Duration of clinical remission and low disease activity impacts on quality of life and its domains in psoriatic arthritis patients: results from an Italian multicentre study.

OBJECTIVES: Long-term quality of life (QoL) is significantly compromised in patients with psoriatic arthritis (PsA) and only partially improves achieving remission or low disease activity. The main aim of this study is to evaluate the QoL in PsA patients and to investigate their possible relationship with clinical remission and low disease activity, and with its duration over time. METHODS: A multicentre cross-sectional observational study has been performed. QoL domains considered were analysed through PROs. Chi2 test was used for analysis of contingency tables, while Mann-Whitney test and Kruskal-Wallis test with Holm's pairwise comparison corrections were used to compare ranks. To evaluate variables associated to the different QoL domains, univariate and multiple linear regressions were used. RESULTS: 143 participants were included in this study. The physical component of the Short Form-36 or Functional Assessment of Chronic Illness Therapy-Fatigue tends to improve with short duration of low or minimal disease activity. However, this is not confirmed for the mental component of SF-36 (MCS), which improved only with longer duration of low/minimal disease activity. CONCLUSIONS: This study proves the existence of an inverse relation between disease activity and QoL domains. Apart from low or minimal disease activity, also its persistence over time has a great influence on the patient's perception of their clinical condition; therefore, persistence over time of clinical remission/low disease activity should be added to the latest definition of treat-to-target in PsA.

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, multicentre, prospective, observational study.

OBJECTIVES: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. METHODS: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. RESULTS: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. CONCLUSIONS: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.

Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort.

OBJECTIVES: Remission in systemic lupus erythematosus (SLE) is defined through a combination of 'clinical SLE Disease Activity Index (cSLEDAI)=0', 'physician's global assessment (PGA) <0.5' and 'prednisone (PDN) ≤5 mg/day'. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index. METHODS: We tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA <0.5; cSLEDAI=0; PGA <0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA <0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated. RESULTS: We included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA <0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA <0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA <0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5 0.532, 0.363 to 0.781, p<0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p<0.0001). Adding PGA <0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (-1.8 and -1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual. CONCLUSIONS: cSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up.

Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease and rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are the most frequently detected autoantibodies (autoAbs). To date, more than 20% of RA cases are still defined as seronegative forms (seronegative RA, SN-RA). The aim of this study was to identify new antigenic targets of autoAbs in RA patients, which can also be recognized in SN-RA. Using a proteomic approach, we tested sera from SN-RA patients by analyzing synovial fluid (SF) proteins from these patients. Sera from SN-RA patients revealed a strong reactive spot, corresponding to alpha 1 antitrypsin (A1AT). Reverse-phase nanoliquid chromatography and tandem mass spectrometry (Matrix Assisted Laser Desorption/Ionization-Time Of Flight, MALDI-TOF/TOF) confirmed the presence of A1AT in SF and showed that homocysteinylation was one of the post-translational modifications of A1AT. Homocysteinylated (Hcy)-A1AT immunoprecipitated from SN-RA patients' SFs and in vitro modified Hcy-A1AT were used as antigens by Enzyme-Linked ImmunoSorbent Assay (ELISA) to test the presence of specific autoAbs in sera from 111 SN-RA patients, 132 seropositive (SP)-RA patients, and from 95 patients with psoriatic arthritis, 40 patients with osteoarthritis, and 41 healthy subjects as control populations. We observed that a large portion of SN-RA patients (75.7%), and also most of SP-RA patients' sera (87.1%) displayed anti-Hcy-A1AT autoAbs (anti-HATA). Native A1AT was targeted at a lower rate by SP-RA patients autoAbs, while virtually no SN-RA patients' sera showed the presence of anti-native A1AT autoAbs. In conclusion, anti-HATA can be considered potential biomarkers for RA, also in the SN forms. The discovery of novel autoAbs targeting specific autoantigens can represent higher clinic significance for all RA patients' population.

Omalizumab in eosinophilic granulomatosis with polyangiitis: friend or foe? A systematic literature review.

