Coronary plaque progression is greater in systemic lupus erythematosus than rheumatoid arthritis.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with a high incidence of cardiovascular disease. Coronary atherosclerosis, particularly total plaque and noncalcified plaque on coronary computed tomography angiography (CCTA) has been correlated with cardiovascular events. We compared baseline coronary plaque burden and progression by serial CCTA in SLE and RA patients. METHODS: We prospectively evaluated 44 patients who underwent serial CCTA examinations to quantify coronary plaque progression, 22 SLE patients, and 22 age- and sex-matched RA patients. Semiautomated plaque software was used for quantitative plaque assessment. Linear regression examined the effect of SLE diagnosis (versus RA) on annualized change in natural log-transformed total normalized atheroma volume (ln-TAV norm ) for low-attenuation, fibrofatty, fibrous, total noncalcified, densely calcified, and total plaque. RESULTS: No quantitative differences for any plaque types were observed at baseline between SLE and RA patients ( P = 0.330-0.990). After adjustment for baseline plaque and cardiovascular risk factors, the increase in ln-TAV norm was higher in SLE than RA patients for fibrous [Exp-ß: 0.202 (0.398), P = 0.0003], total noncalcified [Exp-ß: 0.179 (0.393), P = 0.0001], and total plaque volume [Exp-ß: 0.154 (0.501), P = 0.0007], but not for low-attenuation, fibrofatty, or densely calcified plaque ( P = 0.103-0.489). Patients with SLE had 80% more fibrous, 82% more noncalcified, and 85% more total plaque increase than those with RA. CONCLUSION: Coronary plaque volume was similar in RA and SLE at baseline. Progression was greater in SLE, which may explain the greater cardiovascular risk in this disease. Further research to evaluate screening and management strategies for cardiovascular disease in these high-risk patients is warranted.

Systemic lupus Erythematosus and geomagnetic disturbances: a time series analysis.

BACKGROUND: To examine the influence of solar cycle and geomagnetic effects on SLE disease activity. METHODS: The data used for the analysis consisted of 327 observations of 27-day Physician Global Assessment (PGA) averages from January 1996 to February 2020. The considered geomagnetic indices were the AP index (a daily average level for geomagnetic activity), sunspot number index R (measure of the area of solar surface covered by spots), the F10.7 index (measure of the noise level generated by the sun at a wavelength of 10.7 cm at the earth's orbit), the AU index (upper auroral electrojet index), and high energy (> 60 Mev) proton flux events. Geomagnetic data were obtained from the Goddard Space Flight Center Space Physics Data Facility. A time series decomposition of the PGA averages was performed as the first step. The linear relationships between the PGA and the geomagnetic indices were examined using parametric statistical methods such as Pearson correlation and linear regression, while the nonlinear relationships were examined using nonparametric statistical methods such as Spearman's rho and Kernel regression. RESULTS: After time series deconstruction of PGA averages, the seasonality explained a significant fraction of the variance of the time series (R2 = 38.7%) with one cycle completed every 16 years. The analysis of the short-term (27-day) relationships indicated that increases in geomagnetic activity Ap index (p < 0.1) and high energy proton fluxes (> 60 Mev) (p < 0.05) were associated with decreases in SLE disease activity, while increases in the sunspot number index R anticipated decreases in the SLE disease activity expressed as PGA (p < 0.05). The short-term correlations became statistically insignificant after adjusting for multiple comparisons using Bonferroni correction. The analysis of the long-term (297 day) relationships indicated stronger negative association between changes in the PGA and changes in the sunspot number index R (p < 0.01), AP index (p < 0.01), and the F10.7 index (p < 0.01). The long-term correlations remained statistically significant after adjusting for multiple comparisons using Bonferroni correction. CONCLUSION: The seasonality of the PGA averages (one cycle every 16 years) explains a significant fraction of the variance of the time series. Geomagnetic disturbances, including the level of geomagnetic activity, sunspot numbers, and high proton flux events may influence SLE disease activity. Studies of other geographic locales are needed to validate these findings.

