Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

OBJECTIVE: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

Glucocorticoid trajectories over 2 years in patients with rheumatoid arthritis in a real-life setting.

OBJECTIVES: To analyse glucocorticoid (GC) use and trajectories in a real-life cohort of rheumatoid arthritis (RA). METHODS: Patients with RA included in the longitudinal RCVRIC cohort for initiating or changing biological disease-modifying antirheumatic drugs, were compared for the use of GCs at baseline. Among the GC users, the GC dose was analysed over 2 years of follow-up by group-based trajectory models. Characteristics and outcomes were compared between the trajectories. RESULTS: Among the 184 patients (RA duration 4.2 years (1.3; 12.6), Disease Activity Scores (DAS)28-C reactive protein (CRP) 4.24±2.14), 81 (44%) were on GCs. The GC users were significantly older, had higher CRP and Health Assessment Questionnaire (HAQ), more hypertension and lower lumbar T-score, but similar activity and erosive scores. Among the GC users, two trajectories were identified: trajectory 1 (n=20, 25%) with GC discontinuation in the first year and trajectory 2 (n=61, 75%) with maintenance of low-dose GCs at 2 years. Trajectory 2 was significantly associated with higher HAQ, a longer GC duration and a less frequent methotrexate association. After adjustment for HAQ, GC duration and MTX use, good EULAR responses were less frequent at 6 months and 1 year in the GC maintenance trajectory (38.3% vs 81.3%, p=0.03; 42.0% vs 82.4%, p=0.02). Diabetes, fractures and increased body mass index were noted in trajectory 2. CONCLUSION: GCs were used in almost half of patients with established RA in real-world practice. For the majority of GC users, a long-term low dose of GCs is maintained over 2 years. These results highlight the difficulties with stopping GCs, the lack of consensus for the efficacy-safety balance of GCs, and the need to individualise the best GC tapering.

Comparison of the cardiovascular risk profile of rheumatoid arthritis versus hand osteoarthritis patients.

It is clear that there is an increased cardiovascular (CV) risk in rheumatoid arthritis (RA) as a result of systemic inflammation. Hand osteoarthritis (HOA) patients, also have an increased CV risk, but the causes are still debated. Our objective was to compare CV risk factors and risk scores between HOA and RA patients. Thirty-five HOA patients were matched by age (< 3 years) and sex to 35 RA patients in a case-control study. We compared their CV risk profiles and their risk of occurrence of CV events at 10 years using the risk equations SCORE1, SCORE2, and QRISK3. There was a significant increase in SCORE1, SCORE2, but not in QRISK3 in the RA group compared to the HOA group, provided that the multiplication coefficient for RA was applied. This increase was found to no longer be significant for SCORE1 when RA patients have low disease activity (DAS28 ≤ 3.2; n = 8). There was no difference between groups in the frequency of metabolic syndrome, blood pressure, abdominal circumference, body mass index, uricemia, triglyceridemia, HDL cholesterolemia, or pain intensity. Conversely, HOA patients had higher LDL cholesterol and fasting blood glucose levels, in the main analysis and in the subgroup of moderate/high RA activity patients (DAS28 > 3.2; n = 26). We found a higher CV risk in RA compared to HOA patients with moderate/high disease activity. The increased CV risk reported in OA remains to be confirmed in HOA, but these patients appear to have a pro-atherogenic lipid and glycemic profile.

Omega 3 Fatty Acids Intake Does Not Decrease the Risk of Rheumatoid Arthritis Occurrence: A Meta-Analysis. Comment on Tanski et al. The Relationship between Fatty Acids and the Development, Course and Treatment of Rheumatoid Arthritis. Nutrients 2022, 14, 1030.

In an article published in Nutrients, Tanski et al. performed a systematic review and concluded that omega-3 fatty acids might contribute to a reduced incidence of rheumatoid arthritis (RA) [...].

Post-traumatic stress disorder prior to diagnosis is as rare in spondyloarthritis as in non-inflammatory rheumatic conditions and rheumatoid arthritis.

