Platelet-to-lymphocyte ratios as a haematological marker of synovitis in rheumatoid arthritis with normal acute phase reactant level.

BACKGROUND: Although normal acute phase reactants (APRs) play an important role in assessing disease activity of rheumatoid arthritis (RA), some studies pointed out the discordance between disease activity and APR level. Neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs) and lymphocyte-to-monocyte ratios (LMRs) have been reported to be sensitive measures of inflammatory reaction. This study aims to explore the value of these haematological makers in assessment of APR-negative RA patients. METHODS: Out of a cohort of 418 consecutive patients with RA, we enrolled 135 patients with normal APR for this study. We performed ultrasound assessments to evaluate synovitis and bone erosion in the affected joints. Synovitis was evaluated by ultrasound grey scale (GS) and power Doppler (PD) with semi-quantitative scoring (0-3). Demographic, clinical and laboratory data were collected from the patients. Disease Activity Score-28 joints (DAS28), NLR, MLR and PLR were calculated. RESULTS: In RA patients with normal APR, PLR exhibited a positive correlation with ultrasound-detected synovitis and bone erosion, whereas NLR, MLR showed no significant correlation with ultrasonography parameters. The area under the ROC curve (AUC) for identifying synovitis with a GS grade ≥2 based on a PLR cutoff value of ≥159.6 was 0.7868 (sensitivity: 80.95%, specificity: 74.24%). For synovitis with a PD grade ≥2, the AUC was 0.7690, using a PLR cutoff value of ≥166.1 (sensitivity: 68.0%, specificity: 83.87%). CONCLUSIONS: Our findings suggested that PLR might be a reliable and cost-effective marker for identifying moderate-to-severe synovitis in RA patients with normal APR.

Tofacitinib effectiveness in Blau syndrome: a case series of Chinese paediatric patients.

OBJECTIVE: Blau syndrome (BS), a rare, autosomal-dominant autoinflammatory syndrome, is characterized by a clinical triad of granulomatous recurrent uveitis, dermatitis, and symmetric arthritis and associated with mutations of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Aim of this study was to assess the efficacy of tofacitinib in Chinese paediatric patients with BS. METHODS: Tofacitinib was regularly administered to three BS patients (Patient 1, Patient 2, and Patient 3) at different dosages: 1.7 mg/day (0.11 mg/kg), 2.5 mg/day (0.12 mg/kg), and 2.5 mg/day (0.33 mg/kg). The clinical manifestations of the patients, magnetic resonance imaging results, serological diagnoses, therapeutic measures and outcomes of treatments are described in this report. RESULTS: The clinical characteristics and serological diagnoses of all BS patients were greatly improved after the administration of tofacitinib treatment. All patients reached clinical remission of polyarthritis and improvements in the erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and inflammatory cytokines. CONCLUSION: Tofacitinib, a Janus kinase (JAK) inhibitor, is a promising agent for BS patients who have unsatisfactory responses to corticosteroids, traditional disease-modifying antirheumatic drugs, and biological agents.

Association between Markers of Synovial Inflammation, Matrix Turnover and Symptoms in Knee Osteoarthritis: A Cross-Sectional Study.

To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Data on serum biomarkers, type III collagen degradation (C3M), metabolite of C-reactive protein (CRPM) and cartilage oligomeric matrix protein (COMP), were available at baseline whilst contrast-enhanced (CE) MRI data were acquired in a subsample at baseline and annually. Knee symptoms were assessed using WOMAC at all visits. We examined the cross-sectional association between knee symptoms and three MRI-based and three serum markers of synovitis and matrix turnover, respectively. A total of 447 participants were included in the serum and 136 participants in the MRI analyses. MRI-defined medial perimeniscal synovitis was positively associated with knee pain and, suprapatellar and medial perimeniscal synovitis with knee function in multivariate analysis. We observed a statistically significant, negative association between a higher concentration of serum C3M and CRPM and knee pain, respectively. Furthermore, the highest CRPM quartile was negatively associated with knee function. Our findings suggest that, in established painful radiographic KOA, MRI-defined medial perimeniscal and suprapatellar synovitis were positively associated with knee symptoms. Serum-based C3M and CRPM markers were negatively associated with knee symptoms. Pain fluctuations are common in KOA and a better understanding of the relationship between markers of synovitis and matrix turnover and knee symptoms would facilitate a more accurate assessment of temporal changes in disease progression.

