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1.
Int J Mol Sci ; 24(19)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37834372

ABSTRACT

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.


Subject(s)
Osteoporosis , Spondylarthritis , Humans , Hedgehog Proteins , Spondylarthritis/drug therapy , Bone and Bones , Wnt Signaling Pathway
2.
Clin Exp Rheumatol ; 38(3): 436-441, 2020.
Article in English | MEDLINE | ID: mdl-31858957

ABSTRACT

OBJECTIVES: To investigate clinical and laboratory prognostic factors of remission after one year of follow-up in patients with polymyalgia rheumatica (PMR) treated with low-dose prednisone. METHODS: In this observational study, in a monocentric Italian Rheumatology Unit, we enrolled eighty-one consecutive PMR patients. Clinical and laboratory tests were performed every 3 months. Clinical remission was defined as the lack of symptoms, while laboratory remission was defined as erythrocyte sedimentation rate ≤40 mm/h and C-reactive protein (CRP) ≤0.5 mg/dl. RESULTS: Thirty-eight patients reached complete (clinical and laboratory) remission after 12 months of follow-up. A significant lower percentage of complete remission was seen in female gender compared to male (33.9 % vs. 78.2%, p=0.0001) at univariate analysis. No significant differences were found at baseline according to response to therapy during follow-up, while CRP values at the sixth month were significantly lower in patients who reached complete remission after one year (median: 0.4 mg/dl vs. 1 mg/dl, p=0.017). CRP<0.5 mg/dl at 6 months was independently associated with complete remission at 12 months in the multivariate analysis. CONCLUSIONS: The sixth month of therapy is a target for the management of PMR because it can help to identify patients at greater risk of exacerbations, who may benefit from a tighter follow-up and more aggressive therapeutic strategy. Higher CRP values at 6 months appear to be associated with a higher risk of longer steroid therapy.


Subject(s)
Giant Cell Arteritis/diagnosis , Polymyalgia Rheumatica/diagnosis , Blood Sedimentation , C-Reactive Protein/analysis , Female , Giant Cell Arteritis/drug therapy , Humans , Male , Polymyalgia Rheumatica/drug therapy , Prednisone/therapeutic use , Prognosis , Remission Induction
3.
Clin Exp Rheumatol ; 38(1): 88-93, 2020.
Article in English | MEDLINE | ID: mdl-31140397

ABSTRACT

OBJECTIVES: Axial spondyloarthritides (axSpA) are a group of disorders that share similar pathogenetic mechanisms and clinical picture. The aim of this retrospective multicentric study was to evaluate demographic and clinical differences between ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) patients. METHODS: Patients from 7 rheumatological centres in the Lazio region of Italy were included from January 1st, 2010 to April 1st, 2018, if they had undergone pelvic and/or spine radiographs or magnetic resonance imaging (MRI). Images were evaluated by one experienced radiologist in each centre who already had the clinical suspicion of axSpA. Clinical and therapeutic data were collected at the last observation visit. Categorical variables were presented with percentages and analysed by Chi squared test. Continuous variables were expressed as mean ± standard deviation and compared using the parametric unpaired t-test or the non-parametric Mann-Whitney U-test, when appropriate. p-values <0.05 were considered significant. RESULTS: 210 axSpA patients were included: 65.2% with AS and 34.7% with nr-axSpA. When comparing the two groups, AS patients had longer disease duration, were older, were more frequently males, had a greater diagnostic delay and a higher body mass index than the nr-axSpA patients (p<0.0001, p<0.0001, p=0.003 p=0.007, and p=0.04, respectively). The peripheral joints of the nr-axSpA patients were more frequently involved, had higher frequency of inflammatory bowel disease, higher C-reactive protein levels and lower frequency of HLA-B27 positivity (p=0.005, p=0.007, p=0.01, and p=0.01, respectively). TNF inhibitors were used in 87.8% patients with AS and 78.3% with nr-axSpA (p=0.04). More fat metaplasia was observed on MRI in the nr-axSpA group than in the AS group at sacroiliac joints (p=0.003), and more backfills were detected in the AS group on spine-MRI (p=0.003). Spine-bone marrow oedema was more prevalent in AS than in nr-axSpA (p=0.04), and more sclerosis and backfill were found in AS (p=0.003 and p=0.01, respectively). CONCLUSIONS: In clinical practice, distinctive features in AS and nr-axSpA patients emerged. Imaging is crucial in guiding the choice of treatment in order to control disease activity and inflammation.