OBJECTIVE: Post-traumatic stress disorder (PTSD) may be a risk factor for the development of rheumatoid arthritis (RA). No data are available in spondyloarthritis (SpA). The aim of the present study was to investigate the frequency of traumatic events and PTSD in patients with SpA and its different phenotypes and to compare the results to patients with non inflammatory rheumatic disease and RA patients. METHODS: This was an observational, cross-sectional and bi-centric study. Participants were patients diagnosed with SpA, non-inflammatory rheumatic or autoimmune disease (controls), or RA. Traumatic events were identified by the brief trauma questionnaire (BTQ). PTSD was defined as the presence of a traumatic event and ≥4 symptoms on the short PTSD checklist scale. RESULTS: Among 1389 participants, 510 patients were diagnosed with SpA (167 ankylosing spondylitis, 140 psoriatic arthritis, 130 non-radiographic-axial SpA, and 51 peripheral SpA), 365 with non-inflammatory rheumatic disease and 514 patients with RA. The frequency of trauma in SPA patients was 33.7%, of which 30.5% in AS, 30.7% in PsA, 37.7% in nr-axSpA and 41.2% in peripheral SpA (P=NS). The prevalence of PTSD in SPA patients was 4.9%, (of which 3.6% in AS, 2.9% in PsA, 6.2% in nr-axSpA and 7.8% in peripheral SpA [P=NS]) and was not significantly different from the controls (after IPTW 4.8% vs. 6.7%). The frequency of trauma and PTSD was also comparable between RA and controls and between SPA and RA. CONCLUSION: Traumatic events and PTSD occurring prior to diagnosis is as rare in SpA as in non-inflammatory rheumatic diseases and RA.

Assessment of 99mTc-NTP 15-5 uptake on cartilage, a new proteoglycan tracer: Study protocol for a phase I trial (CARSPECT).

Background: 99mTc-NTP 15-5 is a SPECT radiotracer targeting proteoglycans (PG), components of the cartilaginous extracellular matrix. Imaging of PGs would be useful for the early detection of cartilage disorders (osteoarthritis, arthritis and chondrosarcoma, Aromatase Inhibitor associated arthralgia (AIA) in breast cancer), and the follow-up of patients under treatment. According to preclinical study results, 99mTc-NTP 15-5, is a good candidate for a specific functional molecular imaging of joints. We intend to initiate a first in-human study to confirm and quantify 99mTc-NTP 15-5 uptake in healthy joints. Methods: As the clinical development of this radiotracer would be oriented toward the functional imaging of joint pathologies, we have chosen to include patients with healthy joints (unilateral osteoarthritis of the knee or breast cancer with indication of AI treatment). This phase I study will be an open-label, multicenter, dose-escalation trial of a radiopharmaceutical orientation to determine the recommended level of activity of 99mTc-NTP 15-5 to obtain the best joint tracer contrasts on images, without dose limiting toxicity (DLT). The secondary objectives will include the study of the pharmacology, biodistribution (using planar whole body and SPECT-CT acquisitions), toxicity, and dosimetry of this radiotracer. The dose escalation with 3 activity levels (5, 10, and 15 MBq/kg), will be conditioned by the absence at the previous level of DLT and of a visualized tracer accumulation on more than 80% of healthy joints as observed on scintigraphy performed at ≤ 2 h post-injection. Discussion: This first in-human phase I trial will be proof-of-concept of the relevance of 99mTc-NTP 15-5 as a cartilage tracer, with the determination of the optimal methodology (dose and acquisition time) to obtain the best contrast to provide a functional image of joints with SPECT-CT. Trial registration number: Clinicaltrials.gov: NCT04481230. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2020-000495-37.

Effect of disease-modifying anti-rheumatic drugs in osteoarthritis: A meta-analysis.