A single intra-articular dose of vitamin D analog calcipotriol alleviates synovitis without adverse effects in rats.

1,25-dihydroxyvitamin-D3 and its derivatives have shown anti-arthritic and chondroprotective effects in experimental animal models with prophylactic dosing. The purpose of this preliminary study was to test the efficacy and safety of calcipotriol, vitamin D analog, as a treatment for a fully-developed knee arthritis in Zymosan-induced arthritis (ZIA) model. Forty 5-month-old male Sprague-Dawley rats were randomized into three arthritis groups and a non-arthritic control group with no injections (10 rats/group). A day after Zymosan (0.1 mg) had been administrated into the right knee joints, the same knees were injected with calcipotriol (0.1 mg/kg), dexamethasone (0.1 mg/kg) or vehicle in a 100 µl volume. The left control knees were injected with saline (PBS) on two consecutive days. All injections, blood sampling and measurements were performed under general anesthesia on days 0, 1, 3 and 8. Internal organs and knees were harvested on day 8 and the histology of the whole knees was assessed blinded. Joints treated with calcipotriol showed a milder histological synovitis than those treated with vehicle (p = 0.041), but there was no statistically significant difference between the dexamethasone and vehicle groups. The clinical severity of arthritis did not differ between the arthritis groups measured by body temperature, swelling of the knee, thermal imaging, clinical scoring or cytokine levels on days 1, 3 and 8. Weight loss was bigger in rats treated with dexamethasone, propably due to loss of appetite,compared to other arthritis groups on days 2-3 (p<0.05). Study drugs did not influence serum calcium ion and glucose levels. Taken together, this preliminary study shows that a single intra-articular injection of calcipotriol reduces histological grade of synovitis a week after the local injection, but dexamethasone did not differ from the vehicle. Calcipotriol may have an early disease-modifying effect in the rat ZIA model without obvious side effects.

Auto-antibodies to post-translationally modified proteins in osteoarthritis.

OBJECTIVE: Autoantibodies (AutoAbs) have been observed in osteoarthritis (OA) with broad antigenicity, although their prevalence and role remain unclear. Post-translational modification (PTMs) of proteins (oxidation, carbamylation, citrullination) is associated with synovitis and can lead to AutoAb development. Given the prevalence of synovitis, we explored whether AutoAbs to PTM-antigens are common in OA compared with rheumatoid arthritis (RA). METHODS: Serum (n = 895) was obtained from healthy controls, OA and RA patients; and arthritic synovial fluid (SF, n = 290). ELISAs were used to quantify anti-citrullinated peptide (ACPA), anti-carbamylated protein (anti-CarP), anti-oxidized collagen (anti-ROS-CI/CII) antibodies. RESULTS: In sera, positivity for PTM-antigens AutoAbs was observed at a lower frequency in OA with 64.1% (95%CI: 57.2-70.1%) more ACPA+ and 29.8% (21.0-37.3%) more anti-CarP + patients in RA (both P < 0.0001). Levels of ACPA, anti-CarP were also lower in OA (P < 0.0001). Anti-ROS-CII positivity was lower in OA compared to RA (16.6%, 4.8-28.6%) less frequent, P = 0.033) but not anti-native-CII. There was no impact of age/gender on AutoAbs associations with diseases either looking at positivity or levels. In SF, OA patients were often ACPA+ (45.9%) although less frequently than in RA (P = 0.004). Anti-CarP were rarely observed (<5% all samples). All collagen AutoAbs were more frequent in RA compared to OA (all P < 0.010) but only levels of anti-CII and anti-ROS-CII were significantly higher in they RA (P < 0.050). CONCLUSION: Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation.

