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Objective: Inflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-β, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA., Methods: In this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 10 12 -1.2 × 10 13 genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-β immune responses were evaluated. A data review committee provided safety recommendations., Results: Four patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-β, nor IFN-β antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose., Conclusion: Single IA doses of 0.6 × 10 12 or 1.2 × 10 12 ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation., Trial Registration: NCT02727764., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To investigate determinants of decrease and increase in joint pain in symptomatic finger osteoarthritis (OA) on magnetic resonance (MR) imaging over 2 years., Design: Eighty-five patients (81.2% women, mean age 59.2 years) with primary hand OA (89.4% fulfilling American College of Rheumatology (ACR) classification criteria) from a rheumatology outpatient clinic received contrast-enhanced MR imaging (1.5T) and physical examination of the right interphalangeal finger joints 2-5 at baseline and at follow-up 2 years later. MR images were scored paired in unknown time order, following the Hand OA MRI scoring system (HOAMRIS). Joint pain upon palpation was assessed by research nurses. Odds ratios (ORs; 95% confidence intervals) were estimated on joint level (n = 680), using generalized estimating equations (GEE) to account for the within patient effects. Additional adjustments were made for change in MR-defined osteophytes, synovitis, and bone marrow lesions (BMLs)., Results: Of 116 painful joints at baseline, at follow-up: 76 had less pain, 21 less synovitis, and 13 less BMLs. A decrease in synovitis (OR = 5.9; 1.12─31.0), but not in BMLs (OR = 0.39; 0.10─1.50), was associated with less pain. Of 678 joints without maximum baseline pain, at follow-up: 115 had increased pain, 132 increased synovitis, 96 increased BMLs, and 44 increased osteophytes. Increased synovitis (OR = 1.81; 1.11─2.94), osteophytes (OR = 2.75; 1.59─4.8), but not BMLs (OR = 1.14; 0.81─1.60), was associated with increased pain. Through stratification it became apparent that BMLs were mainly acting as effect modifier of the synovitis-pain association., Conclusion: Decrease in MR-defined synovitis is associated with reduced joint pain, identifying synovitis as a possible target for treatment of finger OA., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: MRI-detected subclinical joint inflammation in the hand joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone., Methods: 1.5-T contrast-enhanced MRI of the unilateral foot (MTP-1-5) and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling the 2010 RA criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n = 193) served as a reference for defining an abnormal MRI. Patients were followed for RA development ≤ 1 year, defined as fulfilling the classification criteria or initiation of disease-modifying antirheumatic drugs because of the expert opinion of RA. The added predictive value of foot MRI to hand MRI was evaluated., Results: Fifty-two percent developed RA. Foot tenosynovitis was predictive (OR 2.55, 95% CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95% CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95% CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95% CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95% CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed the sensitivity from 72 to 73%, specificity from 59 to 54% and AUC from 0.66 to 0.64; the net reclassification index was - 3.5., Conclusion: MRI-detected tenosynovitis of the foot predicts progression to RA. However, adding MRI of the foot does not improve the predictive accuracy compared to MRI of the hand alone. In view of cost reduction, the performance of foot MRI for prognostic purposes in UA can be omitted.

Objective: Because the association and its clinical relevance between comorbidities and primary hand osteoarthritis (OA) disease burden is unclear, we studied this in patients with hand OA from our Hand OSTeoArthritis in Secondary care (HOSTAS) cohort., Methods: Cross-sectional data from the HOSTAS study were used, including consecutive patients with primary hand OA. Nineteen comorbidities were assessed: 18 self-reported (modified Charlson index and osteoporosis) and obesity (body mass index ≥ 30 kg/m 2 ). Mean differences were estimated between patients with versus without comorbidities, adjusted for age and sex: for general disease burden [health-related quality of life (HRQOL), Medical Outcomes Study Short Form-36 physical component scale (0-100)] and disease-specific burden [self-reported hand function (0-36), pain (0-20; Australian/Canadian Hand OA Index), and tender joint count (TJC, 0-30)]. Differences above a minimal clinically important improvement/difference were considered clinically relevant., Results: The study included 538 patients (mean age 61 yrs, 86% women, 88% fulfilled American College of Rheumatology classification criteria). Mean (SD) HRQOL, function, pain, and TJC were 44.7 (8), 15.6 (9), 9.3 (4), and 4.8 (5), respectively. Any comorbidity was present in 54% (287/531) of patients and this was unfavorable [adjusted mean difference presence/absence any comorbidity (95% CI): HRQOL -4.4 (-5.8 to -3.0), function 1.9 (0.4-3.3), pain 1.4 (0.6-2.1), TJC 1.3 (0.4-2.2)]. Number of comorbidities and both musculoskeletal (e.g., connective tissue disease) and nonmusculoskeletal comorbidities (e.g., pulmonary and cardiovascular disease) were associated with disease burden. Associations with HRQOL and function were clinically relevant., Conclusion: Comorbidities showed clinically relevant associations with disease burden. Therefore, the role of comorbidities in hand OA should be considered when interpreting disease outcomes and in patient management.