Intracellular homocysteine metabolites in SLE: plasma S-adenosylhomocysteine correlates with coronary plaque burden.

BACKGROUND AND AIMS: We hypothesised that intracellular homocysteine and homocysteine metabolite levels in patients with SLE are disproportionately elevated compared with the levels seen in healthy subjects and that they are independently associated with coronary plaque in SLE. METHODS: A liquid chromatography-tandem mass spectrometry absolute quantification assay was used for the determination of six analytes in both plasma and peripheral blood mononuclear cells (PBMCs): homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), methionine (Met), cystathionine (Cysta) and 5-methyltetrahydrofolate (5m-THF). We then compared intracellular (PBMC) and extracellular (plasma) Hcy and Hcy metabolite (SAM, SAH, Met, Cysta and 5m-THF) concentrations in 10 patients with SLE and in 10 age, sex and ethnicity matched controls. Subjects with a history of diabetes mellitus, cardiovascular disease, hypertension, alcohol consumption in excess of 3 units per day, anaemia, renal insufficiency (serum creatinine >1.5 mg/dL) and pregnancy were excluded. All patients with SLE had two coronary CT angiography studies as screening for occult coronary atherosclerotic disease. RESULTS: Plasma from patients with SLE had higher levels of Hcy (p<0.0001), SAH (p<0.05), SAM (p<0.001) and lower levels of Met (p<0.05) and Cysta (p<0.001) compared with controls. PBMC intracellular concentrations from patients with SLE had higher levels of Cysta (p<0.05), SAH (p<0.05), SAM (p<0.001) and lower levels of 5m-THF (p<0.001). Plasma SAH showed a positive correlation with total coronary plaque, calcified plaque and non-calcified plaque (p<0.05). CONCLUSION: Intracellular concentrations of Hcy metabolites were significantly different between patients with SLE and controls, despite similar intracellular Hcy levels. Plasma SAH was positively correlated with total coronary plaque, calcified plaque and non-calcified plaque.

Cachexia in Systemic Lupus Erythematosus: Risk Factors and Relation to Disease Activity and Damage.

OBJECTIVE: Cachexia is a disorder characterized by involuntary weight loss in addition to loss of homeostatic control of both energy and protein balance. Despite an abundance of data from other inflammatory diseases, cachexia in systemic lupus erythematosus (SLE) remains a largely undescribed syndrome. The present study was undertaken to define the prevalence of cachexia in SLE and to identify the main factors that place patients at risk of developing cachexia. METHODS: A total of 2,452 patients in a prospective SLE cohort had their weight assessed at each visit. Patients were categorized into 5 predetermined groups based on weight. Cachexia was defined based on modified Fearon criteria (5% stable weight loss in 6 months without starvation relative to the average weight in all prior visits and/or a weight loss of >2% without starvation relative to the average weight in all prior cohort visits and a body mass index [BMI] of <20 kg/m2 ). Risk of cachexia within 5 years of cohort entry was based on Kaplan-Meier estimates. The association of prior disease manifestations with risk of cachexia adjusted by current steroid use was determined using Cox regression. An analysis of variance test was used to determine whether Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores varied based on cachexia status. RESULTS: Within 5 years of cohort entry, 56% of patients developed cachexia, 18% of which never recovered their weight during follow-up. The risk factors for cachexia development were a BMI of <20 kg/m2 , current steroid use, vasculitis, lupus nephritis, serositis, hematologic lupus manifestations, positive anti-double-stranded DNA, anti-Sm, and anti-RNP. Patients with intermittent cachexia had significantly higher SDI scores compared to those with continuous cachexia or without cachexia. CONCLUSION: Cachexia is an underrecognized syndrome in patients with SLE. SLE patients with intermittent cachexia have the highest risk of future organ damage.

High-risk coronary plaque in SLE: low-attenuation non-calcified coronary plaque and positive remodelling index.

