Reactive Arthritis: Treatment Challenges and Future Perspectives.

PURPOSE OF THE REVIEW: Reactive arthritis is synovitis related to an infection away from the joint. The evolution is variable, frequently self-limited, but with the possible evolution to a prolonged form, generating functional incapacity and sequelae. RECENT FINDINGS: New microbiological families have been incriminated and pathophysiological links have been clarified, highlighting the role of the mucous membranes (gut in particular), specific cell populations, and the production of pro-inflammatory cytokines. First-line pharmacological treatment is based on NSAIDs. In case of failure, synthetic and more recently biological DMARDs are indicated. Only open data are available for biological DMARDs but suggest good efficacy and safety. Reactive arthritis has not disappeared. The diagnosis must be mentioned by the clinic and history to allow the rapid introduction of an appropriate treatment.

Impact of obesity, structural severity and their combination on the efficacy of viscosupplementation in patients with knee osteoarthritis.

BACKGROUND: Obesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough to formally refute VS in such patients in whom surgery is sometimes contraindicated? OBJECTIVES: To compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined. METHODS: Post-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.- 2), OARSI radiological grade (1-2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons (obese versus non-obese, OARSI 1-2 versus 3, and both combined) in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test. RESULTS: One-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups (all p < 0.01). At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients (4.9 ± 4.1 versus 7.1 ± 4.9; p = 0.008) and in patients OARSI 1-2 versus 3 (4.8 ± 4.3 versus 6.4 ± 4.5; p = 0.009). However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score. CONCLUSION: These results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS.

Effects of disease-modifying anti-rheumatic drugs on sacroiliac MRI score in axial spondyloarthritis: a systematic review and meta-analysis.

INTRODUCTION: Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). The aim of this meta-analysis is to assess the effect of the different bDMARDs and tsDMARDs on the SPARCC score at 12-16 and 48-52 weeks. METHODS: A systematic review, performed on PubMed (including Medline), Cochrane (CENTRAL) and DOAJ databases, included randomized controlled studies evaluating the sacroiliac joint (SIJ) SPARCC score at 12-16 or 48-52 weeks in patients with axSpA meeting the ASAS 2009 criteria or the modified New York criteria. We included studies evaluating the effects of the different treatments on the SPARCC score of SIJ in axial spondyloarthritis in comparison to a control group. RESULTS: Eighteen studies were included in the meta-analysis. Nine studies evaluated the effect of TNFα inhibitors (TNFi), three for IL-17 inhibitors, and four for JAK inhibitors. At 12 and 16 weeks, SIJ SPARCC score was significantly improved by TNFi (WMD: - 3.29 [95% CI - 4.25; - 2, 34]), by IL-17 inhibitors (WMD: - 4.66 [95% CI - 6.22; - 3.09]), and by JAK inhibitors (JAKi) (WMD: - 3.06 [95% CI - 3.24; - 2.89]). There was no difference between the molecule subgroups. At 48-52 weeks, TNFα inhibitors reduced more SIJ SPARCC, but not significantly (WMD: - 2.26 [95% CI - 4.94; 0.42]), than placebo groups who began a TNFi treatment with delay. CONCLUSION: Our meta-analysis shows a comparable improvement of the SIJ SPARCC score regarding TNFi, JAKi, and IL-17 inhibitors at three months and suggests the presence of an opportunity window. Key Points • Anti-TNF Ab, anti-IL17 Ab, and JAK inhibitor treatments reduce the sacroiliac joint SPARCC scores. • There is no difference between the different treatments in the reduction of the sacroiliac joint SPARCC score after 3 months in axial spondyloarthritis.

Comparison of sacroiliac CT findings in patients with and without ankylosing spondylitis aged over 50 years.

