Concordance and agreement between different activity scores in polymyalgia rheumatica.

OBJECTIVE: The C reactive protein polymyalgia rheumatica activity score (CRP-PMR-AS) is a composite index that includes CRP levels and was developed specifically for PMR. As treatments such as interleukin-6 antagonists can normalise CRP levels, the erythrocyte sedimentation rate (ESR) of PMR-AS, the clinical (clin)-PMR-AS and the imputed-CRP (imp-CRP)-PMR-AS have been developed to avoid such bias. Our primary objective was to measure the correlation of these activity scores. Our secondary objective was to evaluate the concordance between different cutoffs of the PMR-ASs. METHOD: Data from the Safety and Efficacy of tocilizumab versus Placebo in Polymyalgia rHeumatica With glucocORticoid dEpendence (SEMAPHORE) trial, a superiority randomised double-blind placebo-controlled trial, were subjected to post hoc analysis to compare the efficacy of tocilizumab versus placebo in patients with active PMR. The CRP-PMR-AS, ESR-PMR-AS, clin-PMR-AS and imp-CRP-PMR-AS were measured at every visit. The concordance and correlation between these scores were evaluated using kappa correlation coefficients, Bland-Altman correlations, intraclass correlation coefficients (ICCs) and scatter plots. RESULTS: A total of 101 patients were included in the SEMAPHORE trial, and 100 were analysed in this study. The correlation between the PMR-ASs was excellent, as the ICC and kappa were >0.85 from week 4 until week 24 (CRP-PMR-AS ≤10 or >10). Bland-Altman plots revealed that the differences between the CRP-PMR-AS and the other threescores were low. The cut-off values for the clin-PMR-AS were similar to those for the CRP-PMR-AS 86% of the time. CONCLUSION: The correlation between all the PMR-ASs was excellent, reflecting the low weight of CRP. In clinical trials using drugs that have an impact on CRP, the derived activity scores can be used. TRIAL REGISTRATION NUMBER: NTC02908217.

[18F]FDG PET/CT for therapeutic assessment of Abatacept in early-onset polymyalgia rheumatica.

PURPOSE: Evaluate the benefit of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) for the therapeutic assessment of Abatacept (ABA) as first-line therapy in early-onset polymyalgia rheumatica (PMR) patients. METHODS: This was an ancillary study of ALORS trial (Abatacept in earLy Onset polymyalgia Rheumatica Study) assessing the ability of ABA versus placebo to achieve low disease activity (C-Reactive Protein PMR activity score (CRP PMR-AS) ≤ to 10) without glucocorticoid (GC) at week 12 in patients with early-onset PMR. The patients underwent [18F] FDG PET/CT at baseline and after 12 weeks of treatment. Responses to treatments were evaluated according to CRP PMR-AS, Erythrocyte Sedimentation Rate (ESR) PMR-AS, Clin PMR-AS, and CRP-Imputed (Imput-CRP) PMR-AS. Quantitative score by maximal standardized uptake value (SUVmax) and combined qualitative scores according to liver uptake (Leuven, Leuven/Groningen, and Besançon Scores) were used for assessment of [18F] FDG uptake in regions of interest (ROI) usually affected in PMR. Student's t-test was applied to evaluate the clinical, biological, and [18F] FDG uptake variation difference in ABA and placebo groups between W0 and W12. Subgroup analysis by GC rescue was performed. RESULTS: At W12, there was no significant difference according to SUVmax between the ABA and the placebo groups in all ROI. Subgroup analysis according to GC administration demonstrated a significant (p 0.047) decrease in SUVmax within the left sternoclavicular joint ROI in the ABA group (- 0.8) compared to the placebo group (+ 0.6) without GC rescue. Other results did not reveal any significant difference between the ABA and placebo groups. According to combined qualitative scores, there was no significant difference between ABA and placebo groups for the direct comparison analysis and subgroup analysis according to GC rescue. CONCLUSION: [18F] FDG PET/CT uptake did not decrease significantly after ABA compared to placebo in anatomical areas usually affected in PMR patients. These results are correlated with the clinical-biological therapeutic assessment. CLINICAL TRIAL REGISTRATION: The study was approved by the appropriate ethics committee (CPP Sud-Est II Ref CPP: 2018-33), and all patients gave their written informed consent before study enrollment. The protocol was registered on Clinicaltrials.gov (NCT03632187).