OBJECTIVE: Osteoarthritis (OA) displays features of systemic and local inflammation, suggesting that DMARDs used in rheumatoid arthritis could potentially also be effective in OA. However, studies of the effects of DMARDs in OA have yielded conflicting data, and have been insufficiently large to draw conclusions. In this meta-analysis, we aimed to estimate the effect of DMARDs - such as methotrexate, hydroxychloroquine, TNF, and IL-1 inhibitors - on OA. METHODS: We searched for relevant articles of randomized controlled trials published up to March 2022, using Pubmed, EMBASE, and the Cochrane Library. Studies were reviewed in accordance with PRISMA 2020 guidelines. The effects of DMARDs on OA outcomes (symptoms, quality of life, ESR) were expressed as the standardized mean difference. RESULTS: We retrieved 29 references. Among these, 23 randomized controlled trials compared the effects of DMARDs versus placebo or other treatments on disease activity, including 1143 DMARD-treated OA patients and 1155 OA patients in the control group. We found statistically significant improvement of pain and stiffness with methotrexate, especially in knee OA. TNF inhibitors improved the swollen joint count in hand OA, and inflammation parameters, without change in pain, stiffness, or function. Hydroxychloroquine and IL-1 inhibitors were not effective. CONCLUSION: Overall, the presently available data regarding the effects of DMARDs on OA symptoms intensity are disappointing. Only methotrexate might have an analgesic effect, especially in knee OA, which warrants further investigation.

Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis.

BACKGROUND: Polyunsaturated fatty acid (PUFA) supplementation has been reported to improve disease activity in inflammatory rheumatic diseases (IRDs). However, data are often conflicting and studies insufficiently large to draw conclusions. This systematic literature review and meta-analysis aimed to better estimate the effect of oral supplementation with omega (n)-3 and n-6 PUFA on IRD activity in terms of duration, dose, type, and source. METHODS: The literature was searched in PubMed, EMBASE, and Cochrane Library databases up to October 2020. Studies were reviewed in accordance with PRISMA guidelines. The effect of PUFA supplementation on disease activity was expressed as the standardized mean difference (95% CI). Metaregression and subgroup analyses involved type of IRD, Jadad score, PUFA source (animal or vegetable), and doses. RESULTS: We obtained 42 references; 30 randomized controlled studies were included comparing the effects of PUFA versus control on disease activity (710 IRD patients receiving PUFA supplementation and 710 controls, most with rheumatoid arthritis). We found a significant improvement in pain, swollen and tender joint count, Disease Activity Score in 28 joints, and Health Assessment Questionnaire score in IRD patients receiving PUFA supplementation as compared with controls, with a significant decrease in erythrocyte sedimentation rate but not C-reactive protein level. Although meta-regression revealed no difference by IRD type or source or dose of PUFA supplementation, subgroup analysis revealed more parameters significantly improved with animal- than vegetable-derived PUFAs and 3- to 6-month supplementation. Most studies examined high-dose supplementation (>2 g/day). CONCLUSION: PUFA consumption, especially omega-3 from animal source >2 g/day, may improve IRD activity and might be an adjuvant therapy in rheumatoid arthritis. TRIAL REGISTRATION: The protocol was registered at PROSPERO ( CRD42021253685 ).

A Meta-Analysis of the Impact of Nutritional Supplementation on Osteoarthritis Symptoms.

Conflicting evidence exists concerning the effects of nutrient intake in osteoarthritis (OA). A systematic literature review and meta-analysis were performed using PubMed, EMBASE, and Cochrane Library up to November 2021 to assess the effects of nutrients on pain, stiffness, function, quality of life, and inflammation markers. We obtained 52 references including 50 on knee OA. Twelve studies compared 724 curcumin patients and 714 controls. Using the standardized mean difference, improvement was significant with regard to pain and function in the curcumin group compared to placebo, but not with active treatment (i.e., nonsteroidal anti-inflammatory drugs, chondroitin, or paracetamol). Three studies assessed the effects of ginger on OA symptoms in 166 patients compared to 164 placebo controls. Pain was the only clinical parameter that significantly decreased. Vitamin D supplementation caused a significant decrease in pain and function. Omega-3 and vitamin E caused no changes in OA parameters. Herbal formulations effects were significant only for stiffness compared to placebo, but not with active treatment. A significant decrease in inflammatory markers was found, especially with ginger. Thus, curcumin and ginger supplementation can have a favorable impact on knee OA symptoms. Other studies are needed to better assess the effects of omega-3 and vitamin D.

Decision Tree With Only Two Musculoskeletal Sites to Diagnose Polymyalgia Rheumatica Using [18F]FDG PET-CT.