OBJECTIVES: To systematically evaluate, through a Medline search, the role of omalizumab in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: A systematic review was performed with the following inclusion criteria: original articles and case reports written in English and reporting an association between omalizumab and EGPA. RESULTS: We found 18 papers on EGPA (14 case reports, 3 retrospective cohort studies, 1 prospective cohort study). Omalizumab showed to be effective as corticosteroid-sparing agent in EGPA patients with severe asthmatic manifestations. On the contrary, conflicting results concerned its use in refractory forms of EGPA. Plausible is the increased risk of EGPA onset among asthmatic patients treated with omalizumab, probably related to steroid reduction, even if it cannot be excluded that omalizumab might be occasionally directly involved in the pathogenesis. CONCLUSIONS: Our findings support the use of omalizumab in selected forms of EGPA, but caution in the tapering of corticosteroids is also recommended. Quality of evidence is limited, as the source of information was mainly case reports. Clinical trials are required in order to evaluate the role of omalizumab in EGPA and to ascertain the risk of asthmatic patients given omalizumab to develop EGPA.

An observational prospective study on predictors of clinical response at six months in patients with active psoriatic arthritis treated with golimumab.

OBJECTIVES: Recently, research has been focused on the identification of predictors of response to treatment in patients with active psoriatic arthritis (PsA). The objective of this study was to develop a model to predict the clinical response at 6 months in patients with PsA starting the anti-tumour necrosis factor-α golimumab. METHODS: This prospective observational study explored a range of factors, including demographic data and baseline characteristics of the disease, measures of disease activity and functional disability, and potential laboratory biomarkers in the prediction of response, defined as the achievement of modified-minimal disease activity (mMDA), to golimumab in PsA patients. RESULTS: We studied 151 PsA patients starting golimumab because of their active disease. After 6 months, the rate of drug persistence on golimumab was 80%, and mMDA was achieved in 44.3% of patients. Using univariate and multivariate logistic regression models, lower disease activity in PsA score (DAPSA) at baseline (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.89-0.96, p<0.001) was independent predictor of mMDA at 6 months. High sensitivity C-reactive protein value (OR 1.06; 95% CI 1.00-1.13, p=0.026) at baseline also was a predictive factor of mMDA achievement at 6 months in the laboratory-enhanced prediction model. Golimumab was safe and well tolerated. CONCLUSIONS: The identification of factors predictive of response to treatment may help in better understanding the response to golimumab and in identifying PsA patients that are most likely to achieve mMDA following therapy with golimumab.

Demographic and clinical differences between ankylosing spondylitis and non-radiographic axial spondyloarthritis: results from a multicentre retrospective study in the Lazio region of Italy.

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.

Serum adiponectin levels are associated with presence of carotid plaque in women with systemic lupus erythematosus.

BACKGROUND AND AIM: Systemic lupus erythematosus (SLE) is associated with accelerated atherogenesis. Traditional risk factors do not seem to fully explain this process in patients with SLE and no other imaging/serum biomarkers have so far improved risk stratification. Here, we focused on the role of adiponectin in women with SLE. METHODS AND RESULTS: This is a sub-analysis of a validated cohort enrolling eighty females (age 18-65 years) affected by SLE. Patient underwent a single blood sampling and carotid echography. Serum adipocytokines (i.e. leptin, resistin and adiponectin) were assessed by enzyme-linked immunosorbent assay (ELISA). Patients with a carotid plaque (n = 23) were older, with longer duration of the disease, chronic use of corticosteroids, and immunosuppressive therapies. As expected, patients with a carotid plaque had increased vascular risk and high serum levels of inflammatory biomarkers, total and LDL cholesterol and adiponectin. Significant positive correlation between serum adiponectin and presence of a carotid plaque was found independently of patient age, SCORE Risk Charts, duration of disease, and SLE treatments. CONCLUSIONS: These results indicate that high serum adiponectin is associated with accelerated carotid atherosclerosis in SLE young women and it might be useful to improve vascular risk stratification in this patient setting.

Mediterranean diet and Psoriatic Arthritis activity: a multicenter cross-sectional study.

Diet is a modifiable factor implicated in chronic systemic inflammation, and the mediterranean dietary pattern is considered to be a healthy model in terms of morbidity and mortality. The main aim of this study was to evaluate the adherence to the mediterranean diet in patients with Psoriatic Arthritis (PsA) and its impact on disease activity. A cross-sectional observational study was conducted in a cohort of 211 consecutive PsA patients. We evaluated PsA activity by disease activity index for PSoriatic Arthritis (DAPSA) and composite psoriatic disease activity index (CPDAI). The NCEP-ACT III criteria were used to identify subjects with MetS, and in each subject, we evaluated body mass index (BMI). A validated 14-item questionnaire for the assessment of adherence to the mediterranean diet (PREDIMED) was recorded for all the enrolled subjects. Patients showed a median age of 55 (48-62) and disease duration was 76 (36-120) months. 27.01% of patients were classified as having MetS. The median of the mediterranean diet score (MDS) was 7 (6-9). A moderate adherence to mediterranean diet was found in 66.35% of the entire cohort; 15.64% and 18.01% of the patients showed low- and high adherence to the dietary pattern, respectively. We found a negative association between DAPSA and adherence to mediterranean diet (B = - 3.291; 95% CI - 5.884 to - 0.698). DAPSA was positively associated with BMI (B = 0.332; 95% CI 0.047-0.618) and HAQ ( B = 2.176; 95% CI 0.984-3.368). Results from our study evidenced that in PsA patients, higher levels of disease activity as measured by DAPSA correlated with low adherence to mediterranean diet, suggesting potential benefit of antinflammatory properties of this dietary pattern.

