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Objectives: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment., Methods: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis., Results: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease)., Conclusions: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To measure with US the intima-media thickness (IMT) of temporal (superficial, parietal and frontal branches) and axillary arteries in subjects without a diagnosis of GCA and/or PMR with different cardiovascular (CV) risk; and to assess the performance of previously proposed cut-off values for normal IMT., Methods: Subjects ≥ 50 years without a diagnosis of GCA or PMR were included. Bilateral US of the temporal arteries, including the frontal and parietal branches, and axillary arteries was performed by two sonographers using a 10-22 MHz and 6-18 MHz probe. The following previously proposed cut-offs were considered: superficial temporal artery: 0.42 mm; frontal branch: 0.34 mm; parietal branch: 0.29 mm; axillary artery: 1.0 mm., Results: A total of 808 arteries in 101 subjects were evaluated; of these, 31 (30.7%) were classified as very high CV risk, seven (6.9%) as high, 34 (33.7%) as moderate and 29 (28.7%) as low risk. Subjects with very high or high risk showed higher IMT than those with moderate or low risk in the superficial temporal arteries [0.23 (s.d. 0.07) vs 0.20 (s.d. 0.04), P < 0.01] and in the axillary arteries [0.54 (s.d. 0.17) vs 0.48 (s.d. 0.10), P = 0.002] . The IMT was higher than the reference cut-off in 13/808 (1.6%) arteries, in ≥1 artery in 10/101 subjects (10.1%). Of these 10 subjects, 8 (80%) were classified as having very high or high risk., Conclusion: Our results suggest that CV risk might influence the US-determined IMT of the temporal and axillary arteries in subjects without GCA. Therefore, in patients with suspected GCA, particular attention should be paid when measuring the IMT in those patients with very high/high CV risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: According to guidelines, clinical arthritis is mandatory for diagnosing RA. However, in the absence of clinical synovitis, imaging-detected subclinical synovitis is increasingly used instead and is considered as a starting point for DMARD therapy. To search for evidence we studied the natural course of arthralgia patients with subclinical synovitis from three longitudinal cohorts and determined the frequencies of non-progression to clinically apparent inflammatory arthritis (IA) (i.e. 'false positives')., Methods: Subclinical synovitis in the hands or feet of arthralgia patients was visualized with US (two cohorts; definition: greyscale ≥2 and/or power Doppler ≥1) or MRI (one cohort; definition: synovitis score ≥1 by two readers). Patients were followed for 1  year on for IA development; two cohorts also had 3  year data. Analyses were stratified for ACPA., Results: Subclinical synovitis at presentation was present in 36%, 41% and 31% in the three cohorts. Of the ACPA-positive arthralgia patients with subclinical synovitis, 54%, 44% and 68%, respectively, did not develop IA. These percentages were even higher in the ACPA-negative arthralgia patients: 66%, 85% and 89%, respectively. Similar results were seen after 3 years of follow-up., Conclusion: Replacing clinical arthritis with subclinical synovitis to identify RA introduces a high false-positive rate (44-89%). These data suggest an overestimation regarding the value of ACPA positivity in combination with the presence of subclinical synovitis in patients with arthralgia, which harbours the risk of overtreatment if DMARDs are initiated in the absence of clinical arthritis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: We researched the findings of musculoskeletal ultrasound sonography (MSUS) on primary Sjogren's syndrome in childhood (pSS-C) with articular manifestations. The correlation of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were investigated to evaluate the usefulness of MSUS on their articular prognosis. Method: The objective patients are pSS-C cases who visited our hospital complaining joint pain and/or joint swelling and for whom MSUS was performed. Result: Eight patients included 6 female and 2 male, 5 RF-positive patients and 3 ACPA- positive patients. The mean age of onset was 11.1 ± 3.0 years (352 physical joint findings and 284 MSUS findings. The number of joints found clinical articular manifestations was 58/352 joints, and arthritis detected by MSUS was 30/284 joints). In multivariate analysis, the odds ratio of clinical articular manifestations was significant high in RF-positivity (2.9, 95%CI 1.5-6.2). The odds ratio of arthritis detected by MSUS in ACPA-positivity was significant high (3.7, 95%CI 1.5-11.6), although odds ratio in RF-positivity had no statistical significance and a similar trend was seen in odds ratios of subclinical arthritis (4.9, 95%CI 1.6-18.0). Conclusion: It was indicated that MSUS is useful for pSS-C. ACPA-positive pSS-C patients have arthritis and subclinical arthritis more frequently than ACPA-negative patients.