Modulation of αVß6 integrin in osteoarthritis-related synovitis and the interaction with VTN(381-397 a.a.) competing for TGF-ß1 activation.

Osteoarthritis is characterized by structural alteration of joints. Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381-397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-ß1 activation were investigated. A competition study determined the interaction of VTN(381-397 a.a.) with αVß6 integrin. Subsequently, the presence of αVß6 integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, ß6 was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, ß6 expression was increased under TGF-ß1 stimulation; hence, a TGF-ß bioassay was applied. We observed that αVß6 could mediate TGF-ß1 bioavailability and that VTN(381-397 a.a.) could prevent TGF-ß1 activation by interacting with αVß6 in human FLSs and increased α-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC/Chip MS-MS, confirming the increased expression of VTN(381-397 a.a.) in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN(381-397 a.a.) in osteoarthritis but also in other rheumatic diseases. This fragment interacts with αVß6 integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-ß1 precursor in human FLSs.

Comparison of Role of Hand and Wrist Ultrasound in Diagnosis of Subclinical Synovitis in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Retrospective, Single-Center Study.

BACKGROUND This retrospective study aimed to compare the roles of hand and wrist ultrasound in diagnosing subclinical synovitis in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) at a single center in Sichuan, China. MATERIAL AND METHODS Forty-one patients with SLE and 20 patients with RA were included. SLE was diagnosed using the American rheumatology Society (ACR) classification standard. Severity of SLE was evaluated using the SLE disease activity index (SLEDAI). General and clinical manifestations and laboratory indicators were measured. Spearman correlation analysis was used for analyzing correlations between musculoskeletal ultrasound results and indexes. RESULTS Among 41 patients with SLE, 26 (63.4%) had joint pain, and 39 (95.1%) had at least 1 joint abnormality. Thirteen patients with SLE (31.7%) had wrist joint involvement, 7 (17.1%) had metacarpal phalangeal-1 (MCP1) involvement, 8 (19.5%) had MCP2 involvement, 17 (41.5%) had MCP3 involvement, 14 (34.1%) had MCP4 involvement, and 5 (12.2%) had MCP5 involvement. Meanwhile, 2 (4.8%) had proximal interphalangeal-1 (PIP1) involvement, 10 (24.4%) had PIP2 involvement, 17 (41.5%) had PIP3 involvement, 12 (29.3%) had PIP4 involvement, and 3 (7.3%) had PIP4 involvement. Twelve patients demonstrated knee joint involvement. MCP joints had the highest involvement frequency (P=0.003). The most frequently detected disease was synovitis, followed by tenosynovitis, joint effusion, and bone erosion. ESR (P=0.002), CRP (P=0.020), and SLEDAI (P=0.011) of patients with SLE with arthralgia were significantly higher compared to patients without arthralgia. In patients with RA, musculoskeletal ultrasound scores were correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28), and interleukin-6 (IL-6). In patients with SLE, musculoskeletal ultrasound scores were correlated with double-stranded DNA (dsDNA), ribonucleoprotein (RNP), DAS28, and IL-6. CONCLUSIONS Musculoskeletal ultrasound is highly sensitive in evaluating subclinical synovitis in patients with SLE, and its score is positively correlated with dsDNA, RNP IL-6, and DAS28 in patients with SLE.

Detection of synovitis in early knee osteoarthritis by MRI and serum biomarkers in Japanese general population.

