Blau syndrome: a case report from Palestine.

BACKGROUND: This case study documents the first familial case of Blau syndrome (BS) in Palestine characterized with mutation in CARD15/NOD2. CASE PRESENTATION: Eighteen years old female was initially misdiagnosed with Juvenile idiopathic arthritis (JIA). The patient had been on steroids and methotrexate treatment for the last 16 years, but did not respond well to treatment. Initial examination at Saint John of Jerusalem Eye Hospital Group clinic showed bilateral intermediate uveitis with camptodactyly. The patient's sister (aged 19 years) had bilateral intermediate uveitis and camptodactyly. Both eyes of their father had signs of old posterior uveitis. Father's left eye showed 360 degrees posterior synechia, mature cataract with old Keratic precipitates (KPs). He also had camptodactyly. The patient was referred to pediatric rheumatologist to rule out sarcoidosis. Lung CT scan showed bronchiectasis, genetic consultation followed. Complete eye examination, full history, refraction, and Optical coherence tomography (oct) were done. Systemic and topical steroid therapy could not control the ocular inflammation. The family then was referred to a geneticist. Genetic analyses showed that the proband and all three family members had an R334q mutation in the CARD15/Nod2 gene. CONCLUSIONS: BS should be considered in the differential diagnosis of childhood uveitis, especially in low and middle income countries where it is misdiagnosed in many cases, which delay appropriate diagnosis and thus control. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis. Steroids alone are not enough to control the disease, other immunosuppressants and biologics are needed.

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia.

OBJECTIVE: To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS). METHODS: The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores. RESULTS: Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models). CONCLUSIONS: US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.

A novel mutation in early-onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes.

BACKGROUND: Early-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation of NOD2 and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in the NOD2 gene, as well as detection of Propionibacterium acnes (P. acnes) in the granulomatous inflammation. CASE PRESENTATION: An 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, and P. acnes was detected within the sarcoid granulomas by immunohistochemistry with P. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had a NOD2 heterozygous D512V mutation that was novel and not present in either of her parents. The mutant NOD2 showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively. CONCLUSIONS: We presented a case of EOS/BS with a novel D512V mutation in the NOD2 gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report of P. acnes demonstrated in granulomas of EOS/BS. Since intracellular P. acnes activates nuclear factor-kappa B in a NOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result of NOD2 activity in the presence of the ligand muramyl dipeptide, which is a component of P. acnes. These results indicate that recognition of P. acnes through mutant NOD2 is the etiology in this patient with EOS/BS.

Prevalence of early hip OA features on MRI in high-impact athletes. The femoroacetabular impingement and hip osteoarthritis cohort (FORCe) study.

OBJECTIVE: To compare early hip osteoarthritis (OA) features on magnetic resonance imaging (MRI) in high-impact athletes with and without hip and/or groin pain, and to evaluate associations between early hip OA features, the International Hip Outcome Tool (iHOT33) and Copenhagen Hip and Groin Outcome Score (HAGOS). DESIGN: This case-control study evaluated data of the femoroacetabular impingement and hip osteoarthritis cohort (FORCe). One hundred and eighty-two symptomatic (hip and/or groin pain >6 months and positive flexion-adduction-internal-rotation (FADIR) test) and 55 pain-free high-impact athletes (soccer or Australian football (AF)) without definite radiographic hip OA underwent hip MRI. The Scoring Hip Osteoarthritis with MRI (SHOMRI) method quantified and graded the severity of OA features. Each participant completed the iHOT33 and HAGOS. RESULTS: Hip and/or groin pain was associated with higher total SHOMRI (0-96) (mean difference 1.4, 95% CI: 0.7-2.2), labral score (adjusted incidence rate ratio (aIRR) 1.33, 95% CI: 1.1-1.6). Differences in prevalence of cartilage defects, labral tears and paralabral cysts between symptomatic and pain-free participants were inconclusive. There was a lower prevalence of effusion-synovitis in symptomatic participants when compared to pain-free participants (adjusted odds ratio (aOR) 0.46 (95% CI: 0.3-0.8). Early hip OA features were not associated with iHOT33 or HAGOS. CONCLUSIONS: A complex and poorly understood relationship exists between hip and/or groin pain and early hip OA features present on MRI in high-impact athletes without radiographic OA. Hip and/or groin pain was associated with higher SHOMRI and labral scores.