Diagnosis of axial spondyloarthritis (axSpA) is nowadays commonly made with the help of pelvic radiography or magnetic resonance imaging (MRI). However, there is an important inter-observer variability in radiography, and MRI is subject to possible false positives and is not the best modality for studying structural lesions. Conversely, pelvic computed tomography (CT) has excellent specificity and appears to be more effective than radiography for the diagnosis of ankylosing spondylitis (AS). However, its findings in patients over 50 years of age have not yet been studied. The objectives of this study were to describe the CT characteristics of sacro-iliac joints (SIJ) and the presence of intra-articular gas in patients with AS aged over 50 years and to compare them with controls of the same age and sex. This two-center, cross-sectional, observational study was performed using the medical records of the rheumatology departments of two University Hospitals. We included patients with a clinical diagnosis of axSpA, who had both definite radiographic sacroiliitis according to the modified New York criteria and met the ASAS 2009 criteria for axSpA (that is, AS), and who had undergone any CT scan including the whole SIJ. Each patient was matched for age and sex to a control randomly selected on the Picture Archiving and Communication System (PACS), symptomatic or asymptomatic, and without spondyloarthritis. For each individual, CT scans were interpreted blindly by two independent rheumatologists and scored for joint space narrowing (JSN), erosions, sclerosis, intra-articular gas, and diffuse idiopathic skeletal hyperostosis (DISH). Ninety patients and 90 controls were included in the study. The rates of positive JSN, erosion, and sclerosis scores were higher in the AS group (91% vs. 21%, p < 0.0001; 31% vs. 2%, p < 0.0001; 27% vs. 13%, p = 0.03, respectively), but the rates of intra-articular gas and DISH were higher in the control group (24% vs. 68%, p < 0.0001; 7% vs. 33%, p < 0.0001, respectively). 58% of patients had complete bilateral ankylosis. A total of 83 (92.2%) patients had a CT scan considered positive for AS, compared with only seven controls (7.8%). Sclerosis and erosions were predominantly on the anterosuperior part and iliac side of the joint in controls and were more diffuse in patients with AS. CT findings in patients with AS over 50 years of age are mostly represented by changes in the joint space; patients with AS have more erosions and sclerosis changes, but less intra-articular gas than controls.

Subchondral bone attenuation coefficient utility of the sacroiliac margins to differentiate spondyloarthritis and osteitis condensans ilii.

INTRODUCTION: Differentiating ankylosing spondylitis (AS) from osteitis condensans ilii (OCI) remains challenging for clinicians. The aim of this study was to determine whether Subchondral Bone Attenuation Coefficient of the SacroIliac margins (SBAC-SI) is different in AS, OCI and diffuse idiopathic skeletal hyperostosis (DISH). METHODS: A monocentric retrospective observational study was performed at the University Hospital of Besançon. Patients included were followed for AS, DISH or OCI and underwent CT scan including sacroiliac joint. Patients with tumour lesion of bone or a history of pelvic radiotherapy were excluded. AS and OCI patients were matched with a control of the same age and sex. SBAC-SI was evaluated by the sum of 24 identical circular regions of interest, 8 per slice (anterior, middle and posterior). RESULTS: Thirty AS and AS controls, 31 DISH, 29 OCI and OCI controls were included. SBAC-SI score was 9727 (±2430) in the OCI group (p<0.001), 3563 (±1860) in the AS group, 3899 (±1937) in the DISH group, 4224 (±1693) in the AS control group and 5445 (±1205) in the OCI control group. A threshold of 7500 HU had the best discriminative value between OCI and AS (youden index: 0.89). In AS, disease duration is negatively associated with SBAC-SI (r: -0.623; p<0.01) and HLA B27 is associated with lower SBAC-SI (6523 (5198; 7137) vs 2809 (1568; 3371); p<0.001). CONCLUSION: SBAC-SI is significatively different between AS and OCI and could help to distinguish these two diseases.

Frequency and anatomic distribution of magnetic resonance imaging lesions in the sacroiliac joints of spondyloarthritis and non-spondyloarthritis patients.

