Anti-N-methyl-D-aspartate receptor antibodies are associated with fibromyalgia in patients with systemic lupus erythematosus: a case-control study.

OBJECTIVES: The high concordance between systemic lupus erythematosus (SLE) and fibromyalgia (FM) suggests common underlying mechanisms related to pain and distress in both patient groups. Increasing evidence indicates that N-methyl-D-aspartate receptors (NMDARs) play a major role in the induction and maintenance of central sensitisation with chronic pain. In this study, we evaluated the role of anti-NMDAR antibodies in the development of FM in patients with SLE. METHODS: Sera from 104 patients with SLE, 112 patients with FM, and 110 healthy controls were analysed to detect antibodies to the N-terminus of the 2B subunit of NMDARs (GluN2B). Subjects underwent clinical examination and neuropsychiatric evaluation, and completed a questionnaire regarding FM and neuropsychiatric symptoms. RESULTS: Of the 104 patients with SLE, 18 (17.3%) had FM. The anti-GluN2B antibody titer was significantly higher in patients with SLE (p<0.001). Among patients with SLE, those with concomitant FM had higher anti-GluN2B antibody titers (p<0.05). The anti-GluN2B antibody titer was associated positively with the tender point count (p=0.016) and the widespread pain index (p=0.005), but not with other symptom measurements. Anti-GluN2B antibody-positive patients with SLE were more likely to have neuropsychiatric systemic lupus erythematosus (NPSLE) and concomitant FM (p<0.05). Multivariate analysis showed that the anti-GluN2B antibody was an independent predictor of concomitant FM and NPSLE. CONCLUSIONS: To our knowledge, this report is the first to suggest that anti-NMDAR antibodies are associated with the pathogenesis of FM with SLE.

Predictive significance of CCL21 and CXCL13 levels in the minor salivary glands of patients with Sjögren's syndrome.

OBJECTIVES: To investigate whether CCL21 and CXCL13 expression levels in the minor salivary gland are associated with the laboratory and clinical manifestations of Sjögren's syndrome (SS). METHODS: Sociodemographic data on 106 SS patients were obtained and the glandular and extraglandular manifestations of the disease were documented. In addition, minor salivary gland biopsies were performed and the patients' laboratory findings were analysed. European League Against Rheumatism SS disease activity index (ESSDAI) values of SS disease activity at the time of biopsy and the SS disease damage index (SSDDI) values were also recorded. An immunohistochemical approach was used to semiquantitatively measure the CCL21 and CXCL13 expression in the minor salivary glands. RESULTS: The minor salivary glands of SS patients stained positively for CCL21 and CXCL13 in 46.2% (49/106) and 70.7% (75/106) of all cases, respectively. Higher-level expression of CCL21 and CXCL13 was associated with increases in ESR, IgG and rheumatoid factor levels, as well as anti-SS-A and -SS-B titers. A higher focus score and ESSDAI value at the time of biopsy were also associated with these chemokines. In patients with extraglandular manifestations of SS, the prevalence of lymphadenopathy increased with increasing CCL21 levels. CONCLUSIONS: The expression levels of CCL21 and CXCL13 within the lymphocytic infiltrates of SS patients were associated with several laboratory features of the disease as well as lymphadenopathy and the extent of clinical disease activity. CCL21 and CXCL13 levels can therefore serve as useful markers to predict the disease activity and prognosis of patients with SS.

The relationships between bone mineral density and radiographic features of hand or knee osteoarthritis in older adults: data from the Dong-gu Study.

OBJECTIVE: The relationship between OA and osteoporosis has exhibited contradictory features over the past four decades. The aim of this study was to determine using separate analysis of the radiographic features of OA whether various radiographic features of OA were associated differently with BMD in the Korean elderly. METHODS: Data were derived from the Dong-gu cohort; 2354 subjects were enrolled in the present cross-sectional study. Baseline characteristics, the BMDs of the lumbar spine and femoral neck measured by DXA, and X-rays of knees and hands were collected. A semi-quantitative grading system was used to estimate the severities of individual radiographic features. We adjusted for confounders using multiple linear regression modelling to analyse the relationships. RESULTS: After adjustment for confounders, hand and knee OA total scores were negatively associated with the BMDs of the lumbar spine and femoral neck, except for the total knee OA score and lumbar spine BMD. In detail, hand osteophytes and sclerosis exhibited positive relationships with the BMDs of the lumbar spine and femoral neck, except for hand osteophytes and femoral neck BMD. On the contrary, however, knee joint space narrowing (JSN), hand JSN, and hand subchondral cysts were negatively associated with the BMD of the lumbar spine and femoral neck. Knee JSN and hand subchondral cysts exerted the greatest effects on BMD. CONCLUSION: Separate analysis of the radiographic features of OA better reveals associations of OA with the BMD of the lumbar spine and femoral neck.

