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1.
Artigo em Inglês | MEDLINE | ID: mdl-31566238

RESUMO

OBJECTIVES: The use of MR-imaging is recommended for the early detection of RA. Next to the small joints of the hands, foot-joints are often involved. Therefore, imaging inflammation of the feet in addition to hands may be informative, but prolongs scan-time and leads to additional costs. We studied the value of MRI of the feet alone and complementary to MRI of the hands in patients with clinically suspect arthralgia (CSA). METHODS: 357 consecutively included CSA patients underwent contrast-enhanced 1.5 T-MRI of hand (MCP2-5 and wrist) and foot (MTP1-5) joints at baseline. Scans were scored for synovitis, osteitis and tenosynovitis. After ⩾1 year follow-up, the development of clinically apparent inflammatory arthritis (IA) was studied. Cox regression was performed and test characteristics were evaluated. Sensitivity analyses were performed for the outcome RA-development (2010-criteria). RESULTS: MRI-detected tenosynovitis of the feet was associated with IA-development, independently from synovitis and osteitis hazard ratio (HR) (95%CI) 4.75 (2.38; 9.49), and independently from ACPA and CRP, HR 3.13 (1.48; 6.64). From all CSA patients, 11% had inflammation in hands and feet, 29% only in hands and 3% only in feet. In line with this finding, the addition of MRI-feet to MRI-hands did not increase the predictive accuracy; the sensitivity remained 77%, while the specificity decreased from 66% to 62%. Sensitivity analyses with RA development as outcome showed similar results. CONCLUSION: Tenosynovitis at the forefeet in CSA predicted IA and RA development. Addition of foot MRI to hand MRI did not increase the accuracy. Foot MRI can be omitted to reduce scan time and costs and increase the feasibility.

4.
Arthritis Res Ther ; 21(1): 121, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088574

RESUMO

BACKGROUND: Disease-modifying antirheumatic drug (DMARD)-free remission, the sustained absence of synovitis after DMARD cessation, is increasingly achievable, especially in autoantibody-negative rheumatoid arthritis (RA). However, underlying mechanisms are unknown and patient subgroups that achieve this outcome are insufficiently characterized. We evaluated whether serological biomarkers at disease onset, as measured within the multi-biomarker disease activity (MBDA) score, are differently expressed in RA patients who achieve sustained DMARD-free remission. METHODS: Two hundred ninety-nine RA patients were evaluated for achievement of sustained DMARD-free remission during a median follow-up of 4.3 years. Twelve biomarkers, as included in the MBDA score, were determined from the serum obtained at disease onset. Patients were categorized as having a low (< 30), moderate (30-44) or high (> 44) score. Analyses were stratified for anti-citrullinated protein antibodies (ACPA) based under the assumption that ACPA-positive and ACPA-negative RA are different disease entities. RESULTS: Twenty percent achieved sustained DMARD-free remission. Overall, high MBDA scores were associated with achieving DMARD-free remission (high vs. low HR 3.8, 95% CI 1.2-12.2). Among ACPA-negative RA patients, moderate or high scores associated strongly with DMARD-free remission (moderate vs. low HR 9.4, 95% CI 1.2-72.9; high vs. low HR 9.7, 95% CI 1.3-71.1). This association was independent of age and other clinical factors (high vs. low HR 8.2, 95% CI 1.1-61.8). For ACPA-negative RA patients, the biomarkers C-reactive protein, serum amyloid A and matrix metalloproteinase-3 were individually associated with sustained DMARD-free remission. Among ACPA-positive RA patients, scores were not associated with DMARD-free remission. CONCLUSIONS: ACPA-negative RA patients who achieved sustained DMARD-free remission after treatment withdrawal were characterized by moderate to high MBDA scores at diagnosis. This is the first evidence that ACPA-negative RA can be subdivided in clinically relevant subsets at disease onset using a protein profile.