Background: Lesions detected by magnetic resonance imaging (MRI) of the sacroiliac joints are critical to the diagnosis of non-radiographic axial spondyloarthritis. However, inflammatory and structural lesions may be encountered in other conditions. Objectives: The objective of this study was to evaluate and compare the frequency and localization of inflammatory and structural lesions on MRIs of the sacroiliac joint of spondyloarthritis (SpA) and non-spondyloarthritis (non-SpA) patients. Design: This is a retrospective study including 200 patients, each having undergone an MRI of the sacroiliac joints. Methods: Two experienced readers evaluated the whole set of images to detect erosions, subchondral sclerosis, fatty lesions, bone marrow edema (BME) and ankylosis according to the definitions established by the ASAS MRI working group. We divided sacroiliac joints into five segments: upper, antero-middle, intermediate-middle, postero-middle and lower. Results: A total of 96 subjects with SpA (mean age 37.4 ± 11.8 years) and 104 without SpA (mean age 39.9 ± 11.6 years) were included. Of the 96 SpA patients, 65% had inflammatory buttock pain compared with 25% in the non-SpA group. BME was seen in 65% of SpA patients, mainly in the intermediate-middle segment, and in 20% of non-SpA patients, predominantly in the antero-middle segment. Subchondral sclerosis occurred in 44% of non-SpA patients, mostly in the antero-middle segment, and in 36% of SpA patients. Fatty lesions were present in 34% of SpA and in 21% of non-SpA patients. Erosions were seen in 25% of non-SpA and in 60% of SpA patients. BME and structural lesions were minimally observed in the postero-middle segment in non-SpA patients. Conclusion: Inflammatory and structural lesions were observed in all segments of the joint in SpA, mainly in the middle segments, while lesions predominantly affected the antero-middle segment in non-SpA, and were uncommon in the postero-middle segment.

Methotrexate and cardiovascular risk in rheumatic diseases:A comprehensive review.

Introduction: Management of inflammatory rheumatic diseases has evolved based on improved treatment strategies and better management of comorbidities, specifically cardiovascular risk. Methotrexate is one of the first-line treatments in the management of inflammatory rheumatic diseases, but its cardiovascular effects are poorly understood. The purpose of this review is to assess the cardiovascular impact of methotrexate in inflammatory rheumatic disease.Areas covered: Current knowledge about the mechanism of action of methotrexate on cardiovascular tissue is presented. A review of the literature in the Medline, Cochrane and Embase databases was performed. Current data about the cardiovascular effects of methotrexate in rheumatoid arthritis, psoriatic arthritis, and psoriasis are presented.Expert opinion: Mechanism of action of methotrexate is based on the antagonism of purines. It reduces systemic inflammation and oxidative stress and improves the major cardiovascular risk factors. Methotrexate improves cardiovascular risk in rheumatoid arthritis, psoriasis and psoriatic arthritis, but the mechanisms involved are partially identified. Data are controversial regarding its effects on endothelial function and atherosclerosis. Conversely, in the general population and in patients with HIV infection, methotrexate does not modify cardiovascular outcomes. Thus, methotrexate only improves cardiovascular risk by reducing systemic inflammation, and should not be used to prevent cardiovascular events.

Psoriatic arthritis and physical activity: a systematic review.

