Lupus International Collaborating Clinics Damage Research Articles

The additive effects of hydroxychloroquine to maintenance therapy with standard of care in patients with systemic lupus erythematosus.

In this retrospective study, the effect of hydroxychloroquine (HCQ) added to maintenance therapy according to the standard of care (SoC) was evaluated for 1year in 101 patients with systemic lupus erythematosus (SLE). The primary endpoint was the SLE Disease Activity Index (SLEDAI). The secondary endpoints were the British Isles Lupus Assessment Group index, serum complement activity (CH50) levels, anti-double-stranded DNA (dsDNA) antibody titer, concomitant corticosteroid (CS) dose, and Systemic Lupus International Collaborating Clinics (SLICC) damage index. These variables were compared between the SoC+HCQ (n=42) and SoC (n=59) groups. The SLEDAI improved from 2 (0, 6) to 0 (0, 4) in the SoC+HCQ group (P = .038) but significantly deteriorated from 1 (0, 4) to 2 (0, 8) in the SoC group (P = .033). CH50, anti-dsDNA antibody titer, concomitant CS dose, and SLICC damage index did not significantly change. The increase in the SLEDAI and concomitant CS dose after 1year were all significantly greater in the SoC group, and the proportion of patients with SLEDAI flare was significantly lower in the SoC+HCQ group (SoC+HCQ: 4.76% vs SoC: 25.4%, P=.006). Univariate logistic regression analyses identified HCQ as a predictive factor for no SLEDAI flare (P=.003, odds ratio 6.81, 95% confidence interval 1.77-45.00). The use of HCQ effectively improved SLEDAI scores and was a predictive factor for the prevention of SLEDAI flare. Therefore, HCQ may be considered a potential mainstay of maintenance therapy.

Impact of fatigue on health-related quality of life and illness perception in a monocentric cohort of patients with systemic lupus erythematosus

BackgroundFatigue is a very common and debilitating symptom in patients with systemic lupus erythematosus (SLE), even among those with a mild or inactive disease. The objective of this study is...

Galectin-9 as a biomarker for disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by elevated interferon (IFN) signature genes. Galectin-9 (Gal-9) is a β-galactoside-binding lectin that is reportedly useful as a biomarker for IFN gene signatures. In a cross-sectional study of Japanese patients with recent-onset SLE, we aimed to determine whether raised serum Gal-9 levels were associated with the disease activity or organ damage seen in SLE patients. The current study included 58 Japanese patients with SLE and 31 age-matched healthy individuals. Disease activity and organ damage were assessed using SLE Disease Activity 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC) damage index. Serum and cerebrospinal fluid (CSF) Gal-9 concentrations were quantified using ELISA. Correlation analyses between Gal-9 and clinical parameters including disease activity were performed. Serum levels of Gal-9 were significantly increased in patients with SLE compared with the control group (16.6 ng/ml, [interquartile range (IQR); 3.6-59.7] versus 4.74 ng/ml, [IQR; 3.0-9.5], p<0.0001). Gal-9 was significantly correlated with disease activity measures in the SLEDAI-2K. Serum Gal-9 levels were significantly greater in patients with SLE-related organ involvement (23.1 ng/ml, [IQR; 5.1-59.7] versus 12.5ng/ml, [IQR; 3.6-39.0], p = 0.013). Whereas there was no difference in serum levels of CXCL10 or M2BPGi between patients with and without SLE-related organ involvement. Serum levels of Gal-9 were significantly higher in SLE patients with active renal involvement determined by BILAG renal score (A-B) compared to those without active renal involvement (C-E). Whereas there was no significant difference in serum levels of Gal-9 between SLE patients with or without active other organ involvements (neurological or hematological) determined by BILAG score. SLE patients with detectable circulating IFN-α had raised serum Gal-9 levels. Levels of Gal-9 were significantly higher in the CSF from patients with recent-onset neuropsychiatric SLE (NPSLE) than in those from non-SLE controls (3.5 ng/ml, [IQR; 1.0-27.2] versus 1.2 ng/ml, [IQR; 0.9-2.1], p = 0.009). Gal-9 could be a serologic marker of disease activity and organ involvement in SLE patients. Future studies evaluating the role of Gal-9 in the SLE phenotype may provide insights into SLE pathogenesis.

Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial

ObjectivesTo compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease.MethodsA monocentric, 12-month, superiority, open-label, randomised...

Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study.

Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5-3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9-8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01-1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02-1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0-5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03-1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03-1·23], p=0·0144), and age at enrolment (1·04 [1·01-1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43-2·06], p=0·8675). Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

Identifying damage clusters in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) causes irreversible damage to organ systems. Recently, evidence has been obtained for subphenotypes of SLE. This study aimed to identify damage clusters and compare the associated clinical manifestations, SLE disease activity, mortality, and genetic risk scores (GRS). The study was conducted on the Hanyang BAE lupus cohort. Patients with disease duration <5years were excluded to minimize confounding effects of disease duration. They were grouped into 3 clusters based on the Systemic Lupus International Collaborating Clinics Damage Index using k-means cluster analysis. Among the 1130 analyzed patients, musculoskeletal damage was most prevalent (20.2%), followed by ocular (11.4%), renal (10.5%), and neuropsychiatric damage (10.2%). Three significantly different damage clusters were identified. Patients in cluster 1 (n=824) showed the least damage. Cluster 2 (n=195) was characterized by frequent renal (55.4%) and ocular (58.0%) damage, and cluster 3 (n=111) was dominated by neuropsychiatric (100%) and musculoskeletal damage (35.1%). Cluster 2 had the highest adjusted mean AMS (adjusted mean SLE Disease Activity Index score; mean±SD: 5.4±2.9), while cluster 3 had the highest mortality (14.4%). Weighted GRS did not differ significantly between the clusters. Patients in prevalent renal and ocular damage cluster had the highest AMS scores, while the cluster with frequent neuropsychiatric damage had the highest mortality.

Different patterns of cerebral perfusion in SLE patients with and without neuropsychiatric manifestations.

To investigate brain perfusion patterns in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE and non‐NPSLE, respectively) and to identify biomarkers for the diagnosis of NPSLE using noninvasive three‐dimensional (3D) arterial spin labeling (ASL). Thirty‐one NPSLE and 24 non‐NPSLE patients and 32 age‐ and sex‐matched normal controls (NCs) were recruited. Three‐dimensional ASL‐MRI was applied to quantify cerebral perfusion. Whole brain, gray (GM) and white matter (WM), and voxel‐based analysis (VBA) were performed to explore perfusion characteristics. Correlation analysis was performed to find the relationship between the perfusion measures, lesion volumes, and clinical variables. Receiver operating characteristic (ROC) analysis and support vector machine (SVM) classification were applied to differentiate NPSLE patients from non‐NPSLE patients and healthy controls. Compared to NCs, NPSLE patients showed increased cerebral blood flow (CBF) within WM but decreased CBF within GM, while non‐NPSLE patients showed increased CBF within both GM and WM. Compared to non‐NPSLE patients, NPSLE patients showed significantly reduced CBF in the frontal gyrus, cerebellum, and corpus callosum. CBF within several brain regions such as cingulate and corpus callosum showed significant correlations with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index scores. ROC analysis showed moderate performance in distinguishing NPSLE from non‐NPSLE patients with AUCs > 0.7, while SVM analysis demonstrated that CBF within the corpus callosum achieved an accuracy of 83.6% in distinguishing NPSLE from non‐NPSLE patients. Different brain perfusion patterns were observed between NPSLE and non‐NPSLE patients. CBF measured by noninvasive 3D ASL could be a useful biomarker for the diagnosis and disease monitoring of NPSLE and non‐NPSLE patients.

Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort

OBJECTIVE Damage in patients with systemic lupus erythematosus is irreversible change in organs due to disease activity, concomitant disease or medication side-effects. It is measured using the Systemic Lupus International Collaborative Clinics Damage Index (SDI) and is associated with increased mortality. Previous reports have suggested associations between damage accrual and various ethnic, disease and treatment factors, but there is a dearth of long-term follow-up data from large multi-ethnic cohorts. We describe a study of damage and mortality in 300 patients from London, UK followed for up to 40 years. METHODS We carried out retrospective analysis of medical records and SDI scores of 300 patients followed for up to 40 years (median 13.3 years). Characteristics of the groups who did and did not develop damage and those who died or survived to the end of follow-up were compared using univariable and multivariable analysis. Kaplan-Meier analysis was used to analyse factors affecting mortality and accrual of damage. RESULTS Damage developed in 231/300 (77%) of patients. There was a linear accrual of damage over 40 years follow-up. Factors associated with damage were African/Caribbean ethnicity, renal and cerebral involvement, early use of high-dose corticosteroids or immunosuppressants, anti-RNP and antiphospholipid antibodies. Damage was strongly associated with mortality. Of 87 patients who died, 93% had damage compared with 70% of survivors (P < 0.001). CONCLUSION Development of damage is strongly associated with increased mortality. We identified groups at increased risk of developing damage, including those treated with high-dose steroids and immunosuppressants within the first two years.

P4450Atherosclerosis in women with systemic lupus erythematosus with and without nephritis

Abstract Background Nephritis in systemic lupus erythematosus (SLE) is a factor contributing to early development of atherosclerosis (AS). Objectives The aim of the study is to determine differences in cardiovascular risk factors and AS in SLE pts with and without lupus nephritis (LN). Methods The study included 162 females, age 35 [26–43] years (median [interquartile range 25–75%])) with SLE (ACR,1997). We divided SLE pts on two groups, comparable in age: the 1st group is the pts with LN (n=84, 52%), the 2nd - without LN (n=78, 48%). We considered traditional factors of cardiovascular disease (CVD): (smoking, family history of CVD, blood pressure, cholesterol (total, HDL, LDL) and triglyceride (TG) levels, body mass index, diabetes mellitus) and SLE-related factors (age at onset, duration, clinical features, SLE Disease Activity Index (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics damage index (SLICC/DI), treatment with steroids); intima-media thickness (IMT) and the 10-year risk for coronary events. Carotid intima-media wall thickness of common carotid arteries was measured by high resolution B-mode ultrasound. The 10-year risk for coronary events was estimated by the Framingham risk equation. Results Median SLE duration was 8,0 [2,3–17,0] years, SLEDAI 2K – 8 [3–16], SLICC/DI score – 2 [0–3], duration of prednisone treatment – 72 [26–141] months. SLE pts from the 1st group had higher prevalence of hypertension (61% vs 36%, p&lt;0,01), systolic blood pressure (130 [110–150] vs 120 [110–130]mm Hg, p&lt;0,01), diastolic blood pressure (80 [70–95] vs 70 [70–80] mm Hg, p&lt;0,05), TG concentration (136 [98–184] vs 100 [61–162] mg/dl, p&lt;0,01), Framingham Risk Score (5 [1–30] vs 1 [1–27]%, p&lt;0,05), SLEDAI-2K (12 [5–19] vs 4 [2–10], p&lt;0,ehz745.08501), SLICC/DI score (2 [0–4] vs 0 [0–2], p&lt;0,01), prednisone therapy duration (95 [26–192] vs 44 [14–98] months, p&lt;0,05), prednisone cumulative dose (34,4 [13,6–82,5] vs 15,7 [6,2–35,2] g, p&lt;0,001), mean IMT (0,73 [0,65–0,83] vs 0,67 [0,61–0,75] mm, p&lt;0,01), than the pts from the 2nd group. There is no difference in CVD frequency in these groups (17% vs 8%, p=0,084). Conclusions SLE patients with and without LN had no difference in frequency of clinical manifestations of AS (CVD), but had a greater value of mean IMT, Framingham Risk Score and a higher incidence of both traditional (hypertension, TG concentration) and SLE-related (disease activity, prednisone therapy) risk factors for AS.