7.
Arthritis Res Ther ; 21(1): 59, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764862

RESUMO

OBJECTIVE: Ultrasound (US) and magnetic resonance imaging (MRI) are recommended in the diagnostic process of rheumatoid arthritis. Research on its comparability in early disease phases is scarce. Therefore, we compared synovitis and tenosynovitis detected by US and MRI on joint/tendon level. METHODS: Eight hundred forty joints and 700 tendons of 70 consecutive patients, presenting with inflammatory arthritis or clinically suspect arthralgia, underwent US and MRI of MCP (2-5), wrist and MTP (1-5) joints at the same day. Greyscale (GS) and power Doppler (PD) synovitis were scored according to the modified Szkudlarek method (combining synovial effusion and hypertrophy) and the recently published EULAR-OMERACT method (synovial hypertrophy regardless of the presence of effusion) on static images. US-detected tenosynovitis was scored according to the OMERACT. MRI scans were scored according to the RAMRIS. Test characteristics were calculated on joint/tendon level with MRI as reference. Cut-off for US scores were ≥ 1 and ≥ 2 and for MRI ≥ 1. RESULTS: Compared to MRI, GS synovitis according to EULAR-OMERACT (cut-off ≥ 1) had a sensitivity ranging from 29 to 75% for the different joint locations; specificity ranged from 80 to 98%. For the modified Szkudlarek method, the sensitivity was 68-91% and specificity 52-71%. PD synovitis had a sensitivity of 30-54% and specificity 97-99% compared to MRI. The sensitivity to detect GS tenosynovitis was 50-78% and the specificity 80-94%. For PD tenosynovitis, the sensitivity was 19-58% and specificity 98-100%. CONCLUSION: Current data showed that US is less sensitive than MRI in the early detection of synovitis and tenosynovitis, but resulted in only few non-specific findings. The higher sensitivity of MRI is at the expense of less accessibility and higher costs.

8.
Best Pract Res Clin Rheumatol ; 32(2): 174-187, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-30527425

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, which affects approximately 1% of the population. The benefit of early recognition and treatment has led to an increased interest in the early phases of disease. With the aim of classifying patients earlier in their disease course, new RA classification criteria have been developed. Much attention has been devoted to the identification in the prearthritis phase of arthralgia. The discovery of new risk factors and autoantibodies has led to new theories about the putative mechanisms involved in disease development. Finally, the outcome measures have also evolved, with more emphasis on sustained drug-free remission and patient-reported outcomes. This article reviews the new developments in RA research and discusses the latest insights into epidemiology, risk factors, predisease states, and outcomes.


Assuntos
Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Artrite Reumatoide/complicações , Progressão da Doença , Humanos , Fatores de Risco
9.
Eur Radiol ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30421014

RESUMO

OBJECTIVES: Tenosynovitis (inflammation of the synovial lining of the sheath surrounding tendons) is frequently observed on MRI of early arthritis patients. Since visual assessment of tenosynovitis is a laborious task, we investigated the feasibility of automatic quantification of tenosynovitis on MRI of the wrist in a large cohort of early arthritis patients. METHODS: For 563 consecutive early arthritis patients (clinically confirmed arthritis ≥ 1 joint, symptoms < 2 years), MR scans of the wrist were processed in three automatic stages. First, super-resolution reconstruction was applied to fuse coronal and axial scans into a single high-resolution three-dimensional image. Next, 10 extensor/flexor tendon regions were segmented using atlas-based segmentation and marker-based watershed. A measurement region of interest (ROI) was defined around the tendons. Finally, tenosynovitis was quantified by identifying image intensity values associated with tenosynovial inflammation using fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within the measurement ROI. A subset of 60 patients was used for training and the remaining 503 patients for validation. Correlation between quantitative measurements and visual scores was assessed through Pearson correlation coefficient. RESULTS: Pearson correlation between quantitative measurements and visual scores across 503 patients was r = 0.90, p < 0.001. False detections due to blood vessels and synovitis present within the measurement ROI contributed to a median offset from zero equivalent to 13.8% of the largest measurement value. CONCLUSION: Quantitative measurement of tenosynovitis on MRI of the wrist is feasible and largely consistent with visual scores. Further improvements in segmentation and exclusion of false detections are warranted. KEY POINTS: • Automatic measurement of tenosynovitis on MRI of the wrist is feasible and largely consistent with visual scores. • Blood vessels and synovitis in the vicinity of evaluated tendons can contribute to false detections in automatic measurements. • Further improvements in segmentation and exclusion of false detections are important directions of future work on the path to a robust quantification framework.