Diagnostic utility of a second minor salivary gland biopsy in patients with suspected Sjögren's syndrome: A retrospective cohort study.

OBJECTIVE: To determine whether repeated minor salivary gland biopsy (MSGB) has a clinical diagnostic utility in patients with suspicion of Sjögren's syndrome (SS). METHODS: Clinical, biological, pathological data and physician's diagnosis after each MSGB from patients with suspected primary or secondary SS who had benefited from 2 MSGB at Brest University Hospital between January 1st, 1990 and January 14th, 2015, were retrospectively collected. We compared the characteristics of patients with and without first positive MSGB, concordance between the MSGB, and analyzed the modifications of diagnosis after the second MSGB. RESULTS: Ninety-three patients were included, first MSGB was positive for 23 and negative for 70. Patients with first positive MSGB had more often renal involvement (P<0.05) and hypergammaglobulinemia (P=0.01), anti-SSA antibodies (P<0.05) and positive second biopsy with focus score ≥ 1 or Chisholm>2 (P<0.01). The mean time between the 2 MSGB was 5.7±4.3 years. The concordance between the results of the 2 biopsies was low (κ = 0.34). MSGB influenced diagnostic's change in 10 cases where the second MSGB was always guided by new specific clinical manifestations. CONCLUSION: We observed a low concordance between 2 MSGB in patients with suspected pSS in our study. Despite this variability, performing a second MSGB changed the initial diagnosis in only a minority of the patients and was particularly useful when clinical manifestations had deeply evolved.

Abatacept in early polymyalgia rheumatica (ALORS): a proof-of-concept, randomised, placebo-controlled, parallel-group trial.

BACKGROUND: Medium-dose glucocorticoids can improve symptoms in nearly all patients with polymyalgia rheumatica. According to its good safety profile, abatacept could be used instead of glucocorticoids in early polymyalgia rheumatica. We aimed to determine whether the efficacy of abatacept is sufficient to justify larger studies in early polymyalgia rheumatica. METHODS: To evaluate whether abatacept allows low disease activity without glucocorticoids in early polymyalgia rheumatica, we conducted a proof-of-concept, randomised, double-blind, placebo-controlled, parallel-group trial. Participants were recruited from five centres in France (in Brest, Le Mans, Morlaix, Dinan and Saint Malo, and Strasbourg) and were included if they had recent-onset (<6 months) polymyalgia rheumatica with a C-reactive protein (CRP) polymyalgia rheumatica activity score (PMR-AS) of more than 17 without any signs or symptoms of giant cell arteritis (clinical and [18F]fluorodeoxyglucose PET-CT evaluation). Participants were randomly assigned (1:1) to receive weekly subcutaneous abatacept (125 mg) or matching placebo, with glucocorticoid rescue therapy allowed in cases of high disease activity, for 12 weeks, and then glucocorticoid treatment based on disease activity, until week 36. Investigators, patients, outcome assessors, and sponsor personnel were masked to group assignments. The primary endpoint was low disease activity (CRP PMR-AS ≤10) at week 12 without glucocorticoids and without rescue treatment. The study was powered to demonstrate a 60% difference in response rates between groups. Open-ended adverse events were collected at each visit by clinicians and were categorised following system organ class classification after study completion. The ALORS trial is registered with ClinicalTrials.gov, NCT03632187. FINDINGS: 34 patients (22 women and 12 men) were randomly assigned between Dec 13, 2018, and Oct 21, 2021. All patients who had been randomly assigned were included in the analysis. The primary endpoint was reached by eight (50%) of 16 patients in the abatacept group and four (22%) of 18 patients in the placebo group (relative risk 2·2 [0·9-5·5]); crude p=0·15; adjusted p=0·070). Eight (50%) patients in the abatacept and 15 (83%) in the placebo group had adverse events. Four patients (one [6%] in the abatacept group and three [17%] in the placebo group) had serious adverse events. There were no deaths or new safety concerns. INTERPRETATION: This study suggests that the effect of abatacept alone is not strong enough to justify larger studies in early polymyalgia rheumatica. This is only a first step in deciding whether a larger study should be conducted in early polymyalgia rheumatica and does not exclude a potential effect of abatacept in glucocorticoid-dependent polymyalgia rheumatica. FUNDING: BMS Pharma France.

Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

Features and Outcomes of Microcrystalline Arthritis Treated by Biologics: A Retrospective Study.

OBJECTIVES: The usual treatments for crystal-associated arthritis are sometimes contraindicated; thus, new therapies against interleukin-1beta (IL-1) have been developed. We evaluated the characteristics of patients who received biological treatment for crystal-associated arthritis. PATIENTS AND METHODS: We conducted a multicentric retrospective observational study in six rheumatology units in western France. Patients receiving a biological treatment for crystal-associated arthritis between 1 January 2010 and 31 December 2018 were included. Improvement was defined as at least a 50% decrease in the count of synovitis and C-reactive protein level. RESULTS: Forty-six patients were included: 31 (67.4%) were treated for gouty arthritis, and 15 (32.6%) for calcium pyrophosphate crystal deposition disease (CCPD). The first biotherapy used was anakinra for 14 patients (93.3%) with CCPD and 31 patients (100.0%) with gout. The first biotherapy course was more efficient in treating gout than in treating CCPD, with success in 28 patients (90.3%) and 5 patients (35.7%), respectively (p = 0.001). Six patients (42.9%) with CCPD stopped their first biotherapy course because of side effects. Among the patients with gout, urate-lowering therapy was more frequently used after (100%) than before the first biotherapy course (67.7%) (p = 0.002). CONCLUSION: Anakinra was prescribed for cases of refractory crystal-associated arthritis or cases with contraindications for usual treatments. The efficacy of anakinra in treating CCPD was not obvious. Patients with CCPD had more side effects. The biotherapy was introduced with a long-term objective, while anti-IL-1 therapies are approved for acute crises only.

Salivary Glands and Periodontal Changes in a Population of Sjögren's and Sicca Syndrome Treated by Pilocarpine: A Pilot Study.

INTRODUCTION: Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown. METHODS: Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). Vascularization of SG was measured using resistive index (RI) before and after stimulation by lemon juice. Echostructure (measure of glandular length in cm2, evaluation of parotid and submandibular glands parenchymal abnormalities) was assessed at baseline (M0) and after 3 months (M3) of treatment with pilocarpine. A dental consultation was performed at M0 and M3 to evaluate changes in unstimulated salivary flow (USSF), stimulated salivary flow (SSF), and periodontal parameters such as modified gingival index (Lobene), plaque index (Silness), bleeding index, pocket depth, and pH. RESULTS: Nineteen patients were included but only 11 received pilocarpine treatment for 3 months, as six stopped pilocarpine due to side effects and two were excluded for other causes. Among the 11 patients who completed the 3-month follow-up, five had primary Sjögren's syndrome according to the American-European's classification criteria. As expected, statistical differences were found concerning SSF (p = 0.018) and USSF (p = 0.027) between M0 and M3 while no statistical change in both SG echostructure and vascularization or periodontal evaluation was shown. CONCLUSIONS: Pilocarpine improved SSF and USSF measurements in sicca syndrome but no ultrasonography of major salivary glands (SGUS) structural and vascular changes were detected as well as periodontal evaluation.

Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases.