Subject(s)
Spondylarthritis/physiopathology , Spondylitis, Ankylosing/physiopathology , Delayed Diagnosis , Demography , Female , Humans , Italy , Male , Retrospective Studies , Severity of Illness Index , Spondylarthritis/diagnosis , Spondylitis, Ankylosing/diagnosis
4.
Ann Rheum Dis ; 76(7): 1228-1236, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28119289

ABSTRACT

OBJECTIVE: To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. METHODS: Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6

Subject(s)
Adalimumab/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/drug therapy , Arthritis, Rheumatoid/drug therapy , Etanercept/therapeutic use , Adult , Aged , Antigens, CD/metabolism , Antigens, CD20/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/metabolism , Arthritis, Psoriatic/pathology , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , CD3 Complex/metabolism , Collagen/metabolism , Drug Therapy, Combination , Female , Humans , Immunohistochemistry , Male , Methotrexate/therapeutic use , Middle Aged , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Receptors, Complement 3d/metabolism , Recurrence , Remission Induction , Synovial Membrane/diagnostic imaging , Synovial Membrane/metabolism , Synovial Membrane/pathology , Synovitis/diagnostic imaging , Synovitis/metabolism , Synovitis/pathology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Ultrasonography , Ultrasonography, Doppler
8.
Rheumatology (Oxford) ; 53(5): 875-81, 2014 May.
Article in English | MEDLINE | ID: mdl-24407233

ABSTRACT

OBJECTIVE: The objective of this study was to determine whether BMI and gender could lead to a different response rate to anti-TNF agents in patients affected by axial SpA. METHODS: One hundred and seventy patients with active axial SpA (defined as a BASDAI ≥ 4) treated with an anti-TNF agent [adalimumab (ADA), etanercept (ETA), infliximab (IFX)] were retrospectively evaluated. Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30). After 12 months of treatment a 50% improvement of the initial BASDAI (BASDAI50) was the primary end point and BASDAI ≤ 1 was the secondary end point. RESULTS: After 12 months of anti-TNF treatment, 67.8% of men and 46.2% of women reached the BASDAI50 (P = 0.01). According to BMI categories, the rate of BASDAI50 achievement decreased from 72.8% in normal weight subjects to 54.5% in overweight and 30.4% in obese subjects (P < 0.001). In the logistic regression analysis, the best independent predictors of failure to obtain a BASDAI50 response at the 12th month of therapy in axial SpA patients were female gender [odds ratio (OR) 3.23 (95% CI 1.52, 7.14)] and a BMI ≥ 30 [OR 3.57 (95% CI 1.15, 11.11)]. Analysing outcomes based on IFX therapy (the larger subgroup), the BASDAI50 response rate fell from 79.0% in normal weight subjects to 56.7% in overweight and 16.7% in obese subjects (P < 0.001). No significant differences were observed with ADA and ETA. CONCLUSION: Data suggest that being female, overweight and mostly obese is associated with a lower rate of success in obtaining response status in axial SpA patients treated with anti-TNF drugs. Body weight could represent a modifiable factor to reach the best outcome in axial SpA patients treated with TNF blockers.


Subject(s)
Antirheumatic Agents/therapeutic use , Axis, Cervical Vertebra , Body Weight/physiology , Sex Factors , Spondylarthritis/drug therapy , Spondylarthritis/physiopathology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adult , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Body Mass Index , Etanercept , Female , Follow-Up Studies , Humans , Immunoglobulin G/therapeutic use , Infliximab , Logistic Models , Male , Middle Aged , Obesity/complications , Overweight/complications , Receptors, Tumor Necrosis Factor/therapeutic use , Retrospective Studies , Treatment Outcome
9.
Ann Rheum Dis ; 71(9): 1461-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22402140

ABSTRACT

OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. METHODS: BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. RESULTS: VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. CONCLUSIONS: Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.