10.
Arthritis Res Ther ; 20(1): 228, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305156

RESUMO

OBJECTIVE: Musculoskeletal ultrasound (US) is frequently used in several rheumatology practices to detect subclinical inflammation in patients with joint symptoms suspected for progression to inflammatory arthritis. Evaluating the scientific basis for this specific US use, we performed this systematic literature review determining if US features of inflammation are predictive for arthritis development and which US features are of additive value to other, regularly used biomarkers. METHODS: Medical literature databases were systematically searched up to May 2017 for longitudinal studies reporting on the association between greyscale (GSUS) and Power Doppler (PDUS) abnormalities and inflammatory arthritis development in arthralgia patients. Quality of studies was assessed by two independent reviewers using a set of 18 criteria. Studies were marked high quality if scored ≥ 80.6% (which is the median score). Best-evidence synthesis was performed to determine the level of evidence (LoE). Positive and negative likelihood ratios (LR+, LR-) were determined. RESULTS: Of 3061 unique references, six fulfilled inclusion criteria (three rated high quality), of which two reported on the same cohort. Heterogeneity in arthralgia populations, various US machines and scoring systems hampered the comparability of results. LoE for GSUS as predictor was limited and moderate for PDUS; LoE for the additive value of GSUS and PDUS with other biomarkers was limited to moderate. Estimated LR+ values were mostly < 4 and LR- values > 0.5. CONCLUSIONS: Data on the value of GSUS and PDUS abnormalities for predicting inflammatory arthritis development are sparse. Although a potential benefit is not excluded, current LoE is limited to moderate. Future studies are required, preferably performed in clearly defined, well-described arthralgia populations, using standardized US acquisition protocols and scoring systems.

11.
Clin Exp Rheumatol ; 36 Suppl 114(5): 131-138, 2018 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30296973

RESUMO

Tenosynovitis is traditionally recognised at physical examination in patients with inflammatory rheumatic diseases, such as, e.g. psoriatic arthritis and (longstanding) rheumatoid arthritis (RA). The increasing use of sensitive imaging techniques (ultrasound, magnetic resonance imaging (MRI)) has recently revealed that subclinical tenosynovitis is prevalent in early RA and in patients in different phases of RA development (asymptomatic state, arthralgia, early arthritis). In this review, the recent findings on MRI-detected tenosynovitis and associations with RA development are highlighted, and an overview of the most reported inflamed tendon locations within the hand and wrist of patients in different disease phases is provided. The data presented show that tenosynovitis is one of the earliest inflammatory features in patients with imminent RA and associated with impairment of activities in daily life. The value of tenosynovitis as an outcome measure in RA is also discussed.