OBJECTIVES: The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. METHODS: To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5-; n = 190/201) based on selected variables, collected retrospectively, without any missing data. RESULTS: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis. CONCLUSION: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.

Associations of lumbar scoliosis with presentation of suspected early axial spondyloarthritis.

OBJECTIVE: Scoliosis may impact the mechanical loading and cause secondary changes of the sacroiliac joints and lumbar spine. Our goal was to look how lumbar scoliosis modify the clinical and imaging-study in patients with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA). METHODS: Baseline weight-bearing lumbar-spine radiographs obtained in the DESIR cohort of patients aged 18-50 years and having IBP for at least 3 months but less than 3 years suggesting axSpA were studied. After training on scoliosis detection based on Cobb's angle>10° plus Nash-Moe grade≥1, readers blinded to patient data measured spine lumbar scoliosis, sacral horizontal angle, lumbosacral angle and lumbar lordosis on the radiograph of the lumbar and scored sacroiliitis on the radiograph of the pelvis. Baseline MRIs T1 and STIR of the lumbar spine and sacroiliac joints were evaluated for respectively degenerative changes and signs of axSpA. RESULTS: Of the 360 patients (50.8% females) 88.7% had lumbar pain and 69.3% met ASAS criteria for axSpA. Mean Cobb's angle was 3.2°±5.0° and 28 (7.7%) patients had lumbar scoliosis. No statistical differences were observed for radiographic sacroiliitis, MRI sacroiliitis, modified Stoke Ankylosing Spondylitis Spinal Score, Pfirmmann score, high-intensity zone, protrusion, extrusion, MODIC score between patients with and without scoliosis. In both groups, degenerative changes by MRI were rare and predominated at L4-L5 and L5-S1. CONCLUSION: In patients with early IBP suggesting axSpA, lumbar scoliosis was not associated with inflammatory or degenerative changes.

Spinal-pelvic orientation: potential effect on the diagnosis of spondyloarthritis.

OBJECTIVE: To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain. METHODS: Spinal-pelvic orientation was assessed in DESIR cohort patients with recent-onset inflammatory back pain and suspected axSpA, by using lateral lumbar-spine radiographs to categorize sacral horizontal angle (<40° vs ⩾40°), lumbosacral angle (<15° vs ⩾15°) and lumbar lordosis (LL, <50° vs ⩾50°). Associations between these angle groups and variables collected at baseline and 2 years later were assessed using the χ2 test (or Fisher's exact) and the Mann-Whitney test. With Bonferroni's correction, P < 0.001 indicated significant differences. RESULTS: Of 362 patients, 358, 356 and 357 had available sacral horizontal angle, lumbosacral angle and LL values, respectively; means were 39.3°, 14.6° and 53.0°, respectively. The prevalence of sacroiliitis on both radiographs and MRI was higher in the LL < 50° group than in the LL ⩾50° group, but the difference was not statistically significant. Clinical presentation and confidence in a diagnosis of axSpA did not differ across angle groups. No significant differences were identified for degenerative changes according to sacral horizontal angle, lumbosacral angle or LL. CONCLUSION: Spinal-pelvic balance was not statistically associated with the clinical or imaging-study findings suggesting axSpA in patients with recent-onset inflammatory back pain.

Association of lumbosacral transitional vertebra and sacroiliitis in patients with inflammatory back pain suggesting axial spondyloarthritis.