Background: Sacroiliitis, an inflammatory arthropathy associated with ankylosing spondylitis (AS), is found in patients with inflammatory bowel disease (IBD) but may go undiagnosed. The aims of this study were to assess prevalence of sacroiliitis in IBD and to determine association between clinical characteristics of IBD and sacroiliitis., Methods: Inflammatory bowel disease patients undergoing abdomino-pelvic computed tomography (CT) for any indication (2006-2015) were identified. Using standardized CT scoring, sacroiliitis was confirmed. Two blinded readers used a standardised model where presence of ankylosis or erosion score >3 indicated sacroiliitis. Inflammatory bowel disease scoring was blinded to the presence of sacroiliitis. Demographics, IBD characteristics, clinical activity (Harvey Bradshaw Index >4, Mayo >2, as denoted by attending physician), endoscopic activity (Simple Endoscopic Score for Crohn's Disease >4/Mayo subscore >1), and arthritis/extraintestinal manifestations (EIMS) were recorded. Comparisons were made between those with/without sacroiliitis., Results: Three hundred sixteen patients were included (50% male; 74% Crohn's disease [CD]). Computed tomography scoring identified 49 (16%) with sacroiliitis. Radiologists had reported sacroiliitis in 33% of these. Five patients had been to a spondylitis clinic. Thirty-three of 49 had abdominal x-rays; 64% of these fulfilled the imaging component of Modified New York criteria for AS. More than 5 sacroiliac erosions were associated with radiologist-reported sacroiliitis (P < 0.0001). There was no difference in prevalence between CD and ulcerative colitis. Sacroiliitis was associated with male sex (63.3% vs 47.9%; odds ratio [OR], 1.8; P = 0.04), known arthritis (41% vs 12%; OR, 4.7; P < 0.0001), pain as an IBD symptom (77.7% vs 56.9%; P = 0.03), and CD inflammatory phenotype (P = 0.01). Endoscopic activity, location, and extent were not associated., Conclusions: Sacroiliitis is underdiagnosed in IBD and is associated with male sex, arthritis, and inflammatory CD. Data support targeted screening in at-risk patients., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled anti-fibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis., Methods: Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores., Results: Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50%, vs 100% in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented., Conclusion: These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.

Objectives: The use of hand and foot MRI in the diagnostic process of RA has been advocated. Recent studies showed that MRI is helpful in predicting progression from clinically suspect arthralgia (CSA) to clinical arthritis, and from undifferentiated arthritis (UA) to RA. Symptom-free persons can also show inflammation on MRI. This study aimed to evaluate if MRI findings in symptom-free volunteers are relevant when defining a positive MRI., Methods: Two hundred and twenty-five CSA patients and two hundred and one UA patients underwent MRI of MCP, wrist and MTP joints at baseline and were followed for 1 year on progression to arthritis and RA, respectively, as reported previously. MRI was considered positive if ⩾ 1 joint showed inflammation (called uncorrected definition), or if ⩾ 1 joint had inflammation that was present in < 5% of persons of the same age category at the same location (called 5% corrected definition). Test characteristics were compared for both definitions., Results: By using MRI data of symptom-free volunteers as reference, specificity of MRI-detected inflammation increased from 22 to 56% in CSA patients, and from 10 to 36% in UA patients. The sensitivity was not affected; it was 88 and 85% in CSA patients and 93 and 93% in UA patients. The accuracy also increased, from 32 to 60% in CSA patients and 22 to 44% in UA patients., Conclusion: The use of a reference population resulted in a substantial reduction of false-positive results, without influencing the sensitivity. Although common for other tests in medicine, this phenomenon is novel for MRI in the early detection of RA., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objectives: To assess the diagnostic value of MRI for early RA. In some RA patients, a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence for its reliability is limited., Methods: MRI of hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic (229 presented with RA, 159 with other arthritides and 201 with UA). Symptom-free controls provided a reference for defining an abnormal MRI. In preliminary investigations, MRI of patients who presented with RA was compared with MRI of symptom-free controls and of patients with other arthritides. Thereafter, the value of MRI in early RA diagnosis was determined in UA patients using the 1-year follow-up on fulfilling the 1987 RA criteria and start of disease-modifying drugs as outcomes., Results: Preliminary investigations were promising. Of the UA patients, 14% developed RA and 37% started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA development independent of other types of MRI-detected inflammation [odds ratio (OR) = 7.5, 95% CI: 2.4, 23] and also independent of age and other inflammatory measures (swollen joints, CRP) (OR = 4.2, 95% CI: 1.4, 12.9). Within UA patients, the negative predictive value of abnormal tenosynovitis was 95% (95% CI: 89%, 98%) and the positive predictive value 25% (95% CI: 17%, 35%). The performance was best in the subgroup of UA patients presenting with oligoarthritis (18% developed RA): the positive predictive value was 36% (95% CI: 23%, 52%), the negative predictive value was 98% (95% CI: 88%, 100%), the sensitivity was 93% (95% CI: 70%, 99%) and the specificity was 63% (95% CI: 51%, 74%)., Conclusion: MRI contributes to the identification of UA patients who will develop RA, mostly in UA patients presenting with oligoarthritis., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Blau syndrome (BS) is an autosomal dominant autoinflammatory disease associated with NOD2 gene mutations. It is characterized by arthritis, skin rash, and uveitis. Here, we report contrasting outcomes of a daughter and her mother with BS. Their long-term follow-up revealed the efficacy of anti-tumor necrosis factor inhibitor (TNF) with respect to BS. Joint findings of BS feature tenosynovitis over articular synovitis on ultrasonography. BS might be one of the differential diagnoses of juvenile idiopathic arthritis and rheumatoid arthritis.