Subject(s)
Lung Diseases, Interstitial/metabolism , Scleroderma, Systemic/metabolism , Vascular Endothelial Growth Factor A/deficiency , Bronchoalveolar Lavage Fluid/chemistry , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Vascular Endothelial Growth Factor A/analysis
10.
Expert Rev Proteomics ; 9(1): 33-46, 2012.
Article in English | MEDLINE | ID: mdl-22292822

ABSTRACT

The development of new separation techniques and different mass spectrometry instrumental devices, as well as the great availability of specific reactants, offers ample choice to scientists for carrying out high-throughput proteomic studies and being competitive in the field today. However, the different options available often do not provide comparable results, which can be linked to factors such as the strategy adopted, the nature of the sample and the instrumental availability. In this critical review, the results obtained so far in the study of human saliva by different proteomic approaches will be compared and discussed.


Subject(s)
Proteome , Saliva/chemistry , Chromatography, High Pressure Liquid , Electrophoresis, Gel, Two-Dimensional , Humans , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
11.
Clin Immunol ; 138(1): 107-16, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21056009

ABSTRACT

We analyzed peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 16 rheumatoid arthritis (RA), 9 spondyloarthritis (SpA), 3 microcrystal arthritis patients, to define the presence of Th17 and Th1 and their relationship with inflammatory activity, and TCR-zeta chain and ZAP-70 levels. Th17 were significantly higher in SF than in PB and more abundant in microcrystal arthritis patients compared to the other groups. Irrespectively of the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (C reactive protein [CRP], fibrinogen, erythrocyte sedimentation rate) inflammation markers. SF Th1 percentages directly correlated with inflammation and disease activity (CRP, swollen joint count [SJC]) indices in SpA, but not in RA patients. These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. The TCR-zeta(dim) lymphocytes in SF were found to produce the highest amounts of cytokines including IL-17, whereas no ZAP-70 impairment was associated to Th17.


Subject(s)
Arthritis/immunology , Arthritis/pathology , Synovial Fluid/cytology , Th17 Cells/immunology , Th17 Cells/pathology , Adult , Aged , Aged, 80 and over , Arthritis/diagnosis , Arthritis/metabolism , Blood Cells/immunology , Blood Cells/pathology , Blood Sedimentation , C-Reactive Protein/metabolism , Cell Count , Female , Fibrinogen/metabolism , Humans , Inflammation/pathology , Interferon-gamma/metabolism , Leukocytes/pathology , Lymphocyte Activation/immunology , Lymphocytes/pathology , Male , Middle Aged , Monocytes/pathology , Neutrophils/pathology , Receptors, Antigen, T-Cell/metabolism , Synovial Fluid/immunology , Synovial Fluid/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th1 Cells/pathology , Th17 Cells/metabolism , ZAP-70 Protein-Tyrosine Kinase/metabolism
12.
Mol Med ; 17(9-10): 901-9, 2011.
Article in English | MEDLINE | ID: mdl-21607290

ABSTRACT

The aim of the present study was to determine whether different subsets of B cells characterize synovial fluid (SF) or synovial tissue (ST) of seropositive or seronegative rheumatoid arthritis (RA) with respect to the peripheral blood (PB). PB, SF and ST of 14 autoantibody (AB)-positive (rheumatoid factor [RF]-IgM, RF-IgA, anti-citrullinated peptide [CCP]), 13 negative RA and 13 no-RA chronic arthritides were examined for B-cell subsets (Bm1-Bm5 and IgD-CD27 classifications), zeta-associated protein kinase-70 (ZAP70) expression on B cells and cytokine levels (interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, IL-6, IL-8 and monocyte chemotactic protein [MCP]-1). Synovial tissues were classified as aggregate and diffuse patterns. No differences were found in B-cell percentages or in subsets in PB and SF between AB(+) and AB(-) RA and no-RA. In both AB(+) and AB(-) RA (and no-RA), the percentage of CD19(+)/ZAP70(+) was higher in SF than in PB (AB(+): P = 0.03; AB(-): P = 0.01; no-RA: P = 0.01). Moreover, SF of both AB(+) and AB(-) RA (and no-RA) patients was characterized by a higher percentage of IgD-CD27(+) and IgD-CD27(-) B cells and lower percentage of IgD(+)CD27(-) (P < 0.05) B cells compared to PB. In SF, ZAP70 positivity is more represented in B cell CD27(+)/IgD(-)/CD38(-). The aggregate synovitis pattern was characterized by higher percentages of Bm5 cells in SF compared with the diffuse pattern (P = 0.05). These data suggest that no difference exists between AB(+) and AB(-) in B-cell subset compartmentalization. CD27(+)/IgD(-)/ZAP70(+) memory B cells accumulate preferentially in the joints of RA, suggesting a dynamic maturation of the B cells in this compartment.