Serum osteopontin negatively impacts on intima-media thickness in patients with systemic lupus erythematosus.

BACKGROUND: Ultrasound evaluation of carotid intima-media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients' categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE. MATERIALS AND METHODS: Eighty females (age 18-65 years) affected by SLE and eighty age-matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high-sensitivity C-reactive protein (hs-CRP) and OPN. RESULTS: Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r = 0.364; P = 0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti-dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack-year, Heart SCORE, disease length and steroid therapy length. CONCLUSIONS: These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials.

Clinical features of patients with systemic lupus erythematosus according to health-related quality of life, entity of pain, fatigue and depression: a cluster analysis.

OBJECTIVES: To identify the distribution of patients with systemic lupus erythematosus (SLE) in clusters according to the levels of health-related quality of life (HRQoL), entity of pain, fatigue and depression. METHODS: We performed a hierarchical cluster analysis. The following measures were used as clustering variables, after canonical transformation: the SF36 physical and mental component summary (PCS and MCS), the Beck Depression Inventory II (entity of depression), the Facit-Fatigue, all assessed during the last visit. Consecutive SLE patients were enrolled from two Italian cohorts. Lupus remission was retrospectively assessed over a period of 5 years before the last visit and was defined as a continuative period of no clinical disease activity according to SLEDAI2K and the maximum dose of prednisone allowed of 5 mg/day. RESULTS: We enrolled 130 female SLE patients. We identified three clusters. The first cluster (43 patients) was characterised by the highest levels of MCS and PCS and the lowest entity of pain, fatigue and depression. Cluster 2 (35 patients) was defined by a reduction of MCS and increase of pain, fatigue and depression; conversely, PCS levels were similar to cluster 1. In cluster 3 (52 patients) we found a reduction of MCS and increase of depression and fatigue (similar to cluster 2) but also a decrease in PCS levels and Bodily Pain (meaning increase in pain). In cluster 3 we found a decreased prevalence of remission ≥5 years. CONCLUSIONS: Identification of clusters of patients according to HRQoL levels could be useful to improve SLE management, aiming at personalised medicine.

Factors related to alexithymia in patients with systemic sclerosis: a tight relationship with facial image dissatisfaction.

To assess clinical and psychosocial factors related to alexithymia in systemic sclerosis (SSc). We enrolled 40 consecutive SSc patients in a cross-sectional study evaluating alexithymia with Toronto Alexithymia scale (TAS-20). We measured Beck Depression inventory (BDI), Hamilton Anxiety rating scale (HAM-H), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Visual Analog Scale (VAS) pain, Pittsburgh Sleep Quality Index (PSQI), Satisfaction with Appearance Scale (SWAP), and Mouth Handicap in Systemic Sclerosis (MHISS). The prevalence of alexithymia was 42%. Alexithymic patients presented increased depressive (p = ≤ 0.001) and anxiety symptoms (p = ≤ 0.001), sleep disorders (p = 0.03), pain (p = 0.02), esthetic concerns (p = 0.03), disability in activities (p = 0.03) and reduced scores of SF-36 in mental components summary (MCS) (p = ≤ 0.001) and physical components summary (PCS) (p = 0.01). We found significant correlations with sleep disorders (r = 0.41, p = ≤ 0.001), BID (r = 0.35, p = 0.04), facial image dissatisfaction (r = 0.35, p = 0.04), mouth disability (r = 0.51, p = 0.005), depressive (r = 0.6, p = ≤ 0.001), and anxiety symptoms (r = 0.48, p = ≤ 0.001), fatigue (r = - 0.45 p = 0.005), SF-36 PCS (r = - 0.51, p = ≤ 0.001) and MCS (r = - 0.65, p = ≤ 0.001). In multiple linear regression analysis, SWAP facial was the only variable associated with TAS-20 [0.99 (0.48) p = 0.05]. Alexithymia correlates with several psychosocial factors but seems strongly related to facial image dissatisfaction.

