Are MRI-detected erosions specific for RA? A large explorative cross-sectional study.

OBJECTIVES: MRI is recommended in the diagnostic process of rheumatoid arthritis (RA) to detect joint damage early. MRI-detected erosions are also present in symptom-free controls, especially at older age. It is unclear if RA-specific MRI-detected erosions can be distinguished from 'physiological' erosions in symptom-free individuals. This study compared MRI-detected erosions of patients with RA with healthy controls and with other arthritides. METHODS: 589 newly presenting patients with early arthritis (238 RA, 351 other arthritides) and 193 symptom-free controls underwent contrast-enhanced 1.5T MRI of unilateral metacarpophalangeal and metatarsophalangeal (MTP) joints. Total erosion score (according to the Rheumatoid Arthritis MRI Scoring System), number, severity, location of erosions and simultaneous presence of MRI-detected inflammation (synovitis and/or bone marrow oedema) were compared; participants were categorised in three age groups (<40, 40-59, ≥60). RESULTS: Patients with RA had statistically significant higher total erosion scores than controls but scores of individual persons largely overlapped. Grade ≥2 erosions and MTP5 erosions were specific for RA (specificity 98%-100% and 90%-98% for different age groups). MTP1 erosions were only specific if aged <40 (specificity 98%) and erosions with inflammation if aged <60 (specificity 91%-100%). ≥1 of the mentioned erosion characteristics were present in 29% of patients with RA. Comparing patients with RA with other arthritides revealed that grade ≥2 erosions and MTP5 erosions remained specific for RA (specificity ≥89%) as well as MTP1 erosions if aged <40 (specificity 93%), in contrast to erosions combined with inflammation (specificity 49%-85%). CONCLUSIONS: Total erosion scores of individual persons were largely overlapping. Erosion characteristics specific for RA were identified, but were infrequently present. Caution is needed not to overestimate the value of MRI erosions in the diagnostic process.

Automatic quantification of bone marrow edema on MRI of the wrist in patients with early arthritis: A feasibility study.

PURPOSE: To investigate the feasibility of automatic quantification of bone marrow edema (BME) on MRI of the wrist in patients with early arthritis. METHODS: For 485 early arthritis patients (clinically confirmed arthritis of one or more joints, symptoms for less than 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 3D image. Next, the carpal bones were located and delineated using atlas-based segmentation. Finally, the extent of BME within each bone was quantified by identifying image intensity values characteristic of BME by fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within each bone. Correlation with visual BME scores was assessed through Pearson correlation coefficient. RESULTS: Pearson correlation between quantitative and visual BME scores across 485 patients was r=0.83, P<0.001. CONCLUSIONS: Quantitative measurement of BME on MRI of the wrist has the potential to provide a feasible alternative to visual scoring. Complete automation requires automatic detection and compensation of acquisition artifacts. Magn Reson Med 79:1127-1134, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Using a reference when defining an abnormal MRI reduces false-positive MRI results-a longitudinal study in two cohorts at risk for rheumatoid arthritis.

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.

Evaluation of the diagnostic accuracy of hand and foot MRI for early Rheumatoid Arthritis.

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.

Older age is associated with more MRI-detected inflammation in hand and foot joints.