Objectives: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS)., Methods: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months)., Results: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively., Conclusion: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Musculoskeletal symptoms are common in SLE and are associated with significant morbidity. However, assessing their nature can be challenging, with implications for treatment decisions and measuring response. US has been shown to be valid and reliable for the assessment of other inflammatory arthritides, but data in SLE are more limited. The objectives of this systematic literature review were to determine the characteristics of musculoskeletal US abnormalities in SLE and to evaluate the metric properties of US in the detection and quantification of musculoskeletal symptoms., Methods: We systematically searched the literature using the PubMed, Embase and Cochrane Library databases for studies using musculoskeletal US for assessing SLE. Studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies tool and for their metric qualities, including reliability and validity., Results: Nine studies were identified. Most studies investigated construct validity. Rates of abnormality were highly variable: synovitis and tenosynovitis were reported in 25-94% and 28-65% of patients, respectively; power Doppler and erosions were reported in 10-82% and 2-41% of patients, respectively. There was poor to moderate association between US abnormalities and disease activity indices and immunological findings. There was moderate to high risk of bias and there were concerns about applicability in most studies., Conclusion: US has potential value in the assessment of musculoskeletal symptoms in SLE. However, there is methodological variation between studies that may account for lack of consensus on US abnormalities. Studies that address these problems are required before US can used as an outcome measure in SLE., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To report baseline articular, functional and ocular findings of the first international prospective cohort study of Blau syndrome (BS)., Methods: Three-year, multicentre, observational study on articular, functional (HAQ, Childhood HAQ and VAS global and pain), ophthalmological, therapeutic and radiological data in BS patients., Results: Baseline data on the first 31 recruited patients (12 females and 19 males) from 18 centres in 11 countries are presented. Of the 31 patients, 11 carried the p.R334W NOD2 mutation, 9 the p.R334Q and 11 various other NOD2 missense mutations; 20 patients were sporadic and 11 from five BS pedigrees. Median disease duration was 12.8 years (1.1-57). Arthritis, documented in all but one patient, was oligoarticular in 7, polyarticular in 23. The median active joint count was 21. Functional capacity was normal in 41%, mildly impaired in 31% and moderate-severe in 28% of patients. The most frequently involved joints at presentation were wrists, ankles, knees and PIPs. On radiographs, a symmetrical non-erosive arthropathy was shown. Previously unknown dysplastic bony changes were found in two-thirds of patients. Ocular disease was documented in 25 of 31 patients, with vitreous inflammation in 64% and moderate-severe visual loss in 33%. Expanded manifestations (visceral, vascular) beyond the classic clinical triad were seen in 52%., Conclusion: BS is associated with severe ocular and articular morbidity. Visceral involvement is common and may be life-threatening. Bone dysplastic changes may show diagnostic value and suggest a previously unknown role of NOD2 in bone morphogenesis. BS is resistant to current drugs, suggesting the need for novel targeted therapies., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to determine whether the presence of peripheral arthritis can affect radiographic structural damage in patients with AS., Methods: A total of 915 subjects comprising 363 patients with a history of peripheral arthritis and 552 patients without a history of peripheral arthritis obtained from the Observation Study of the Korean SpA Registry (OSKAR) were analysed looking at the relationship of peripheral arthritis history in a cross-sectional survey as well as the radiographic damage score according to the presence or absence of peripheral arthritis. Radiographs and clinical information were available for 501 subjects (205 peripheral arthritis patients and 296 without peripheral arthritis) at a mean follow-up of 2.7 years. The modified Stoke AS Spinal Score (mSASSS) was examined by two experienced radiologists to validate the results. Reliability was evaluated using the intraclass correlation coefficient for each radiograph., Results: The agreement between the two readers regarding the mSASSS was good. On simple comparison there was a significant difference in the mSASSS between patients with a history of peripheral arthritis and those without [mean 14.62 (s.e.m. 0.83) vs 18.78 (0.79), P < 0.001]. The mSASSS change was stratified according to the presence or absence of peripheral arthritis at baseline. After adjusting for multiple comparisons by Bonferroni correction, the patients with peripheral arthritis had less mSASSS change than those without peripheral arthritis [3.08 (s.e.m. 0.61) vs 5.18 (0.47), P = 0.008]., Conclusion: The presence of peripheral arthritis delays spinal radiographic progression in AS., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To study the role of different imaging modalities, ultrasonography, conventional radiography (CR) and CT, in visualization of chondrocalcinosis of the knees in patients with CPDD., Methods: Twenty-five patients (14 males and 11 females) with CPDD were enrolled in the study. Diagnosis was made according to D.J. McCarty classification criteria. All patients had arthritis of the knee and underwent aspiration of SF from the knee and microscopic investigation of SF samples. Diagnosis of CPDD was crystal proven. Three imaging methods were performed in patients: CR, CT and US of the knees., Results: CR of the knee confirmed cartilage calcification (CC) in 13 patients, CT in 18 patients and US in 25 patients. No difference in age or disease duration between patients with CC detected by different imaging methods was found., Conclusion: US appeared to be a helpful tool, possibly better than CR or CT, in revealing CC in patients with CPDD. Informativity of CT and CR in the detection of CC is almost equal.