INTRODUCTION: The positive effects of physical activity in both rheumatoid arthritis and ankylosing spondylitis have been proven, but no clear data is yet published regarding psoriatic arthritis (PsA). The aims of this study were (i) to assess the level of physical activity (PA) in these patients and (ii) to review the effects of PA on articular disease, extra articular symptoms, and overall well-being. METHODS: The research strategy was performed on Pubmed, Cochrane, PEDro databases using the following keywords: "psoriatic arthritis AND physical activity" without restriction. The PRISMA methodology was used to select and analyze articles. We searched for all studies published online and in English before January 2021. RESULTS: A total of 319 studies were retrieved by our search but only 13 could be included. Two reports showed that 17 and 68% of patients reported practicing regularly physical activity. Exercise improved the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), the general symptoms (pain and fatigue), and the quality of life. Muscle strength and some of cardiovascular comorbidities were also improved. While the studies concerning the risk of enthesitis or flare induced by physical activity are conflicting, recent clinical trials did not mention any adverse event. Finally, rehabilitation programs were associated with a reduction mainly of pain and fatigue. CONCLUSION: Studies show clear beneficial effects of exercise in PsA on disease activity, on well-being, and on comorbidities, and they seem to outweigh the risk of enthesitis induced by mechanical stress. Further investigations are necessary to confirm these results and to precise the modalities of exercise. Key Points • Psoriatic arthritis patients have a sedentary lifestyle • Physical activity has beneficial effects on disease activity, well-being and reduced some cardiovascular risk factor in psoriatic arthritis • Risk of enthesitis and flares is low with exercise in psoriatic arthritis.

Efficacy of Rituximab on Rheumatoid Leptomeningitis as the First Symptom of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized mainly by arthritis, with the possible occurrence of extra-articular manifestations. We report the case of a patient who developed leptomeningitis as the first sign of RA, one year before the diagnosis of RA. Methylprednisolone 1000 mg was given intravenously. Because of the onset of seizures and cognitive impairment, rituximab was started. After three cycles of rituximab (1000 mg on day 0 and 1000 mg on day 15, every 6 months), neurological clinical examination, MRI and electroencephalogram findings were significantly improved. LEARNING POINTS: Rheumatoid meningitis may occur in the disease course of rheumatoid arthritis with varied and non-specific symptoms.Cerebrospinal fluid examination, MRI and tests for rheumatoid factor or anti-citrullinated protein antibodies in serum or in cerebrospinal fluid are key examinations for diagnosing rheumatoid meningitis.Rituximab has good efficacy in rheumatoid meningitis.

Prognostic factors of good response to DMARDs in psoriatic arthritis: a narrative review.

INTRODUCTION: The management of Psoriatic arthritis (PsA) has evolved in the last decade with a significant increase in treatment options making the choice for clinicians difficult. Thus, the different factors of good prognosis for each treatment are presented in this review. AREAS COVERED: Current available treatment and assessment tools for the response of treatment are presented. A systematic review of the literature, on Pubmed, Medline and Cochrane databases and abstracts from the last three EULAR and ACR annual conferences was performed. Factors associated with a good response to csDMARDs, tsDMARDs and bDMARDs are presented. EXPERT OPINION: Dactylitis and axial involvement are associated with a poor response to methotrexate. Leflunomide has shown better efficacy in the presence of established polyarticular involvement. TNF inhibitors are to be preferred in young men with an elevated CRP while obesity, high disease activity and long disease duration are factors associated with poor response. Apremilast and ustekinumab are more effective in mono and oligo articular disease. Abatacept is more effective in patients with high CRP, high disease activity and polyarticular involvement. Finally, there are no available data with the anti IL17 These factors are some arguments to help clinicians, but comparative study are needed to conclude.

Ultrasonographic Involvement of the anterior chest wall in Spondyloarthritis: Factors associated with 5-years structural progression. A prospective study in 58 patients.

INTRODUCTION: To evaluate, factors associated with new ultrasonographic lesions of the anterior chest wall in spondyloarthritis (SpA) after a follow up of 5 years. METHODS: SpA Patients included in 2013 in a first study were evaluated five years later. Ultrasound B mode and power Doppler examination of the two sternoclavicular joints and the manubrio-sternal joint were performed by the same two examinators at baseline and five years later. The presence of erosion, synovitis, ankylosis, power Doppler signal, joint effusion and joint space narrowing were assessed blind of the first evaluation. RESULTS: Among the 131 patients at baseline, 58 patients were evaluated 5 years later. The mean age was 48.2±11.9 years old, with 86% of male and mainly an axial disease (78%). Patient characteristics are comparable to the original cohort. The most frequent lesions were ankylosis of the manubriosternal joint (38%) and erosions of the sternoclavicular joint (29%). 31 patients (53%) developed a new lesion of the ACW. There is a statistically significant association between new lesions of the ACW and higher ASDAS CRP (1,86±1,07 VS 3,0±2,17 P<0,01) and with CRP (5,34±7,85 VS 16,2±35, P=0,035) in the moment of the examination. There was no baseline factor associated with the structural progression. CONCLUSION: The occurrence of new lesions of the anterior chest wall is associated with a higher disease activity and a higher CRP at 5 years.