Subject(s)
Arthritis, Rheumatoid/immunology , Autoantibodies/immunology , B-Lymphocyte Subsets/immunology , Joints/immunology , ZAP-70 Protein-Tyrosine Kinase/immunology , Adult , Aged , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Autoantibodies/blood , Autoantibodies/metabolism , B-Lymphocyte Subsets/metabolism , B-Lymphocyte Subsets/pathology , Biomarkers/metabolism , Cytokines/immunology , Cytokines/metabolism , Female , Flow Cytometry , Humans , Immunoglobulin D/immunology , Immunoglobulin D/metabolism , Immunohistochemistry , Immunologic Memory/immunology , Interleukins/immunology , Interleukins/metabolism , Joints/metabolism , Joints/pathology , Male , Middle Aged , Rheumatoid Factor/immunology , Rheumatoid Factor/metabolism , Synovial Fluid/immunology , Synovial Fluid/metabolism , Synovial Membrane/immunology , Synovial Membrane/metabolism , Synovial Membrane/pathology , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism , Young Adult , ZAP-70 Protein-Tyrosine Kinase/genetics , ZAP-70 Protein-Tyrosine Kinase/metabolism
13.
Ann Rheum Dis ; 70(1): 172-5, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21097799

ABSTRACT

OBJECTIVES: Treatment of rheumatoid arthritis (RA) should aim at full remission. The aims of this study were to define: (1) how many patients reached ultrasound power Doppler (US-PD) remission in a cohort of patients with early RA (ERA) compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission; and (3) how many patients with and without US-PD remission relapsed after 1 year of follow-up in ERA and LSRA. METHODS: 48 patients with ERA and 46 with LSRA with disease activity score <1.6 underwent US assessment. Six hand and wrist joints were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those with LSRA fulfilled American College of Rheumatology (ACR) remission criteria. RESULTS: 43.7% of patients with ERA and 17.4% of those with LSRA had no evidence of synovitis at US evaluation. Using a stricter clinical definition of remission (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of patients with ERA and 26.1% of those with LSRA. Early disease was predictive of clinical US remission. 20.0% of patients with RA who had a negative PD signal at the US evaluation had a flare during the 12-month follow-up period compared with 47.1% of patients who had a positive PD signal. CONCLUSION: US-PD remission occurs in half of patients with ERA and in a minority of patients with LSRA in clinical remission. Early disease seems to be the major determinant of full remission.


Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Adult , Aged , Antirheumatic Agents/therapeutic use , Epidemiologic Methods , Female , Hand Joints/diagnostic imaging , Humans , Male , Middle Aged , Prognosis , Recurrence , Remission Induction , Synovitis/diagnostic imaging , Treatment Outcome , Ultrasonography, Doppler, Color , Wrist Joint/diagnostic imaging
14.
Ann Rheum Dis ; 70(7): 1292-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21515600

ABSTRACT

OBJECTIVES: To identify predictors of clinical remission as well as of no x-ray progression in a cohort of early rheumatoid arthritis (ERA) treated with a tight-control protocol. METHODS: A total of 121 consecutive patients with ERA were treated to reach European League Against Rheumatism (EULAR) and/or American College of Rheumatology (ACR) clinical remission with methotrexate (MTX) for 3 months, then with a combination with anti-tumour necrosis factor if the patient did not achieve a 44-joint Disease Activity Score (DAS44) ≤2.4. At baseline and after 12 months all the patients had hand and foot joint radiographs. Very early rheumatoid arthritis (VERA) was defined as a disease with symptoms of less than 12 weeks. RESULTS: In all, 46.3% of the patients reached DAS remission and 24.8% achieved ACR remission. More than 60% of patients reached remission with MTX. Male sex and an erythrocyte sedimentation rate <35 mm/h at onset arose as significant predictors of EULAR remission, while VERA disease was the only predictor of ACR remission. At baseline, 28.1% of the patients were erosive. Multivariate analysis demonstrated that the only independent predictor of erosiveness was 'not having VERA disease'. After 12 months, VERA was the only factor predicting a lack of new erosions. CONCLUSIONS: VERA represents the best therapeutic opportunity in clinical practice to achieve a complete remission and to stop the erosive course of rheumatoid arthritis.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Adult , Aged , Arthritis, Rheumatoid/diagnostic imaging , Blood Sedimentation , Disease Progression , Drug Therapy, Combination , Early Diagnosis , Epidemiologic Methods , Female , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Prognosis , Radiography , Remission Induction , Sex Factors , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors
15.
Respir Res ; 12: 22, 2011 Feb 11.
Article in English | MEDLINE | ID: mdl-21314931

