Declining levels of serum chemokine (C-X-C motif) ligand 10 over time are associated with new onset of psoriatic arthritis in patients with psoriasis: a new biomarker?

BACKGROUND: We previously found that serum levels of chemokine (C-X-C motif) ligand 10 (CXCL10) decreased after the onset of psoriatic arthritis (PsA). OBJECTIVES: We measured CXCL10 levels over time in patients with psoriasis who developed PsA to determine whether the drop in CXCL10 was specific to these patients and further assess its association with PsA development. METHODS: Prospectively followed patients with psoriasis without arthritis [cutaneous psoriasis (PsC)] were assessed yearly by rheumatologists for the presence of PsA. Patients with PsC who developed PsA (converters) were matched to those that did not develop PsA (nonconverters) based on psoriasis duration and the interval between follow-up visits. The duration between baseline and the first visit postconversion in converters was used to assign a pseudoconversion date in nonconverters. Linear mixed-effects models were used to model the expression of CXCL10 over time. RESULTS: CXCL10 significantly declined over time in converters prior to PsA development with a significant difference in the trend over time between converters (n = 29) and nonconverters (n = 52; P < 0·001). CXCL10 continued to decline after PsA onset in a subset of converters. There was a significant difference in the trend of CXCL10 levels between converters (n = 24) and nonconverters (n = 16; P = 0·01) preconversion/pseudoconversion. This difference remained postconversion (P = 0·006) and was not different from the preconversion period (P = 0·75). CONCLUSIONS: A large difference in CXCL10 was identified in patients with PsC that are destined to develop PsA over time. This exploratory analysis supports the association of CXCL10 with PsA development in patients with PsC and warrants further study of the predictive ability of this chemokine. What is already known about this topic? Chemokine (C-X-C motif) ligand 10 (CXCL10) is elevated in psoriatic affected tissues and serum and/or plasma. Patients with psoriasis that develop psoriatic arthritis (PsA) have elevated CXCL10 levels at baseline and these levels drop after arthritis onset. What does this study add? By monitoring levels of CXCL10 in serum over multiple visits in patients with psoriasis that develop PsA as well as those that do not develop PsA, an association was identified between CXCL10 and PsA development. What is the translational message? CXCL10 is a strong candidate for use by physicians for the detection of patients with psoriasis that are at risk of developing PsA. Linked Comment: Kirby and Fitzgerald. Br J Dermatol 2020; 183:805-806.

Disease course patterns in systemic lupus erythematosus.

BACKGROUND: Disease activity in systemic lupus erythematosus follows three different courses: long quiescent, relapsing remitting and persistently active. However, the patterns of disease course since diagnosis are not known. This study aimed to assess the prevalence and characteristics of such patterns over 10 years. PATIENTS AND METHODS: The inception cohort of the Toronto Lupus Clinic (≥10 year follow up, between visit interval ≤18 months) was investigated. Prolonged remission was defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 achieved within 5 years of enrolment and maintained for ≥10 years. The relapsing-remitting pattern was defined based on ≥2 remission periods (clinical Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 for two consecutive visits). Patients with no remission were categorized as persistently active. Groups were compared for baseline characteristics, cumulative damage, flare rate, mortality and certain co-morbidities. RESULTS: Of 267 patients, 27 (10.1%) achieved prolonged remission, 180 (67.4%) relapsing-remitting and 25 (9.4%) persistently active. In total, 35 (13.1%) had only one remission period (hybrid). At enrollment, there were no differences regarding clinical and immunological variables. At 10 years, persistently active patients had accumulated significantly more damage than the prolonged remission and relapsing-remitting patients. Being of Black race and higher adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 over the first 2 years were associated with a more severe disease course. Relapsing-remitting and persistently active patients had an increased flare rate and accrued more osteoporosis, osteonecrosis and cardiovascular events. CONCLUSIONS: Approximately 70% of systemic lupus erythematosus patients followed a relapsing-remitting course, whereas 10% displayed prolonged remission and another 10% a persistently active course. Early response to treatment was associated with a less severe course and better prognosis.

Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study.

BACKGROUND: Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study. METHODS: PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. RESULTS: In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission + LDA at week 16 with secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years. CONCLUSIONS: Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Severe brady-arrhythmias in systemic lupus erythematosus: prevalence, etiology and associated factors.