Muscle involvement on 18F-FDG PET-CT in polymyalgia rheumatica. A controlled retrospective study of 101 patients.

18F-fluoro deoxy glucose PET scanner (18F-FDG-PET-CT) has shown its interest in the diagnosis of polymyalgia rheumatica (PMR) and makes possible to evaluate the metabolic activity of the entire musculoskeletal system and in particular muscular structures. The purpose of this study was to evaluate muscle involvement using 18F-FDG-PET-CT in the case of PMR, compared to a non PMR population. METHODS: This is a monocentric retrospective study of patients with PMR (ACR/EULAR 2012 criteria) who had an 18F-FDG-PET-CT examination. A control group composed of subjects without rheumatological manifestations who had such an examination as part of neoplastic research or follow-up of neoplastic diseases was also evaluated. The PET assessment included 17 sites suggesting a PMR, as previously reported. Areas of muscle hypermetabolism were classified in the same way according to the same semi quantitative classification. Muscle activity sites were identified. A comparison of patients with PMR with and without muscle damage was performed using the exact Mann-Whitney or Fisher test. RESULTS: Two hundred and one cases were examined, involving 101 PMRs (mean age 68.6 years) and 100 controls (mean age 67.7 years). Overall, PET muscle damage was observed in 34 cases (34%) in PMR and 10 cases (10%) in controls (P=0.004). Lesions are bi or multi-focal in half of the cases. The affected muscle sites are: spinal muscles 19, scapular girdle 14, pelvic girdle 13, and thigh 6. Fasciitis was found in 3 cases. In patients with PMR, PET muscle involvement was not associated with age, CRP or overall PMR PET score. CONCLUSION: Muscle damage assessed by 18F-Fluorodeoxyglucose PET-CT is common in PMR (1/3 of cases), located at the usual sites of disease symptoms, without association with age, CRP levels or the overall PET PMR score. The muscle must be carefully evaluated during a PET examination in cases of PMR.

Value of serum procalcitonin for the diagnosis of bacterial septic arthritis in daily practice in rheumatology.

INTRODUCTION/OBJECTIVES: Septic arthritis is a diagnostic and therapeutic emergency because of a high morbidity and mortality. Nevertheless, the etiologic diagnosis is often difficult. The aim of our study was to determine if serum procalcitonin was a discriminatory biomarker in case of arthritis of undetermined etiology. METHOD: Patients were separated in five groups: gouty arthritis, calcium pyrophosphate deposition arthritis, osteoarthritis or post-traumatic arthritis ("mechanical" arthritis), chronic inflammatory rheumatic arthritis, and septic arthritis. Levels of serum white blood cells, C-reactive protein and procalcitonin were measured. RESULTS: Ninety-eight patients were included: 18 in the "gout" group, 26 in the "calcium pyrophosphate deposition arthritis" group, 16 in the mechanical group, 18 in the "chronic inflammatory rheumatic" group, and 20 in the "sepsis" group. The area under the receiver operating characteristic curve of white blood cells, C-reactive protein, and procalcitonin levels to diagnose a septic arthritis were 0.69 (IC95% 0.55-0.83), 0.82 (IC95% 0.73-0.91), and 0.87 (IC95% 0.76-0.98) respectively. For a cutoff of 0.5 ng/ml, procalcitonin sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 65%, 91%, 65%, 91%, 7.2, and 0.4, respectively. Serum C-reactive protein and procalcitonin levels were correlated, were not different in sepsis or gout groups, and were higher in non-septic arthritis with poly-arthritis than with mono-arthritis (p < 0.05). CONCLUSIONS: Serum procalcitonin is a useful biomarker in arthritis management with diagnosis performances higher than those of other biomarkers (white blood cells, C-reactive protein).Key Points• Diagnostic performances of serum procalcitonin level in septic arthritis are higher than those of serum C-reactive protein or white blood cells levels.• Serum procalcitonin levels are not different in septic arthritis or gouty arthritis.• Serum procalcitonin levels are higher in non-septic arthritis with poly-arthritis than with mono-arthritis.