Introduction: The aim of this study was to find the best ordered combination of two FDG positive musculoskeletal sites with a machine learning algorithm to diagnose polymyalgia rheumatica (PMR) vs. other rheumatisms in a cohort of patients with inflammatory rheumatisms. Methods: This retrospective study included 140 patients who underwent [18F]FDG PET-CT and whose final diagnosis was inflammatory rheumatism. The cohort was randomized, stratified on the final diagnosis into a training and a validation cohort. FDG uptake of 17 musculoskeletal sites was evaluated visually and set positive if uptake was at least equal to that of the liver. A decision tree classifier was trained and validated to find the best combination of two positives sites to diagnose PMR. Diagnosis performances were measured first, for each musculoskeletal site, secondly for combination of two positive sites and thirdly using the decision tree created with machine learning. Results: 55 patients with PMR and 85 patients with other inflammatory rheumatisms were included. Musculoskeletal sites, used either individually or in combination of two, were highly imbalanced to diagnose PMR with a high specificity and a low sensitivity. The machine learning algorithm identified an optimal ordered combination of two sites to diagnose PMR. This required a positive interspinous bursa or, if negative, a positive trochanteric bursa. Following the decision tree, sensitivity and specificity to diagnose PMR were respectively 73.2 and 87.5% in the training cohort and 78.6 and 80.1% in the validation cohort. Conclusion: Ordered combination of two visually positive sites leads to PMR diagnosis with an accurate sensitivity and specificity vs. other rheumatisms in a large cohort of patients with inflammatory rheumatisms.

The Effect of TNF and Non-TNF-Targeted Biologics on Body Composition in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with a decrease in lean mass and stability or even an increase in fat and ectopic adipose tissue. A few data are available on body composition changes under treatment, and data are still controversial. Body composition was assessed before initiation of biologic disease-modifying antirheumatic drug (bDMARD) and after 6 and 12 months of stable treatment. Eighty-three RA patients were included (75% of women, mean age 58.5 ± 10.8 years) of whom 47 patients treated with TNF inhibitor (TNFi), 18 with non-TNF-targeted biologic (Non-TNFi), and 18 with conventional DMARD (cDMARD) alone. In the TNFi group, total lean mass, fat-free mass index, and skeletal muscle mass index significantly increased at 1 year. An increase in subcutaneous adipose tissue (SAT) without change for the visceral or body fat composition was associated. These changes were associated with an improvement in strength and walking test. In non-TNFi or cDMARD groups, no significant changes for body composition or muscle function were observed at 1 year. However, no significant differences for treatment x time interaction were noted between group treatments. In active RA patients starting first bDMARD, treatment with TNFi over 1 year was associated with favorable changes of the body composition and muscle function.

Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography in Inflammatory Rheumatism, Particularly Polymyalgia Rheumatica: A Retrospective Study of 222 PET/CT.

Purpose: The objective of this study was to evaluate periarticular FDG uptake scores from 18F-FDG-PET/CT to identify polymyalgia rheumatica (PMR) within a population presenting rheumatic diseases. Methods: A French retrospective study from 2011 to 2015 was conducted. Patients who underwent 18F-FDG-PET/CT for diagnosis or follow-up of a rheumatism or an unexplained biological inflammatory syndrome were included. Clinical data and final diagnosis were reviewed. Seventeen periarticular sites were sorted by a visual reading enabling us to calculate two scores: mean FDG visual uptake score, number of sites with significant uptake same as that or higher than liver uptake intensity and by a semi-quantitative analysis using mean maximum standardized uptake value (SUVmax). Optimal cutoffs of visual score and SUVmax to diagnose PMR were determined using receiver operating characteristics curves. Results: Among 222 18F-FDG PET/CT selected for 215 patients, 161 18F-FDG PET/CT were performed in patients who presented inflammatory rheumatism as a final diagnosis (of whom 57 PMR). The presence of at least three sites with significant uptake identified PMR with a sensitivity of 86% and a specificity of 85.5% (AUC 0.872, 95% CI [0.81-0.93]). The mean FDG visual score cutoff to diagnose a PMR was 0.765 with a sensitivity of 82.5% and a specificity of 75.8% (AUC 0.854; 95% CI [0.80-0.91]). The mean SUVmax cutoff to diagnose PMR was 2.168 with a sensitivity of 77.2% and a specificity of 77.6% (AUC 0.842; 95% CI [0.79-0.89]). Conclusions: This study suggests that 18F-FDG PET/CT had good performances to identify PMR within a population presenting rheumatic diseases.