BACKGROUND: Positive remodelling index and presence of low-attenuation non-calcified plaque (LANCP) are characteristic vessel changes in unstable coronary plaques. We sought to characterise these high-risk plaque features in patients with systemic lupus erythematosus (SLE) and to compare them with controls. METHODS: A total of 72 patients who satisfied the SLICC classification criteria for SLE had coronary CT angiography (CCTA) studies, 30 of which had follow-up CCTA, as screening for occult coronary atherosclerotic disease in asymptomatic individuals. A total of 100 consecutive controls with no known history of lupus, heart disease or revascularisation who had two coronary CT angiograms at least 1 year apart were included in the study. These were asymptomatic patients referred by their primary physicians for screening of coronary artery disease and the screening interval was decided by the primary physicians. The methodology for image acquisition was identical. RESULTS: LANCP burden at baseline was significantly greater in patients with SLE compared with controls. LANCP volume was significantly greater in patients over 60 years of age (p<0.05) and in those with current prednisone dose >10 mg/day. LANCP burden remained stable over follow-up. There were no significant differences in remodelling index compared with controls. CONCLUSION: This is the first study describing high-risk CCTA features of coronary plaque in patients with SLE. Both LANCP and positive remodelling are common in SLE. These characteristic vessel changes may identify patients with SLE at increased risk of cardiovascular events and those in need for more frequent cardiac monitoring.

A Spatiotemporal Analysis of Organ-Specific Lupus Flares in Relation to Atmospheric Variables and Fine Particulate Matter Pollution.

OBJECTIVE: To identify potential clusters of systemic lupus erythematosus (SLE) organ-specific flares and their relationship to fine particulate matter pollution (PM2.5), temperature, ozone concentration, resultant wind, relative humidity, and barometric pressure in the Hopkins Lupus Cohort, using spatiotemporal cluster analysis. METHODS: A total of 1,628 patients who fulfilled the Systemic Lupus International Collaborating Clinics classification criteria for SLE and who had a home address recorded were included in the analysis. Disease activity was assessed using the Lupus Activity Index. Assessment of rash, joint involvement, serositis, and neurologic, pulmonary, renal, and hematologic activity was quantified on a 0-3 visual analog scale (VAS). An organ-specific flare was defined as an increase in VAS of ≥1 point compared to the previous visit. Spatiotemporal clusters were detected using SaTScan software. Regression models were used for cluster adjustment and included individual, county-level, and environmental variables. RESULTS: Significant clusters unadjusted for environmental variables were identified for joint flares (P < 0.05; n = 3), rash flares (P < 0.05; n = 4), hematologic flares (P < 0.05; n = 3), neurologic flares (P < 0.05; n = 2), renal flares (P < 0.001; n = 4), serositis (P < 0.001; n = 2), and pulmonary flares (P < 0.001; n = 2). The majority of the clusters identified changed in significance, temporal extent, or spatial extent after adjustment for environmental variables. CONCLUSION: We describe the first spatiotemporal clusters of lupus organ-specific flares. Seasonal, as well as multi-year, cluster patterns were identified, differing in extent and location for the various organ-specific flare types. Further studies focusing on each individual organ-specific flare are needed to better understand the driving forces behind these observed changes.

Blood Pressure Variability and Age-related Blood Pressure Patterns in Systemic Lupus Erythematosus.

OBJECTIVE: Despite the high prevalence of cardiovascular (CV) disease among patients with systemic lupus erythematosus (SLE), the relationship between age, blood pressure (BP), and BP variability (BPV) is not well understood. We studied visit-to-visit BPV, its relationship to age, clinical, and demographic characteristics, and its potential role as a CV risk factor in patients with SLE. METHODS: We analyzed systolic (SBP) and diastolic BP (DBP) measures in our cohort using mixed-effects regression models. From these models, we then obtained estimates of the mean BP, the visit-to-visit SD, and the between-person SD. The estimated means were compared to the general population using data from the National Health Statistics Reports from 2001 to 2008. In addition, we examined the relationship between BP (means, variances), patient demographic and clinical characteristics, and subsequent CV events. RESULTS: The mean SBP in SLE increased with age and was significantly higher in younger patients compared to the general population. BPV in SLE was elevated across all ages. BPV was significantly higher in African Americans, in patients with traditional CV risk factors, those with high disease activity, and in patients taking prednisone. Hydroxychloroquine was associated with significantly lower BPV. Within-person variability in DBP of ≥ 9 mmHg was highly associated with CV events in a multivariate analysis. CONCLUSION: Age-related BP patterns in SLE differ from the general population. Increased visit-to-visit BPV is affected by many disease-specific and traditional CV factors. Increased DBP variability is highly associated with CV events in SLE.