Objective: Peripheral bone mineral density (BMD) may be decreased in early rheumatoid arthritis (RA) but it is unknown whether BMD loss emerges before arthritis is clinically apparent. We aimed to study whether BMD loss occurs in patients with clinically suspect arthralgia (CSA), and whether it is associated with progression to clinical arthritis and magnetic resonance imaging (MRI)-detected subclinical inflammation., Method: Patients with CSA had arthralgia for <1 year and were at risk of progressing to RA according to their rheumatologists. At baseline, a 1.5 T MRI was performed of unilateral metacarpophalangeal, wrist, and metatarsophalangeal joints, and scored on synovitis, bone marrow oedema, and tenosynovitis;. summing these features yielded the total MRI inflammation score. Digital X-ray radiogrammetry (DXR) was used to estimate BMD on two sequential conventional hand radiographs (mean interval between radiographs 4.4 months). The change in BMD was studied; BMD loss was defined as a decrease of ≥2.5 mg/cm 2 /month. Patients were followed for arthritis development for a median of 18.4 months., Results: In CSA patients (n = 108), change in BMD was negatively associated with age (β = -0.03, p = 0.007). BMD loss in CSA patients was associated with arthritis development [adjusted for age hazard ratio (HR) = 6.1, 95% confidence interval (CI) 1.7 to 21.4] and was most frequently estimated in the months before clinical arthritis development. The total MRI inflammation scores were associated with the change in BMD (adjusted for age β = -0.05, p = 0.047). The total MRI inflammation score and BMD loss were both independently associated with arthritis development (HR = 1.1, 95% CI 1.1 to 1.2, and HR = 4.6, 95% CI 1.2 to 17.2, respectively)., Conclusion: In CSA patients, severe BMD loss is associated with MRI-detectable subclinical inflammation and with progression to clinical arthritis.

Objective: To study the association of magnetic resonance (MR) features with radiographic progression of hand osteoarthritis over 2 years., Methods: Of 87 primary patients with hand osteoarthritis (82% women, mean age 59 years), baseline distal and proximal interphalangeal joint contrast-enhanced MR images were scored 0-3 for bone marrow lesions (BMLs) and synovitis following the Oslo score. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence (KL) (0-4) and OsteoArthritis Research Society International (OARSI) scoring methods (0-3 osteophytes, joint space narrowing (JSN)). Increase ≥1 defined progression. Associations between MR features and radiographic progression were explored on joint and on patient level, adjusting for age, sex, body mass index, synovitis and BML. Joints in end-stage were excluded., Results: Of 696 analysed joints, 324 had baseline KL=0, 28 KL=4 and after 2 years 78 joints progressed. BML grade 2/3 was associated with KL progression (2/3 vs 0: adjusted risk ratio (RR) (95% CI) 3.3 (2.1 to 5.3)) and with osteophyte or JSN progression, as was synovitis. Summated scores were associated with radiographic progression on patient level (RR crude BML 1.08 (1.01 to 1.2), synovitis 1.09 (1.04 to 1.1), adjusted synovitis 1.08 (1.03 to 1.1))., Conclusions: BMLs, next to synovitis, show, already after 2 years, graded associations with radiographic progression, suggesting that both joint tissues could be important targets for therapy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: The use of magnetic resonance imaging (MRI)-detected inflammation and joint damage in the diagnosis of rheumatoid arthritis is recommended by a European League Against Rheumatism imaging task force. This recommendation is based on the sensitivity of MRI and not