Objective: The main aim of this study was to investigate the short-term efficacy of CS loco-regional treatment performed under US guidance in tenosynovitis of patients with chronic inflammatory arthritis., Methods: Thirty consecutive patients affected by chronic arthritis and with clinical suspicion of tenosynovitis were recruited to undergo US assessment. In the sonographically proven cases, US-guided CS injection was performed. A visual analogue scale for pain (ranging from 0 to 10) and a tenderness score (ranging from 0 to 3) were used for the clinical evaluation. Sonographic pathological findings indicative of tenosynovitis were scored using a semi-quantitative 4-grade scoring system, for both grey-scale and power Doppler US, at baseline and during a follow-up visit at 2 weeks after the CS injection., Results: In 21 (70%) of 30 patients, the clinical suspicion of tenosynovitis was confirmed (9 with RA, 11 with PsA and 1 with ReA). In the other nine patients, US revealed synovitis of the adjacent joints, bursitis, oedema of the s.c. tissue or a partial tear. In all cases the appropriate needle placement and subsequent CS injection into the tendon sheath were obtained with US confirmation. A significant reduction in all clinical and sonographic scorings was found during the follow-up visit., Conclusions: The present study shows the efficacy of US-guided peritendinous CS injections in the management of patients with chronic inflammatory arthritis presenting as US-proven tenosynovitis.

The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.

Objective: Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint oligoarthritis., Methods: Patients with SpA-related oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 0-45). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA., Results: Forty-four patients were recruited [mean age 32 years (range 15-59 years), 70% male] with a mean disease duration at baseline of 9.75 months (1-48 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.4-12.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes., Conclusion: SpA-related knee joint oligoarthritis has significant long-term clinical and radiological morbidity despite standard treatments. HLA-B27 and MRI BMO were not predictors of poor outcome as they are in axial SpA; however, the presence of psoriasis predicted significantly worse outcome.

We report a case of fibroblastic rheumatism (FR) in a 61-year-old woman. The patient showed sclerodactyly and polyarthritis that involved both her hands and feet joints. Levels of C-reactive protein and matrix metallopeptidase-3 were within normal range. We diagnosed her condition as FR according to both the clinical features characterized with the destructive change of multiple joints and the histological sample. This is the first FR published case of FR in an Asian individual, and 23 published cases were reviewed.

Objective: To determine the first signs and symptoms, and the clinical, biological and radiological characteristics of patients with early SpA., Methods: A total of 150 SpA patients were selected from 2367 listed in REGISPONSER (Registro Español de Espondiloartritis de la Sociedad Española de Reumatología). The inclusion criterion was a disease course of

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective-tissue disease with a complex phenotype and varying disease course. Although SLE often causes a polyarticular synovitis, there are only a few case reports of abnormalities of the synovial lined sacroiliac joints. We report a case with an overlap syndrome of SLE and dermatomyositis who subsequently developed bilateral symptomatic sacroiliitis. We conclude that sacroiliitis, although rare, can occur in patients with active SLE as a manifestation of the disease per se.

Objective: To evaluate the metric qualities of power Doppler ultrasound (PDUS) for different quantification methods and devices in the assessment of arthritis during anti-inflammatory treatment., Methods: Twenty-four patients with active arthritis and first-time treatment with the TNF-alpha inhibitor adalimumab underwent sequential clinical, laboratory and US examination at baseline, weeks 2, 6 and 12. 2D and 3D PDUS was performed by two independent investigators. The images and movies were scored from 0 to 3 and the amount of colour pixels and voxels was calculated. In addition, the resistance index of a synovial artery was measured. Thirteen patients were examined with a second US machine., Results: Treatment response was already observed at week 2 with a significant reduction of 2D (P < 0.01) and 3D scores (P < 0.001). A moderate correlation to 28-joint disease activity score was found for 3D voxel count (r(s) = 0.35, P < 0.001). Interobserver agreement was kappa or ICC >or= 0.8 for all methods except the resistance index (ICC = 0.60). Intermachine agreement was kappa = 0.57 for 2D PDUS score., Conclusions: The study demonstrates good to excellent interobserver and moderate intermachine reliability of different PDUS assessment methods in a longitudinal open-label study.

