P=0.0004) and UBCH7 protein expression (P=0.0068). The results suggest that variants carried on the SLE-associated UBE2L3 risk haplotype influence autoimmunity by modulating UBCH7 expression.