OBJECTIVE: Lumbosacral transitional vertebras (LSTVs) are common in the general population, but their potential impact on the sacroiliac joints is unclear. We aimed to determine the prevalence of LSTVs and to assess their associations with sacroiliitis by standard radiography and MRI in a population with suspected axial spondyloarthritis. METHODS: The data were from the DESIR cohort of 688 patients aged 18-50 years with inflammatory low back pain for ⩾3 months but <3 years suggesting axial spondyloarthritis. The baseline pelvic radiographs were read by two blinded readers for the presence and type (Castellvi classification) of LSTVs. Associations between LSTVs and other variables collected at baseline and at the diagnosis were assessed using the χ2 test (or Fisher's exact test) or the Mann-Whitney test. RESULTS: LSTV was found in 200/688 (29.1%) patients. Castellvi type was Ia in 54 (7.8%), Ib in 76 (11.0%), IIa in 20 (2.9%), IIb in 12 (1.7%), IIIa in 7 (1.0%), IIIb in 21 (3.0%) and IV in 10 (1.4%) patients. Compared with the group without LSTVs, the group with LSTVs had higher proportions of patients meeting modified New York criteria for radiographic sacroiliitis (19% vs 27%, respectively; P = 0.013) and Assessment of SpondyloArthritis international Society MRI criteria for sacroiliitis (29% vs 39%, respectively; P = 0.019). CONCLUSION: In patients with inflammatory back pain suggesting axial spondyloarthritis, LSTVs are associated with both radiographic and MRI sacroiliitis.

Screening for and management of comorbidities after a nurse-led program: results of a 3-year longitudinal study in 769 established rheumatoid arthritis patients.

Background/purpose: Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling. Methods: This was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0-100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data. Results: Of the 970 recruited patients, 776 (80%) were followed-up at 2-4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most. Conclusions: Comorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA. Trial registration number: NCT01315652.

Localized Myofascial Inflammation Revealed by Magnetic Resonance Imaging in Recent-onset Polymyalgia Rheumatica and Effect of Tocilizumab Therapy.

OBJECTIVE: To assess the prevalence of myofascial inflammatory lesions visible by magnetic resonance imaging (MRI) and their changes after tocilizumab (TCZ) therapy in active polymyalgia rheumatica (PMR). METHODS: We conducted a posthoc analysis of data from the TENOR study of TCZ monotherapy in PMR. The 18 patients each received TCZ injections at weeks 0, 4, and 8. The shoulder and pelvic girdles were assessed at baseline then at weeks 2 and 12 using T1- and T2- short-tau inversion recovery-weighted MRI. Radiologists blinded to patient data assessed each muscle group for localized myofascial inflammation on baseline, Week 2, and Week 12 MRI. Reproducibility was estimated by having 2 radiologists assess the Week 2 MRI of 13 patients, then computing the κ coefficient. RESULTS: For myofascial lesion detection, intraobserver reproducibility was almost perfect (κ = 0.890) and interobserver reproducibility was substantial (κ = 0.758). At baseline, all patients had at least 1 inflammatory myofascial lesion; sites involved were the shoulder in 10 (71.4%) patients, hip in 13 (86.7%), ischial tuberosity in 9 (60.0%), and pubic symphysis in 12 (80.0%). Sites involved at Week 12 were the shoulder in 8 patients (53.3%), hip in 5 (33.3%), ischial tuberosity in 1, and pubic symphysis in 3 (20.0%). At Week 12, of 103 muscle groups studied in all, 43 (41.7%) had no inflammatory lesions, compared to 33 at baseline (p = 0.002); improvements were noted in 66 (64.1%) muscle groups, worsening in 2 (1.9%), no change in 35 (34.0%; p = 0.034). CONCLUSION: Localized myofascial inflammatory lesions are common in recent-onset PMR and improve during TCZ therapy. Clinicaltrials.gov (NCT01713842).

Peripheral-blood b-cell subset disturbances in inflammatory joint diseases induced by Tropheryma whipplei.