Neutrophil/lymphocyte and platelet/lymphocyte ratios are useful predictors comparable to serum IL6 for disease activity and damage in naive and relapsing patients with lupus nephritis

Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have become recently useful as predictive and prognostic tools in patients with various medical conditions. Aim of the workTo evaluate NLR and PLR in systemic lupus erythematosus (SLE) and their relation to disease clinical characteristics, nephritis, disease activity and damage. Patients and methodThe study involved 110 Egyptian SLE patients; 80 with lupus nephritis (naive and relapsing) and 30 without as well as 50 matched control. Patients were subjected to full clinical examination, SLE disease activity index (SLEDAI) scoring, and damage using Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). Laboratory and immunology profiles included the complete blood count (CBC) with differential white blood cell counts and estimation of both NLR and PLR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), protein/creatinine ratio, anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA), serum complements and interleukin-6 (IL-6) levels. ResultBoth NLR and PLR were significantly higher in SLE patients (4.8 ± 1.4 and 281.7 ± 66.7 respectively) compared to controls (3.8 ± 2 and 138.2 ± 50.4). Both ratios were significantly elevated in patients with active lupus nephritis (at presentation or as a flare) and were comparable between naive and relapsing lupus nephritis patients. In lupus nephritis patients, NLR and PLR significantly correlated with proteinuria, ESR, hypocomplementemia, IL6, SLEDAI and SLICC-DI. The best NLR cut-off value to predict nephritis activity was 5.65, whereas the best PLR cut-off value was 316.5. ConclusionNLR and PLR appear to be potentially useful cheap parameters of activity, relapse and severity in SLE patients with nephritis.

Retinal Complications in Patients with Systemic Lupus Erythematosus Treated with Antimalarial Drugs.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are key drugs in systemic lupus (SLE) and related diseases. Retinal toxicity remains the most worrisome complication. We studied factors potentially associated with retinal toxicity, using case-control analyses. Within our SLE clinic cohort, we identified patients with retinal changes using the Systemic Lupus International Collaborating Clinics Damage Index. We confirmed HCQ/CQ retinopathy with chart review, and selected up to 3 SLE controls for each case, matched by age at SLE diagnosis and SLE duration. Over an average 12.8 years of followup, within 326 patients exposed to antimalarial drugs, 18 (5.5%) developed retinal toxicity. The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years (maximum 33 yrs). Median HCQ/CQ duration was statistically similar in cases [19 yrs, interquartile range (IQR) 14-20] and controls (16 yrs, IQR 11-22), likely due to our matching on SLE duration. Versus controls, cases tended to have more renal disease (cases 22.2%, controls 14.8%) and were slightly less likely to be white (cases 61.1%, controls 74.1%), but neither variable reached statistical significance. Among patients with retinal toxicity, the number previously exposed to CQ was more than 3 times that in controls. Just over 5% of patients developed antimalarial retinal complications, over an average of 12.8 years. No cases were detected in the first 5 years of therapy. Past CQ use was more common in cases versus controls. Future studies using larger cohorts are under way to better define the roles of therapy duration, race/ethnicity, and other factors.

Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort.

ObjectiveDamage in patients with systemic lupus erythematosus is irreversible change in organs due to disease activity, concomitant disease or medication side-effects. It is measured using the Systemic Lupus International Collaborative Clinics Damage Index (SDI) and is associated with increased mortality. Previous reports have suggested associations between damage accrual and various ethnic, disease and treatment factors, but there is a dearth of long-term follow-up data from large multi-ethnic cohorts. We describe a study of damage and mortality in 300 patients from London, UK followed for up to 40 years.MethodsWe carried out retrospective analysis of medical records and SDI scores of 300 patients followed for up to 40 years (median 13.3 years). Characteristics of the groups who did and did not develop damage and those who died or survived to the end of follow-up were compared using univariable and multivariable analysis. Kaplan-Meier analysis was used to analyse factors affecting mortality and accrual of damage.ResultsDamage developed in 231/300 (77%) of patients. There was a linear accrual of damage over 40 years follow-up. Factors associated with damage were African/Caribbean ethnicity, renal and cerebral involvement, early use of high-dose corticosteroids or immunosuppressants, anti-RNP and antiphospholipid antibodies. Damage was strongly associated with mortality. Of 87 patients who died, 93% had damage compared with 70% of survivors (P < 0.001).ConclusionDevelopment of damage is strongly associated with increased mortality. We identified groups at increased risk of developing damage, including those treated with high-dose steroids and immunosuppressants within the first two years.