To investigate synovitis' influence on early knee osteoarthritis (EKOA) by serum biomarkers and magnetic resonance imaging (MRI) findings in Japanese women. We enrolled 255 women aged 30-70 without radiographic abnormalities (Kellgren-Lawrence grade ≥ 2). Knee injury, OA outcome scores (KOOS), clinical examinations, and standing radiograph were used for classification criteria of EKOA. Participants were classified into normal knee group and EKOA group. All participants underwent MRIs of their right knee. The amount of effusion-synovitis volume was quantified. We compared serum matrix metalloproteinases-3 levels (MMP-3), high-sensitivity C-reactive protein, interleukin-6, and adiponectin between the groups. The relationship between synovitis and EOKA was investigated using multiple linear regression. Fifty-four participants (21%) were classified as EKOA. Serum MMP-3 concentration and effusion-synovitis volume were higher in patients with EKOA (p = 0.025 and p = 0.001, respectively). Effusion-synovitis volume negatively correlated with all KOOS subscales and positively correlated with serum MMP-3 concentration. Serum MMP-3 concentration was associated with effusion-synovitis volume ß = 0.60, p < 0.001). There was mildly active but definitive synovitis in EKOA. This was an observational study so that no conclusions can be drawn regarding cause-effect for synovitis and symptoms. Future studies should conduct follow-up of participants with synovitis to assess the progression of knee OA.

Alterations of peripheral gene expression in response to lipopolysaccharide-induced synovitis as a model for inflammation in horses.

While the use of lipopolysaccharide (LPS) to induce inflammation has been well described in the horse, the object of this study was to evaluate the effect of repeated intra-articular LPS injections and determine whether this method may be of use to assess changes in gene expression related to inflammation. Six mixed breed horses were utilized for this study, with three horses aged 10-17 years (older group) and three horses aged 3 years (younger group). One milliliter of phosphate-buffered saline containing 3 µg of LPS from Escherichia coli O111:B4 was aseptically injected into either the radiocarpal or front fetlock joint a total of four times, with at least two weeks between each injection and a different joint injected each time. Serum for protein concentration quantification and whole blood for expression analysis of 20 different genes were collected before each injection, as well as at multiple times post-injection. Statistical analysis was performed using analysis of variance (one-way and two-way) (P < 0.05). All horses experienced minimal or non-weight bearing lameness at 4-6 hours post-LPS injection, which generally improved by 24 h and resolved by 48 h. Multiple genes exhibited significantly differential expression when compared to both the pre-injection and sham injection time points, including CD14, TLR4, MMP1, MMP9, IL-1ß, IL1RN, IL-10, ALOX5AP, IL-8, TNFα, CCL8, IGF1, and PTGS2. Additionally, multiple genes exhibited increased expression in horses where the radiocarpal joint was injected when compared to the fetlock joint, as well as in younger horses compared to older horses. Serum concentrations of serum amyloid A (SAA) were negative prior to injection while all horses demonstrated an increase by 9 h post-injection, which often remained until at least 144 h. Attempts to measure in vivo serum cytokine levels using a multiplex assay were not successful and believed to be due to the lower limits of detection for the assays. The measurement of mRNA expression of pro- and anti-inflammatory genes provide sensitive and rapid information regarding the inflammatory response to an acute, localized stimulus, although care must be taken when selecting target joints or age groups of horses as the transcriptional response may vary based on these choices.

The burden of subclinical intra-articular inflammation in gout.

OBJECTIVE: To assess the burden of subclinical intra-articular inflammation using ultrasound in people with gout. METHODS: A pilot, prospective longitudinal cohort of 28 participants with gout were examined twice, once during a gout flare (n = 25) and then during an inter-critical phase (n = 27). At each visit, a 52 joint count was done followed by ultrasound examination for detection of intra-articular power Doppler (PD) signal. Clinically active joints were defined as tender and swollen. Data was collected on patient reported gout pain - visual analog scale (VAS) (painVAS), physician global VAS (physicianVAS), Health Assessment Questionnaire (HAQ), serum uric acid, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (HsCRP). RESULTS: At the flare visit, participants had a median of 1 clinically active joint (interquartile range [IQR] 1-2), and a median of 5 joints with a PD score ≥ 2 (IQR 4-10, P < .001). At the inter-critical visit, participants reported an median of 0 clinically active joints (IQR 0-0), and a median of 4 joints with a PD score ≥ 2 (IQR 3-7, P < .001). Physician VAS (5.69 vs 3.40, P < .001), painVAS (6 vs 0, P < .001), HAQ (0.75 vs 0.12, P = .032), and ESR (29 vs 13.5 mm/h, P = .02) were higher at the acute visit, but HsCRP levels were similar (8.88 vs 5.15 mg/L, P = .062). CONCLUSION: This pilot study established the presence of subclinical intra-articular inflammation in gout at both acute and inter-critical phases. Despite the apparent resolution of symptoms after an acute flare, a relatively high proportion of joints had subclinical inflammation in the inter-critical visit. The long-term implications of untreated subclinical joint inflammation are not clear.

