Subject(s)
Spondylitis, Ankylosing , Humans , Cardiac Conduction System Disease/diagnosis , Cardiac Conduction System Disease/physiopathology , Cardiac Conduction System Disease/therapy , Cardiac Conduction System Disease/etiology , Spondylitis, Ankylosing/physiopathology , Spondylitis, Ankylosing/complicationsABSTRACT
OBJECTIVE: Serum calprotectin appears to be an interesting biomarker associated with renal vascular disease activity in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to assess whether serum calprotectin levels can predict decline in renal function in AAV patients receiving maintenance therapy. METHODS: Serum calprotectin levels were assessed at inclusion and month 6 in AAV patients, in complete remission after induction therapy, randomly assigned to rituximab or azathioprine. Renal function decline was defined as a 25% decrease in estimated glomerular filtration rate (eGFR) and a change in the eGFR category, or a decrease of 15 mL/min/1.73 m2. Relapse was defined as a Birmingham Vasculitis Activity Score >0 attributable to active vasculitis. RESULTS: Seventy-six AAV were included. Serum calprotectin increased from baseline to month 6 in patients with renal function decline (7940 (-226.0, 28 691) ng/ml vs -4800 (-18 777, 3708) ng/ml; p<0.001). An increase of calprotectin level was associated with a higher risk of subsequent renal function decline even after adjustment (OR 6.50 (95% CI 1.7 to 24.9) p=0.006). A significantly higher risk of relapse was observed in proteinase 3- AAV patients with an increase of serum calprotectin levels (OR 5.6 (95% CI 1.0 to 31.2), p=0.03). CONCLUSION: An increase in serum calprotectin by month 6 compared with inclusion during remission-maintenance therapy in AAV was associated with a higher risk of renal function decline in the following 12 months. TRIAL REGISTRATION NUMBER: NCT00748644.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Leukocyte L1 Antigen Complex , Humans , Rituximab , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Recurrence , Kidney/physiologyABSTRACT
OBJECTIVE: To investigate whether bone marrow edema (BME) fulfilling the ASAS definition of magnetic resonance imaging (MRI) sacroiliitis is associated with non-inflammatory spine abnormalities in patients with definite mechanical chronic back pain (CBP). METHODS: Patients with definite mechanical CBP, according to the physician, started before the age of 45 and be lasting for more than 3months but less than 3years underwent a protocolized MRI and radiographs of sacroiliac joint (SIJ) and spine. BME and structural changes were scored, by three readers, for SIJ as well as non-inflammatory abnormalities for spine, including degenerative lesions and static disorders. Univariate analysis by Chi2 test was performed to search a statistical association between BME fulfilling the ASAS definition of MRI sacroiliitis and the presence of at least one non-inflammatory spine abnormality. RESULTS: A total of 94 patients were analyzed, 27 (29%) patients had BME and 16 (17%) patients had BME fulfilling the ASAS definition of MRI sacroiliitis; 86 (91.5%) patients had at least one non-inflammatory spine abnormality which are associated into 3 distinct clusters. BME was slightly more frequent at the lower and posterior part of the SIJ. MRI sacroiliitis was associated with interspinous bursitis, facet joint effusion and lateral spinal deviation and was more likely in patients with at least one non-inflammatory spine abnormality (OR: 4.96, 95% CI [1.47; 16.72]). CONCLUSIONS: BME fulfilling the ASAS definition of MRI sacroiliitis is significantly associated with non-inflammatory spine abnormalities in patients with mechanical CBP.