ABSTRACT

BACKGROUND: ß-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins ß4, ß4 sulfoxide, and ß10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters. METHODS: ß-thymosins concentrations were determined by reverse phase-high performance liquid chromatography-electrospray-mass spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls. RESULTS: Thymosin ß4, ß4 sulfoxide, and ß10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin ß4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin ß4 levels seem to have a protective role against lung tissue damage. Thymosin ß4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis. CONCLUSIONS: We describe for the first time ß-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin ß4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.


Subject(s)
Lung Diseases, Interstitial/metabolism , Lung/metabolism , Scleroderma, Systemic/metabolism , Thymosin/metabolism , Adult , Aged , Bronchoalveolar Lavage Fluid/chemistry , Case-Control Studies , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Female , Follow-Up Studies , Humans , Lung/diagnostic imaging , Lung/immunology , Lung/physiopathology , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Odds Ratio , Pulmonary Diffusing Capacity , Rome , Scleroderma, Systemic/diagnostic imaging , Scleroderma, Systemic/immunology , Scleroderma, Systemic/physiopathology , Spectrometry, Mass, Electrospray Ionization , Time Factors , Tomography, X-Ray Computed , Vital Capacity
16.
Front Med (Lausanne) ; 8: 669397, 2021.
Article in English | MEDLINE | ID: mdl-34513861

ABSTRACT

Background: Cardiovascular events (CVEs) are the first cause of death in patients with psoriatic arthritis (PsA). Depression is a recognized risk factor in cardiovascular events and is frequently associated with PsA. Flow-mediated dilatation (FMD) is a widely used method for assessing endothelial dysfunction, a parameter with strong prognostic implications for CVEs. The study aims to explore the relationship between FMD, depressive symptoms and serum cytokines in a cohort of patients with PsA. Patients and Methods: FMD was assessed in 50 consecutive PsA patients aged between 30 and 75 years without known cerebrovascular and coronary heart disease or diabetes. Depressive symptoms were reported using the related subscale of the Hospital Anxiety and Depression Scale (HDS). Disease features, activity indexes, and adjusted Framingham risk score (aFRS) were calculated. Serum level of IL-6, TNF-α, and IL-17A were also assessed. Results: In PsA patients (age 50.7 ± 10.2 years, male 42%, disease duration 5.9 ± 3.3 years, Disease Activity in PSoriatic Arthritis (DAPSA) score 14.0 ± 9.4) FMD inversely correlated with the severity of depressive symptoms according to HDS (ρ = -0.339, p = 0.016), age (ρ = -0.507, p = 0.001), aFRS (rs = -0.453, p < 0.001), duration of PsA (ρ = -0.507, p = 0.001), intensity of pain (ρ = -0.507, p = 0.001), and DAPSA (ρ = -0.507, p = 0.001). No statistically significant correlation was found between FMD or HDS and serum cytokines concentrations. HDS predicted FMD in a model adjusted for age, aFRS, PsA duration, and pain intensity (ß = -0.271, p = 0.008), with depressive symptoms contributing directly to 6.4% of the variance. Conclusions: Depressive symptoms correlate with endothelial dysfunction with an exposure-response pattern in our cohort of PsA patients.

17.
Clin Rheumatol ; 40(5): 1893-1902, 2021 May.
Article in English | MEDLINE | ID: mdl-33009969

ABSTRACT

OBJECTIVES: Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu. METHODS: One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A. RESULTS: Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p < 0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p < 0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p < 0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p < 0.01). CONCLUSIONS: Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.