Pristane-induced arthritis in dark Agouti rat is a relevant model for mimicking vascular dysfunction and lipid paradox in rheumatoid arthritis.

OBJECTIVES: To understand the pathophysiology of cardiovascular (CV) dysfunction in rheumatoid arthritis (RA) is crucial, but limited by the paucity of animal models able to mimic CV impairments. We wanted to determine if the rat model of Pristane-Induced Arthritis (PIA) reproduced cardiometabolic impairments of RA. METHODS: Dark Agouti rats received an injection of pristane or saline (controls) at day 0. Reactivity to vasoconstrictors and vasodilators was studied in aortic rings and mesenteric arteries at day 28 (acute) and day 120 post-induction (chronic phase). Circulating markers of inflammation, lipid and glucose levels, arthritis and radiographic scores were assessed. RESULTS: In aortic rings, PIA induced a reduced vasoconstriction to phenylephrine and serotonin in both phases of the model. The relaxant effect of acetylcholine was decreased in PIA in acute (P < 0.05) but not in chronic phase. In mesenteric arteries, only the acetylcholine-induced vasorelaxation was impaired in PIA rats in the chronic phase (P < 0.001). Serum interleukin-6 levels were higher, total cholesterol and triglycerides levels were lower in PIA in both phases (P < 0.001) whereas myeloperoxidase activity and blood glucose were unchanged. Adiponectine levels were lower in PIA in acute (P < 0.001) but not in chronic phase. Endothelial function correlated with interleukin-6, total cholesterol levels and arthritis score in aorta but not in mesenteric arteries. CONCLUSIONS: As new information, PIA induces endothelial dysfunction in micro-/macro-vascular beds and low lipid levels, like in RA. This model of chronic arthritis might be useful to study CV pathophysiology and to screen new therapeutic options for reducing CV risk in RA.

Correlation between catastrophizing and Lequesne index in case of osteoarthritis of the knee: A prospective study.

OBJECTIVE: Catastrophizing is known to be associated with lower analgesia and results in total knee arthroplasty justifying its evaluation. The aim of this study is to evaluate the correlation between the functional status and the catastrophizing in patients with knee osteoarthritis. METHODS: We included patients consulting for knee osteoarthritis one of the three general practitioners participating in the study or a rheumatologist at University Hospital of Besançon. We excluded those with surgical indication. For each patient we registered the epidemiological data, the radiographic stage, the Lequesne index and the Pain Catastrophizing Score (PCS). The correlation between the different scores was assessed with a Spearman test. RESULTS: Hundred patients were included, 50 patients consulting a general practitioner and 50 consulting a rheumatologist, between November 2015 and April 2016. There were mainly women (57%) with a mean age of 64.8±1.17 years old. The mean radiographic stage was 2.66±0.11 on the Kellgren and Lawrence scale. The Mean PCS was 12.98±1.18 and the mean Lequesne index was 10.46±0.47. Patients seen by rheumatologists had a more important PCS score than those seen by general practitioners, although these patients had statistically equivalent radiographic scale and Lequesne index. There was a weak correlation (r=0.3, P=0.006) between the Lequesne index and the radiographic scale but no correlation between the PCS and the radiographic scale. However, the correlation between the PCS and the Lequesne index was moderate (r=0.47; P<0.0001). CONCLUSION: Psychological factors like catastrophizing correlated with Lequesne index.