12.
RMD Open ; 4(2): e000748, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233813

RESUMO

Introduction: Subclinical inflammation, detected by MRI, in patients with arthralgia is predictive for development of inflammatory arthritis (IA). However, within patients that develop IA, the course of inflammation at the joint level during this transition is unknown. This longitudinal study assessed progression of inflammation at the joint level. Methods: 350 joints (unilateral metacarpophalangeals (MCPs), wrist, metatarsophalangeal (MTP) joints) of 35 patients presenting with clinically suspect arthralgia (CSA) that progressed to IA were studied at presentation with CSA and subsequently when clinical synovitis was first identified at joint examination (median time interval 17 weeks). At both time points, subclinical inflammation (bone marrow oedema, synovitis, tenosynovitis) was evaluated with MRI and joint examination was performed. Results: At presentation with CSA, 71 joints showed subclinical inflammation. During progression to IA, 20% of these joints had resolution of inflammation, 60% had persistent inflammation and 20% progressed to clinical synovitis. Of all joints that had developed clinical synovitis (n = 45), no prior subclinical inflammation was detected in 69%. Similar results were observed for anticitrullinated protein antibodies (ACPA)-positive and ACPA-negative patients. Conclusions: This longitudinal study demonstrated moderate correlations between joints with subclinical inflammation and joints that developed clinical synovitis. These data imply that IA development is a more systemic rather than a locally outgrowing process.

14.
Clin Exp Rheumatol ; 36 Suppl 113(4): 109-117, 2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30148428

RESUMO

OBJECTIVES: To evaluate the additive value of autoantibodies in identifying systemic sclerosis (SSc) patients with high complication risk. METHODS: Patients entering the Combined Care In SSc cohort, Leiden University Medical Centre between April 2009 and May 2016 were included. Subgroups of patients were determined using hierarchical clustering, performed on Principal Component Analysis scores, 1) using baseline data of demographic and clinical variables only and 2) with additional use of antibody status. Disease-risk within subgroups was assessed by evaluating 5-year mortality rates. Clinical and autoantibody characteristics of obtained subgroups were compared. RESULTS: In total 407 SSc patients were included, of which 91% (n=371) fulfilled ACR/EULAR 2013 criteria for SSc. Prevalences of autoantibodies were: anti-centromere 37%, anti-topoisomerase (ATA) 24%, anti-RNA polymerase III 5%, anti-fibrillarin 4% and anti-Pm/Scl 5%. Clinical cluster analysis identified 4 subgroups, with two subgroups showing higher than average mortality (resp. 17% and 7% vs. total group mortality of 4%). ATA-positivity ranged from 10 to 21% in low-risk groups and from 30 to 49% among high-risk groups. Adding autoantibody status to the cluster process resulted in 5 subgroups with 3 showing higher than average mortality. Still, 22% of ATA- positive patients were clustered into a low-risk subgroup, while the total number of patients stratified to a high-risk subgroup increased. CONCLUSIONS: Autoantibodies only partially contribute to risk-stratification and clinical subsetting in SSc. The current findings confirm that not all ATA-positive patients have worse prognosis and as such, additional biomarkers are needed to guide clinical follow-up in SSc.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30137540

RESUMO

Objectives: The development of RA includes a phase of arthralgia preceding clinical arthritis. The aetiology of symptoms of arthralgia is unclear. Since subclinical joint inflammation is expected to be causally related to pain, we aimed to study associations between subclinical MRI-detected inflammation and pain in patients with arthralgia suspicious for progression to RA. Methods: Unilateral MRIs of the wrist, MCP (2-5) and MTP (1-5) joints of 325 patients who fulfilled the EULAR definition of arthralgia suspicious for progression to RA were scored by two readers on subclinical inflammation (synovitis, bone marrow oedema and tenosynovitis). Associations between MRI-detected inflammation and overall pain severity at patient level (measured using the visual analogue scale), as well as with local joint tenderness, were studied. Analyses were stratified for ACPA. Results: At patient level, synovitis (ß = 0.10, P = 0.048) and tenosynovitis (ß = 0.11, P = 0.026) associated with the visual analogue scale pain. Of the 1620 imaged joints, 447 (28%) were tender. MRI-detected synovitis associated independently with joint tenderness in all patients (odds ratio 1.74, P < 0.001), and in the ACPA-negative stratum (odds ratio 1.96, P < 0.001). In the ACPA-positive stratum only bone marrow oedema (osteitis) was independently associated with tenderness (odds ratio 2.39, P = 0.005). Sensitivity analyses in patients who developed inflammatory arthritis during follow-up (n = 61) revealed similar associations. Subclinical inflammation was present in 51% of tender joints and 39% of non-tender joints. Conclusion: In patients with arthralgia suspicious for progression to RA, MRI-detected subclinical inflammation is associated with overall pain and local joint tenderness. However, the association is partial, indicating that subclinical inflammation is not the sole explanation of the arthralgia.