Prevalence of Migraine and Neuropathic Pain in Rheumatic Diseases.

To investigate the physiopathology of pain in chronic inflammatory rheumatic diseases (CIRDs), we assessed the prevalence of migraine and neuropathic pain in 499 patients with CIRDs. We studied 238 patients with rheumatoid arthritis, 188 with spondyloarthritis (SpA), 72 with psoriatic arthritis (PsA), and 1 unclassified. Migraine was diagnosed according to IHS migraine diagnostic criteria. Neuropathic pain was diagnosed when patients scored at least 3 on the DN4 questionnaire. Participants completed a validated self-assessment questionnaire. Migraine prevalence was 34% (165/484), and it was highest in PsA. Risk factors for migraine were a high level of anxiety, female sex, young age, and TNF-alpha inhibitor treatment (OR = 1.90 (1.13-3.25)). Besides, high disease activity was a risk factor in SpA. Blood CRP level was not significantly associated with migraine. Of 493 patients with CIRDs, 21.5% had chronic pain with neuropathic characteristics. Compared to the French general population, these patients had significantly higher prevalences of migraine (two-fold) and neuropathic pain (three-fold). This study showed that migraine and neuropathic pain frequently occurred in patients with rheumatic diseases. Therefore, upon reporting residual pain, these patients should be checked for the presence of migraine or neuropathic pain, despite adequate clinical control of rheumatic disease.

Chronic bursitis and tenosynovitis revealing Whipple's disease.

Joint complaints, most commonly intermittent arthritis, are the initial manifestation in about three-fourths of Whipple's disease cases. We herein report on two cases wherein Whipple's disease manifested itself as chronic bursitis and tenosynovitis at several sites. A 42 year-old man had bilateral olecranon bursitis, a right patellar bursitis and an extensor tenosynovitis on the left wrist and a 54 year-old man had extensor tenosynovitis at both wrists and a bilateral tenosynovitis of the extensors at both ankle. Methotrexate in both patients and etanercept in one of them were not effective. Polymerase chain reaction testing revealed Tropheryma whipplei on feces, bursitis and articular fluid samples. Duodenal biopsy proved to be normal. Doxycycline and hydroxychloroquine were rapidly effective. Chronic bursitis and tenosynovitis must be added to the list of rheumatologic manifestations that may evoke the diagnosis of Whipple disease.

Dupuytren's Disease and exposure to vibration: Systematic review and Meta-analysis.

INTRODUCTION: Dupuytren's Disease (DD) occurs frequently in the entire population. Several risk factors are well known, including diabetes, alcohol, and age. In this meta-analysis, we assessed the role of occupational vibration exposure in the risk of DD, an issue currently under debate. METHODS: We searched PubMed, Google Scholar, and the Cochrane Library to find references up to June 2019. DD prevalence was calculated using meta-proportion analysis. Differences in characteristics between DD patients and controls were expressed as standardized mean differences using the inverse of variance method or percentages using also meta-proportion analysis. We performed meta-regression analyses to assess the effects of alcohol, smoking, age, and sex on the DD incidence for the patients with DD that were exposed to vibrations. RESULTS: We included 9 studies, comprising a total of 60,570 patients, including 1,804 DD patients. Prevalence of DD was 9.8% (95%CI: 5.9-14.4%). Compared with controls, patients with DD were older, more diabetic, more smokers and with a higher consumption of alcohol. Meta-analysis of the nine longitudinal studies comparing DD occurrence between patients exposed to vibration (626 of 6825) or not (1220 of 52,502) revealed a significantly increased DD incidence among patients with vibration exposure compared with controls (OR=2.87; 95%CI: 1.41-5.84). In metaregression we found no significant influence of all parameters on DD. CONCLUSION: Age and environmental factors had no effect on DD prevalence among patients exposed to vibrations, despite a 10% prevalence in this group. Using vibration tools at work should be recognized as an important risk factor of developing DD.