Objective: Describe four generations (11 members) of a family with a cryopyrin-associated periodic syndrome (CAPS), including joint destruction, associated with a CIAS1-gene mutation and good responses to anakinra., Methods: In addition to detailed questioning and physical examination, six family members underwent haematological, immunological and biochemical testing. Exon 3 of the CIAS1 gene was sequenced in search of a mutation in the 1q44 region., Results: During childhood or adolescence, four family members developed different combinations of the following CAPS manifestations: deafness (3/4); arthritis (4/4) with joint destruction for two of them; nervous (cerebral demyelinization, 2/4), cutaneous (livedo and/or urticaria, 3/4) and eye lesions (episcleritis and/or papilloedema, 4/4); IgA hypergammaglobulinaemia (4/4) and inflammatory syndrome (3/4). Sequencing of six family members' CIAS1-gene exon 3 identified a heterozygous mutation, c.1043C > T. Pertinently, this CAPS is distinct from chronic infantile neurological cutaneous and arthritis syndrome/neonatal onset multisystemic inflammatory disease syndrome and Muckle-Wells syndrome (MWS), which also result from exon 3 mutations in this gene. Moreover, this family did not have the usual neurological manifestations, typical morphological features and frequent amyloidosis of MWS., Conclusions: We describe a previously unreported form of CAPS with atypical neurological signs, joint destruction and livedo. This observation extends the clinical spectrum associated with CIAS1 mutations. Anakinra, an interleukin-1-receptor antagonist, prescribed to two family members, was highly effective.

Objectives: To examine whether patients with arthritic diseases and carpal tunnel syndrome (CTS) have increased cross-sectional areas of the median nerves measured by ultrasonography (US). Enlarged cross-sectional areas have previously been found in non-arthritic patients with idiopathic CTS., Methods: During 1 yr, all 12 patients with rheumatoid arthritis (RA) or other arthritic diseases hospitalized in our department for surgery for CTS were included. Nine of the patients had bilateral CTS, giving a total of 21 pathological nerves. The median duration of CTS symptoms was 9.5 months. The controls were 30 randomly selected RA patients without symptoms of CTS and 30 healthy persons. Both CTS patients and controls were examined bilaterally by use of US at the entrance of the carpal tunnel, and the cross-sectional areas of the median nerves were calculated., Results: Cross-sectional areas of the median nerves were significantly higher in the CTS patients compared with the RA controls and healthy persons; median (range) areas were 15.7 mm(2) (11.1-21.8), 8.5 mm(2) (5.8-11.0) and 8.0 mm(2) (4.9-12.0), respectively (P<0.0001). No significant differences in cross-sectional areas were observed between the two control groups, or between the right and left hand in the control groups., Conclusions: Higher cross-sectional areas were found in the arthritic patients with CTS than in RA patients and healthy persons without CTS. This supports previous studies of idiopathic CTS in which increased cross-sectional areas have been found. Thus, as in idiopathic CTS, arthritic patients may be examined by US of the median nerve when CTS is suspected.

Objective: To investigate the progression of radiographic changes of the temporomandibular joint (TMJ) with reference to plasma levels of interleukin-1beta (IL-1beta), C-reactive protein (CRP) and disease duration., Methods: Twenty-one patients with chronic inflammatory joint disease and TMJ involvement were included. Individualized tomography of the TMJ was performed twice with an interval of at least 12 months. Blood samples were analysed for IL-1beta and CRP., Results: Significant progression of the overall grade of radiographic changes occurred during the observation period, whereas erosions showed great interindividual variability. Progression of TMJ bone loss was correlated to raised levels of CRP and, in patients with a diagnosis of rheumatoid arthritis, or with shorter duration, also to plasma IL-1beta., Conclusion: Progression of overall grade of radiographic changes in the TMJ occurs in patients with chronic inflammatory joint disease. Raised levels of serum CRP are associated with progression of TMJ bone loss.

Bone scintigraphy is requested as part of the investigation of foot pain, but its contribution to clinical management has not been comprehensively documented. Previously published data are limited; the most comprehensive series identified scintigraphic abnormalities in patients with primarily orthopaedic problems and a control group was not included (Maurice HD et al. J Bone Joint Surg 1987;69B:448 52). The aim of this study was to evaluate whether bone scintigraphy may be useful in different clinical circumstances indicated by referral request details. Regions of scintigraphic abnormality were scored and compared with clinical details drawn from case notes of 60 patients with foot pain. The commonest clinical indications for scans were: confirmation of the clinical suspicion of plantar fasciitis, documentation of the extent of inflammatory arthritis and location of focal pathology. A group of 30 asymptomatic, age- and sex-matched controls were also studied. In 14 out of 19 symptomatic feet in the plantar fasciitis group, focal uptake at the medial calcaneal tubercle was present, confirming the diagnosis. In patients with non-specific, diffuse foot pain, the bone scan identified focal abnormalities in 11 out of 14 cases, thus directing the clinician to the site of pathology. Scintigraphy also proved useful in mapping local inflammatory disease. Technetium-99m methylene diphosphonate image abnormalities occurred in the control group most commonly in the midfoot (16 regions in 13 subjects) and first metatarsophalangeal joint (19 regions in 14 subjects).

The plasminogen activation system is one of the enzyme systems held responsible for bone and cartilage degradation in rheumatoid arthritis (RA). In this study, we evaluated the effect of tranexamic acid (TEA), an inhibitor of plasminogen activation, on urinary collagen cross-link excretion and radiological joint damage in rat adjuvant arthritis (AA) and on urinary collagen cross-link excretion in patients with RA. In the animal study, adjuvant arthritis was induced in male Lewis rats. From day 7 onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo was administered orally. Study groups consisted of TEA-treated normal rats (C + TEA), placebo-treated normal rats (C + plac), AA rats treated with TEA (AA + TEA) or with placebo (AA + plac). To monitor joint destruction, urinary collagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) was measured by high-performance liquid chromatography at days 14 and 21. Radiological evaluation of joints was performed at day 21. In the patient study, TEA was administered to nine patients with RA as adjuvant medication (approximately 20 mg/kg body weight, three times daily) for 12 weeks. Urinary HP and LP excretion levels were measured before and during TEA treatment, and 4 weeks after the cessation of TEA treatment. In AA + TEA rats, a significant reduction of HP and a tendency towards a reduction of LP excretion were found compared with AA + plac rats (P < 0.05), at day 14, whereas the HP/LP ratio did not change. No difference was observed in HP, LP excretion, HP/LP ratio and radiological damage score between the TEA- and placebo-treated AA rats at day 21. In RA patients, a significant reduction of HP and LP excretion was found during the TEA treatment period (P < 0.05). After the cessation of TEA treatment, HP and LP excretion increased towards baseline levels. No effect on disease activity was observed. The plasmin antagonist TEA reduced the excretion of collagen pyridinoline cross-links in both experimental and rheumatoid arthritis. As such, this study not only supports the involvement of the plasminogen activation system in the destructive phase of arthritis, but also suggests a beneficial effect of therapeutic strategies directed against inhibition of matrix proteolysis.

Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent self-limiting attacks of joint, chest and abdominal pain associated with fever. The most serious complication in FMF is the development of amyloidosis, which usually leads to death from renal failure within a year. The use of colchicine has dramatically reduced this complication. We describe a 56-yr-old female patient with FMF in whom the arthropathy became the dominant clinical feature, resulting in the development of an erosive large and small joint arthritis during the course of the disease. The patient was treated with colchicine, but despite this, later developed amyloidosis confirmed on rectal biopsy, and chlorambucil was added to her treatment. For 10 yr, she also suffered intermittent abdominal pain and had terminal ileal changes suggestive of Crohn's disease. However, she was found to have ischaemic colitis at post mortem secondary to amyloidosis. Ischaemic bowel disease is an extremely unusual event in FMF. Other factors which may have contributed to the terminal ischaemia in this patient include anaemia secondary to blood loss and a drug-induced myelodysplasia, as well as hypotension during the final septicaemic illness. Clinicians should consider an ischaemic colitis as a possible differential diagnosis of abdominal pain in patients with FMF even in the absence of other clinical evidence of systemic amyloidosis.

We evaluated 31 painful shoulders of 30 patients with chronic arthritis by ultrasonography (US) and compared the results with those of magnetic resonance imaging (MRI). Both US and MRI revealed effusion in the subacromial-subdeltoid (SA-SD) bursa, biceps tendon sheath (BTS) and glenohumeral (GH) joint, but MRI was more accurate in depicting joint inflammation because of its ability to visualize synovial hypertrophy. US visualized biceps tendon ruptures equally well as MRI. MRI was better able to reveal full-thickness tear of the supraspinatus tendon, whereas US showed better other changes of the supraspinatus tendon (degeneration or partial-thickness tear). Both of the imaging methods were able to depict erosions of the humeral head, but the locations occasionally differed. Inexpensive and easily available US can be recommended as the first imaging method for the detection of soft-tissue changes in the arthritic shoulder, but in rotator cuff problems both methods may be needed.

The clinical, histopathological, and immunophenotypic characteristics of four cases of malignancy-associated multicentric reticulohistiocytosis (MMR) and one case each of diffuse cutaneous reticulohistiocytosis (DCR) and isolated reticulohistiocytoma (IR), are reviewed. In all four cases of MMR the cutaneous lesions and joint manifestations were judged to be concurrent with the diagnosis of malignancy. Malignancies observed included one case each of pancreatic adenocarcinoma, squamous cell carcinoma of the lung, metastatic melanoma and intraperitoneal grade 4 mucinous adenocarcinoma of uncertain origin. Histologically, all six cases demonstrated the typical changes of a diffuse histiocytic and multinucleated giant cell infiltrate with ground-glass cytoplasm, predominantly in the upper dermis. Immunohistochemical investigation revealed strong cytoplasmic staining with KP-1 (CD68) in all six cases. Prominent membrane staining was noted with leucocyte common antigen (CD45) in four cases (three MMR and one IR), and CD3 in four cases (three MMR and one IR). Weak membrane staining with Leu 22 (CD43) was noted in two MMR cases. UCHL-1 (CD45RO), L26 (CD20), S-100 and BerH2 stains were all uniformly negative. A prominent number of perilesional factor XIIIa-positive dermal dendrocytes were noted in the single case of IR, in contrast with the other five cases. We conclude that MMR, DCR and IR are histopathologically and immunohistochemically similar. The pattern of immunoreactivity observed is consistent with a monocyte-macrophage origin of the infiltrating tumour cells. We emphasize the paraneoplastic association of multicentric reticulohistiocytosis, which we have observed in four of 13 such cases (31%) evaluated at our institution.