16.
RMD Open ; 4(1): e000728, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29955387

RESUMO

In 2003, the Nobel Prize for Medicine was awarded for contribution to the invention of MRI, reflecting the incredible value of MRI for medicine. Since 2003, enormous technical advancements have been made in acquiring MR images. However, MRI has a complicated, accident-prone dark side; images are not calibrated and respective images are dependent on all kinds of subjective choices in the settings of the machine, acquisition technique parameters, reconstruction techniques, data transmission, filtering and postprocessing techniques. The bright side is that understanding MR techniques increases opportunities to unravel characteristics of tissue. In this viewpoint, we summarise the different subjective choices that can be made to generate MR images and stress the importance of communication between radiologists and rheumatologists to correctly interpret images.

17.
Artigo em Inglês | MEDLINE | ID: mdl-29853189

RESUMO

OBJECTIVE: MRI-detected inflammation is considered of diagnostic value for rheumatoid arthritis (RA), but its evaluation involves a time-consuming scoring of 61 joint-level features. It is not clear, however, which of these features are specific for RA and whether evaluating a subset of specific features is sufficient to differentiate RA patients. This study aimed to identify a subset of RA-specific features in a case-control setting and validate them in a longitudinal cohort of arthralgia patients. METHODS: The difference in frequency of MRI-detected inflammation (bone marrow edema, synovitis, and tenosynovitis) between 199 RA patients and 193 controls was studied in 61 features across the wrist, metacarpophalangeal, and metatarsophalangeal joints. A subset of RA-specific features was obtained by applying a cutoff on the frequency difference while maximizing discriminative performance. For validation, this subset was used to predict arthritis development in 225 clinically suspect arthralgia (CSA) patients. Diagnostic performance was compared to a reference method that uses the complete set of 61 features normalized for inflammation levels in age-matched controls. RESULTS: Subset of 30 features, mainly (teno)synovitis, was obtained from the case-control setting. Validation in CSA patients yielded an area of 0.69 (95% CI: 0.59-0.78) under the ROC curve and a positive predictive value (PPV) of 31%, compared to 0.68 (95% CI: 0.60-0.77) and 29% PPV of the reference method with 61 features. CONCLUSION: Subset of 30 MRI-detected inflammatory features, dominated by (teno)synovitis, offers a considerable reduction of scoring efforts without compromising accuracy for prediction of arthritis development in CSA patients.

18.
Arthritis Rheumatol ; 70(11): 1721-1731, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29781231

RESUMO

OBJECTIVE: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly used to aid in the diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPAs and RF alone. In addition, anti-carbamylated protein (anti-CarP) antibodies have diagnostic and prognostic value, since their presence is associated with joint damage in RA patients and also associated with the future development of RA in patients with arthralgia. Therefore, the aim of the present study was to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA. METHODS: A literature search resulted in identification of 12 relevant studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients, and healthy control subjects, in which data on RF, ACPAs, and anti-CarP antibody status were available. Using these data, random effects meta-analyses were carried out for several antibody combinations. RESULTS: The individual antibodies were highly prevalent in patients with RA (34-80%) compared to the control groups, but were also present in non-RA controls (0-23%). For the classification of most subjects correctly as having RA or as a non-RA control, the combination of ACPAs and/or RF often performed well (specificity 65-100%, sensitivity 59-88%). However, triple positivity for ACPAs, RF, and anti-CarP antibodies resulted in a higher specificity for RA (98-100%), accompanied by a lower sensitivity (11-39%). CONCLUSION: As the rheumatology field is moving toward very early identification of RA and possible screening for individuals at maximum risk of RA in populations with a low pretest probability, an autoantibody profile of triple positivity for ACPAs, RF, and anti-CarP provides interesting information that might help identify individuals at risk of developing RA.