Autologous protein solution as selective treatment for advanced patellofemoral osteoarthritis in the middle-aged female patient: 54% response rate at 1 year follow-up.

PURPOSE: The study wanted to investigate the benefit, durability and safety of autologous protein solution (APS) injection(s) in a middle-aged female-only cohort suffering predominantly from patellofemoral osteoarthritis. METHODS: Fifty females (aged 50.4 ± 6.5) with mainly moderate-severe (86%) patellofemoral cartilage wear (PFCW) were treated with a unilateral intra-articular APS injection. The KOOS, NRS, Kujala, UCLA and EQ-5D were assessed at baseline and 1, 3, 6, and 12 months post-injection. Therapeutic response rate (TRR) was based on KOOS pain improvement > 10 points. Absolute improvement for, respectively, therapy responders and non-responders was determined. Second APS injection was administered if improvement was deemed insufficient by the patient after 3 months. RESULTS: The TRR remained stable averaging to 53.7% at final follow-up with subjects improving overall from 40.3 ± 18.7 to 57.3 ± 24.8 points on KOOS pain (p = 0.0002) and from 48.4 ± 13.0 to 56.3 ± 18.1 points on Kujala (p = 0.0203) at 12 months. Significant improvement was observed for the other KOOS subscales and NRS at each follow-up. In absolute values, APS responders improved with 30.5 ± 11.4 points on KOOS pain at 12 months. In contrast, non-responders deteriorated with 5.9 ± 8.9 points relative to baseline. A second APS injection was administered in 28 subjects. Patients with definite synovitis improved more on KOOS symptoms (p = 0.017) and KOOS ADL (p = 0.037) at 12 months compared to non-synovitis subjects. Mild-moderate arthralgia (46%) and effusion (29%) were commonly observed during the first month post-injection. CONCLUSION: This study evidenced a 54% response rate at 12 months to a single or second APS injection in a middle-aged female population with advanced patellofemoral cartilage wear. Moderate temporary flares can be expected without affecting clinical outcomes. Second APS injection has low efficacy in initially poor responding patients after 3 months. Major synovitis on baseline MRI appeared to be a beneficial prognosticator for pain relief and functional improvement after APS. LEVEL OF EVIDENCE: IV.

Two-Year Changes in Magnetic Resonance Imaging Features and Pain in Thumb Base Osteoarthritis.

OBJECTIVE: To investigate the two-year course of pain and osteoarthritic features on magnetic resonance imaging (MRI) in the thumb base. METHODS: Patients in the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort who had received radiographic examination, MRI, and clinical examination of the right thumb base at baseline and who had a 2-year follow-up period were studied. Pain on palpation of the thumb base was assessed on a 0-3 scale. MRIs were analyzed with the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis MRI scoring system for synovitis, bone marrow lesions (BMLs), subchondral bone defects, cartilage space loss, osteophytes, and subluxation. Radiographs were assessed for osteophytes and joint space narrowing. We studied the associations of changes in synovitis and BMLs with changes in pain using a logistic regression model adjusted for radiographic damage, with values expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Of 165 patients, 83% were women and the mean age was 60.7 years. At baseline, 65 patients had thumb base pain. At 2-year follow-up, pain had decreased in 32 patients and increased in 33 patients. MRI features remained stable in most patients. Structural MRI features generally deteriorated, while synovitis and BMLs improved in some individuals and deteriorated in others. Change in radiographic osteophytes rarely occurred (n = 10). Increased synovitis (odds ratio [OR] 3.4 [95% CI 1.3-9.3]) and increased BMLs (OR 5.1 [95% CI 2.1-12.6]) were associated with increased pain. Decreased BMLs appeared to be associated with decreased pain (OR 2.7 [95% CI 0.8-8.9]), and reductions in synovitis occurred too infrequently to calculate associations. CONCLUSION: Over 2 years, thumb base pain fluctuated, while MRI features changed in a minority of patients with hand osteoarthritis. Changes in synovitis and BMLs were associated with changes in pain on palpation, even after adjustment for radiographic damage.

Predictors for an unsuccessful conservative treatment of patients with medial patellar plica syndrome.