Predictors of a favourable outcome in patients with fibromyalgia: results of 1-year follow-up.

OBJECTIVES: To determine the outcomes of Korean patients with fibromyalgia (FM) and to identify prognostic factors associated with improvement at 1-year follow-up. METHODS: Forty-eight patients with FM were enrolled and examined every 3 months for 1 year. At the time of enrollment, we interviewed all patients using a structured questionnaire that recorded socio-demographic data, current or past FM symptoms, and current use of relevant medications. Tender point counts and scores were assessed by thumb palpation. Patients were asked to complete the Korean versions of the Fibromyalgia Impact Questionnaire (FIQ), the Brief Fatigue Inventory, the SF-36, the Beck Depression Inventory, the State-Trait Anxiety Inventory (STAI), the Self-Efficacy Scale, and the Social Support Scale. Tender points, FIQ scores, and the use of relevant medications were recorded during one year of follow-up. RESULTS: Of the 48 patients, 32 (66.7%) had improved FIQ scores 1 year after enrollment. Improved patients had higher baseline FIQ scores (68.4±13.9 vs. 48.4±20.8, p=0.001) and STAI-II scores (55.8±10.9 vs. 11.5±11.5, p=0.022). Patients treated with pregabalin were more likely to improve after 1 year, based on the FIQ scores (71.9% vs. 37.5%, p=0.031). On multivariate logistic regression analysis, a higher STAI-II score at the time of enrollment and pregabalin treatment during one year of follow-up were the predictors of improvement. CONCLUSIONS: Two-thirds of our Korean FM patients experienced some clinical improvement by 1-year follow-up. A high baseline STAI-II score and treatment with pregabalin were the important predictor of improved FM.

Associations between body composition measurements of obesity and radiographic osteoarthritis in older adults: Data from the Dong-gu Study.

BACKGROUND: We examined the effects of fat deposition on radiographic osteoarthritis (OA) to determine the role of obesity in the pathogenesis of radiographic OA. METHODS: Data were taken from the Dong-gu cohort, a cross-sectional study of 2,367 subjects. Baseline characteristics, waist circumference (WC), waist-to-hip ratio (WHR), fat mass, and fat percentage were collected, along with X-rays of the knees and hands. Total knee and hand radiographic OA scores were summed using a semi-quantitative grading system, and then stratified by gender using a multiple linear regression model. RESULTS: After adjusting for confounders, weight was the only factor significantly associated with knee radiographic OA, regardless of gender (all p < 0.01). Regarding the hand, fat percentage had the largest effect on radiographic OA in males (p = 0.008), while WHR was the most significant factor in females (p = 0.001). For the knee, fat mass was the most important factor for radiographic OA in males (p = 0.001), while in females, body mass index was the most important factor (p < 0.001). Among the variables, only fat percentage was significantly related to both hand and knee radiographic OA in both genders (all p < 0.01). CONCLUSIONS: Regardless of gender, weight was significantly associated with knee radiographic OA. Otherwise, fat deposition correlated with hand and knee radiographic OA in both genders, while the distribution of fat tissue was significantly associated with hand and knee radiographic OA only in females.

The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjögren's Syndrome.

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjögren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.

Risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis.