Epidemiology of systemic lupus erythematosus: an update.

PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease with a significant disease burden across the world among different ethnic, racial, and age groups. The pathophysiological understanding of SLE is constantly evolving and with it, the need for a better definition of the disease itself, for understanding the risk among the different affected populations, and for identifying the factors responsible for the damage accrual through the years. RECENT FINDINGS: More accurate estimates of incidence and prevalence of SLE among different ethnicities and minority groups not only in the USA, but also in Europe, Middle East, and Asia have provided new insights into the disease burden around the world. Despite advances in treatment, mortality among SLE patients remains high with significant ethnic and geographic variations. SUMMARY: Sex, race, and ethnicity significantly affect SLE incidence, prevalence, and mortality.

Pediatric siMS score: A new, simple and accurate continuous metabolic syndrome score for everyday use in pediatrics.

BACKGROUND: The dichotomous nature of the current definition of metabolic syndrome (MS) in youth results in loss of information. On the other hand, the calculation of continuous MS scores using standardized residuals in linear regression (Z scores) or factor scores of principal component analysis (PCA) is highly impractical for clinical use. Recently, a novel, easily calculated continuous MS score called siMS score was developed based on the IDF MS criteria for the adult population. OBJECTIVE: To develop a Pediatric siMS score (PsiMS), a modified continuous MS score for use in the obese youth, based on the original siMS score, while keeping the score as simple as possible and retaining high correlation with more complex scores. SUBJECTS AND METHODS: The database consisted of clinical data on 153 obese (BMI ≥95th percentile) children and adolescents. Continuous MS scores were calculated using Z scores and PCA, as well as the original siMS score. Four variants of PsiMS score were developed in accordance with IDF criteria for MS in youth and correlation of these scores with PCA and Z score derived MS continuous scores was assessed. RESULTS: PsiMS score calculated using formula: (2xWaist/Height) + (Glucose(mmol/l)/5.6) + (triglycerides(mmol/l)/1.7) + (Systolic BP/130)-(HDL(mmol/l)/1.02) showed the highest correlation with most of the complex continuous scores (0.792-0.901). The original siMS score also showed high correlation with continuous MS scores. CONCLUSION: PsiMS score represents a practical and accurate score for the evaluation of MS in the obese youth. The original siMS score should be used when evaluating large cohorts consisting of both adults and children.

After-Hours Versus Office-Hours Dental Injuries in Children: Does Timing Influence Outcome?

AIM: The aim of this study was to analyze the outcomes and factors associated with after-hours dental trauma. METHODS: Study sample consisted of 1762 permanent teeth injuries in children, gender and age matched with office-hours injuries. Epidemiological and clinical data were collected from 4 university dental trauma centers. RESULTS: During median follow-up time of 4.3 years, complications have occurred in 14.5% of injured teeth. Age, type, and degree of tissue injury and after-hours time of injury were significantly associated with complications. Unfavorable outcomes were 34% more likely in the after-hours group compared with office-hours. Urgent treatment was significantly delayed in after-hours group with a delay of more than 3 hours in 90.5% versus 38.9% in the office-hours group. Multivariate regression model showed that after-hours time of injury was significant predictor of complications. CONCLUSION: Delayed urgent treatment was one of the main factors associated with unfavorable outcome of after-hours injuries.

Constrictive pleuropericarditis: a dominant clinical manifestation in Whipple's disease.