INTRODUCTION: In several cases persistent medial knee pain remains after conservative treatment in patients with medial patellar plica syndrome. In recent literature accepted criteria for surgical indication are lacking. In this retrospective study patients after conservative treatment were evaluated to identify predictors for an unsuccessful outcome. MATERIALS AND METHODS: 117 Patients with medial patellar plica syndrome between 2016 and 2019 were retrospectively evaluated. All patients received conservative treatment for three months. Surgery was indicated due to failed conservative treatment (n = 76) with persistent medial knee pain and restriction of activity after 3 months. Preoperative MRI analysis, Lysholm score, pain by the visual analog scale (VAS), postoperative sports participation (RTS) and Tegner activity score were collected at least 12 months after definite treatment. Statistical analysis was performed to evaluate differences between patients with successful and unsuccessful conservative treatment. RESULTS: There were significant differences in the clinical and radiological findings between patients with successful and unsuccessful conservative treatment. Patients with failed conservative treatment showed a significant larger diameter of the medial patellar plica (0.8 ± 0.3 mm vs. 1.6 ± 0.4 mm; p < 0.05) and a significant higher rate of contact of the plica to the adjacent cartilage. Furthermore, these patients reported a significant higher rate of medial knee pain from flexion to extension and snapping symptoms. At final follow-up the patient-reported outcome by means of Lysholm score (96.25 vs. 95.93), RTS (96.2% vs. 97%) and Tegner activity score (6.0 vs. 6.01) was excellent after conservative and surgical treatment. There were no statistical differences in the preoperative and postoperative outcomes between both. CONCLUSIONS: The diameter of a medial patellar plica and contact of the plica to the retropatellar cartilage as well as clinical signs like persistent medial knee pain from flexion to extension with snapping symptoms might be predictors for an unsuccessful conservative treatment and the need for surgical intervention in patients with painful medial patellar plica syndrome.

Comparison Between Clinical and Ultrasound Assessment of the Ankle Region in Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: To compare the frequency of joint and tendon disease on ultrasound (US) and clinical examination, and to investigate agreement between US and clinical evaluation in ankles with clinically active juvenile idiopathic arthritis (JIA). METHODS: US and clinical evaluation were performed independently in the joint and tendon compartments of 105 ankles. Gray-scale (GS) US and power Doppler (PD) US joint abnormalities were scored on a 4-point semiquantitative scale. A joint with a GS score ≥2 and/or a PD score ≥1 was defined as active on US. Agreement was tested using kappa statistics. RESULTS: A total of 163 joints in 89 ankles had active synovitis on US. The tibiotalar (TT) joint was the most commonly affected joint on US and on clinical evaluation. The intertarsal (IT) joint and the subtalar (ST) joint were the second in frequency on US and on clinical evaluation, respectively. Tenosynovitis was found more commonly on US than on clinical evaluation (70.5% and 32.4%, respectively), and was more frequent in the medial and lateral than in the anterior tendon compartment. Isolated tenosynovitis was detected on US in 12 of 105 ankles. Agreement between US and clinical evaluation for detection of active synovitis and tenosynovitis was less than acceptable (κ <0.4). No correlation was found between any feature of active disease recorded on clinical evaluation (joint swelling, tenderness/pain on motion, and restricted motion) and active synovitis on US in the TT joint, ST joint, and IT joint. CONCLUSION: Coupling clinical evaluation with US aids in correctly localizing pathology. US training of practitioners is recommended to manage ankle disease in JIA.

Association between changes in knee load and effusion-synovitis: evidence of mechano-inflammation in knee osteoarthritis using high tibial osteotomy as a model.

OBJECTIVE: Although mechanically-induced inflammation is an appealing explanation linking different etiologic factors in osteoarthritis (OA), clinical research investigating changes in both biomechanics and joint inflammation is limited. The purpose of this study was to evaluate the association between change in surrogate measures of knee load and knee effusion-synovitis in patients with medial compartment knee OA undergoing high tibial osteotomy (HTO). METHODS: Thirty-six patients with medial compartment knee OA and varus alignment underwent 3D gait analysis and 3T magnetic resonance imaging (MRI) preoperatively and 1 year after medial opening wedge HTO. Primary outcome measures were the change in the external knee adduction moment impulse during walking and change in knee suprapatellar effusion-synovitis volume manually segmented on MRI by one blinded assessor. RESULTS: Mean (SD) knee adduction moment impulse [24.0 (6.5) Nm•s] and knee effusion-synovitis volume [8976.7 (8016.9) mm3] suggested substantial preoperative medial knee load and inflammation. 1-year postoperative changes in knee adduction moment impulse [-10.1 Nm•s (95%CI: -12.7, -7.4)], and knee effusion-synovitis volume [-1856 mm3 (95%CI: -3830, 117)] were positively correlated [r = 0.60 (95% CI 0.34, 0.78)]. Simple linear regression suggested a 448 mm3 (95%CI: 241, 656) reduction in knee effusion-synovitis volume per 1 Nm•s reduction in knee adduction moment impulse. Change in knee adduction moment impulse explained 36% (R2 = 0.36) of the variance of change in knee effusion-synovitis volume. CONCLUSIONS: Reduction in medial knee load is positively associated with reduction in knee inflammation after HTO, suggesting the phenomenon of mechano-inflammation in patients with knee OA.