19.
Arthritis Res Ther ; 20(1): 93, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29724244

RESUMO

BACKGROUND: Within established rheumatoid arthritis (RA), stress can have pro-inflammatory effects by activating the immune system via the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. It is unknown if stress levels also promote inflammation during RA development. We studied whether the psychological stress response was increased in clinically suspect arthralgia (CSA) and if this associated with inflammation at presentation with arthralgia and with progression to clinical arthritis. METHODS: In 241 CSA patients, psychological stress was measured by the Mental Health Inventory (MHI-5) and the Perceived Stress Scale (PSS-10) at first presentation and during follow-up. Systemic inflammation was measured by C-reactive protein (CRP) and joint inflammation by 1.5 T-MRI of wrist, MCP, and MTP joints. RESULTS: At baseline, 12% (24/197) of CSA patients had a high psychological stress response according to the MHI-5. This was not different for patients presenting with or without an elevated CRP, with or without subclinical MRI-detected inflammation and for patients who did or did not develop arthritis. Similar findings were obtained with the PSS-10. When developing clinical arthritis, the percentage of patients with 'high psychological stress' increased to 31% (p = 0.025); during the first year of treatment this decreased to 8% (p = 0.020). 'High psychological stress' in non-progressors remained infrequent over time (range 7-13%). Stress was associated with fatigue (p = 0.003) and wellbeing (p < 0.001). CONCLUSIONS: Psychological stress was not increased in the phase of arthralgia, raised at the time of diagnoses and decreased thereafter. The lack of an association with inflammation in arthralgia and this temporal relationship, argue against psychological stress having a significant contribution to progression from CSA to inflammatory arthritis.

20.
Arthritis Res Ther ; 20(1): 94, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29724250

RESUMO

BACKGROUND: The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA patients lack both these autoantibodies. Recently, several novel autoantibodies have been identified but their value for the classification of RA patients is unclear. Therefore, we studied the value of novel autoantibodies using the presence of anticarbamylated protein (anti-CarP) antibodies as an example for predicting RA development in patients with undifferentiated arthritis (UA). METHODS: There were 1352 UA patients included in the Leiden Early Arthritis Clinic (EAC) cohort according to the 1987 criteria. When the 2010 criteria were used, there were 838 UA patients. Of these, we evaluated whether they fulfilled the 1987 or 2010 criteria after 1 year, respectively. Logistic regression analyses were performed with RA as outcome and ACPA, RF, and anti-CarP antibodies as predictors. Analyses were repeated after stratification for ACPA and RF. RESULTS: Thirty-three percent of the 1987-UA patients and 6% of the 2010-UA patients progressed to RA during the first year of follow-up. For the 1987-UA patients, anti-CarP antibodies were associated with progression to RA, an association which remained when a correction was made for the presence of ACPA and RF (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.2-2.4). After stratification for ACPA and RF, anti-CarP antibodies were associated with progression to RA only for ACPA- and RF-negative patients (OR 2.1, 95% CI 1.3-3.7). For the 2010-UA patients, anti-CarP antibodies were associated with progression to RA; however, they were not when a correction was made for the presence of ACPA and RF (OR 0.8, 95% CI 0.3-2.1). CONCLUSIONS: Our finding that anti-CarP antibodies have no additional value when RA is defined according to the 2010 criteria might be inherent to the composition of the 2010 criteria and therefore might also apply to other novel autoantibodies. Potentially it would be interesting to evaluate other, non-autoantibody biomarkers.

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