OBJECTIVES: Although MRI is recommended for diagnostic use in detecting joint inflammation, its value in clinical practice has not been settled. Older symptom-free persons show more MRI-detected inflammation in their hands and feet. Within arthritis patients, a similar effect could be present (a general age effect). The association of age with MRI inflammation could also be enhanced by disease (disease-dependent age effect). Because both effects could have diagnostic consequences, we evaluated the association between age-at-onset and MRI-detected inflammation in early arthritis and RA. METHODS: Unilateral contrast-enhanced MRI of the MCP joint, wrist and MTP joints was performed in 589 newly presenting early arthritis patients, of whom 229 had RA. Bone marrow oedema, synovitis and tenosynovitis were summed, yielding the MRI inflammation score. MRI findings were associated with age and compared with those of 193 (previously reported) symptom-free controls. RESULTS: Early arthritis and RA-patients had, respectively, 2.6 (95% CI: 2.3, 3.0, P < 0.001) and 3.7 times (95% CI: 3.2, 4.3, P < 0.001) higher MRI inflammation scores than controls (adjusted for age). At higher age of onset, early arthritis and RA patients had higher MRI inflammation scores (1.03/year, P < 0.001). A similar effect was observed in controls (1.03/year, P < 0.001). The interaction term age*group (arthritis/RA vs controls) was non-significant (P = 0.80 and P = 0.23), suggesting that the age effect was not disease dependent. At the joint level, older RA patients had more extended MRI inflammation, but the preferential locations were similar. CONCLUSION: Older age is associated with more MRI-detected inflammation, and the effect was similar in arthritis and controls. This age effect should be considered when interpreting hand and foot MRI for diagnostic purposes.

Magnetic resonance imaging-detected inflammation is associated with functional disability in early arthritis-results of a cross-sectional study.

OBJECTIVES: MRI sensitively detects inflammation, but the clinical relevance of MRI-detected inflammation is undetermined in early arthritis. Therefore, the aim of this cross-sectional study was to investigate the association between MRI-detected inflammation of hands and feet and functional disability in early arthritis. METHODS: Five hundred and fourteen early arthritis patients, consecutively included in the Leiden Early Arthritis Clinic, were studied. At baseline a unilateral 1.5 T MRI of the wrist, MCP and MTP joints was performed and functional disability was measured using the HAQ. MRIs were scored for tenosynovitis, synovitis and bone marrow oedema (BME) by two readers. The sum of these types of MRI-detected inflammation yielded the total MRI-inflammation score. Linear and nonlinear regression analyses were performed with HAQ as outcome. RESULTS: The total MRI-inflammation score was associated with the HAQ score (ß = 0.014, P < 0.001), as were tenosynovitis (ß = 0.046, P < 0.001), synovitis (ß = 0.039, P < 0.001) and bone marrow oedema scores (ß = 0.015, P < 0.001) separately. Analysing these three types of MRI-detected inflammation in one multivariable model revealed that only tenosynovitis was independently associated with the HAQ score (ß = 0.039, P < 0.001). Also after correction for age, gender, joint counts, CRP and auto-antibodies, this association remained significant (ß = 0.034, P < 0.001). MRI-detected inflammation at wrists or MCP joints associated significantly with impairments in hand functioning (e.g. difficulties with opening milk cartons or jars). Exploring the relation between MRI-detected inflammation and HAQ scores showed no evidence of a floor effect, suggesting that even low scores of MRI-detected inflammation are functionally relevant. CONCLUSION: MRI-detected inflammation, and tenosynovitis in particular, is associated with functional disability. This demonstrates the functional relevance of MRI-detected inflammation in early arthritis.

Moderate use of alcohol is associated with lower levels of C reactive protein but not with less severe joint inflammation: a cross-sectional study in early RA and healthy volunteers.

OBJECTIVES: Moderate alcohol consumption is protective against rheumatoid arthritis (RA) development and associated with lower levels of systemic inflammation in RA and in the general population. We therefore hypothesised that moderate alcohol consumption is associated with less severe local inflammation in joints in RA, detected by MRI. Since asymptomatic persons can have low-grade MRI-detected inflammation, we also hypothesised that alcohol consumption is associated with the extent of MRI inflammation in asymptomatic volunteers. METHODS: 188 newly presenting patients with RA and 192 asymptomatic volunteers underwent a unilateral contrast-enhanced 1.5T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints. The MRIs were scored on synovitis, bone marrow oedema and tenosynovitis; the sum of these yielded the MRI inflammation score. MRI data were evaluated in relation to current alcohol consumption, categorised as non-drinkers, consuming 1-7 drinks/week, 8-14 drinks/week and >14 drinks/week. Association between C reactive protein (CRP) level and alcohol was studied in 1070 newly presenting patients with RA. RESULTS: Alcohol consumption was not associated with the severity of MRI-detected inflammation in hand and foot joints of patients with RA (P=0.55) and asymptomatic volunteers (P=0.33). A J-shaped curve was observed in the association between alcohol consumption and CRP level, with the lowest levels in patients consuming 1-7 drinks/week (P=0.037). CONCLUSION: Despite the fact that moderate alcohol consumption has been shown protective against RA, and our data confirm a J-shaped association of alcohol consumption with CRP levels in RA, alcohol was not associated with the severity of joint inflammation. The present data suggest that the pathophysiological mechanism underlying the effect of alcohol consists of a systemic effect that might not involve the joints.

Body mass index and extent of MRI-detected inflammation: opposite effects in rheumatoid arthritis versus other arthritides and asymptomatic persons.

BACKGROUND: In the population a high body mass index (BMI) has been associated with slightly increased inflammatory markers. Within rheumatoid arthritis (RA), however, a high BMI has been associated with less radiographic progression; this phenomenon is unexplained. We hypothesized that the phenomenon is caused by an inverse relationship between BMI and inflammation in hand and foot joints with RA. To explore this hypothesis, local inflammation was measured using magnetic resonance imaging (MRI) in early arthritis patients presenting with RA or other arthritides and in asymptomatic volunteers. METHODS: A total of 195 RA patients, 159 patients with other inflammatory arthritides included in the Leiden Early Arthritis Clinic, and 193 asymptomatic volunteers underwent a unilateral contrast-enhanced 1.5 T MRI scan of metacarpophalangeal, wrist, and metatarsophalangeal joints. Each MRI scan was scored by two readers on synovitis, bone marrow edema (BME), and tenosynovitis; the sum yielded the total MRI inflammation score. Linear regression on log-transformed MRI data was used. RESULTS: A higher BMI was associated with higher MRI inflammation scores in arthritides other than RA (ß = 1.082, p < 0.001) and in asymptomatic volunteers (ß = 1.029, p = 0.040), whereas it was associated with lower MRI inflammation scores in RA (ß = 0.97, p = 0.005). Evaluating the different types of inflammation, a higher BMI was associated with higher synovitis, BME, and tenosynovitis scores in arthritides other than RA (respectively ß = 1.084, p < 0.001, ß = 1.021, p = 0.24, and ß = 1.054, p = 0.003), but with lower synovitis and BME scores in RA (respectively ß = 0.98, p = 0.047 and ß = 0.95, p = 0.002). CONCLUSIONS: Increased BMI is correlated with less severe MRI-detected synovitis and BME in RA. This might explain the paradox in RA where obesity correlates with less severe radiographic progression.

The Course of Bone Marrow Edema in Early Undifferentiated Arthritis and Rheumatoid Arthritis: A Longitudinal Magnetic Resonance Imaging Study at Bone Level.

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.

MRI-detected osteitis is not associated with the presence or level of ACPA alone, but with the combined presence of ACPA and RF.

BACKGROUND: In rheumatoid arthritis (RA) bone marrow edema (BME, osteitis) and anti-citrullinated protein antibodies (ACPA) are associated with radiographic progression. ACPA have been associated with BME, but it is unknown if this association is confined to ACPA and BME. We performed cross-sectional analysis of the association of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies with BME and other types of inflammation (synovitis, tenosynovitis) detected by magnetic resonance imaging (MRI). METHODS: Disease-modifying antirheumatic drug (DMARD)-naïve patients with early arthritis (n = 589), included in the Leiden Early Arthritis Clinic cohort, underwent contrast-enhanced 1.5 T MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal-joints at baseline. BME, synovitis and tenosynovitis were scored by two readers. ACPA, rheumatoid factor (RF) and anti-CarP were determined at baseline. RESULTS: In univariable analyses ACPA-positive patients had higher BME scores than ACPA-negative patients (median 4.5 vs. 2.0, p < 0.001), but not more synovitis and tenosynovitis. Also RF (median 3.75 vs. 2.0, p < 0.001) and anti-CarP antibodies (median 3.5 vs. 2.5, p = 0.012) were associated with higher BME scores. Because the autoantibodies were concomitantly present, analyses were stratified for the presence of different autoantibody combinations. ACPA-positive (ACPA+), RF-negative (RF-), anti-CarP-negative (anti-CarP-) patients did not have higher BME-scores than ACPA-negative (ACPA-), RF-, anti-CarP- patients. However ACPA+, RF-positive (RF+), anti-CarP- patients and ACPA+, RF+, anti-CarP-positive (anti-CarP+) patients had higher BME scores than ACPA-, RF-, anti-CarP- patients (median 5.0 and 4.5 vs. 2.0, p < 0.001 and p < 0.001). ACPA levels were not associated with BME scores. Analyses within RA- and UA-patients revealed similar results. CONCLUSIONS: The presence of ACPA alone or ACPA level was not statistically significantly associated with BME scores, but the combined presence of ACPA and RF was associated with more BME. This suggests an additive role of RF to ACPA in mediating osteitis.

Evaluation of magnetic resonance imaging-detected tenosynovitis in the hand and wrist in early arthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) is a sensitive method to detect inflammation in rheumatoid arthritis (RA), visualizing synovitis, bone marrow edema, and tenosynovitis. The prevalence of MRI-detected tenosynovitis and its diagnostic value in early arthritis are unclear. This study was undertaken to identify the frequency of MRI-detectable tenosynovitis at the metacarpophalangeal (MCP) and wrist joints in early arthritis and the association of these with RA and the severity of RA. METHODS: A total of 178 patients with early arthritis underwent unilateral 1.5T extremity MRI at baseline. The MCP and wrist joints were scored using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system and Haavardsholm's tenosynovitis score. Sixty-nine patients fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA during the first year and were compared with the non-RA patients. Among the RA patients, comparisons were made with regard to anti-citrullinated protein antibody (ACPA) positivity and radiographic progression during year 1. RESULTS: Of all patients, 65% had MRI-detected tenosynovitis. RA patients had tenosynovitis more often than non-RA patients (75% versus 59%; P = 0.023). The flexor tendons at MCP5 and the extensor tendons at MCP2 and MCP4 and in extensor compartment I of the wrist were more frequently affected in RA patients than in other patients (odds ratios 2.8 [95% confidence interval (95% CI) 1.2-7.0], 9.1 [95% CI 1.9-42.8], 14.2 [95% CI 1.7-115.9], and 4.0 [95% CI 1.4-11.1], respectively). These associations were independent of local MRI synovitis. Specificities were all ≥82%. Within the group of RA patients, tenosynovitis scores were not associated with ACPA positivity or radiographic progression. CONCLUSION: MRI-detected tenosynovitis is commonly seen in early arthritis. The flexor tendons at MCP5, the extensor tendons at MCP2 and MCP4, and the first extensor compartment of the wrist are more often affected in RA, independent of local synovitis.

[Guideline 'Coeliac disease and dermatitis herpetiformis']. / Richtlijn 'Coeliakie en dermatitis herpetiformis'.

The Dutch evidence-based guideline 'Coeliac disease and dermatitis herpetiformis' contains instructions for detection and treatment of coeliac disease. Coeliac disease has a high prevalence: 0.5 - 1.3%. The disease has a broad spectrum of symptoms, frequently also outside the gastrointestinal tract. Relatives of patients and persons with autoimmune diseases, microscopic colitis, IgA deficiency and syndromes of Down, Turner and Williams have an increased risk of coeliac disease. Detection is carried out by determination of IgA antibodies to tissue transglutaminase and endomysium. Testing for IgA antibodies to gliadin is only recommended in children younger than 2 years. Absence of HLA-DQ2 and DQ8 indicates that coeliac disease is most unlikely. The diagnosis should be confirmed by small bowel biopsy. Single biopsy following gluten ingestion is sufficient for diagnosis at all ages. After the diagnosis, patients should be referred to a dietician. Additionally, a yearly follow-up by a paediatrician or internal medical specialist with appropriate gastroenterology specialisation is recommended.