BACKGROUND: Whipple's disease is a rare, multisystemic, chronic infectious disease which classically presents as a wasting illness characterized by polyarthralgia, diarrhea, fever, and lymphadenopathy. Pleuropericardial involvement is a common pathologic finding in patients with Whipple's disease, but rarely causes clinical symptoms. We report the first case of severe fibrosing pleuropericarditis necessitating pleural decortication in a patient with Whipple's disease. CASE PRESENTATION: Our patient, an elderly gentleman, had a chronic inflammatory illness dominated by constrictive pericarditis and later severe fibrosing pleuritis associated with a mildly elevated serum IgG4 level. A pericardial biopsy showed dense fibrosis without IgG4 plasmacytic infiltration. The patient received immunosuppressive therapy for possible IgG4-related disease. His poor response to this therapy prompted a re-examination of the diagnosis, including a request for the pericardial biopsy tissue to be stained for Tropheryma whipplei. CONCLUSIONS: Despite a high prevalence of pleuropericardial involvement in Whipple's disease, constrictive pleuropericarditis is rare, particularly as the dominant disease manifestation. The diagnosis of Whipple's disease is often delayed in such atypical presentations since the etiologic agent, Tropheryma whipplei, is not routinely sought in histopathology specimens of pleura or pericardium. A diagnosis of Whipple's disease should be considered in middle-aged or elderly men with polyarthralgia and constrictive pericarditis, even in the absence of gastrointestinal symptoms. Although Tropheryma whipplei PCR has limited sensitivity and specificity, especially in the analysis of peripheral blood samples, it may have diagnostic value in inflammatory disorders of uncertain etiology, including cases of polyserositis. The optimal approach to managing constrictive pericarditis in patients with Whipple's disease is uncertain, but limited clinical experience suggests that a combination of pericardiectomy and antibiotic therapy is of benefit.

Pulmonary manifestations of Sjögren's syndrome.

Sjögren's syndrome (SS) is primarily defined by its impact on the oral and ocular system resulting in xerostomia and xerophthalmia. However, SS can also manifest throughout the respiratory system. Subclinical pulmonary involvement is common. Clinically significant involvement can result in a 4-fold increased risk of death. Thus, recognizing the many potential presentations of SS in the lung is critical in caring for patients with SS. Additionally, SS should be included in the differential diagnosis of a number of forms of interstitial lung disease.

Atherosclerosis in systemic lupus erythematosus.

Accelerated atherosclerosis and its long-term sequelae are a major cause of late mortality among patients with systemic lupus erythematosus (SLE). Traditional Framingham risk factors such as hypertension, hypercholesterolemia, diabetes, and smoking do not account in entirety for this risk. SLE specific factors like disease activity and duration, use of corticosteroids, presence of antiphospholipid antibodies, and others are important risk factors. SLE is considered a coronary heart disease; equivalent and aggressive management of all traditional risk factors is recommended. Despite their role in primary and secondary prevention in the general population, statins seem to have no effect on cardiovascular outcomes in adult or pediatric SLE populations. The use of hydroxychloroquine has a cardioprotective effect, and mycophenolate mofetil may reduce cardiovascular events based on basic science data and data from the transplant population. The role of vitamin D supplementation and treatment of hyperhomocysteinemia remain controversial, but due to the safety of therapy and the potential benefit, they remain as optional therapies.

Flares of systemic lupus erythematosus during pregnancy and the puerperium: prevention, diagnosis and management.

Systemic lupus erythematosus is a systemic autoimmune disease that primarily affects women in their reproductive age years. Pregnancy in systemic lupus erythematosus now has favorable outcomes for the majority of women. However, flares of disease activity, preeclampsia, fetal loss, intrauterine growth retardation and preterm birth are established risks of such pregnancies. Active lupus nephritis at the time of conception poses the greatest risk for disease flares and poor obstetric outcomes. Patients should delay conception until their lupus has been in remission for at least 6 months. In addition, certain lupus medications are potentially teratogenic and need to be stopped before conception. The signs and symptoms of a lupus flare may mimic those of normal pregnancy, impeding its recognition during pregnancy. Hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone and azathioprine are commonly used to treat lupus flares during pregnancy.