EULAR definition of "arthralgia suspicious for progression to rheumatoid arthritis" in a large cohort of patients included in a program for rapid diagnosis: role of auto-antibodies and ultrasound.

OBJECTIVES: To evaluate the performance of the European League Against Rheumatism (EULAR) definition of arthralgias suspicious for progression to RA in patients with hand arthralgias and to estimate the added value of both auto-antibodies and ultrasound (US) with power Doppler (PD). METHODS: Consecutive patients admitted for hand arthralgias to "Reuma-check" ® program were included. This program includes the following at baseline: clinical assessment, laboratory tests, US with PD of both hands, and radiography of both hands and feet. All patients were followed-up after baseline evaluation by their treating rheumatologists, and a definitive diagnosis of RA (ACR/EULAR 2010 criteria) was established or not. RESULTS: A total of 465 consecutive patients were included. During follow-up, 44 (9.4%) were diagnosed with RA. Mean of baseline EULAR features describing arthralgia suspicious for progression to RA was 4.1 in patients with final diagnosis of RA vs 2.3 in non-RA patients (p < 0.0001). The AUC for the EULAR defined features describing arthralgia suspicious for progression to RA for the final diagnosis of RA was 0.7827, while adding US with PD, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACPA) data, the AUC was 0.9172 (p < 0.0001). In the multivariate regression logistic analysis, baseline features associated with a final diagnosis of RA were difficulty with making a fist, RF, ACPA, and US with PD. CONCLUSIONS: EULAR definition of arthralgia suspicious for progression to RA had an acceptable performance to predict the future development of RA and improves adding information of both RF, ACPA and US with PD data.Key Points• Clinically suspect arthralgia may trigger rheumatologists to monitor patients closely for an early diagnosis.• EULAR definition of arthralgia suspicious for progression to RA predicts future development of arthritis.• Auto-antibodies and ultrasound improve EULAR definition of arthralgia suspicious for progression to RA.

Increased serum levels of microfibrillar-associated protein 4 (MFAP4) are not associated with clinical synovitis in rheumatoid arthritis but may reflect underlying cardiovascular comorbidity.

OBJECTIVES: To study circulating MFAP4 in rheumatoid arthritis (RA) and its associations with clinical phenotype. METHODS: Early RA (ERA): 47 patients with newly diagnosed, treatment naïve RA were included. Serum MFAP4, clinical and laboratory disease variables were recorded serially during 12 months of intensive synovitis suppressive treatment. Long-standing RA (LRA): 317 patients participated, all receiving DMARD treatment. Disease activity, autoantibody status, extra-articular manifestations and cardiovascular morbidity were recorded. Paired serum and synovial fluid samples were obtained from 13 untreated ERA patients. Healthy blood donors served as reference points. MFAP4 was quantified by AlphaLISA immunoassay. Univariate, multivariate and mixed effects regression models were applied in the statistical analysis. RESULTS: ERA: MFAP4 increased from baseline and was significantly elevated at the 12-month follow-up, 17.8 U/l [12.6;24.1] vs. healthy controls, 12.7 U/l [9.5;15.6], p<0.001. MFAP4 did not correlate with joint counts or C-reactive protein. LRA: MFAP4 was increased, 25.9 U/l [20.4;33.7] vs. healthy controls, 17.6 U/l [13.7;21.2], p<0.0001, but did not correlate with disease activity measures or presence of extra-articular manifestations. Notably, MFAP4 correlated inversely with smoking (p<0.0001) and presence of antibodies against cyclic citrullinated peptides (anti-CCP), p=0.005. There was a positive association with systolic blood pressure, p=0.001 and co-occurrence of three cardiovascular events and/or risk factors, p<0.0001. The serum:synovial fluid MFAP4 ratio was 2:1. CONCLUSIONS: MFAP4 increases from diagnostic baseline despite intensive treatment but does not associate with synovitis at early or late stages of RA. Correlation patterns indicate that increased MFAP4 may reflect enhanced RA-related vascular remodelling.