OBJECTIVE: No available anti-osteoporotic medication has been shown to completely prevent declines in bone mineral density (BMD) and the resulting increased risk of fracture. The objective of this study was to investigate the risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis (RA). METHODS: A retrospective cohort study of 103 patients with RA and osteoporosis was conducted. Patients were divided into two groups for comparison: those whose osteoporosis treatment was effective and those whose treatment failed. Risk factors for treatment failure were identified by univariate and multivariate logistic regression using variables that differed significantly between the groups. RESULTS: Osteoporosis treatment failed in 66 of 103 patients (64.1%). During 14.01 months of follow-up, non-adherence to bisphosphonate use was the most powerful risk factor for treatment failure. Daily glucocorticoid dosage ≥ 7.5 mg/day before the first BMD measurement, immobilization > 3 months, and Disease Activity Score in 28 joints (DAS28) ≥ 3.2 were also significantly related to treatment failure. CONCLUSION: Our findings indicate that osteoporosis treatment fails frequently in RA patients and adherence to bisphosphonate use, daily glucocorticoid dosage, immobilization, and DAS28 score should be taken into consideration when treating osteoporotic patients with RA.

Protective role of anti-ribosomal P antibody in patients with lupus nephritis.

AIM: The aim of this study was to define clinical, histopathologic, and prognostic differences according to the presence of anti-ribosomal P antibody (anti-P) in Korean patients with biopsy-proven lupus nephritis (LN). METHODS: We studied 79 patients who underwent kidney biopsies prior to the start of induction treatment, and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than 6 months. Anti-P was measured by immunoblot analysis at the time of renal biopsy. RESULTS: Of all patients, 35.4% were anti-P-positive. Such patients exhibited earlier LN onset, a higher Systemic Lupus Erythematosus Disease Activity Index 2000 score, and a higher estimated glomerular filtration rate at the time of renal biopsy, than did those without antibodies. Upon renal histopathological analysis, patients with anti-P exhibited less interstitial inflammation in terms of the activity index, less glomerular sclerosis, less tubular atrophy, and less interstitial fibrosis in terms of the chronicity index. Furthermore, anti-P was associated with lower chronicity scores. At a median follow-up time of 47 months, renal function was preserved in 27 of 28 patients who had anti-P, but only 38 of 51 patients without such antibodies did not progress to chronic renal disease. After multivariate logistic regression, we found that anti-P positivity was associated with a reduced rate of progression to chronic kidney disease after adjusting for gender, baseline creatinine, activity and chronicity score, and treatment response (odds ratio = 0.196, 95% CI: 0.039-0.989, P = 0.048). CONCLUSION: Anti-P was associated with better histological findings, and anti-P-positive patients had better renal outcomes than those without anti-P.

Comparison of heart rate variability and classic autonomic testing for detection of cardiac autonomic dysfunction in patients with fibromyalgia.

AIM: Cardiac autonomic dysfunction (CAD) is frequently found in patients with fibromyalgia (FM). Thus, we evaluated whether heart rate variability (HRV) is superior to the Ewing tests in detecting CAD in FM patients. METHODS: We studied 35 females with FM and 25 age-matched healthy females. In Ewing tests, results were added to yield an overall score. An abnormal result on deep breathing, the Valsalva maneuver, or orthostatic standing was counted as 1 point. A change in systolic blood pressure (SBP) of > 10 mmHg while standing counted as 1 point, and a change of > 20 mmHg as 2 points. A score of 0 was regarded as no CAD, a score of ≥ 2 as severe CAD and a score of 1 as mild CAD. HRV was measured in two ways: by R-R intervals (time-domain analysis) and by spectral analysis of a series of successive R-R intervals (frequency-domain analysis). RESULTS: FM patients had significantly lower expiratory/inspiratory (E/I) ratios, lower Valsalva ratios and higher SBP values than healthy controls (P < 0.05, P < 0.05, P < 0.01, respectively). In the frequency domain, very low-frequency and low-frequency bands were also lower in FM patients than controls (both P < 0.05). Based on the discriminant analysis of the Ewing tests, 54.4% of cases were correctly classified. The addition of HRV parameters did not improve the reclassification. CONCLUSION: HRV does not improve detection of CAD in FM patients over classic autonomic testing.

The value of high-sensitivity C-reactive protein in hand and knee radiographic osteoarthritis: data from the Dong-gu Study.