Risk factors for cataracts in a cohort of Egyptian systemic lupus erythematosus patients

Aim of the workThis study was undertaken to evaluate cataract risk factors in Egyptian systemic lupus erythematosus (SLE) patients. Patients and methodsA cohort of 150 consecutive adult SLE patients was included. None of the patients was diabetic or had cataract before steroids treatment for SLE. Detailed medical and ophthalmological histories were taken. Thorough clinical examination was performed with assessment of SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics damage index (SLICC DI), along with routine blood tests. Slit lamp examination was done to assess the anterior segment of the eye especially the lens to detect the type and degree of cataract. Results150 SLE patients were studied with a mean age of 37.16 ± 11 years; 129 females and 21 males and a mean disease duration of 11 ± 5.7 years. Their mean SLEDAI was 4.1 ± 3.78 and SLICC/DI 2.1 ± 1.3. The frequency of cataract was 18% (n = 27); 22.2% of them were cortical and 77.8% were posterior subcapsular with mild-moderate degree. Glaucoma was present in only 2%. A significant increase in age, disease duration, age at onset, SLICC/DI, cumulative steroid dose and hydroxychloroquine (HCQ) dose was found in those with cataract compared to non-cataract patients (p < 0.05). The age, age at onset, disease duration, SLICC/DI and cumulative steroid dose were significant independent factors increasing the probability of cataract occurrence among SLE patients (p < 0.01). ConclusionAlthough corticosteroids are prescribed to control SLE symptoms, these results highlight potential risks associated with their use, especially cataracts, which require careful and routine ophthalmologic examination and follow up.

Prevalence of cognitive impairment using the Montreal Cognitive Assessment questionnaire among patients with systemic lupus erythematosus: a cross-sectional study at two tertiary centres in Malaysia.

Cognitive impairment is a common neuropsychiatric manifestation of systemic lupus erythematosus (SLE). However, it is not routinely assessed for despite its high prevalence and significant disease burden. This study aimed to determine the prevalence of mild cognitive impairment (MCI) using the Montreal Cognitive Assessment (MoCA) and its associated factors among patients diagnosed with SLE in Malaysia. A total of 200 SLE patients were recruited prospectively from the outpatient clinics of two tertiary hospitals in Malaysia. Standardized clinical interview was utilized to obtain information on socio-demographic characteristics. All patients were then assessed using the MoCA questionnaire for presence of cognitive impairment; the Patient Health Questionnaire 9 (PHQ-9) for presence of depressive symptoms; and the Wong-Baker Faces Pain Scale (WBFPS) for severity of pain. The evaluation of disease activity and severity were performed by the treating rheumatologists and nephrologists using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC DI). The prevalence of MCI was 35%. The significant associated factors from the bivariate analysis were male gender (p = 0.04), educational level (p = 0.00), WBFPS score (p = 0.035) and anticardiolipin IgM (p = 0.01). Further analysis using logistic regression model found that male gender (OR = 7.43, 95% confidence interval 1.06-52.06, p = 0.04), lower educational level (OR = 4.4, 95% confidence interval 1.47-13.21, p = 0.01) and presence of anticardiolipin IgM (OR = 6.81, 95% confidence interval 1.45-32.01, p = 0.031) were associated with impaired MoCA scores. Also, increasing pain scores increased the risk of patients being affected by cognitive impairment. Over one-third of patients with SLE in our cohort were found to have MCI. Risk factors included male gender, lower educational level, higher pain score and presence of anticardiolipin IgM. Physicians are encouraged to perform routine screening to detect cognitive dysfunction in patients with SLE in their clinical practice as part of a more comprehensive management.

Lymphopenia in systemic lupus erythematosus patients: Is it more than a laboratory finding?