Evaluating the role of serum sclerostin as an indicator of activity and damage in Egyptian patients with rheumatoid arthritis: university hospital experience.

OBJECTIVE: Sclerostin is an osteocyte-derived glycoprotein which inhibits the canonical Wnt pathway essential for osteoblastic activity decreasing bone formation. Its potential role in rheumatoid arthritis (RA) pathogenesis was highlighted by experimental studies. Here we measured the serum sclerostin in RA patients and evaluated its relationship with disease activity and damage. METHODS: One hundred RA patients and 80 age and sex-matched healthy controls were enrolled in the study. Bone biomarkers were evaluated for all participants including total calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D, and intact parathyroid hormone, in addition to fibroblast growth factor-23 (FGF23) and serum sclerostin. For RA patients, carotid intima-media thickness, brachial artery flow dilatation, and musculoskeletal ultrasonography using ultrasonography-7 joint score were done, and DAS28-ESR was calculated. RESULTS: Median serum sclerostin in our patients was 186.5 ± 22.7 pg/ml which was significantly higher than in controls 60.6 ± 7.1 pg/ml (p < 0.002). Serum sclerostin showed no correlation with disease activity, bone erosions, carotid intima-media thickness, brachial flow dilatation, and the examined bone biomarkers. However, it had a strong correlation with FGF23 (r coefficient 0.988, p < 0.000). CONCLUSION: Although serum sclerostin was elevated in RA patients, it could not be used as a prognostic marker for disease activity, bone erosions or atherosclerosis.Key Points• Serum sclerostin may not reflect changes in the joint microenvironment being not correlated with ultrasonography-detected synovitis or erosions.• Serum sclerostin was elevated in RA patients irrespective to their age or gender.• The positive correlation with FGF23 may provide evidence for sclerostin contribution in bone demineralization in RA patients.

Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.

[Seronegative symmetrical synovitis with edema in both hands in patient with central cord injury]. / Sinovitis simétrica seronegativa con edema en ambas manos en paciente con lesión centromedular.

A 55-year-old man with post-traumatic central cord injury, diagnosed with remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome). The clinical picture begins with an acute pain in hands, swelling and stiffness. The physical examination revealed edema with fovea on the back of both hands, with pain and swelling in the metacarpophalangeal joints. Given this, different analytical tests and radiography of hands were requested. We started treatment with 30mg of prednisone, showing significant clinical improvement, disappearing arthritis and edema, and normalization of the analytical values. The peculiarity of presentation of RS3PE syndrome in a patient with a central cord injury is due to the difficulty of identifying it due to the superposition of clinical manifestations together with the lack of knowledge of it, being in the absence of this lesion, an easily diagnosable pathology, do not require excessive complementary tests, and with an excellent prognosis after the appropriate early treatment.

Predictive factors associated with the therapeutic response in patients with polymyalgia rheumatica and remitting seronegative symmetrical synovitis with pitting edema syndrome.

Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigate predictive factors which correspond to subsequent disease control of PMR and RS3PE syndrome. Twenty four patients, which contained 18 PMR and 6 RS3PE syndrome, were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosage of prednisolone was then tapered. Significantly higher initial CRP was observed in patients with poor disease control than in those with good disease control afterwards. The number of patients with negative CRP after 4 weeks was significantly more in patients with good disease control after 1 year than in those with poor disease control. Patients were shown to be in good disease control status after 1 year when CRP after 4 weeks became negative even if they had initial high CRP. Our study clarify that to make CRP negative after 4 weeks is associated with subsequent suppression of the disease activity and with decreased dosages of corticosteroids. J. Med. Invest. 66 : 112-118, February, 2019.

Combination of ultrasound power Doppler-verified synovitis and seropositivity accurately identifies patients with early-stage rheumatoid arthritis.

AIM: We conducted this retrospective study to identify objective and comprehensive diagnostic criteria for early-stage rheumatoid arthritis (RA) that are based on ultrasound (US) and serologic findings. METHOD: From August 2014 to May 2016, we recruited 216 consecutive patients at Hospital 1 and 223 consecutive patients at Hospital 2 who were suspected to have RA and underwent US of bilateral hands. In the US of bilateral hands from 22 sites, the findings obtained by grayscale and power Doppler (PD) assessments were each graded on a semi-quantitative scale from 0 to 3. We also examined the assessment of the novel outcome measures in rheumatology (OMERACT)-European League Against Rheumatism (EULAR) combined power Doppler ultrasound score (ie the cPD score) and the Global OMERACT-EULAR Synovitis Score. We used the US findings and the combination of US and serologic findings to evaluate the diagnostic performance of these modalities. RESULTS: Seventy patients (32.4%) at Hospital 1 and 59 patients (26.5%) at Hospital 2 were diagnosed as having RA. The best-balanced diagnostic performance at each hospital was achieved using a combination, such as (1) the presence of PD grade ≥2 articular synovitis or (2) the presence of PD grade ≥1 articular synovitis and serologic positivity, as well as by using (1) the presence of cPD grade = 3 or (2) a cPD grade ≥2 and serologic positivity. CONCLUSION: The combination of a PD assessment or the cPD score with the measurement of autoantibodies of rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies can accurately identify patients with early-stage RA.

Serum cartilage oligomeric matrix protein (COMP) expression in individuals who sustained a youth sport-related intra-articular knee injury 3-10 years previously and uninjured matched controls.

OBJECTIVE: This study investigates the relationship between a youth sport-related intra-articular knee injury and cartilage oligomeric matrix protein (COMP), a biomarker of cartilage turnover. DESIGN: Participants included a sub-sample (n = 170) of the Alberta Youth Prevention of Early Osteoarthritis (PrE-OA) study group. Specifically, 85 individuals with a 3-10 year history of sport-related intra-articular knee injury and 85 age, sex and sport-matched controls. COMP levels were investigated in serum. Between group differences in COMP levels, COMP fragmentation patterns and, the relationship between serum COMP and clinical outcomes (i.e., Magnetic Resonance Imaging (MRI) Osteoarthritis Knee Score; MOAKS, Knee Osteoarthritis Outcome Score; KOOS, Fat mass index; FMI) were examined. RESULTS: Participant median age was 22.3 years (range 16-26) and 63% were female. Although there was no difference in COMP levels between previously injured and uninjured females, previously injured males demonstrated an ∼15% greater (171.5 ng/ml, 95% CI 11.0-428.0, P = 0.04) serum COMP level than uninjured males. However after controlling for FMI, this difference was absent. Within the injured participants, COMP levels were associated with MOAKSSYNOVITIS and FMI. Furthermore, COMP fragmentation patterns were distinct between injured and uninjured individuals. CONCLUSIONS: In this study group, serum COMP levels were greater in injured males, but not females, compared to matched controls. However, after controlling for FMI, no differences in COMP were observed. A unique COMP fragmentation pattern was observed in injured vs uninjured participants. These results further the hypothesis that COMP levels and/or degradation of the protein may be a marker of cartilage injury which could predispose to later OA.