on specificity. Knowledge of the prevalence of MRI-detected features in symptom-free persons, however, is pivotal when considering MRI for diagnostic purposes., Methods: From November 2013 to December 2014, 196 symptom-free persons of different ages were recruited from the general population. Inclusion criteria were no history of inflammatory arthritis, no joint symptoms during the previous month, and no clinically detectable arthritis on physical examination. Contrast-enhanced MRIs of the dominant metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints were obtained using a 1.5T scanner and scored by 2 readers for synovitis, bone marrow edema, tenosynovitis, and erosions. For analyses at the joint level, MRI-detected inflammation was considered present if both readers scored the image as positive., Results: Of 193 persons scanned (ages 19-89 years), only 28% had no single inflammatory feature and 22% had no erosions. Primarily low-grade features were observed. All MRI features were positively correlated with age (P < 0.001). Preferential locations for synovitis were MCP2, MCP3, the wrists, and MTP1. Bone marrow edema was frequently present in MCP3, the scaphoid, and MTP1. Tenosynovitis was infrequent, except for in the extensor carpi ulnaris. Preferential locations for erosions were MCP2, MCP3, MCP5, the distal ulna, MTP1, and MTP5. Tables with age-, location-, and inflammation type-dependent frequencies were constructed. Simultaneous colocalized presence of synovitis, bone marrow edema, tenosynovitis, or erosions occurred., Conclusion: MRI-detected inflammation and erosions are prevalent in symptom-free persons from the general population, especially at older ages and at preferential locations., (© 2016, American College of Rheumatology.)

Objective: In patients with rheumatoid arthritis (RA), bone marrow edema (BME) scores are associated with development of erosions. However, little is known about the course and outcome of BME at bone level. We undertook this study to determine the association of BME and synovitis with the development of erosions in the same bone longitudinally., Methods: Using 1.5T magnetic resonance imaging at baseline and at 4- and 12-month follow-up, we studied 1,947 bones of the metacarpophalangeal, wrist, and metatarsophalangeal joints in 59 patients presenting with RA or undifferentiated arthritis. Scanning and scoring of BME, synovitis, and erosions were performed according to the Outcome Measures in Rheumatology Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. We evaluated the relationship of the course of BME and synovitis with erosive progression at bone level during 1 year., Results: Of the bones showing BME at baseline (n = 203), BME persisted in 56%, disappeared in 39%, and disappeared and then reappeared in 5%. Stratified analyses at baseline revealed that BME was associated with erosive progression both in the presence and in the absence of local synovitis, with odds ratios (ORs) of 7.5 (95% confidence interval [95% CI] 3.8-14.9) and 6.9 (95% CI 1.9-25.6), respectively. However, local synovitis was not associated with erosive progression in the presence or in the absence of BME (ORs of 2.0 [95% CI 0.6-7.0] and 1.9 [95% CI 0.8-4.1], respectively). In multivariable generalized estimating equation analyses, persistent BME was strongly associated with erosive progression (OR 60.5 [95% CI 16.8-218.1]) in contrast to persistent synovitis (OR 1.3 [95% CI 0.4-4.4])., Conclusion: BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independently of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for comprehending the development of erosions in RA., (© 2016, American College of Rheumatology.)

Objective: To investigate the association between features of ultrasound-detected inflammation and development of erosive disease in patients with hand osteoarthritis (OA) over 2.3 years of followup., Methods: The study group comprised 56 consecutive patients with hand OA (mean age 61 years, 86% female) fulfilling the American College of Rheumatology criteria. Effusion, synovial thickening, and power Doppler signal in all interphalangeal (IP) joints were assessed with ultrasonography, using standardized methods, at baseline and followup. Radiographs were scored at both time points for osteophytes/joint space narrowing using the Osteoarthritis Research Society International method and for erosive disease (E phase [erosive] and R phase [remodeling]) using the method described by Verbruggen and Veys. Erosion development was defined as progression from N phase (normal) to E phase or R phase. Joints that were in E phase or R phase at baseline were excluded. Associations were analyzed using generalized estimating equations with adjustment for age, sex, body mass index, and baseline structural abnormalities., Results: At baseline, 51 IP joints (in 18 patients) and at followup 89 IP joints (in 26 patients) had erosions; thus, erosions developed in 38 IP joints. Moderate/severe synovial thickening and a power Doppler signal at baseline were associated with erosion development (adjusted odds ratio [OR] 8.8, 95% confidence interval [95% CI] 2.4-32.3 and OR 7.1, 95% CI 1.9-26.9, respectively). Persistent inflammation was particularly associated with the development of erosions., Conclusion: Ultrasound-detected features of inflammation are associated with the development of erosions in patients with hand OA, suggesting that inflammation plays a role in the pathogenesis of hand OA and could be a therapeutic target., (© 2016, American College of Rheumatology.)

Objective: To study the development of inflammatory features and it's relation to structural damage over a 2.3-year period in patients with hand osteoarthritis (HOA)., Methods: Synovial thickening, effusion and power Doppler signal (PDS) in distal interphalangeal (DIP), proximal interphalangeal (PIP), 1st carpometacarpal (CMC) metacarpal phalangeal (MCP) and 1st interphalangeal (IP) joints were assessed using ultrasonography in 56 consecutive HOA patients (mean age 61.2 years, 85.7% female) fulfilling American College of Rheumatology (ACR) classification criteria, at baseline and follow-up. Radiographic progression of osteophytes and joint space narrowing (JSN) was scored using the OARSI atlas. With generalised estimating equations (GEE), OR with 95% CIs were calculated for the associations between inflammatory ultrasound features and radiographic progression taking in account patient effect, age, gender, Body Mass Index, baseline osteophytes and JSN scores, and other inflammatory ultrasound features., Results: Of 1680 joints, 8.4%, 8.7%, and 19.8% had synovial thickening, PDS or effusion at baseline, respectively. 7.1% and 5.7% of joints had progression of osteophytes and JSN, respectively. Independent associations were found between synovial thickening, effusion and PDS (grade 2-3 vs 0), and progression of osteophytes (OR (95% CI): 2.6 (1.02 to 6.5), 3.5 (1.7 to 7.4) and 5.7 (1.5 to 21.1)) and of JSN (OR (95% CI): 3.4 (1.3 to 8.4), 3.3 (1.5 to 7.6) and 3.1 (1.01 to 9.2)). Persistent inflammatory features at baseline and follow-up showed stronger associations with radiographic progression than fluctuating inflammatory features in comparison with no inflammatory features., Conclusions: Inflammatory features, especially when persistently present, are independently associated with radiological progression in HOA after 2.3 years, indicating a role of inflammation in the aetiology of structural damage in HOA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate criterion validity and intraobserver reliability of magnetic resonance imaging (MRI) in hand osteoarthritis (HOA)., Methods: In 16 patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI scans with gadolinium-chelate administration of right second to fifth distal interphalangeal/proximal interphalangeal joints were scored according to the Oslo HOA scoring method for synovial thickening, bone marrow lesions (BML), osteophytes, joint space narrowing (JSN), and erosions (grade 0-3). Ultrasound (US) was scored for synovial thickening and osteophytes, radiographs for osteophytes and JSN (Osteoarthritis Research Society International score), and anatomical phases (Verbruggen-Veys score). Pain was assessed during physical examination. Correlations of MRI with US and radiographic features were assessed with generalizability theory. With generalized estimating equations analyses, MRI features were associated with pain, adjusting for confounding., Results: Forty-three percent, 27%, 77%, and 61% of joints had synovial thickening (moderate/severe), BML, osteophytes, and erosions on MRI, respectively. Intraobserver reliability, assessed in 6 patients, was good (ICC 0.77-1.00). Correlations between osteophytes, JSN, and erosions on radiographs and MRI were moderate, substantial, and fair (ICC 0.53, 0.68, and 0.32, respectively); MRI showed more lesions than radiography. Correlation between synovial thickening and osteophytes on MRI and US was moderate (ICC 0.43 and 0.49, respectively). MRI was more sensitive for synovial thickening, US for osteophytes. Pain was associated with moderate/severe synovial thickening (adjusted OR 2.4, 95% CI 1.06-5.5), collateral ligaments (4.2, 2.2-8.3), BML (3.5, 1.6-7.7), erosions (4.5, 1.7-12.2), and osteophytes (2.4, 1.1-5.2)., Conclusion: MRI is a reliable and valid method to assess inflammatory and structural features in HOA. It gives additional information over radiographs and US.

Background: The phase of arthralgia is the earliest moment to clinically recognize patients who may develop Rheumatoid Arthritis (RA). Previous imaging studies in the arthralgia phase have shown that inflammation precedes RA development. It is unknown which symptoms/characteristics relate to subclinical joint inflammation as measured by MRI. Among all patients with arthralgia, those with clinically suspect arthralgia (CSA) are suspected to progress to arthritis according to the clinical judgement of their rheumatologists. We determined the symptoms/characteristics of patients with CSA who had inflammation on MRI., Methods: 102 patients with CSA and without clinical arthritis were included. They completed questionnaires, underwent joint counts and unilateral 1.5 T MRI of MCP joints 2-4, wrist and MTP joints 1-5. Synovitis, bone marrow oedema (BME) and tenosynovitis were scored according to the OMERACT rheumatoid arthritis MRI scoring system. Symptoms and signs were related to MRI inflammation (based on MRI scores in symptom-free controls; a sum of synovitis, BME and tenosynovitis scores ≥3 was considered positive). Whether certain clinical characteristics frequently occurred together with MRI inflammation was studied by partial least squares analysis., Results: MRI was performed in 93 patients with CSA, 44% of whom had subclinical MRI inflammation. Synovitis was the most prevalent inflammatory feature on MRI (20%). Patients with MRI inflammation were older and were more frequently positive for anti-citrullinated peptide antibodies than patients without MRI inflammation (p<0.001 and 0.049). In PLS analysis, including 16 clinical and serological characteristics as independent variables and MRI inflammation as dependent variable, no clear clusters of patients with and without MRI inflammation were identified., Conclusions: Subclinical inflammation as measured by MRI is present in 44% of patients with CSA. A combination of symptoms/characteristics incompletely differentiated patients with and without MRI inflammation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Baseline erosions are characteristic for rheumatoid arthritis (RA) and predictive for a severe disease course. The mechanisms leading to baseline erosions being a strong predictor for radiological progression are unknown. We aimed to increase this understanding by mediation analyses in an observational cohort and a cross-sectional MRI study., Methods: 3256 hands and feet radiographs of 653 early RA patients assessed during 7 years of disease were scored using the Sharp-van der Heijde method. Mediation models and multivariate regression analyses were used to explore the association between baseline erosions, other predictors and radiological damage over time. 603 joints (MCP2-5 and MTP1-5) of 67 RA patients underwent 1.5 T MRI at baseline. Data on MRI inflammation were compared with clinical inflammation and baseline radiological erosions., Results: Patients with baseline erosions had, at any point in time during 7 years, 3.45 times more joint damage than patients without erosions (p<0.001, 95% CI 3.00 to 3.98). Baseline erosions were an independent predictor and not a mediator between symptom duration, systemic or local clinical inflammation (erythrocyte sedimentation rate (ESR), swollen joint count (SJC)) or autoantibodies (anti-citrullinated-peptide antibodies, rheumatoid factor) and radiological damage. Subclinical MRI inflammation was studied in relation to erosions, revealing that 83% of the non-swollen joints with baseline erosions had subclinical MRI inflammation compared with 25% of the non-swollen joints without baseline erosions (OR 15.2 95% CI 3.1 to 102.1). The association between MRI inflammation and baseline erosions was independent of symptom duration, ESR, SJC and autoantibodies., Conclusions: Baseline erosions are a predictor for future joint damage, independent of known predictors as time, autoantibodies or clinical measurable inflammation. Subclinical inflammation is suggested as an underlying mechanism., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: MRI is increasingly used to measure inflammation in rheumatoid arthritis (RA) research, but the correlation to clinical assessment is unexplored. This study determined the association and concordance between inflammation of small joints measured with MRI and physical examination., Methods: 179 patients with early arthritis underwent a 68 tender joint count and 66 swollen joint count and 1.5T MRI of MCP (2-5), wrist and MTP (1-5) joints at the most painful side. Two readers scored synovitis and bone marrow oedema (BME) according to the OMERACT RA MRI scoring method and assessed tenosynovitis. The MRI data were first analysed continuously and then dichotomised to analyse the concordance with inflammation at joint examination., Results: 1790 joints of 179 patients were studied. Synovitis and tenosynovitis on MRI were independently associated with clinical swelling, in contrast to BME. In 86% of the swollen MCP joints and in 92% of the swollen wrist joints any inflammation on MRI was present. In 27% of the non-swollen MCP joints and in 66% of the non-swollen wrist joints any MRI inflammation was present. Vice versa, of all MCP, wrist and MTP joints with inflammation on MRI 64%, 61% and 77%, respectively, were not swollen. BME, also in case of severe lesions, occurred frequently in clinically non-swollen joints. Similar results were observed for joint tenderness., Conclusions: Inflammation on MRI is not only present in clinically swollen but also in non-swollen joints. In particular BME occurred in clinically non-inflamed joints. The relevance of subclinical inflammation for the disease course is a subject for further studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To study inflammatory ultrasound (US) features and pain over a 3-month period in hand osteoarthritis (HOA)., Design: In 25 consecutive HOA patients (mean age 60 years, 76% female), fulfilling the American College of Rheumatology (ACR) criteria, visual analogue scale (VAS) pain scores were collected at baseline and 3 months. In 750 [all first carpometacarpal (CMC), metacarpalphalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP) and first interphalangeal (IP)] joints, pain was assessed upon palpation and synovial thickening, effusion and power Doppler signal (PDS) were scored with standardized methods by US. Associations between inflammatory features and painful joints were analysed using generalized estimated equations to account for patient effects, adjusting for confounders, and presented as odds ratios (ORs) with 95% confidence intervals (95%CI)., Results: Inflammatory US features were seen in (nearly) all patients. The median number (range) of inflammatory joints per patient did not change over time: 9 (0-16) to 9 (2-18). In 18.7% of joints inflammatory features were present at both time points; in 20.5% inflammatory features occurred only at baseline or follow-up. Pain decreased over time: median VAS pain 49-39 mm; median number of painful joints 8-3. Synovial thickening, effusion and PDS were associated with pain upon palpation both at baseline and follow-up: OR 2.9 (1.4, 5.7), 2.7 (1.7, 4.3), 3.6 (2.1, 6.3) and 7.3 (3.2, 16.5), 3.3 (2.3, 4.7), 4.1 (2.1, 7.9). respectively., Conclusions: In HOA inflammatory US features are stable over time at patient level, but vary on joint level. Pain diminished after 3 months, while associations between painful joints and inflammation seem to increase, emphasizing the multifactorial aetiology of pain., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess whether subclinical inflammatory changes are present on magnetic resonance imaging (MRI) in patients with inflammatory bowel disease (IBD) and arthralgia., Method: In this pilot study, painful hand joints [metacarpophalangeal (MCP), proximal interphalangeal (PIP), and/or distal interphalangeal (DIP)] of 11 IBD patients (age 18-45 years) with continuous pain for > 6 weeks were scanned on a 1.5-T extremity MRI system. A control group of 11 IBD patients without joint pain who were matched for type and disease duration of IBD, gender, and age was included. All patients were clinically examined by a rheumatologist for the presence of pain and arthritis. Imaging was performed according to a standard arthritis protocol with intravenous contrast administration on the same day. Images (blinded for clinical information) were evaluated by two readers in consensus for the presence of joint fluid, synovitis, tenosynovitis, enthesitis, erosions, cartilage defects, and bone marrow oedema., Results: Enthesitis was seen in three hand joints (MCP 2, MCP 3, PIP 3) of 2/11 (18%) arthralgia patients and in none of the control group (p = 0.48). A small amount of subchondral bone marrow oedema was seen in the metacarpal head of two controls. No other abnormalities were observed., Conclusions: Several young IBD patients with chronic hand pain had subclinical inflammation on MRI, which invites for further study in a larger group of patients.

Objective: Although a few consistent osteoarthritis (OA) susceptibility genes have been identified, little is known on OA progression. Since OA progression is clinically the most relevant phenotype, we investigate the association between asporin (ASPN), bone morphogenetic protein 5 (BMP5) and growth differentiation factor 5 (GDF5) polymorphisms and progression of hand OA., Methods: Single-nucleotide polymorphisms (SNPs) ASPN rs13301537, BMP5 rs373444 and GDF5 rs143383 were genotyped in 251 hand OA patients from the Genetics osteoARthritis and Progression (GARP) study and 725 controls. In a case-control comparison we assessed the association between these SNPs and radiographic progression of hand OA over 6 years, which was based on change in osteophytes or joint space narrowing (JSN), above the smallest detectable change. SNPs with suggestive evidence for association were further analysed for their effect on progression over 2 years, and for the mean change in osteophytes and JSN., Results: The minor allele of ASPN SNP rs13301537 was associated with hand OA progression over 6 years (odds ratio (OR) (95% CI) 1.49 (1.06-2.07); P = 0.020). The mean change in osteophytes and JSN was higher in carriers of the minor allele compared to homozygous carriers of the common allele with mean difference of 0.73 (95% CI - 0.07-1.56; P = 0.073) and 0.82 (95% CI 0.12-1.52; P = 0.022), respectively. An association with similar effect size was found between ASPN SNP rs13301537 and 2-year progression, and the mean change in osteophytes and JSN was significantly higher in homozygotes., Conclusion: ASPN is associated with hand OA progression. This gives insight in the pathogenesis of hand OA progression and identified a potential target for therapeutic approaches., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the associations between structural abnormalities on ultrasound (US) or conventional x-rays (CR) and pain in hand osteoarthritis (HOA)., Methods: In 55 consecutive patients with HOA (mean age 61 years, 86% women) fulfilling the American College of Rheumatology criteria, pain in 30 separate hand joints was assessed upon palpation; osteophytes were assessed by US and CR and joint space narrowing (JSN) by CR. Associations between structural abnormalities and pain per joint were analysed using generalised estimated equations to account for patient effects and adjusted for age, sex, body mass index, US inflammatory features and other remaining structural abnormalities., Results: In 1649 joints, 69% and 46% had osteophytes on US and CR, respectively and 47% had JSN. Osteophytes and JSN showed independent associations with pain per joint adjusted: OR for osteophytes: 4.8 (95% CI 3.1 to 7.5) for US and 4.1 (95% CI 2.4 to 7.1) for CR; for JSN: 4.2 (95% CI 2.0 to 9.0)., Conclusions: Osteophytes and JSN are independently associated with pain in individual HOA joints, taking into account patient effects.

Objectives: To investigate the association of ultrasound (US) features-grey scale (GS) synovitis, synovial thickening, effusion and power Doppler signal (PDS)-with symptoms in hand osteoarthritis (HOA)., Methods: Fifty-five consecutive patients (mean age 62 years, 87% women) with HOA, fulfilling the American College of Rheumatology criteria, were assessed for pain upon palpation and filled in Australian/Canadian Osteoarthritis Index (AUSCAN) scores, visual analogue scale pain and Short Form-36 (SF-36). US was performed in all metacarpophalangeal, proximal interphalangeal, distal interphalangeal, first interphalangeal and first carpometacarpal joints, and features were semiquantitatively scored (0-3). Generalised estimating equations were used to calculate OR (95% CI) for the association between US features and pain per joint adjusted for relevant confounders. The association between US features summated scores and self-reported outcomes was studied by linear regression analysis., Results: GS synovitis, effusion, synovial thickening and PDS were shown in 96%, 91%, 73% and 86% of patients, respectively. US features were dose-dependently associated with pain upon palpation (OR 4.5 (95% CI 2.2 to 9.0), 4.4 (2.0 to 9.4), 4.9 (2.2 to 11.0) and 4.1 (2.2 to 7.9)). GS synovitis was associated with AUSCAN pain, stiffness and SF-36, and effusion with AUSCAN pain., Conclusions: GS synovitis, effusion, synovial thickening and PDS are associated with pain in HOA, suggesting a role for inflammation. Further follow-up studies are warranted.