Chang-Nam Son

Sleep quality in rheumatoid arthritis, and its association with disease activity in a Korean population

Background/Aims The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. Methods A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 ≤ 3.2, 3.2 < DAS28 < 5.1, and DAS28 ≥ 5.1, respectively). Results The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 ± 4.19, 38.5%) than in the control subjects (3.57 ± 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI ≤ 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. Conclusions Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.

Follow-up testing of interferon-gamma release assays are useful in ankylosing spondylitis patients receiving anti-tumor necrosis factor alpha for latent tuberculosis infection.

We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFα). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFα and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFα, including type and treatment duration. The median duration of anti-TNFα was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFα in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFα. Graphical Abstract

Monckeberg’s sclerosis in a patient with systemic sclerosis

Monckeberg’s sclerosis (MS) is one of the non-inflammatory vascular diseases characterized by calcification of the media of small and medium-sized muscular arteries, but is distinct from atherosclerosis. We present a case of MS that was incidentally detected by plain X-ray in a patient with systemic sclerosis. We took CT angiographs of the patient’s lower extremities for the differential diagnosis of vascular calcification, which was confirmed. To determine if systemic sclerosis is a risk factor for MS, we reviewed plain X-rays from 43 well-documented systemic sclerosis patients, but we did not detect any cases of MS. We therefore conclude that systemic sclerosis may not be a risk factor for MS.

Pain, xerostomia, and younger age are major determinants of fatigue in Korean patients with primary Sjögren’s syndrome: a cohort study

Objectives: Fatigue is a common clinical manifestation in patients with primary Sjögren’s syndrome (pSS). The aims of this study were to investigate the association between fatigue severity and other clinical characteristics in pSS patients and to determine the factors contributing to fatigue. Method: We analysed 257 participants from the Korean Initiative of pSS (KISS), a prospective pSS cohort. Fatigue was assessed according to the fatigue domain of the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient-Reported Index (ESSPRI). Health-related quality of life (HRQoL) was evaluated using the EuroQol-5 dimensions (EQ-5D) questionnaire. Multiple linear regression analysis was used to estimate the effect of each variable on fatigue severity. Results: The median total ESSPRI score was 5 [interquartile range (IQR) 4–6]. Thirty-four per cent of patients reported a fatigue score > 5. Younger and premenopausal patients presented with more fatigue (p = 0.013 and p < 0.001, respectively). Higher Xerostomia Inventory (XI) scale (p < 0.001) and Ocular Surface Dryness Index (OSDI) (p < 0.001) scores were observed in patients with a fatigue score > 5. Pain, xerostomia, and age were determined to be significantly associated with fatigue severity after adjusting for depression/anxiety, OSDI score, and the presence of fibromyalgia using a multivariate general linear model. The ESSPRI fatigue score was correlated with the EQ-5D by time trade-off (TTO) values and visual analogue scale (VAS) scores. Conclusions: In Korean patients with pSS, younger age, xerostomia, and pain were correlated significantly with fatigue, and fatigue was associated with HRQoL.

Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway.

Background/Aims: Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. Methods: Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. Results: GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. Conclusions: Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.

Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research.

Backgrounds Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors. Methods Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually. Findings Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8–66.7] months). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis.

Caspase-1 Level in Synovial Fluid Is High in Patients with Spondyloarthropathy but Not in Patients with Gout

Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis. The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to elucidate the clinical significance of caspase-1 levels in synovial fluid. Caspase-1, IL-1β, IL-18, and uric acid were measured in synovial fluid from 112 patients with gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondyloarthropathy was 35.9 ± 86.7, 49.7 ± 107.7, 2.1 ± 7.0, and 152.6 ± 155.7 pg/mL, respectively. The mean level and the frequency of high levels (≥125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than those in the other arthritides including gout. Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis, the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.