Due to the inconsistent association between high-sensitivity C-reactive protein (hs-CRP) and osteoarthritis (OA), we evaluated the relationship between hs-CRP and various radiographic findings in older adults with OA. This cross-sectional study recruited 2376 participants from the population-based Dong-gu cohort. The scores of radiographic features in OA on X-rays of the knees and hands were computed using a semi-quantitative grading system. The hs-CRP levels were measured using a particle-enhanced immunonephelometry assay. Correlations showing the relationship between hs-CRP and OA were calculated using multiple linear correlation analysis. The hs-CRP levels were significantly higher in older subjects (p < 0.001), those with a higher body mass index (BMI) (p < 0.001), current smokers (p < 0.001), current alcohol drinkers (p = 0.011), those who were less physically active (p = 0.002), and those with a lower level of education (p = 0.043). After adjusting for BMI and other confounders, the total OA scores (knee, p = 0.022; hand, p = 0.029) and sclerosis score (knee, p = 0.007; hand, p = 0.030) in the knees and hands were all significantly positively correlated with hs-CRP. A significant association was also observed between hs-CRP and hand erosion score (p = 0.045), hand malalignment score (p = 0.015), and tibial attrition score (p = 0.039). In this large cross-sectional study, a higher hs-CRP level was significantly associated with radiographic OA severity. Of the various types of radiographic damage, all of sclerosis, erosion, and malalignment were significantly associated with hs-CRP levels.

Association between grip strength and hand and knee radiographic osteoarthritis in Korean adults: Data from the Dong-gu study.

OBJECTIVES: We assessed whether grip strength was related to various types of radiographic damage in Korean adults with osteoarthritis (OA). METHODS: Data from 2,251 subjects enrolled in the Dong-gu study, who had no hand joint pain, were analyzed to investigate the relationship between grip strength and OA. Hand grip strength was measured using a hand-held dynamometer, and radiographs of the hand and knee were scored according to a semi-quantitative grading system. Multiple linear regressions were used to explore associations between grip strength and radiographic features of OA. RESULTS: Grip strength in men and women was negatively related to hand (both p < 0.001) and knee (men, p < 0.001; women, p = 0.010) OA after adjusting for confounders. Hand (men, p < 0.001; women, p = 0.001) and knee (both p < 0.001) joint space narrowing (JSN) showed the strongest associations with low grip strength, regardless of gender. Moreover, the severity of hand osteophytes in women (p = 0.001), and subchondral cysts (men, p < 0.001) was correlated with low grip strength in both genders. CONCLUSIONS: Among subjects without hand joint pain, low grip strength was associated significantly with hand and knee radiographic OA, regardless of gender. Among all types of OA radiographic damage, low grip strength showed the strongest association with JSN.

Exploring Genetic Susceptibility to Fibromyalgia.

Fibromyalgia (FM) affects 1% to 5% of the population, and approximately 90% of the affected individuals are women. FM patients experience impaired quality of life and the disorder places a considerable economic burden on the medical care system. With the recognition of FM as a major health problem, many recent studies have evaluated the pathophysiology of FM. Although the etiology of FM remains unknown, it is thought to involve some combination of genetic susceptibility and environmental exposure that triggers further alterations in gene expression. Because FM shows marked familial aggregation, most previous research has focused on genetic predisposition to FM and has revealed associations between genetic factors and the development of FM, including specific gene polymorphisms involved in the serotonergic, dopaminergic, and catecholaminergic pathways. The aim of this review was to discuss the current evidence regarding genetic factors that may play a role in the development and symptom severity of FM.

Predictors of Switching Anti-Tumor Necrosis Factor Therapy in Patients with Ankylosing Spondylitis.

The aim of this study was to investigate the potential predictors of switching tumor necrosis factor (TNF)-α inhibitors in Korean patients with ankylosing spondylitis (AS). The patients who had been treated with TNF-α inhibitors were divided into two groups depending on whether they had switched TNF-α inhibitors. Demographic, clinical, laboratory, and treatment data at the time of initiation of TNF-α inhibitor treatment were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Of the 269 patients, 70 (23%) had switched TNF-α inhibitors once; of these, 11 switched again. The median follow-up time was 52.7 months. Three- and five-year drug survival rates were 52%/48% for infliximab, 62%/42% for etanercept, and 71%/51% for adalimumab, respectively. Switchers were more likely to be prescribed disease-modifying anti-rheumatic drugs than non-switchers. A history of joint surgery and complete ankylosis of the sacroiliac joint was more frequent in switchers. Multivariate Cox's proportional hazard analysis showed that the use of adalimumab as the first TNF-α inhibitor was less likely to lead to switching and complete ankylosis of the sacroiliac joints was more likely to lead to switching. The principal reasons for switching were drug inefficacy and adverse events, but the differences in the clinical data of these two groups of switchers were not significant. In AS patients who are candidates for TNF-α inhibitor therapy, switching may improve the therapeutic outcome based on clinical information.