Endothelial cell stimulating angiogenesis factor (ESAF) is raised in conditions of neovascularization, such as may occur at the endochondral surface of the bone growth plate or in association with syndesmophyte formation. Syndesmophytes are formed in response to chronic enthesitis. Twenty unselected patients with AS were studied and enthesitis was measured clinically using a previously validated enthesitis index. Biochemical and haematological markers of disease activity were measured along with ESAF. Radiographs were scored for the degree of sacroiliitis and syndesmophyte formation and all these measurements were correlated to the enthesitis index. ESAF was raised in AS compared with normal controls. ESAF correlated positively with the enthesitis index but not with any of the biochemical or haematological indices. Higher levels of ESAF were found in those with more advanced sacroiliitis. High ESAF activity may be reflecting the angiogenic process involved in new bone formation associated with sacroiliitis and syndesmophyte formation. ESAF may be a biochemical marker for disease activity in AS.

Arthritis is a recognized complication of untreated coeliac disease. Symptoms and signs usually respond to the institution of a gluten-free diet. We report a case of occult coeliac disease presenting as a monoarthritis. Severe and progressive erosive damage has occurred in his talo-navicular joint despite a response to the institution of a gluten-free diet.

Radiographs of the sacroiliac joints of 34 patients with Behçet's disease were read blind by a senior radiologist. They were compared with those from 25 controls, 14 of whom were healthy. The remainder (11) had other rheumatological disorders including six who had AS. One patient with Behçet's disease had radiologically proven sacroiliitis only but her history was atypical and she was B27 positive. All patients with AS had definite sacroiliitis. Five out of 34 patients with Behçet's disease and four of 25 controls (three healthy, one with SLE) had equivocal sacroiliitis. Whilst appreciating that the numbers in this study are not large, we find no evidence of an increased prevalence of sacroiliitis in Behçet's disease.

A patient with polyarthritis had radiographs of the wrists taken at presentation and again at 6 months. At presentation radiographs were normal, but repeat X-rays at 6 months showed complete erosion of both ulnar styloid processes. This did not correlate with the clinical picture of a mild synovitis. A third X-ray showed normal wrists, revealing the cause to be a positional artefact during the X-ray procedure. Clinicians should be aware of this 'catch'.

We carried out a prospective study of the clinical, laboratory and radiological features of 180 patients with psoriatic arthritis. We initially classified our patients into five groups as described in the publications of Moll and Wright. Thirty-seven per cent had oligoarthritis, 36% polyarthritis, 23% spondarthritis (sacroiliitis and/or spondylitis) and 4% had the mutilans form. The distal joint arthritis type did not exist as an entity and the distal interphalangeal (DIP) joints were affected in all groups. The spondarthritis form includes patients with exclusively axial manifestations and also those who in addition have peripheral arthritis (oligoarthritis, polyarthritis, DIP arthritis). Only 53% of our patients had nail involvement. We found an increase of IgA levels in patients with axial disease. This suggests a relationship between ankylosing spondylitis and psoriatic spondylitis. The HLA-B17/Cw6 association increased in the oligoarticular form. The increase of antigen B17 correlated with the spondarthritic and oligoarthritis forms whereas Cw6 was more important in the oligoarthritis form. An increase of the HLA-B27/Cw1 association and the spondarthritic form was also found. Moreover, we detected a greater incidence of the HLA-B27 antigen in patients with bilateral sacroiliitis (85%) than in patients with unilateral sacroiliitis (22%). Our work revealed that PA is not a harmless disease; 57% of our patients had erosive arthritis while 19% had ARA class III or IV functional impairment.

Proteoglycan levels were measured in a series of synovial fluid samples from patients with acute and chronic joint diseases using a modified chemical dye binding method. Levels found in 50 miscellaneous inflammatory arthritis fluids (mean = 173.2 +/- 90.9 micrograms/ml) were higher than found in either 50 with rheumatoid arthritis (96.3 +/- 31.3 micrograms/ml) or 50 with osteoarthritis (83.8 +/- 27.3 micrograms/ml). For comparison, proteoglycan levels were measured in 15 cadaver synovial fluids (98.9 +/- 44.2 micrograms/ml) and 12 synovial fluids from patients with sports injury (163.7 +/- 79.4 micrograms/ml). Patients were recruited into a trial where synovial fluid was aspirated as often as possible over a 6-month period during which the patients were followed using a number of well proven clinical parameters. No correlation was found between the degree of joint destruction as measured by X-ray damage and the concentration or total amount of proteoglycan in the synovial fluid. In addition, there was no correlation between the level or total amount of proteoglycan and any clinical parameter of disease activity.