Subject(s)
Bone Marrow Diseases , Musculoskeletal Abnormalities , Sacroiliitis , Spondylarthritis , Humans , Child, Preschool , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Sacroiliitis/diagnostic imaging , Spondylarthritis/complications , Spondylarthritis/diagnostic imaging , Spondylarthritis/pathology , Edema/diagnostic imaging , Edema/pathology , Bone Marrow Diseases/diagnostic imaging , Bone Marrow Diseases/complications , Bone Marrow Diseases/pathology , Back Pain/diagnostic imaging , Back Pain/etiology , Magnetic Resonance Imaging/methodsABSTRACT
OBJECTIVES: Axial Spondyloarthritis (ax-SpA) is associated with increased risk of cardiovascular disease (CVD)-specific deaths. We aimed to assess the prevalence of left ventricular (LV) systolic and diastolic dysfunction and valvular heart disease (VHD) by transthoracic echocardiography (TTE) in ax-SpA patients without history of CVD. METHODS: A systematic literature review was performed in PUBMED, Embase, Cochrane Library databases published before April 2020. We included all controlled studies assessing myocardial function and heart valve by TTE in ax-SpA without history of CVD. A meta-analysis was performed with random or fixed effects model estimating mean differences (MD) and odds ratio (OR). RESULTS: Literature search selected 189 abstracts and 28 articles were included (1471 ax-SpA and 1115 controls). ax-SpA had a statistically slight alteration of LV ejection fraction (MD=0.64%, 95%CI: 0.14-1.14). ax-SpA had more frequently LV diastolic dysfunction (OR=3.43, 95%CI: 1.78-6.59) and an alteration of E/A ratio (MD=0.15, 95%CI: 0.08-0.21), deceleration time (MD=13.07ms, 95%CI: 7.75-18.40), isovolumetric relaxation time (MD=7.90ms, 95%CI: 4.50-11.30), left-ventricular end diastolic (MD=0.57mm, 95%CI: 0.19-0.95) and systolic (MD=0.77mm, 95%CI: 0.36-1.17) diameters. Three studies (15%) used a combination of TTE parameters to diagnose LV diastolic dysfunction. Prevalence of mitral regurgitation and aortic regurgitation were similar in ax-SpA patients and healthy individuals. CONCLUSION: ax-SpA have a non-clinically relevant alteration of LV ejection fraction and similar prevalence of VHD compared to healthy individuals. LV diastolic TTE parameters are altered in ax-SpA. However, most studies do not combine set of parameters to recognize diastolic dysfunction. The clinical relevance of diastolic dysfunction observed by TTE remains to be determined in future longitudinal studies.
Subject(s)
Axial Spondyloarthritis , Ventricular Dysfunction, Left , Echocardiography , Heart Valves , Humans , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/epidemiology , Ventricular Function, LeftABSTRACT
OBJECTIVE: ZAP-70W163C BALB/c (SKG) mice develop reactive arthritis (ReA) following infection with Chlamydia muridarum. Since intracellular pathogens enhance their replicative fitness in stressed host cells, we examined how myeloid cells infected with C muridarum drive arthritis. METHODS: SKG, Il17a-deficient SKG, and BALB/c female mice were infected with C muridarum or C muridarum luciferase in the genitals. C muridarum dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti-tumor necrosis factor (anti-TNF) and anti-interleukin-23p19 (anti-IL-23p19) were administered after infection or arthritis onset. Gene expression of Hspa5, Tgtp1, Il23a, Il17a, Il12b, and Tnf was compared in SKG mice and BALB/c mice. RESULTS: One week following infection with C muridarum, macrophages and neutrophils were observed to have infiltrated the uteri of mice and were also shown to have carried C muridarum DNA to the spleen. C muridarum load was higher in SKG mice than in BALB/c mice. Macrophage depletion was shown to reduce C muridarum load and prevent development of arthritis. Compared with BALB/c mice, expression of Il23a and Il17a was increased in the uterine and splenic neutrophils of SKG mice. The presence of anti-IL-23p19 during infection or Il17a deficiency suppressed arthritis. Tnf was overexpressed in the joints of SKG mice within 1 week postinfection, and persisted beyond the first week. TNF inhibition during infection or at arthritis onset suppressed the development of arthritis. Levels of endoplasmic reticulum stress were constitutively increased in the joints of SKG mice but were induced, in conjunction with immunity-related GTPase, by C muridarum infection in the uterus. CONCLUSION: C muridarum load is higher in SKG mice than in BALB/c mice. Whereas proinflammatory IL-23 produced by neutrophils contributes to the initiation of C muridarum-mediated ReA, macrophage depletion reduces C muridarum dissemination to other tissues, tissue burden, and the development of arthritis. TNF inhibition was also shown to suppress arthritis development. Our data suggest that enhanced bacterial dissemination in macrophages of SKG mice drives the TNF production needed for persistent arthritis.