Successful treatment of a ruptured subclavian artery aneurysm presenting as hemoptysis with a covered stent.

An aneurysm of the subclavian artery is rare. Recently, we experienced a case of a ruptured subclavian artery aneurysm presenting as hemoptysis. The patient had experienced atypical chest discomfort, and computed tomography (CT) revealed a small aneurysm of the left subclavian artery (SCA). Hemoptysis occurred 2 weeks later. Follow-up CT showed a ruptured aneurysm at the proximal left SCA. Endovascular treatment with a graft stent was performed by bilateral arterial access with a 12-Fr introducer sheath placed via cutdown of the left axillary artery and an 8-Fr sheath in the right femoral artery. A self-expandable Viabahn covered stent measuring 13×5 mm was introduced retrogradely via the left axillary sheath and was positioned under contrast guidance with an 8-Fr JR4 guide through the femoral sheath. After the procedure, hemoptysis was not found, and the 3-month follow-up CT showed luminal patency of the left proximal SCA and considerable reduction of the hematoma.

Effects of Low Dose versus High Dose Statin Therapy on the Changes of Endothelial Function and Carotid Intima-Media Thickness in Patients with Variant Angina.

BACKGROUND: To compare the effects of low dose and high dose of statin treatment on endothelial function and carotid intima-media thickness (IMT) in patients with variant angina (VAP). METHODS: A total of 70 patients with VAP were divided into two groups; atorvastatin 10 mg treatment group (group I: n = 35, 54.2 ± 12.5 years) versus atorvastatin 40 mg treatment group (group II: n = 35, 52.6 ± 9.8 years). Flow mediated vasodilation (FMD) of the brachial artery and IMT of the carotid artery were compared between the groups after 6 months of statin treatment. RESULTS: The baseline FMD and carotid IMT were not different between the groups. After 6 months of statin therapy, FMD was significantly improved in both groups (7.7 ± 2.5% to 8.9 ± 2.2% in group I, p = 0.001, 7.9 ± 2.7% to 9.5 ± 2.8% in group II, p < 0.001), but the degree of FMD change and FMD at 6 month were not different between the groups. Carotid IMT were not changed in both groups after 6 months of statin therapy. CONCLUSION: The use of statin for 6 months significantly improved endothelial function in patients with VAP, but carotid IMT was not changed. The use of high dose statin did not show significant additional benefit as compared with the use of low dose statin. The present study suggested that statin therapy would be beneficial in the treatment of VAP.

Differences of aortic stiffness and aortic intima-media thickness according to the type of initial presentation in patients with ischemic stroke.

BACKGROUND: Aortic stiffness and intima-media thickness (IMT) are known to be associated with ischemic stroke. The aim of the present study was to investigate the differences of aortic stiffness and IMT between cerebral infarction (CI) and transient ischemic attack (TIA). METHODS: A total of 500 patients with acute stroke were divided into 2 groups: the TIA group (n = 230, 62.4 ± 12 years, 144 males) versus CI group (n = 270, 63.4 ± 11 years, 181 males). Aortic stiffness index and IMT, as well as conventional cardiovascular risk factors, were compared. RESULTS: The prevalence of hypertension, diabetes, and dyslipidemia were significantly higher, and left atrial volume and E/E' were significantly elevated in the CI group than in the TIA group. Carotid IMT was significantly thicker in the CI group than in the TIA group. Aortic stiffness index ß was significantly higher (7.99 ± 2.70 vs. 7.02 ± 4.30, p = 0.043) and aortic IMT was significantly thicker (1.53 ± 0.41 vs. 1.45 ± 0.39 mm, p = 0.040) in the CI group than in the TIA group. Aortic stiffness index ß was significantly correlated with the IMT of the aorta (r = 0.279, p = 0.014), right (r = 412, p < 0.001) and left carotid artery (r = 441, p < 0.001). CONCLUSION: Aortic stiffness index ß and IMT were significantly higher in patients with CI than TIA. The result of the present study suggested that CI is associated with more advanced degree of atherosclerotic and arteriosclerotic process than TIA.