The relationship between anti-C-reactive protein and disease activity in patients with systemic lupus erythematosus

Background/Aims Anti-C-reactive protein (CRP) antibody has been introduced as a potential biologic marker in Systemic lupus erythematosus (SLE). The aim of study is to evaluate the level of anti-CRP antibody in patients with SLE. Methods This study investigated the relationship between levels of anti-CRP antibodies and disease activity markers, such as complement, anti-double-stranded DNA antibody, and SLE disease activity index in 34 patients with SLE. Results The serum anti-CRP antibody levels of the patients with SLE were significantly higher than those of the healthy controls (11.3 ± 5.6 µg/mL vs. 9.1 ± 2.8 µg/mL). The percentages of the positive anti-CRP antibody were 52.9% in SLE and 27.8% in controls. Disease duration of SLE showed significant correlation with the anti-CRP antibody (r = 0.234, p = 0.026). However no significant relationship was observed between the levels of anti-CRP antibodies and disease activity markers. Conclusions These data show that the anti-CRP antibody levels of the patients with SLE were significantly higher than those of healthy controls. We observed that the presence of the anti-CRP anti-CRP antibody was not associated with disease activity of SLE.

A neurometabolite study of chronic daily headache in patients with systemic lupus erythematosus using magnetic resonance spectroscopy: comparison with fibromyalgia patients and healthy controls

Background/Aims Neuropsychiatric systemic lupus erythematosus (SLE) includes a broad spectrum of neurologic and psychiatric manifestations. One of the most commonly observed neuropsychiatric symptoms is headache. However, the lack of specific clinical distinctions for headache in SLE has made it difficult to elucidate its pathophysiology. The aim of this study is to evaluate the neurometabolic changes using Proton Magnetic Resonance Spectroscopy (1H-MRS) in patients with SLE who suffer from chronic daily headache (CDH). Methods SLE and fibromyalgia patients with CDH and healthy controls were recruited (n = 9, n = 5, and n = 6, respectively). 1H-MRS metabolite ratios were evaluated in bilateral basal ganglia (BG) and bilateral peritrigonal white matter (PWM). Results 1H-MRS showed a significantly decreased N-acetylaspartate (NAA)/creatine (Cr) ratio in right BG in SLE patients with CDH compared to fibromyalgia patients with CDH and normal controls (p = 0.029 and p = 0.020, respectively). Left PWM NAA/Cr and choline/Cr ratios in SLE patients with CDH were lower than those in fibromyalgia patients with CDH (p = 0.019 and p = 0.029, respectively). Conclusions This study suggests the possibility that CDH in patients with SLE might be associated with neuronal dysfunction and neurometabolic changes.

Infliximab partially alleviates the bite force reduction in a mouse model of temporomandibular joint pain.

Temporomandibular joint (TMJ) disorder is clinically important because of its prevalence, chronicity, and therapy-refractoriness of the pain. In this study, we investigated the effect of infliximab in a mouse model of TMJ pain using a specially-engineered transducer for evaluating the changes in bite force (BF). The mice were randomly divided into three groups (7 mice per group): the control group, the complete Freunds adjuvant (CFA) group, and the infliximab group. BF was measured at day 0 (baseline BF). After measuring the baseline BF, CFA or incomplete Freunds adjuvant was injected into both TMJs and then the changes in BF were measured at days 1, 3, 5, 7, 9, and 13 after the TMJ injection. For measuring the BF, we used a custom-built BF transducer. Control, CFA, and infliximab groups showed similar baseline BF at day 0. From day 1, a significant reduction in BF was observed in the CFA group, and this reduction in BF was statistically significant compared to that in the control group (P < 0.05). This reduction in BF was maintained until day 7, and BF started to recover gradually from day 9. In the infliximab group also, the reduction in BF was observed on day 1, and this reduction was maintained until day 7. However, the degree of reduction in BF was less remarkable compared to that in the CFA group. The reduction in BF caused by injection of CFA into the TMJ could be partially alleviated by the injection of anti-tumor necrosis factor alpha, infliximab. Graphical Abstract