Aim of the workTo investigate the relation between lymphopenia and clinical manifestations, laboratory findings, disease activity and damage index in systemic lupus erythematosus (SLE) patients. Patients and methods124 SLE patients were recruited from the Rheumatology Department in-patient and outpatient clinic, Faculty of medicine, Cairo University Hospitals. SLE disease activity index (SLEDAI) and the systemic lupus international collaborating clinics damage index (SLICC-DI) were assessed. Patients were divided into two groups according to presence or absence of lymphopenia (lymphocyte count ≤1500 cells/mm3), and were compared as regards different disease parameters. ResultsThe 124 patients were 113 females (91.1%) and 11 males (8.9%). Their mean age was 28.54 ± 8.25 years and median disease duration was 48 (24–105) months. 86 (69.4%) had renal involvement, complement C3 was consumed in 84 (67.7%) and C4 in 44 (35.5%). All were receiving steroids and a high dose was more frequent in those with lymphopenia (17 (29.8%) compared to those without (in 9 (13.4%). Lymphopenia was found in 57 (46%) patients. Lymphopenic patients had higher frequency of renal involvement (p = 0.002) (OR = 3.37, CI = 1.5–7.8), complement consumption (p = 0.03), 24 h urinary proteins (p = 0.034), higher steroid doses (p = 0.012) and cyclophosphamide administration (p = 0.03). SLEDAI was severe in 29.8% of lymphopenic patients (p = 0.16), and SLICC-DI median was 2 in both groups (p = 0.4). ConclusionLymphopenia is a common finding in SLE patients and was significantly associated with lupus nephritis, complement consumption, higher steroid doses and cyclophosphamide administration. Lymphopenia might be a promising marker for renal involvement in SLE.

Epidemiologic Profile of Erectile Dysfunction in Patients with Systemic Lupus Erythematosus: The Latin American Landscape.

The aim of this study was to describe the prevalence of erectile dysfunction (ED), as well as associated demographic and clinical features, in men with systemic lupus erythematosus (SLE), by means of a systematic, standardized evaluation. We performed a transversal study in 8 tertiary care centers in Latin America. We included male patients ≥ 16 years who fulfilled ≥ 4 American College of Rheumatology criteria for SLE and had regular sexual activity, and evaluated them with the International Index of Erectile Function-5 questionnaire. Relevant demographic, clinical, and serological characteristics were recorded. We included 2 control groups: the first was made up of healthy men and the second of men with autoimmune diseases other than SLE (non-SLE group). We included 590 subjects (174 SLE, 55 non-SLE, and 361 healthy controls). The prevalence of ED in the SLE group was 69%. Mean age in that group was 36.3 ± 1.03 years. Among SLE patients with and without ED, these factors were significantly different: the presence of persistent lymphopenia (p = 0.006), prednisone dose (9.3 ± 1.2 vs 5.3 ± 1.3 mg, p = 0.026), and the Systemic Lupus International Collaborating Clinics damage score (1.25 ± 0.14 vs 0.8 ± 0.16 points, p = 0.042). Independent risk factors for ED in patients with SLE were persistent lymphopenia (OR 2.79, 95% CI 1.37-5.70, p = 0.001) and corticosteroid use in the previous year (OR 2.15, 95% CI 1.37-3.37, p = 0.001). Regardless of comorbidities, treatment (excluding steroids), and type of disease activity, patients with SLE have a high prevalence of ED, especially considering that most patients are young. Recent corticosteroid use and persistent lymphopenia, which could be related to endothelial dysfunction, are risk factors for this complication in men with SLE.

Risk factors for irreversible organ damages in peri- and postmenopausal women with systemic lupus erythematosus

Objective: to identify irreversible organ damages and factors influencing their development and to compare existing musculoskeletal injuries with the activity of systemic lupus erythematosus (SLE).Patients and methods. The investigation enrolled 197 peri- and postmenopausal female outpatients (mean age, 50.94±9.1 years) with SLE, who were followed up at Clinical Rheumatology Hospital Twenty-Five, Saint Petersburg. The mean disease duration was 9.7±7.5 years. Cytostatic and glucocorticoid (GC) treatment regimens and dosages in the examinees were analyzed on the basis of their primary medical records. The investigators assessed the current disease activity by the SLE Disease Activity Index (SLEDAI-2K) and the Lupus Low Disease Activity State (LLDAS) and irreversible organ damages by the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (DI).Results and discussion. 93.4% of the patients continued to receive GS therapy at the time of inclusion in the study. The median GS maintenance dose was 12.5 mg/day. Almost half of the patients (n=86/43.7%) were in menopause (its mean duration was 12.8±7.1 years). Half of the examinees were noted to have remission (n=36/18.3%) or low SLE activity (n=92/46.7%) according to the SLEDAI-2K. Fifty-seven (28.9%) patients met all 5 LLDAS criteria; at the same time other 96 (48.7%) patients met 4 out of the 5 criteria, the 5th criterion being a high GC maintenance dose. High DI scores of ≥4 were found in two thirds (n=131/66.5%) of the examinees. Musculoskeletal system injuries ranked first among other disorders: osteoporosis (OP) and muscle weakness were detected in 76 (38.6%) and 69 (35.0%) patients, respectively. Regression analysis involving all statistically significant factors showed that the degree of damage was influenced by age (p=0.013215), total GS dose (p=0.000047), and previous therapy with cyclophosphamide (p=0.041505).Conclusion. The contribution of GS therapy to irreversible damage accrual is obvious in peri- and postmenopausal women with SLE. Timely dose adjustment or complete withdrawal of GS during remission in SLE is one of the key factors that substantially reduce the risk of progression of irreversible organ damages due to the prevention of OP and osteoporotic fractures in these patients.