Out of a population of 97 haemodialysis patients, 36 patients with dialysis arthropathy were identified. Dialysis arthropathy is a chronic symmetrical polyarthritis which affected 97 per cent of the patients who had been undergoing cuprophane haemodialysis for more than 10 years. It commonly affected the shoulders, hips, hands, knees and wrists, worsening with time and extending to other joints. Fifty-eight per cent of the patients complained of morning stiffness and 47 per cent complained of exacerbation of shoulder pain during or after haemodialysis. Half of the patients also suffered from carpal tunnel syndrome, which recurred and was associated with a long-lasting disability. The most common radiological abnormality was periarticular bone cysts, followed by articular erosions and a destructive spondyloarthropathy, but clinical symptoms were more common than radiological signs. Patients with dialysis arthropathy had a higher C-reactive protein level than patients without arthropathy (18.6 mg/l versus 11.4 mg/l), indicative of an inflammatory process. Some of the clinical manifestations of the disease correlated with levels of C-reactive protein and ferritin. Serum ferritin levels correlated strongly with the units of blood transfused in the past five years (RS = 0.83), and the logarithm of ferritin level correlated weakly with C-reactive protein (r = 0.32). Haemarthroses were documented in 19 per cent of patients. Mean serum beta 2-microglobulin was elevated in the patients with (57.3 mg/l) and without arthropathy (50.7 mg/l), and there was no difference in the parathormone or aluminium levels between these groups. Articular tissue was obtained in 25 patients; beta 2-microglobulin amyloid was present in 24. Larger deposits were present in the capsular tissue, and these appeared to replace collagen bundles in eight cases. Amyloid deposits replaced the lining layer in six cases. It is likely therefore that amyloid disrupts normal joint function by replacing normal joint tissue. Mild chronic synovitis with haemosiderin deposition were found in approximately 60 per cent of cases. These findings suggest that amyloid derived from beta 2-microglobulin has a primary role in the pathogenesis of dialysis arthropathy, but there was also evidence of inflammatory processes. It is suggested that iron overload or haemarthroses might contribute to the inflammation, but other factors, such as dialysis-related bioincompatibility reactions, may also have a role.

Five hundred and forty patients attending a rheumatology ward were screened for antinuclear antibodies (ANA) by indirect immunofluorescence (IFL). Seventy had a significant titre of ANA. Twenty-three had U1-ribonucleoprotein antibodies (U1-RNP-ab). The clinical findings in U1-RNP-ab-positive patients were consistent with mixed connective tissue disease (MCTD). Disease was more serious in the U1-RNP-ab-positive patients in terms of polyarthritis severity as well as mortality due to rheumatic disease. Thus, in this arthritis patient population, U1-RNP-ab positivity predicted an aggressive disease characterized by an erosive arthritis.

We report the case history of a 57 year old man who has suffered from typical deforming, relapsing polychondritis for 13 years. He has also developed erosive destructive seronegative polyarthritis involving some of his distal interphalangeal, proximal interphalangeal, metacarpophalangeal, intercarpal, wrist, intertarsal and metatarsophalangeal joints. The distribution of joint involvement in the small joints of the hands and feet is asymmetrical. Both hips and knee joints have also been involved necessitating bilateral total hip and right total knee replacement. The articular associations with relapsing polychondritis are discussed.

Synovial fluid from 16 normal subjects was compared with that from 149 patients with a variety of rheumatic disorders. Normal fluid had fewer cells and a lower content of beta-glucuronidase than osteoarthritic samples. Particles, including occasional birefringent crystals, were seen in normal fluids as well as pathological samples. Alizarin red staining particles (presumed to contain apatite) were seen in all diagnostic groups; their numbers showed some correlation with radiological calcification in and around the joints and with a hypertrophic subchondral bone response. Lactate levels were highest in septic arthritis. No assay showed disease specificity.

Fifty-seven patients with arthritis associated with non-gonococcal genital infection have been studied. Synovitis characteristically affected one or a few joints, expecially the knee, ankle or metatarsophalangeal joints and was accompanied by tenosynovitis and enthesopathies--each in about one third of the patients. A quarter of the patients had ocular, cutaneous, or mucous membrane lesions (Reiter's syndrome). Although six patients developed a chronic or relapsing course, average duration of the acute episode in the majority was three to five months. Available evidence strongly suggests that infection following sexual intercourse, usually but not always with a new partner, was instrumental in the initiation of the disease. We have suggested the term 'sexually acquired reactive arthritis (SARA)' to emphasize the mode of acquisition of the disease, and note that similar syndromes are seen associated with gut infection. We consider that usage of the term Reiter's syndrome is correctly applied to only those cases which exhibited the characteristic triad of urethritis, arthritis and conjunctivitis with or without other cutaneous and mucous membrane lesions. Thirty-six of the 54 patients who were HLA typed (67 per cent) possessed the antigen HLA-B27. Of 30 who presented directly to a rheumatology unit 25 (82 per cent) were HLA-B27 positive. The other 24 patients initially attended a venereology clinic and only 11 (46 per cent) of these bore the antigen. This appears to reflect disease severity, HLA-B27 positive patients having a significantly longer duration of disease symptoms and a higher frequency of extra-articular manifestations, than those lacking this antigen.