Subject(s)
Arthritis, Reactive/immunology , Chlamydia Infections/immunology , Interleukin-23 Subunit p19/immunology , Interleukin-23/immunology , Macrophages/immunology , Tumor Necrosis Factor-alpha/immunology , Animals , Arthritis, Experimental/genetics , Arthritis, Reactive/genetics , Chlamydia muridarum , Endoplasmic Reticulum Chaperone BiP , Female , Gene Expression Profiling , Heat-Shock Proteins/genetics , Heat-Shock Proteins/immunology , Interleukin-12 Subunit p40/genetics , Interleukin-12 Subunit p40/immunology , Interleukin-17/genetics , Interleukin-17/immunology , Interleukin-23 Subunit p19/genetics , Macrophages/microbiology , Mice , Mice, Inbred BALB C , Monomeric GTP-Binding Proteins/genetics , Monomeric GTP-Binding Proteins/immunology , Tumor Necrosis Factor-alpha/genetics , ZAP-70 Protein-Tyrosine Kinase/geneticsABSTRACT
OBJECTIVE: To propose a list of variables to be collected right after the diagnosis has been made and during the follow-up of patients with axial spondyloarthritis (ax-SpA) for an optimal management in daily practice. METHODS: The process comprised (1) the evaluation of the interest of 51 variables proposed for the assessment of ax-SpA by means of a systematic literature research; (2) a consensus process involving 78 hospital-based or office-based rheumatologists, considering the collection of each variable in a 4 grade scale from "not very useful/useless" to "mandatory"; (3) a consensus on the minimum interval of time for periodic assessment of the selected variables on a 5 grade scale from "at each visit" to "never to be re-collected". RESULTS: The systematic literature research retrieved a total of 14,133 abstracts, of which 213 were included in the final qualitative synthesis. Data to be collected at the initial systematic review comprised 5 patient's self-administered questionnaires, 3 variables of the physician's interview, 2 variables of the physical examination, 2 variables of the specific ax-SpA imaging and 2 other investigations. Two variables were recommended to be systematically collected at each visit, 1 variable twice a year, 6 variables yearly and 1 variable every 2 years. CONCLUSIONS: Using an evidence-based and an expert consensus approaches, this initiative defined a core set of variables to be collected and reported right after the diagnosis and during follow-up of patients with ax-SpA in daily practice.
Subject(s)
Spondylarthritis , Consensus , Diagnostic Imaging , Humans , Rheumatologists , Spondylarthritis/diagnosis , Spondylarthritis/therapy , Surveys and QuestionnairesABSTRACT
OBJECTIVES: Central neurological manifestations of rheumatoid arthritis (RA) like rheumatoid meningitis (RM) are rare, little known and have a high rate of morbi-mortality. METHODS: We described six cases of RM that were directly related to RA activity after exhaustive assessment. RESULTS: They were mainly women, aged of 50 to 69. All were positive for anti-cyclic citrullinated peptide antibodies and half for rheumatoid factors. RA activity, duration, and treatments were heterogeneous including oral steroids, conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs. Symptoms were various, with acute or progressive beginning; main were: generalized or focal seizure (4/6), fever (3/6), headaches (3/6), and frontal syndrome (2/6). Imaging lesions were four leptomeningitis, one pachymeningitis, and one association of both. MRI usually showed hypersignal in various territories in T2-FLAIR (fluid attenuated inversion recovery) mode, and enhancement in T1-weighted mode after gadolinium injection. All patients had lumbar puncture that found sterile cerebrospinal fluid, no neoplasic cell, elevated cell count in 5/6 cases and elevated proteins concentration in 3/6 cases. Cerebral biopsy was possible for three patients, and definitively confirmed the diagnosis of aseptic lepto- or pachymenintis, excluding vasculitis and lymphoma. Different treatments were used like intravenous high dose steroids, immunoglobulins or biologic DMARDs, with variable clinical and imaging outcome: one death, one complete recovery, and four recoveries with sequelae. CONCLUSIONS: Clinical symptoms, imaging, lumbar puncture, and serological studies are often nonspecific, only histologic examination can confirm the diagnosis of RM. Any central neurological manifestation in RA patients, even in quiescent and ancient RA, should warn the physician.
Subject(s)
Arthritis, Rheumatoid , Periodontitis , Disease Progression , Humans , Porphyromonas gingivalisSubject(s)
Arthritis, Rheumatoid , Periodontitis , Animals , Disease Progression , Porphyromonas gingivalis , RatsABSTRACT
OBJECTIVE: We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides. METHODS: Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P-value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model. RESULTS: A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l. CONCLUSION: Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort.