The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis

Aim of the workTo investigate whether serum leptin levels are elevated in patients with rheumatoid arthritis (RA) and whether these levels correlate with disease activity.Patients and methodsA case-control study was made on 37 patients with RA and 34 healthy control subjects. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts, disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analog scale (VAS) of pain and serum leptin concentrations.ResultsPatients with RA had mild to moderate (DAS28 < 5.1) disease activity. The mean serum leptin in patients with RA (12.15 ± 11.48 ng/mL) was significantly higher (p < 0.001) than controls (3.99 ± 1.84 ng/mL). Serum leptin levels were significantly (p < 0.001) higher in female RA patients than in female controls. A nonsignificant difference (p = 0.41) was found between male patients with RA and male controls. Serum leptin levels were significantly (p < 0.001) higher in women than in men in both patients and controls. Serum leptin levels did not show correlation with age, disease duration, duration of morning stiffness, VAS, number of swollen and tender joints, DAS28, HAQ, ESR or CRP in patients with RA. Serum leptin levels were correlated positively with BMI in RA patients. The BMI was significantly higher (p < 0.001) in female than in male patients with RA.ConclusionAlthough leptin levels were higher in RA patients, there was no correlation with disease activity parameters, therefore, leptin levels cannot be used to reflect disease activity.     

Proteinase-activated receptor 2 expression on peripheral blood monocytes and T-cells in patients with rheumatoid arthritis

Aim of the workProteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. The aim of this work was to evaluate the expression of PAR2 on peripheral blood monocytes and T-cells in rheumatoid arthritis (RA) patients and its correlation with disease activity.Patients and methodsForty RA patients and 16 healthy controls were enrolled in this study. Flow cytometry was performed to detect PAR2 expression. Disease activity score (DAS28) was assessed.ResultsPAR2 expression was significantly higher on monocytes in RA patients with active disease compared with patients in remission and healthy controls (75.4 ± 7.68; 56 ± 13.93 and 46.5 ± 9.8 respectively; p < 0.001). It was higher in RA patients in remission compared to healthy control (p = 0.01). No significant difference was found between patients with moderate and high disease activity. It significantly correlated with the erythrocyte sedimentation rate (ESR) and DAS28 (p < 0.001). It was significantly higher in patients with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positivity (p = 0.01, p < 0.001, respectively). It was not significantly associated with C-reactive protein (CRP) positivity and was not significantly different between early and long standing RA patients. PAR2 expression on CD3⁺ T-cells was not significantly different between patients with RA disease activity, patients in remission and healthy controls. Also it was not significantly associated with the ESR, DAS28, anti-CCP, RF and CRP positivity.ConclusionPAR2 expression on monocytes is consistent with a pathogenic role for PAR2 in RA and suggests that PAR2 may have utility as a marker for RA disease activity.     

Significance of serum levels of angiopoietin-2 and its relationship to Doppler ultrasonographic findings in rheumatoid arthritis patients

BackgroundAngiopoietin-2 (Ang-2) is connected to angiogenesis in synovial regions, but the significance of its levels in patients with rheumatoid arthritis (RA) is still unclear.Aim of the workTo evaluate the significance of serum levels of Ang-2 in patients with RA. Also, to determine Ang-2 relationship to the findings of joints Doppler ultrasonographic findings.Patients and methodsThis study included 40 patients with RA, and 25 matched healthy controls. All patients were subjected to assessment of pain using visual analogue scale (VAS), assessment of personal activity using the Health Assessment Questionnaire (HAQ) score, and calculation of disease activity score (DAS 28). Laboratory assays of complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) titre, and measurement of serum levels of Ang-2 by ELISA. Doppler ultrasonography (US) assessment for eight joints, with calculation of synovial thickness and total signal score (TSS), was done.ResultsSerum Ang-2 levels were significantly higher among patients (3191.3 ± 594.9 pg/ml) than controls (1771.7 ± 103.1 pg/ml) (p < 0.001). Serum Ang-2 levels were significantly correlated with ESR, CRP, DAS28, and duration of morning stiffness (p < 0.001, p < 0.001, p < 0.001, and p = 0.025, respectively). There was a significant correlation between serum Ang-2 levels and findings of US, regarding joint synovial thickness, and TSS (p < 0.001, for both).ConclusionPatients with RA had significantly higher levels of serum Ang-2 versus controls. In those patients, serum Ang-2 levels were significantly correlated with disease activity markers (ESR, CRP), DAS28, and duration of morning stiffness. Moreover, these levels were significantly correlated with synovial thickness, and TSS. The role of Ang-2 in RA pathogenesis might open the door to the development of new therapeutic strategies, particularly which target angiogenesis.     

The relationship between disease activity and depression in Egyptian patients with rheumatoid arthritis

Aim of the workTo estimate the prevalence of depression and its relationship with disease activity parameters in Egyptian patients with RA.Patients and methodsA cross sectional study was conducted on 170 patients with RA. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts (SJC and TJC), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analogue scale (VAS) of pain and hospital anxiety and depression scale-depression subscale (HADS-D).ResultsThe prevalence of depression was 15.29% (26 RA patients). In the depressed RA patients, positive significant correlations were found between HADS-D score and age, disease duration, HAQ score, VAS, DAS28 score and CRP. However, no significant correlation was found between HADS-D score and ESR, number of swollen and tender joints. No significant difference (P > 0.05) was found between depressed male and female patients with RA.ConclusionPatients with RA and co-morbid depression have worse health outcomes. RA cases should be monitored for accompanying depression during follow-up. The identification and treatment of depression in RA paramount to the overall management of RA.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

The impact of fibromyalgia on disease assessment in rheumatoid arthritis patients

Aim of workTo explore the influence of the presence of concomitant fibromyalgia (FM) on the evaluation of disease activity score assessing 28 joints (DAS28), clinical disease activity index (CDAI) and modified health assessment questionnaire (MHAQ) in Egyptian patients with rheumatoid arthritis (RA).Patients and methodsThis study included 50 female RA patients; out of which 25 had concomitant FM (RAF group), the other 25 RA patients who served as controls did not have concomitant FM (RA group). All patients were subjected to an assessment of disease activity using the DAS 28 and the CDAI and assessment of functional outcome using MHAQ score.ResultsThe mean DAS 28 was significantly higher in RAF than RA patients (5.6 ± 1.1 versus 4.5 ± 1.3, P = 0.009). Also, the mean CDAI score was significantly higher in the RAF group (mean 23.3 ± 12.1 versus 13.7 ± 11.0, P = 0.002). The difference was attributed to significantly higher subjective items such as Tender joint count (TJC) and patient’s global assessment of general health (VAS-GH) in the RAF group. Mean MHAQ score was also higher in the RAF group (0.7 ± 0.6 versus 0.31 ± 0.4, P = 0.006).ConclusionFM is related to worse scores on the DAS28, CDAI and MHAQ in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 and CDAI scores because it is related to higher scores independently of objective evidence of RA activity.     

Fatigue in rheumatoid arthritis and its relation to interleukin-6 serum level

Patients and methodsThe study included 30 patients with RA diagnosed according to the 2010 ACR-EULAR classification criteria for RA and 15 healthy controls. Patients were included if they were above 18 years and fulfilled a score ?6 over 10 of the 2010 ACR-EULAR classification criteria for RA. Disease activity was assessed using 28 joint disease activity score (DAS28), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP). Fatigue was assessed with the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) and serum IL-6 level was measured in patients and controls.ResultsThe BRAF-MDQ was significantly higher among patients (mean = 50.6 ± 15.2) than controls (mean = 7.8 ± 3.7) (p < 0.001). Patients’ mean IL-6 serum level was 35.05 ± 21.23 pg/ml and 4.72 ± 3.09 pg/ml among control subjects (p < 0.001). DAS 28 ranged between 4.33 and 7.67, mean 1st hour ESR was 43.57 mm and CRP was positive in 76.7% of patients. Significant correlations were found between BRAF-MDQ score and serum IL-6 level (r = 0.947, p < 0.001), ESR (r = 0.509, p < 0.001) as well as CRP positivity (r = 0.411, p = 0.005) in RA patients. Serum IL-6 level correlated with ESR (r = 0.463, p < 0.001) and CRP (r = 0.376, p = 0.01) among patients.ConclusionFatigue is a common symptom and scores higher among RA patients than healthy controls and should be measured in all RA patients with simple fatigue questionnaires matching with different cultures. Fatigue becomes more prominent as serum IL-6 level increases independently of the disease duration and activity.     

Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications

ObjectivesTo study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage.MethodsA total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP.ResultsRF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p = .02), RF titer (p < .001), ANA (p < .001), DAS28-ESR (p = .026), and DAS28-CRP (p = .003). Anti-La antibodies correlated positively with SJC (p = .001), TJC (p = .001), ANA (p < .001), DAS-28 ESR (p = .007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p ≤ .001), RF titer (p = .037) and ANA (p ≤ .001). Anti-RNP antibodies correlated positively with disease duration (p ≤ .001), ACPA titer (p ≤ .001) and ANA (p = .014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies.ConclusionsIn RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.     

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in rheumatoid arthritis patients: Correlation with serum osteopontin levels and disease activity

BackgroundRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease with genetic predisposition. Osteopontin (OPN) is overexpressed in RA and plays a key role in the perpetuation of synovitis. Not all RA patients show the same level of response to methotrexate (MTX) suggesting genetic variations in the drug-metabolizing enzymes.Aim of the workTo detect methylene-tetra-hydrofolate reductase (MTHFR) 677C/T and 1298A/C gene polymorphisms in RA patients treated with MTX and to investigate the relationship with serum OPN levels and disease activity.Patients and methods62 RA patients and 21 healthy controls were included. Serum OPN was measured using ELISA. Genotyping of MTHFR gene was carried out by polymerase chain reaction-restriction fragment length polymorphism. Disease activity score in 28 joints (DAS28) and the modified health assessment questionnaire (MHAQ) were assessed.ResultsThe patients’ age was 42.7 ± 12.7 years, F:M (4.6:1) and a disease duration of 5.7 ± 4.6 years. Their DAS28 was 4.1 ± 1.6 and the MHAQ (median 1; range 0–2.3). Serum OPN levels in RA patients (median 8.8; range 4–44.5 ng/ml) were significantly higher than in control (5.6; 2.1–10.9) (p = 0.002). In RA patients, serum OPN significantly correlated with the duration of morning stiffness (p = 0.009), ESR (p < 0.0001) and DAS28 (p < 0.0001). MTHFR (677C>T) polymorphisms significantly correlated with MHAQ (p = 0.012) while (1298A>C) polymorphisms significantly correlated with tender joint count (p = 0.04). OPN levels were higher among patients with MTHFR (1298A/C) AC genotype (8.9; 4.1–33.9 ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1–44.5).ConclusionSerum OPN level relates with the degree of rheumatoid activity.     

Correlation between serum osteoprotegerin and atherosclerotic vascular disorders in rheumatoid arthritis patients

Aim of the workThe aim of the present study was to investigate the association of serum osteoprotegerin (OPG) level with the presence of angiographically documented asymptomatic coronary artery disease (CAD) in patients with rheumatoid arthritis (RA) and to evaluate its relationship with plasma thrombomodulin (TM), as a marker of endothelial dysfunction and with carotid artery intima media thickness (IMT), as a marker of atherosclerosis.Patients and methodsThe study included 20 rheumatoid patients without CAD (negative results on exercise ECG stress test) and other 20 rheumatoid patients with CAD (positive results on exercise ECG stress test and confirmed by coronary angiography). In addition, 20 age and sex matched normal control subjects were studied. Serum OPG and plasma TM levels were measured and carotid artery IMT was determined.ResultsThe study revealed that serum OPG levels were significantly higher in rheumatoid patients with and without CAD than in controls (P < 0.001, P < 0.01; respectively) and were positively correlated with age, duration of disease, Disease active score 28(DAS28), Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and carotid IMT in rheumatoid patients with and without CAD. Serum OPG level was correlated significantly with plasma TM only in rheumatoid patients with CAD (P < 0.001).ConclusionOsteoprotegerin is a clinically important molecule independently associated with the presence of coronary artery disease and may be a good indicator of atherosclerotic vascular damage and macroangiopathy in asymptomatic rheumatoid patients. Hence, measurement of serum OPG merits further investigation as a simple test for improving early diagnosis of asymptomatic CAD in rheumatoid patients.     

Anti-CCP hs (high sensitive) in Egyptian rheumatoid arthritis patients associated with chronic hepatitis C virus infection

Aim of the workThe objectives of this study were to evaluate the use of anti-cyclic citrullinated peptide high sensitive (anti-CCP hs) in the differentiation between rheumatoid arthritis (RA) and chronic hepatitis C virus (HCV) associated arthropathy and its correlation with disease activity and the degree of liver cirrhosis in RA associated with chronic HCV infection.Patients and methodThis study was carried out on 90 chronic HCV infection patients, 90 HCV negative RA patients and 90 HCV positive RA patients, in addition to 90 healthy volunteers. Hepatic assessment, rheumatological examination, quantitative HCV RNA test and abdominal ultrasonography were assessed in all HCV patients. Disease activity score (DAS-28) was assessed in RA patients. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies (ANA), cryoglobulins, rheumatoid factor (RF), anti-CCP3, anti-CCP hs test were assessed for all patients.ResultsThe higher frequency of anti-CCP hs was found in RA (HCV+ve) (88.9%) compared to RA (HCV-ve) (75.5%) and HCV patients (14.4%), its sensitivity in RA patients was 75.6% and specificity was 85.6%. In HCV patients anti-CCP hs significantly correlated with cryoglobulinemia and scoring for liver fibrosis (p < 0.001). In RA patients, anti-CCP hs significantly correlated with RF, anti-CCP3, DAS-28, ESR and CRP (p < 0.001).ConclusionsSerum anti-CCP hs is sensitive but not a specific marker for RA patients and cannot be used as a diagnostic marker to differentiate between RA and chronic HCV associated arthropathy, in addition it cannot be used as a marker of activity in RA especially when associated with HCV.     

Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

BackgroundCell free deoxyribonucleic acid (cf-DNA) is now emerging as a useful tool for non-invasive diagnostic methods related to a wide range of clinical conditions including autoimmune diseases.Aim of the workTo estimate the concentration of plasma cf-DNA in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients compared with healthy subjects and to correlate the results with clinical and laboratory parameters of disease activity.Patients and methodsThe study included 30 RA patients, 35 SLE patients and 25 matched control. Plasma cf-DNA was estimated by real-time quantitative PCR. Disease activity parameters for each disease were assessed; Disease Activity Score-28 (DAS28) was used for RA and SLE disease activity index 2000 (SLEDAI-2K) for SLE patients.ResultsThe RA patients (F:M 4:1) had a mean age of 36.8 ± 9.6 years and disease duration of 8.3 ± 1.1 years while the SLE patients (F:M 7.75:1) had a mean age of 35.6 ± 8.8 years and disease duration of 8.1 ± 0.87 years. There was a highly significant increase in the cf-DNA level in SLE patients (17.33 ± 2.4 ng/ml) and RA patients (11.15 ± 2.3 ng/ml) compared to the level in the control (4.15 ± 1.4 ng/ml) (p = 0.0005). The cf-DNA significantly correlated with the erythrocyte sedimentation rate (ESR) (p = 0.04), C-reactive protein (p = 0.04) and the DAS28 (p = 0.005) in the RA patients and with the ESR (p = 0.03), anti-ds-DNA (p = 0.008), complement-4 (p = 0.04) and SLEDAI-2K (p = 0.002).ConclusionThe increased cf-DNA implicates a possible role in the pathogenesis of both RA and SLE and appears to be a useful marker of disease activity in addition to other laboratory tests.     

Quality of life assessment in Egyptian rheumatoid arthritis patients: Relation to clinical features and disease activity

Aim of workTo assess the impact of rheumatoid arthritis (RA) on the health related quality of life (QoL) of patients, using the 36-item short form (SF-36) and to study the influence of different disease variables.Patients and methodsEighty-six RA patients were recruited from the Rheumatology and Rehabilitation outpatient of Assiut University Hospital. Forty-three, age and sex matched subjects were included as controls. The QoL was measured in all subjects using the SF-36 health survey. Disease activity was assessed in RA patients by the disease activity score (DAS28).ResultsAll domains of the SF36 were significantly lower in the patients (p < 0.0001). Patients with a lower educational level and those unemployed had significantly lower SF36 components. Those with a disease duration >5 years, positive rheumatoid factor and higher disease activity had a significantly lower SF36 physical component. Patients receiving hydroxychloroquine or prednisolone had significantly lower mental component. Significant negative correlation of the SF36 physical and mental components was found with both disease duration (p = 0.01 and p < 00001 respectively) and DAS28 (p < 0.0001 for both). Rheumatoid factor negatively correlated with the physical component (p < 0.0001). Regression analysis showed that disease duration was the most profound predictor of both SF36 components (p < 0.0001).ConclusionThe quality of life is impaired in Egyptian RA patients and disease duration was the most significant predictor. Routine assessment of the health-related QoL in those patients is recommended to detect and monitor the impact of the disease and medications used on different aspects of their quality of life.     

Serum level of interleukin-33 in rheumatoid arthritis patients and its association with bone erosion and interstitial lung disease

Aim of the workTo analyze the serum levels of IL-33 in RA patients and to investigate its relation to the clinical characteristics, laboratory investigations, joint erosions, functional status and disease activity. Its relation to the presence of interstitial lung disease (ILD) was well thought-out.Patients and methodsThe study included 50 RA patients and 30 matched control. Thorough clinical examination, investigations, disease activity score (DAS-28) and health assessment questionnaire (HAQ) were considered in the patients. Bone erosion was evaluated and interstitial lung disease (ILD) was identified on high-resolution computed tomography. The serum level of IL-33 was measured by enzyme-linked immunosorbent assay.ResultsSerum levels of IL-33 are significantly higher in RA patients (106.96 ± 52.6 pg/ml) than in healthy controls (46.9 ± 23 pg/ml) (p < 0.001). A significant correlation was found between IL-33 and the DAS28 (r = 0.4, p = 0.001), level of rheumatoid factor (r = 0.45, p = 0.001) and with the presence of ILD (r = 0.3, p = 0.04). There were no gender differences and the level did not significantly correlate with the age or disease duration. The medications received had no obvious effect on the IL-33 level. The level did not correlate with the HAQ. There was a significant correlation between the CT bone erosion scores the patient’s age, disease duration, rheumatoid nodules and DAS28. The erosion score also significantly correlated with the serum IL-33 levels in RA patients (r = 0.71, p = 0.001).ConclusionThese data support the hypothesis that IL-33 may be involved in RA pathogenesis and it may partly contribute to the bone erosion and ILD in RA patients.     

Assessment of health-related quality of life,anxiety and depression in patients with early rheumatoid arthritis

Aim of the workTo assess the effect of clinical manifestations, disease activity and medications on health-related quality of life (HRQoL) among patients with early rheumatoid arthritis (RA).Patients and methodsTwenty-six early RA patients (mean age 43.31 ± 10.51 years, disease duration: 16.5 ± 5.2 months) diagnosed according to the 2010 RA classification criteria were recruited from the outpatient clinic of the Rheumatology and Rehabilitation Department, Sohag University, and 22 age and sex matched healthy persons participated in a case control study. Demographic data were taken from all participants in the study. The 36-item short-form health survey (SF-36) and Hamilton Anxiety Rating Scale (HAM-A) were assessed as measures of HRQoL and psychiatric comorbidity for both patients and controls. Disease activity in RA was assessed using the disease activity score (DAS28). Scoring algorithms were applied to produce the physical and mental component scores (PCS and MCS).ResultsThere was statistically significant difference in the total SF36 score, anxiety and depression scores of HAM-A scale between patients and controls. The PCS showed the highest significant difference (p < 0.0001), followed by SF36 (p = 0.01) and MCS (p = 0.024). There were no significant differences according to the age, gender, occupation or level of education of the patients. Anxiety and depression scores significantly correlated with the bodily pain and DAS28 scores and inversely with the PCS and MCS. The DAS28 strongly negatively correlated with the PCS and MCS.ConclusionRheumatoid arthritis has a major impact on many areas of an individual’s life and tends to have a profound impact on the health-related quality of life.     

Prognostic Factors for Sustained Remission in a “Real Life” Cohort of Rheumatoid Arthritis Patients

IntroductionRheumatoid arthritis (RA) is the most frequent chronic polyarthritis. The current goal of RA treatment is to achieve clinical remission.ObjectiveThe goal of this study was to determine the prevalence of remission in a cohort of patients from clinical practice, and to identify potentially modifiable factors associated with remission.MethodsA retrospective study was performed on a cohort of RA patients seen at the first consultation at the HUGC Rheumatology Service Dr. Negrín (HUGCDN) between first of January 2000 and thirtieth of April 2014. Sustained remission was defined as DAS28 less than 2.6 in the last two available visits in the medical history.ResultsA total of 463 patients were consecutively included, most (75%) women, with a mean age at the onset of RA of 50 years and a mean duration of the disease at follow-up of 8 years. 46% of the patients achieved sustained remission. Multiple logistic regression analyses found male sex (P = .031, OR 1.7, 95% CI 1.05–2.82), diagnosis in the first year of symptoms (P = .023, OR 1.7, 95% CI 1.07–2.69) and the initial DAS28 (P = .035) to be independent predictors for sustained remission.ConclusionsThe 46% of the patients with RA followed in the HUGC Dr. Negrín are in persistent remission, being the early diagnosis a modifiable factor predictor of remission. Thus, an objective of the Rheumatology Service should be to improve the diagnostic delay of RA in the health area.     

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs

BackgroundRheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage.ObjectiveTo determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF.MethodsHospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0 = none to 3 = severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N = 37) and combination therapy with DMARD and anti-TNF (N = 21) groups. A p-value <0.05 was considered statistically significant.ResultsOut of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found.ConclusionsPersistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission.     

Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity

Aim of the workTo investigate the role of T-helper 17 (Th17) cells in peripheral blood and serum interleukin-17 (IL-17) in rheumatoid arthritis (RA) patients, and their correlation with disease activity and joint destruction.Patients and methodsThis study included forty RA patients and twenty matched healthy controls. Disease activity score in 28 joints (DAS-28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, tumor necrosis factor alpha (TNF-α), serum IL-17 and Th17 cells in peripheral blood were measured. Radiological assessment using modified Sharp/van der Heijde (mSvH) score for hand and feet in addition to MRI score for the wrist and metacarpophalangeal (MCP) joints were performed for detection of synovitis and bone erosion.ResultsThe patients were 38 females and 2 males with a mean of 41.15 ± 5.85 years and disease duration of 15.6 ± 4.62 years. Serum IL-17 and Th17 cells in peripheral blood were found to be significantly increased in RA patients (204.1 ± 33.8 pg/ml and 4.62 ± 1.13%) than in controls (25.36 ± 5.39 pg/ml and 0.7 ± 0.021%) (p < 0.001). Th17 cells significantly correlated with serum IL-17 (r 0.88, p < 0.001). Both Th17 cells and serum IL-17 significantly correlated with DAS-28, ESR, CRP, TNF-α, Van der Heijde modification score and MRI scores for wrist and MCP joints for synovitis and bone erosion (all with a p < 0.001).ConclusionThis study demonstrates an important role for Th-17 cells and serum IL-17 in the pathogenesis of the inflammatory and destructive pattern characteristic of RA.     

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3 ± 520.9 pg/ml) and hs-CRP (2.8 ± 1.9 mg/l) than the control (92.5 ± 86.3 pg/ml and 0.9 ± 1.5 mg/l respectively) (p < 0.001 each). There was no significant difference in MGP levels between the patients and control (p = 0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p = 0.4 and p = 0.8 respectively). Age positively correlated with OPG (r = 0.32, p = 0.02), but not with MGP concentration (r = 0.05, p = 0.64) in the RA patients.ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.     

Assessment of synovitis in early rheumatoid arthritis by CXCL13 serum levels and power Doppler ultrasonography: Correlation with disease activity

Aim of the workAssessment of synovitis in rheumatoid arthritis (RA) is a major issue for proper treatment; it has been proven that high resolution ultrasound (US) examination could be of valuable help. The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. We aimed to find out the presence of synovitis in patients with recent-onset RA and its correlation with disease activity.Patients and methodsWe evaluated 30 patients with early RA for the presence and degree of synovitis by performing high resolution US and obtaining serum CXCL13 levels. In addition, we correlated these results with disease activity score 28 (DAS 28). Results of high resolution US and serum CXCL13 were also obtained for 20 healthy age- and sex-matched volunteers and served as controls.ResultsSerum CXCL13 level was significantly increased in early RA patients vs. controls (p < 0.001). High resolution US revealed that RA patients had a significant increased synovial thickness and high power Doppler US score. In RA patients, DAS 28 had a significant correlation with serum CXCL13 (r = 0.42, p = 0.02), synovial thickness (r = 0.39, p = 0.03) and power Doppler US score (r = 0.43, p = 0.02). Serum CXCL13 level correlated with synovial thickness (r = 0.63, p = 0.001) and power Doppler US score (r = 0.69, p = 0.001).ConclusionRecent-onset RA patients suffer from synovitis as evidenced by significantly increased serum CXCL13 and by high resolution US. Serum CXCL13 is a reliable marker of synovial inflammation which correlates better with synovial thickening and power Doppler US scores than DAS28.