Late-onset biopsy-proven lupus nephritis without other associated autoimmune diseases: severity and long-term outcome.

Lupus nephritis (LN) usually develops within the first years of systemic lupus erythematosus (SLE) onset and rarely after that. There are scarce studies comparing early- versus late-onset nephritis (before versus after five years of SLE diagnosis). The aim of this study was to compare the severity and long-term outcome (after 7 years) in these two, late-onset and early-onset, nephritis groups. This study included 93 patients from rheumatology tertiary centers from Brazil and Italy, all of them with biopsy-proven LN with > 7 years follow-up. Patients were divided in two groups: early-onset nephritis ( n = 75) and late-onset nephritis ( n = 18). Clinical and laboratorial data were obtained using a standardized electronic chart database protocol carried out at 1-6 months interval and established in 2000. Patients >50 years or with concomitant autoimmune diseases were excluded. Variables evaluated at the LN presentation were Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), creatinine, albumin, anti-DNA positivity and nephritis class. Variables evaluated at the long-term outcome (after 7 years) were Systemic Lupus International Collaborating Clinics Damage Index (SDI), creatinine, dialysis and mortality. The average time of LN presentation was 10.94 ± 3.73 years for the late-onset and 1.20 ± 1.60 years for the early-onset group. Their similar nephritis duration (12.44 ± 3.2 versus 13.28 ± 4.03 years, p = 0.41) and comparable mean ages (49.17 ± 9.9 versus 44.11 ± 10.8 years old, p = 0.06) allow a more accurate comparison. Regarding severity, late-onset was similar to early-onset group: SLEDAI (8 (range: 6-22) versus 12 (range: 2-24), p = 0.47), creatinine (1.36 ± 0.94 versus 1.36 ± 1.13 mg/dl, p = 0.99); albumin (2.84 ± 0.65 versus 2.59 ± 0.84 mg/dl, p = 0.30); proteinuria (3.77 ± 2.18 versus 5.01 ± 4.51 g/vol, p = 0.26); proliferative nephritis (44% ( n = 8) versus 60% ( n = 45), p = 0.23). There was also no difference in the long-term outcomes between groups: SDI (1 (range: 0-5) versus 0.5 (range: 0-5), p = 0.27); creatinine (2.04 ± 2.38 versus 1.69 ± 2.26 mg/dl, p = 0.56); dialysis (22% ( n = 4) versus 13% ( n = 10), p = 0.46) and mortality (0% ( n = 0) versus 12% ( n = 9), p = 0.19). This study provides novel evidence of comparable long-term outcomes between late-onset and early-onset nephritis, which is most likely explained by the observation that at presentation, the clinical, laboratorial and histological features of late-onset and early-onset nephritis are similar. This suggests that there should be no distinct treatment targets and therapeutic interventions for the late- and early-onset groups.

Progression of subclinical and clinical cardiovascular disease in a UK SLE cohort: the role of classic and SLE-related factors

ObjectivesWe aimed to describe the rate and determinants of carotid plaque progression and the onset of clinical cardiovascular disease (CVD) in a UK SLE cohort.MethodsFemale patients with SLE of white...

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

ObjectivesTo identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. MethodsThis is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. ResultsMean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). ConclusionsIn a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.