OBJECTIVE: To look for abnormalities in circulating B-cell subsets in patients with rheumatic symptoms of Whipple's disease (WD). METHOD: Consecutive patients seen between 2010 and 2016 for suspected inflammatory joint disease were identified retrospectively. Results of standardized immunological and serological tests and of peripheral-blood B-cell and T-cell subset analysis by flow cytometry were collected. Patients with criteria suggesting WD underwent PCR testing for Tropheryma whipplei, and those with diagnosis of WD (cases) were compared to those without diagnosis (controls). We used ROC curve analysis to evaluate the diagnostic value of flow cytometry findings for WD. RESULTS: Among 2917 patients seen for suspected inflammatory joint disease, 121 had suspected WD, including 9 (9/121, 7.4%) confirmed WD. Proportions of T cells and NK cells were similar between suspected and confirmed WD, whereas cases had a lower proportion of circulating memory B cells (IgD-CD38low, 18.0%±9.7% vs. 26.0%±14.2%, P = 0.041) and higher ratio of activated B cells over memory B cells (4.4±2.0 vs. 2.9±2.2, P = 0.023). Among peripheral-blood B-cells, the proportion of IgD+CD27- naive B cells was higher (66.2%±18.2% vs. 54.6%±18.4%, P = 0.047) and that of IgD-CD27+ switched memory B cells lower (13.3%±5.7% vs. 21.4%±11.9%, P = 0.023), in cases vs. controls. The criterion with the best diagnostic performance was a proportion of IgD+CD27- naive B cells above 70.5%, which had 73% sensitivity and 80% specificity. CONCLUSION: Our study provides data on peripheral-blood B-cell disturbances that may have implications for the diagnosis and pathogenetic understanding of WD.

Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between clinical examination and ultrasonography.

OBJECTIVE: Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. METHODS: Outpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. RESULTS: Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76-1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42-0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. CONCLUSION: Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.

Ultrasonography and detection of subclinical joints and tendons involvements in Systemic Lupus erythematosus (SLE) patients: A cross-sectional multicenter study.

OBJECTIVES: The aims of this study in SLE population were (1) to describe ultrasonography (US) joint abnormalities, (2) to estimate the reliability of clinical swollen joint count (C-SJC) and SLEDAI (C-SLEDAI) versus US-SJC and US-SLEDAI scores, (3) to highlight specific patterns of lupus patients with Power Doppler (PD) abnormalities. METHOD: For this cross-sectional multicenter study, 151 consecutive adult SLE patients were recruited. Evaluation included a clinical standardized joint assessment, B-mode and PD US of 40 joints and 26 tendons blinded for clinical examination. Reliability and agreement between clinical and B-mode US were calculated using the intraclass correlation coefficients (ICC [95% Confidence Interval]). RESULTS: We found a very high frequency of subclinical US abnormalities in asymptomatic patients: 85% of patients without joint symptoms had at least 1 US abnormality. Among them 46 patients (87%) had a history of joint involvement. The most frequent abnormalities were joint effusmaions (108 patients), synovial hypertrophy (SH, 109 patients) and synovitis (61 patients). Joint or tendon PD signal (grade>1) was found in 44% of patients (67/151). Synovitis were mainly located especially on MCPs and wrists. Even if reliability between clinical and grey-scale US SJC assessments was poor, reliability between clinical and US SLEDAI was good. Comparison between SLE patients with and without PD signal did not show any specific SLE pattern. CONCLUSION: US may be useful to assess joint involvement in SLE patients but did not significantly change SLEDAI score.

Assessing polymyalgia rheumatica activity when C-reactive protein is unavailable or uninterpretable.

Objective: The PMR activity score (PMR-AS) includes the CRP value, which may be lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop alternatives to PMR-AS that do not require CRP. Methods: We used the Club Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent-onset PMR naive to glucocorticoid who received three tocilizumab infusions, at weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI cohort, we evaluated correlations between PMR-AS items to select the best item for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin-PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin-PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during tocilizumab therapy. Results: In the CRI cohort, agreement between PMR-AS and clin-PMR-AS was excellent (κ = 0.90). Linear regression between PMR-AS and clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP-imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24 (8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used. Conclusion: Alternatives to the PMR-AS obtained without CRP can be used to monitor PMR activity in everyday practice in patients without available CRP values and in those receiving IL-6 antagonist therapy.