Differing time-orders of inflammation decrease between ACPA subsets in RA patients suggest differences in underlying inflammatory pathways.

OBJECTIVES: Advanced imaging modalities have shown that not only joints but also bones and tendon sheaths can be inflamed at diagnosis of RA. We aimed to better understand the time-order in which the inflamed tissues respond to DMARD treatment. Also, because ACPA status may reflect a different pathophysiology, differences in time-order of inflammation decrease were hypothesized between these disease types. METHODS: A total of 216 consecutive patients presenting with RA (n = 176) or undifferentiated arthritis (n = 40), who all started with conventional synthetic DMARD treatment, were studied. 1.5T contrast-enhanced hand and foot MRIs were performed before treatment and after 4, 12 and 24 months. Cross-lagged models evaluated the influence of two time patterns: a simultaneous pattern ('change in one inflammatory feature associated with change in another feature') and a subsequent pattern ('change in one inflammatory feature preceded change in another feature'). ACPA stratification was performed. RESULTS: The median symptom duration at presentation was 13 weeks. Forty-four percent of patients was ACPA-positive. All pairs of inflammatory features decreased simultaneously in all time intervals (0-4/4-12/12-24 months; P < 0.05). Moreover, time-orders were identified: synovitis decrease preceded tenosynovitis decrease (0-4 to >4-12 months; P = 0.02 and 4-12 to >12-24 months; P = 0.03). Largely similar results were obtained in both ACPA subgroups. Additionally, in ACPA-positive but not ACPA-negative patients, synovitis decrease preceded osteitis decrease (4-12 to >12-24 moths; P = 0.002). CONCLUSION: This study increased the understanding of the response to treatment on the tissue level. In addition to simultaneous decrease of inflammation, synovitis decrease preceded tenosynovitis decrease. Differences in time-order of inflammation decrease between ACPA subgroups suggest differences in underlying inflammatory pathways.

Hand dominance in early and established rheumatoid arthritis: evaluation by dynamometer, Ritchie index and musculoskeletal ultrasound: a cross sectional study.

Rheumatoid arthritis (RA) usually occurs as a symmetrical disease, which mainly affects the small joints of the hands and feet. The correlation of handedness with radiological changes shows significantly greater radiological changes in the dominant hand than in the non-dominant one. Additionally, the dominant hand is more severely affected in terms of strength, function and deformity. Our objective is to evaluate the influence of handedness on musculoskeletal ultrasound (US), Ritchie articular index (RAI) and digital dynamometer findings in patients with active RA (early, group B, vs. established, group A). A total number of 113 patients with established RA and 44 patients with early RA with active disease (DAS28-ESR >3.2) were included in the study. US assessments of both hands were performed to assess synovitis, tenosynovitis, and erosions. RAI was used to evaluate three joint groups in each hand. Handgrip strength was measured with a digital dynamometer. The US5 score showed that the dominant hand was more affected than the non-dominant one. This was significant in group A for the synovitis Power Doppler (PD) mode (p=0.032) and tenosynovitis PD (p=0.005) scores, and in group B for synovitis Grey Scale (GS) mode (p<0.001), synovitis PD (p=0.037) and erosions (p=0.027) scores. RAI was significantly higher in the dominant hand (p=0.013) in group A and even greater in group B (p=0.011). The dominant hand was stronger than the non-dominant hand in both groups. The dominant hand is generally affected in early RA. Subsequently, the disease tends to become more symmetrical with disease progression.

Hip Joint Effusion-Synovitis Is Associated With Hip Pain and Sports/Recreation Function in Female Professional Ballet Dancers.

OBJECTIVE: To compare hip joint effusion-synovitis prevalence in professional ballet dancers with nondancing athletes and to evaluate the relationship between effusion-synovitis and clinical measures and cartilage defects. DESIGN: Case-control study. SETTING: Elite ballet and sport. PARTICIPANTS: Forty-nine professional ballet dancers and 49 age-matched and sex-matched athletes. INDEPENDENT VARIABLES: Group (dancers/athletes), sex, age, years of training, Copenhagen Hip and Groin Outcome Scores (HAGOSs), hip rotation range of motion (ROM), generalized joint hypermobility (GJH), and hip cartilage defect scores. MAIN OUTCOME MEASURES: Hip joint effusion-synovitis (absent, grade 1 = 2-4 mm, grade 2 = >4 mm) scored with 3-Tesla magnetic resonance imaging. RESULTS: Hip joint effusion-synovitis was found in 22 (45%) dancers and 13 (26.5%) athletes (P = 0.06). Grade 2 effusion-synovitis was only found in dancers (n = 8, r = 0.31, P = 0.009). The prevalence of effusion-synovitis was similar in men (n = 11, 26%) and women (n = 24, 43%, P = 0.09). Female dancers with effusion-synovitis had lower HAGOS pain (r = 0.63, P = 0.001) and sports/recreation scores (r = 0.66, P = 0.001) compared with those without effusion-synovitis. The HAGOS scores were not related to effusion-synovitis in male dancers or female and male athletes (P > 0.01 for all). Effusion-synovitis was not related to hip ROM, GJH, or cartilage defect scores (P > 0.05 for all). CONCLUSIONS: Hip joint effusion-synovitis was related to higher levels of pain and lower sports/recreation function in female ballet dancers. Effusion-synovitis was not related to hip rotation ROM, GJH or cartilage defects. Larger sized joint effusion-synovitis was exclusively found in dancers.

Altered Lymphatic Vessel Anatomy and Markedly Diminished Lymph Clearance in Affected Hands of Patients With Active Rheumatoid Arthritis.

OBJECTIVE: To assess differences between lymphatic function in the affected hands of rheumatoid arthritis (RA) patients with active synovitis and that of healthy controls, using indocyanine green (ICG) dye and near-infrared (NIR) imaging. METHODS: NIR imaging of the hands of 8 patients with active RA and 13 healthy controls was performed following web space injection of 0.1 ml of 100 µM ICG. The percentage of ICG retention in the web spaces was determined by NIR imaging at baseline and at 7 days (±1 day) after the initial injections; image analysis provided contraction frequency. ICG+ lymphatic vessel (LV) length and branching architecture were assessed. RESULTS: Retention of ICG in RA hands was higher compared to controls (P < 0.01). The average contraction frequency of ICG+ LVs in RA patients and in controls did not differ (mean ± SD 0.53 ± 0.39 contractions/minute versus 0.51 ± 0.35 contractions/minute). Total ICG+ LV length in RA hands was lower compared to healthy controls (58.3 ± 15.0 cm versus 71.4 ± 16.1 cm; P < 0.001), concomitant with a decrease in the number of ICG+ basilic LVs in the hands of RA patients (P < 0.05). CONCLUSION: Lymphatic drainage in the hands of RA patients with active disease was reduced compared to controls. This reduction was associated with a decrease in total length of ICG+ LVs on the dorsal surface of the hands, which continued to contract at a similar rate to that observed in controls. These findings provide a plausible mechanism for exacerbation of synovitis and joint damage, specifically the accumulation and retention of inflammatory cells and catabolic factors in RA joints due to impaired efferent lymphatic flow. NIR/ICG imaging of RA hands is feasible and warrants formal investigation as a primary outcome measure for arthritis disease severity and/or persistence in future clinical trials.

Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis.

Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITGα5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis.

Contribution of tenosynovitis of small joints to the symptom morning stiffness in patients presenting with undifferentiated and rheumatoid arthritis.

Objective: Morning stiffness (MS) is characteristic of rheumatoid arthritis (RA). Despite its association with functional disability, the extent to which local inflammatory processes contribute to this symptom is unknown. Magnetic resonance imaging (MRI)-detected tenosynovitis of small joints is recognized as an early feature of RA, which is also associated with functional impairments. It has been proposed that tenosynovitis contributes to MS. Therefore, we assessed the relationship between MS and MRI-detected inflammation, in particular tenosynovitis.Method: In total, 286 consecutive patients newly presenting with undifferentiated arthritis and RA underwent contrast-enhanced 1.5 T MRI of (2-5) metacarpophalangeal, wrist, and (1-5) metatarsophalangeal joints. Scans were scored for tenosynovitis according to Haavardsholm, and for synovitis by Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). MS was dichotomized as ≥ 60 min or not. Associations between MS and tenosynovitis/synovitis were tested with logistic regression, data were categorized (solitary or simultaneous presence of synovitis/tenosynovitis), and the presence of an additive interaction was assessed.Results: MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS [80% vs 65%, odds ratio (OR) 2.11, 95% confidence interval (1.21;3.69)]. Synovitis was more often present in patients with MS [58% vs 44%, OR 1.79 (1.11;2.91)]. In categorized analyses, concurrent synovitis and tenosynovitis had the largest association [OR 2.43 (1.30;4.54)], in contrast to solitary synovitis [OR 0.85 (0.21;3.47)]. The additive interaction was non-significant. The variance explained in all analyses was small (range 4-5%).Conclusion: Tenosynovitis, combined with synovitis, at small joints is associated with MS and contributes to the pathophysiology of MS.

Profile of osteoarticular tuberculosis in children.

OBJECTIVE: To determine clinical profile of osteoarticular tuberculosis (TB) in children. METHODS: Cross-sectional analysis from 2007 to 2013. All patients diagnosed with bone TB, spinal TB or TB abscesses were included. RESULTS: Out of 1318 children with TB, 39 (2.96%) had osteoarticular TB, of which 16 (42%) had osteomyelitis, 8 (20.5%) had spinal involvement, 7 (17.9%) had TB synovitis, 2 (5.1%) had psoas abscess and 6 (15.4%) had abscesses. The mean age of presentation was 7.1 ± 3.5 years (range 2-14 years). Of the 33 cases in which a culture was done, 25 (64%) showed a positive culture. Drug sensitivity tests were done in 21 patients of which 10 (47.6%) tested were drug resistant, of which 4 (36.4%) were multidrug resistant (MDR), 2 (18.2%) were extensively drug resistant (XDR), 3 were pre-XDR (27.3%) and 1 was polyresistant (9.1%). Nine (23.1%) patients had TB in the past with a treatment duration of 8.3 ± 5.3 months. Contact with a TB patient had occurred in 10 (25.6%) cases. Associated pulmonary TB were seen in 6 (15.39%) and TB meningitis were seen in 1 (2.6%) patients. Surgical intervention was needed in 11 (28.2%) patients of which 5 (45.5%) underwent curettage, drainage was done in 1 (9.1%), arthrotomy in 4 (36.4%) and spinal surgery in 1 (9.1%) patient. CONCLUSION: Drug resistant osteoarticular TB is an emerging problem in children.

Higher body mass index is associated with lower foot health in patients with rheumatoid arthritis: baseline results of the Amsterdam-Foot cohort.

Objective: Obesity is highly prevalent in patients with rheumatoid arthritis (RA), with likely impact on weight-bearing foot joints. We explored the associations between body mass index (BMI) and measures of foot health in patients with RA and foot complaints.Method: We examined patients with RA presenting for their first custom-made therapeutic footwear or foot orthoses. Domains of foot health comprised: foot pain, foot-related activity limitations, forefoot plantar pressure, foot synovitis, and foot deformity. In regression analyses, BMI was the independent variable and foot health domains were the dependent variables.Results: The cohort at baseline comprised 230 patients [mean ± sd age 58 ± 13 years, 80% female, mean ± sd disease duration 10 ± 9 years, and median (interquartile range) BMI 26.7 (23.5-30.1) kg/m2]. Small to modest statistically significant associations were found in the majority of the measures studied between a higher BMI and more foot pain, more foot-related activity limitations, higher in-shoe measured forefoot plantar pressure, and the presence of foot synovitis. No relationships were found between BMI and barefoot measured forefoot plantar pressure or foot deformity.Conclusion: BMI is negatively associated with foot health in patients with RA. Although the clinical relevance of our findings for an individual patient is not immediately obvious, future research should consider BMI as a potential therapeutic target to improve foot health.

Predominant ultrasonographic extracapsular changes in symptomatic psoriatic dactylitis: results from a multicenter cross-sectional study comparing symptomatic and asymptomatic hand dactylitis.

OBJECTIVE: Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis. METHODS: One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones. RESULTS: Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p < 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p < 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade > 2, soft tissue edema and subcutaneous PDUS signal (p < 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p < 0.001). CONCLUSIONS: Digital tenderness and pain are linked to US tenosynovitis of grade > 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade> 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.