Subject(s)
Arthritis, Psoriatic , Depression , Arthritis, Psoriatic/complications , Cytokines , Depression/complications , Depression/epidemiology , Female , Humans , Inflammation , Tumor Necrosis Factor-alpha
18.
Arthritis Rheumatol ; 73(9): 1601-1613, 2021 09.
Article in English | MEDLINE | ID: mdl-33750008

ABSTRACT

OBJECTIVE: This study applied a synovitis score obtained during routine care from ultrasound (US)-guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment-naive rheumatoid arthritis (RA) patients. METHODS: The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal-induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US-guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat-to-target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation. RESULTS: The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment-naive RA patients. Moreover, at baseline, treatment-naive RA patients achieving 6-month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment-naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28-based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment-naive RA patients yielded an up to 81.7% probability of achieving 6-month remission according to the DAS28. CONCLUSION: The KSS is a reliable tool for synovitis assessment on US-guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response-predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Synovial Membrane/diagnostic imaging , Synovitis/diagnostic imaging , Aged , Arthritis, Rheumatoid/diagnostic imaging , Female , Humans , Male , Middle Aged , Nomograms , Remission Induction , Severity of Illness Index , Ultrasonography
19.
Clin Chem Lab Med ; 48(6): 829-34, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20298138

ABSTRACT

BACKGROUND: The goal of our study was to evaluate the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) assay in patients with autoimmune and inflammatory disorders. METHODS: We tested the specificity and sensitivity of anti-CCP2 antibodies measured by ELISA in 787 patients with rheumatoid arthritis (RA), 1024 patients with other autoimmune/inflammatory rheumatic disease and 401 subjects without autoimmune rheumatic disease. The optimal cut-off value was defined as the value with the highest diagnostic accuracy (receiver operating characteristic curve analysis). Interval-specific likelihood ratios (LRs) were calculated for each range bounded by defined anti-CCP2 values. RESULTS: To distinguish between patients with RA and controls, the cut-off value with the highest diagnostic accuracy for anti-CCP2 was 2.8 U/mL. Comparing the optimal cut-off value for anti-CCP2 to that recommended by the manufacturer (5.0 U/mL), an increase in prevalence between the proportions of test-positive patients was found for RA, undifferentiated connective tissue disease and undifferentiated arthritis. Evaluating interval-specific LRs for the selected ranges bound by two anti-CCP2 values, in RA and diseased controls, the LRs were 0.40 for values <5.0 U/mL, 6.66 for 5.0-15.0 U/mL, 27.01 for 15.1-30.0 U/mL and 28.89 for >30.0 U/mL. CONCLUSIONS: The cut-off value of 2.8 U/mL for anti-CCP2 has the highest diagnostic accuracy. A value of anti-CCP2 >15 U/mL is associated with an increase in the likelihood of RA disease.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Autoantibodies/blood , Peptides, Cyclic/immunology , Adult , Aged , Enzyme-Linked Immunosorbent Assay , Female , Humans , Likelihood Functions , Male , Middle Aged , ROC Curve , Rheumatic Diseases/diagnosis
20.
Expert Opin Biol Ther ; 20(7): 813-821, 2020 07.
Article in English | MEDLINE | ID: mdl-32401062

ABSTRACT

BACKGROUND: Secukinumab (SEC) is effective for ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomized trials, but real-life data are lacking. RESEARCH DESIGN AND METHODS: Real-life, prospective observational study on 169 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 130 PsA, 77%). RESULTS: Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes like VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2 = 0.4; p = 0.009) and peripheral joint involvement (R2 = 0.4; p = 0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2 = 0.65; p = 0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2 = 0.34; p = 0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2 = 0.42; p = 0.003). In PsA patients, reduction of DAPSA score from T0 to T12 is negatively correlated with the presence of metabolic syndrome (R2 = 0.41; p = 0.0025). SEC was well tolerated; 10 patients discontinued treatment for non-severe adverse events. CONCLUSIONS: Secukinumab is effective and safe in patients with AS and PsA in a real-life setting.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Psoriatic/drug therapy , Dermatologic Agents/therapeutic use , Spondylitis, Ankylosing/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/pathology , Body Mass Index , Delayed Diagnosis , Dermatologic Agents/adverse effects , Female , Humans , Hypersensitivity/etiology , Male , Medication Adherence , Middle Aged , Patient Reported Outcome Measures , Severity of Illness Index , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/pathology , Treatment Outcome
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