Background Severe brady-arrhythmias, requiring a permanent pacemaker (PPM), have been sparsely reported in systemic lupus erythematosus (SLE). The aim of this study was to describe the characteristics of such arrhythmias in a defined lupus cohort. Patients and methods The database of the Toronto Lupus Clinic ( n = 1366) was searched for patients who received a PPM. Demographic, clinical, immunological and therapeutic variables along with electrocardiographic (ECG) and echocardiographic findings (based on the last available test prior to PPM) were analyzed. Patients with a PPM (cases) were compared with age-, sex- and disease duration-matched patients without a PPM (controls). Analysis was performed with SAS 9.0; p < 0.05 was considered significant. Results Eighteen patients were identified, 13 (0.95%) with complete atrioventricular block and 5 (0.37%) with sick sinus syndrome. Disease duration at PPM implantation was 22 ± 12 years. Compared to controls, cases had more frequently coronary artery disease, hypertension, dyslipidemia and longer antimalarial (AM) treatment duration. The prevalence of first-degree atrioventricular block, right bundle branch block, left anterior fascicular block and septal hypertrophy was also higher. AM treatment was significantly associated with brady-arrhythmias (OR = 1.128, 95% CI = 1.003-1.267, p = 0.044). Nine patients had prior heart disease and one received a PPM two years after renal transplantation. Eight patients did not have any potential risk factors; prolonged AM therapy (mean 22 years) might have been the cause. Conclusions Apart from known causes, prolonged AM treatment may be associated with severe brady-arrhythmias in SLE. Certain ECG and echocardiographic characteristics may represent indicators of an ongoing damage in the conduction system.

Lupus myocarditis: a single center experience and a comparative analysis of observational cohort studies.

Background Lupus myocarditis (LM) is reported in 3-9% of patients with systemic lupus erythematosus (SLE) but limited evidence exists regarding optimal treatment and prognosis. This study aims to describe LM in a defined lupus cohort as compared with the existing literature. Patients and methods Patients with LM were identified from the University of Toronto Lupus Clinic database. Diagnosis was based on clinical manifestations and electrocardiographic, imaging, and biochemical criteria. Demographic, clinical, diagnostic and therapeutic variables and outcomes were collected in a standardized data retrieval form. A literature review was performed to identify cohort studies reporting on LM treatment and outcome. A comparative analysis was conducted between our patients and the combined cohort of the existing studies. Results Thirty patients were diagnosed with LM (prevalence 1.6%) and compared with a cumulative cohort of 117 patients from five distinct studies. No significant differences were found regarding the age at diagnosis (32.6 ± 13.4 years) and SLE duration (2.5 years median). Concomitant lupus activity from other organ systems was observed in 97% of the patients. Chest pain was more frequently reported in our cohort whereas dyspnea was more prominent in the other studies. Diagnostic criteria were similar across studies. Therapeutic approach was comparable and consisted of glucocorticosteroids (96.6%) and immunosuppressives (70%). Mortality was approximately 20% whereas another 20% of the patients achieved partial and 60% complete recovery. Conclusions LM usually occurs early in the disease course and in the context of generalized lupus activity. Despite aggressive therapy, approximately 40% of the patients died or had residual heart damage.

Sustained complete renal remission is a predictor of reduced mortality, chronic kidney disease and end-stage renal disease in lupus nephritis.

Objective The objective of this paper is to identify the relationship between patients with lupus nephritis (LN) who achieve sustained complete renal remission (CR) and renal outcome and survival. Methods From a longitudinal cohort study we identified patients with LN with CR. We compared the outcomes of patients who achieved sustained CR for at least five years (Group A) with those less than five years (Group B). The outcomes were death, SLICC/ACR damage index (SDI), renal flare, end-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) < 50 ml/min, and doubling of serum creatinine. Regression analyses were used to identify predictors of the outcomes. Results A total of 345 patients were identified, 132 patients in Group A and 213 patients in Group B. The duration of CR in Group A was 11.76 ± 7.34 years but only 1.24 ± 1.24 years in Group B ( p < 0.001). Death, increasing renal SDI, renal flare, renal transplantation, ESRD or eGFR < 50 ml/min, and doubling of serum creatinine in Group A were significantly lower than Group B. Multivariable analysis revealed that Group A patients were at a lower risk of death (hazard ratio (HR) = 0.20; 95% confidence interval (CI), 0.07-0.61; p = 0.004), increasing renal SDI (HR = 0.41; 95% CI, 0.21-0.76; p = 0.01), developing ESRD or eGFR < 50 ml/min (HR = 0.27; 95% CI, 0.12-0.61; p = 0.001), and doubling of serum creatinine (HR = 0.29; 95% CI, 0.14-0.61; p = 0.001) compared with Group B. Conclusion Sustained CR for at least five years is a predictor of better prognosis in patients with LN.

Shrinking lung syndrome in systemic lupus erythematosus: a single-centre experience.

Introduction Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE), characterized by decreased lung volumes and extra-pulmonary restriction. The aim of this study was to describe the characteristics of SLS in our lupus cohort with emphasis on prevalence, presentation, treatment and outcomes. Patients and methods Patients attending the Toronto Lupus Clinic since 1980 ( n = 1439) and who had pulmonary function tests (PFTs) performed during follow-up were enrolled ( n = 278). PFT records were reviewed to characterize the pattern of pulmonary disease. SLS definition was based on a restrictive ventilatory defect with normal or slightly reduced corrected diffusing lung capacity for carbon monoxide (DLCO) in the presence of suggestive clinical (dyspnea, chest pain) and radiological (elevated diaphragm) manifestations. Data on clinical symptoms, functional abnormalities, imaging, treatment and outcomes were extracted in a dedicated data retrieval form. Results Twenty-two patients (20 females) were identified with SLS for a prevalence of 1.53%. Their mean age was 29.5 ± 13.3 years at SLE and 35.7 ± 14.6 years at SLS diagnosis. Main clinical manifestations included dyspnea (21/22, 95.5%) and pleuritic chest pain (20/22, 90.9%). PFTs were available in 20 patients; 16 (80%) had decreased maximal inspiratory (MIP) and/or expiratory pressure (MEP). Elevated hemidiaphragm was demonstrated in 12 patients (60%). Treatment with prednisone and/or immunosuppressives led to clinical improvement in 19/20 cases (95%), while spirometrical improvement was observed in 14/16 patients and was mostly partial. Conclusions SLS prevalence in SLE was 1.53%. Treatment with glucocorticosteroids and immunosuppressives was generally effective. However, a chronic restrictive ventilatory defect usually persisted.

Osteonecrosis in SLE: prevalence, patterns, outcomes and predictors.

Objective Osteonecrosis is a serious comorbidity in patients with systemic lupus erythematosus. The aims of this study were to describe the prevalence of symptomatic osteonecrosis, determine the pattern of joint involvement, identify the outcomes and investigate predictive factors in a large cohort of patients with systemic lupus erythematosus followed prospectively. Methods At the Toronto Lupus Clinic patients have been followed prospectively according to a standard protocol since 1970. Osteonecrosis is recorded if patients are symptomatic and is confirmed by imaging. The site of osteonecrosis is recorded and whether or not surgery was performed. For determination of prevalence, pattern and outcome of osteonecrosis a longitudinal cohort design was performed. For the predictive factors, only patients with incident osteonecrosis were included and were matched for gender, year of entry to clinic (within 5 years), year of birth (within 5 years) and disease duration (within 3 years) with systemic lupus erythematosus patients without osteonecrosis. Results Of 1729 patients with systemic lupus erythematosus registered in the database, 234 (13.5%) developed symptomatic osteonecrosis in 581 sites. Hips and knees were most commonly affected and 47% of the patients had multiple sites involved. More than half of the joints involved at first occurrence of osteonecrosis had surgery. Univariate analysis identified black race, damage, elevated cholesterol and glucocorticosteroids as predictive factors, but glucocorticosteroids remained as the primary predictor for the development of osteonecrosis on multivariable analysis. Conclusion Despite advancements in the assessment and treatment of systemic lupus erythematosus, symptomatic osteonecrosis continues to be a significant comorbidity. Strategies to minimize glucocorticosteroid use are necessary to prevent this serious complication.

Antimalarial-induced cardiomyopathy: a systematic review of the literature.

Background Antimalarials (AMs) are widely used in the treatment of connective tissue diseases. Their main side effect is retinal damage, while heart disease has been described in isolated cases. The aim of this study is to systematically review the existing literature on AM-induced cardiomyopathy (AMIC). Methods The PubMed database was searched for heart biopsy-confirmed AMIC cases. Information on demographics, clinical presentation, concomitant AM-related toxicity, cardiological investigations, treatment and outcome were collected. Descriptive statistics were used. Results Forty-seven cases (42 females) were identified with a mean age at diagnosis 56.4 ± 12.6 and mean AM treatment duration 12.7 ± 8.2 years. Systemic lupus erythematosus ( n = 19) and rheumatoid arthritis ( n = 18) were the most common primary diseases. Clinical presentation was that of congestive heart failure in 77%, while eight patients presented with syncope (17%). Complete atrioventricular block was reported in 17 patients; 24 received a permanent pacemaker (51%). Impaired systolic function was detected in 52.8%, bi-ventricular hypertrophy in 51.4% and restrictive filling pattern of the left ventricle in 18 patients. Cardiac magnetic resonance showed late gadolinium enhancement in seven cases, with a non-vascular pattern in the interventricular septum. Cardiomyocyte vacuolation was reported in all cases; intravacuolar lamellar and curvilinear bodies were observed in 46 (98%) and 42 (89.4%) respectively. Mortality rate was 45% (18/40). Conclusion AMIC is a rare, probably under-recognized, complication of prolonged AM treatment. It presents as a hypertrophic, restrictive cardiomyopathy with or without conduction abnormalities. Early recognition and drug withdrawal are critical with a survival rate of almost 55%.

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Disease evolution in late-onset and early-onset systemic lupus erythematosus.

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Breast cancer in systemic lupus.

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.

OBJECTIVE: To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. METHODS: The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. RESULTS: 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. CONCLUSIONS: In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.

Antimalarials as a risk factor for elevated muscle enzymes in systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between antimalarials (AM) and elevated muscle enzymes in systemic lupus erythematosus (SLE). PATIENTSMETHODS: 325 lupus patients with abnormal creatine phosphokinase (CPK) for at least two consecutive clinic visits were enrolled; 54 patients on statins/fibrates (n = 43) and/or active myositis (n = 14) were excluded. The control group consisted of 1453 lupus patients with no CPK elevation during follow-up. Descriptive statistics and Cox regression analyses were performed, p < 0.05 was considered significant. RESULTS: Cases and controls did not differ regarding age at SLE diagnosis, gender ratio, or disease duration. AM use was more frequent in cases, which had more prolonged AM use. Total frequency of elevated CPK in AM users was 216/1322 (16.3%). Chloroquine was associated with a 3.3-fold, and hydroxychloroquine with a 3.1-fold, increased risk for CPK elevation. Black race was associated with higher CPK (HR = 2.941), whereas female gender was protective (HR = 0.697). 203 patients were followed for 7.3 ± 5.6 years; 49.8% had persistent and 14.8% intermittent CPK elevation, while in 35.4% CPK was normalized. Clinical proximal muscle weakness developed in 5/203 patients. CONCLUSIONS: Chronic AM use is a potential risk factor for muscle enzyme elevation in SLE patients. CPK abnormalities persist in almost two thirds of the patients, but this remains mainly a biochemical finding, evolving to clinical myopathy in about 2.5%.

Prognostic implications of active discoid lupus erythematosus and malar rash at the time of diagnosis of systemic lupus erythematosus: Results from a prospective cohort study.

OBJECTIVE: Cutaneous lupus erythematosus (CLE) may have prognostic implications for systemic lupus erythematosus (SLE). We aimed to determine the impact of discoid lupus erythematosus (DLE) and malar rash on SLE disease activity. METHODS: Data were analyzed from the Toronto Lupus Clinic prospective cohort study. We compared SLE patients with active DLE or malar rash at SLE diagnosis to SLE patients who never developed CLE. Outcomes were assessed at one and five years, including Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (AMS). RESULTS: A total of 524 SLE patients (284 without CLE, 65 with DLE, and 175 with malar rash) were included. Mean AMS scores in patients without CLE at one and five years were 5.96 ± 5.06 and 4.00 ± 3.52, which did not differ significantly from scores at one (6.93 ± 5.31, p = 0.17) and five years (4.29 ± 2.62, p = 0.63) in the DLE group. In patients with malar rash, AMS scores at one (8.30 ± 6.80, p < 0.001) and five years (5.23 ± 3.06, p = 0.004) were higher than controls without CLE. CONCLUSIONS: Malar rash may be a marker of more severe systemic disease over time, while DLE has no significant impact on general SLE disease activity.

Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Vascular- and pregnancy-related outcomes in patients with systemic lupus erythematosus with positive antiphospholipid profile and thrombocytopenia.

This study aimed to investigate whether patients with lupus and a positive antiphospholipid profile with thrombocytopenia are at a higher risk for obstetric complications or thrombotic events than patients without thrombocytopenia. We conducted a case-control study matched 3:1 by sex, age of systemic lupus erythematosus diagnosis, age at study start, disease duration and length of follow-up time. Time to first event following study start was compared using Kaplan-Meier curves and log-rank tests and it was not statistically significant. In this study setting and population, thrombocytopenia was not associated with a higher risk for obstetrical complications or thrombotic events.

The correlation between carotid artery atherosclerosis and clinical ischemic heart disease in lupus patients.

AIM: The extent of subclinical atherosclerosis can be assessed by ultrasound measurement of carotid intima-media thickness (cIMT) and total plaque area (TPA). We aimed to investigate the correlation between measures of atherosclerosis as documented on imaging studies of the carotid vasculature and clinical coronary artery disease (CAD) in systemic lupus erythematosus (SLE). METHODS: The study patients were recruited from the University of Toronto prospective cohort of SLE patients. Patients who had a history of CAD were compared to those without CAD. TPA and cIMT were measured using high-resolution optimized ultrasound systems. Logistic regression models were used to investigate the strength of association between ultrasound measures of atherosclerosis and CAD. The strength of association as expressed by odds ratio (OR) was compared between TPA and cIMT. RESULTS: A total of 103 SLE patients were analyzed (27 patients with a history of CAD). Carotid IMT correlated only moderately with TPA (r = 0.43, p < 0.001). Both measures were significantly associated with the presence of CAD. However, TPA showed a stronger association than cIMT (OR 9.55 vs. 2.02, respectively). TPA was also more strongly associated with dyslipidemia and hypertension compared to cIMT. CONCLUSIONS: In SLE patients, cIMT correlates only moderately with TPA, suggesting that they measure different phenotypes of atherosclerosis. Carotid TPA correlated better than cIMT with cardiovascular risk factors and CAD, suggesting that it may serve as a better tool for the investigation of atherosclerosis in SLE.

Radiological characteristics of the calcaneal spurs in psoriatic arthritis.

OBJECTIVES: Inflammation at the entheses is a distinguishing feature of psoriatic arthritis (PsA). Enthesitis at the heel is the most common location at the Achilles and plantar fascia insertions on the calcaneus. This study aimed to 1) describe the morphological features and measurements of plantar calcaneal spurs in subjects with PsA and controls and 2) determine radiological features that differentiate between inflammatory and non-inflammatory calcaneal spurs. METHODS: Weight bearing lateral foot radiographs of 101 subjects with PsA and 38 control subjects without inflammatory arthritis were examined for plantar calcaneal and Achilles spurs. Three measurements were taken from each radiograph: plantar spur base, mid-segment, and length in millimeters. The differences in radiographic measurements, and the presence of fluffy periostitis of the plantar spurs were then compared between PsA patients and controls. RESULTS: Of the 101 subjects with PsA, 76 (75%) had at least one plantar calcaneal spur and 32 (31.5%) had at least one Achilles tendon spur, compared to 18 (47%) and 3 (8%) respectively in control group (p=0.004). Fluffy plantar periostitis was identified in 14 PsA subjects and none of the controls (p=0.01). The dimensions of plantar spurs were significantly different between groups - longer mid-segment distinguished patients with PsA from controls. CONCLUSIONS: Calcaneal spurs are more common in subjects with PsA than controls. Longer mid-segment measurement was associated with PsA. This study indicates that the presence of fluffy plantar periostitis and broad based and longer mid-segment dimensions are radiological features for inflammatory spurs.

Prevalence and predictors of reduced work productivity in patients with psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is a unique inflammatory musculoskeletal disorder associated with psoriasis. Although high rates of absenteeism have been associated with PsA, less is known about the impact of the disease on the productivity of patients who remain at work. The aim of this study was to identify factors associated with reduced work productivity, as measured by the Work Limitations Questionnaire (WLQ), among patients with PsA. METHODS: Patients attending a single Psoriatic Arthritis Clinic were recruited for participation. Employed participants (including homemakers) first completed a Questionnaire for the Assessment of Work-Related Factors (QAWRF). Eligible participants then completed the WLQ. WLQ scores were used as the dependent variable in linear and logistic regression analyses. Independent variables assessed in this study include work characteristics, demographic factors, and clinical measures. RESULTS: One hundred and eighty-six eligible patients (60.9% males) returned their assessment forms for analysis. The mean reduction in work productivity due to illness was 4.3%. In univariate linear regression analysis, work productivity was significantly associated with sex, education status, Psoriasis Area and Severity Index (PASI), AJC, ESR, Functional Co-morbidity Index (FCI), and support at work; associations with gender, ESR, FCI, and medications were also significant in a reduced multivariate model. CONCLUSIONS: Work productivity was associated with demographic, clinical, and work-related factors in PsA. These variables may be useful in identifying patients who require more aggressive intervention, including the use of effective drugs to control disease activity and advocacy for a more supportive work environment.