In systemic sclerosis, microvascular and hands digital arteries damage correlates with serum levels of endostatin.

OBJECTIVE: In SSc, vascular injury leads to endothelial dysfunction with reduced capillary blood flow and tissue hypoxia. In SSc, the angiogenesis is impaired and implicated in the microvascular damage. In severe vascular damage, VEGF is reduced and endostatin is increased. The aim of this study was to evaluate the correlation between endostatin serum levels and microvascular and digital arteries damage. METHODS: Seventeen patients with SSc were enrolled in this study. Serum endostatin levels were determined. All patients underwent a NVC, CDUS, and LDPI. RESULTS: The serum level of endostatin significantly (P < .05) increased with NVC progression damage. The mean perfusion significantly (P < .05) decreased with NVC progression damage. Multiple regression analysis showed a significant correlation between endostatin serum level and RI (r = .34, P < .05), PI (r = .60, P < .01), S/D ratio (r = .76, P < .0001), and mean perfusion (r = -.68, P < .001). Endostatin serum levels significantly (P < .05) increased with progression of CDUS damage. CONCLUSIONS: Increased serum endostatin levels are associated with digital vascular damage. In patients with SSc, endostatin is a marker of skin perfusion and digital arteries damage of hands.

Immediate treatment with tumour necrosis factor inhibitors in synthetic disease-modifying anti-rheumatic drugs-naïve patients with rheumatoid arthritis: results of a modified Italian Expert Consensus.

Objective: To establish clinical consensus for the optimal placement of TNF inhibitor (TNFi) in DMARDs-naïve RA patients. Methods: The steering group was composed of 15 Italian rheumatologists expert in the field of RA, who proposed and selected by consensus the clinically relevant questions on the role of TNFi treatment in DMARDs-naïve RA patients. The question was rephrased according to the population, intervention, comparison and outcome statement. The available scientific evidence on this topic were collected by updating the systematic literature reviews used for the EULAR 2013 recommendations up to January 2016. The aspects evaluated in the studies concerned clinical efficacy, radiographic structural damage and safety. After the systematic literature review the expert panel formulated a consensus statement, and a modified Delphi panel evaluated the level of agreement between panellists (strength of recommendation). Results: From a total of 1080 records we have included 6 studies, 2 randomized clinical trials and 4 open-label extension trials. Evidence from publications generated three statements for the final consensus document. The systematic literature review and the consensus statements developed showed that, for patients with early RA and in the presence of a treat-to-target strategy, the immediate use of anti-TNFi compared with an early (within 12 weeks) step-up to anti-TNF therapy did not confer a significant advantage regarding clinical, functional and radiographic outcomes. Conclusion: The most appropriate placement of the TNFi therapy in the treatment algorithm of early RA still remains a challenging clinical question that needs to be further addressed.

Fatigue in systemic sclerosis: a systematic review.

OBJECTIVES: To systematically review fatigue in systemic sclerosis (SSc) in terms of prevalence, features, correlates, predictors and management. METHODS: We performed a literature search in PubMed (Medline), EBSCO and COCHRANE databases up to June 2017 selecting articles regarding fatigue in SSc. The articles finally selected fulfilled the following eligibility criteria: written in English, referred to fatigue in SSc, reporting original data, including validated questionnaires measuring fatigue. RESULTS: A total of 43 records were included. Fatigue in SSc has a prevalence similar to that of other rheumatic diseases and is one of the most prevalent and debilitating symptom experienced by SSc patients. Fatigue leads to a significant impairment of quality of life, parenting, household and work ability. Fatigue is associated with psychosocial factors (depression, pain and sleep disorders), sociodemographic factors and clinical manifestations of the disease (pulmonary and gastrointestinal involvement). Indeed, the relationship with scores of disease activity is uncertain. Pharmacological therapeutic approaches were broadly ineffective in reducing fatigue. More encouraging results concern physical activity, complementary and alternative medicine. CONCLUSIONS: Adequate management of fatigue could lead to a marked improvement of the patient's quality of life, also contributing to reduction in SSc indirect costs.

Parasympathetic activity increases with digital microvascular damage and vascular endothelial growth factor in systemic sclerosis.

OBJECTIVES: The imbalance between angiogenic and angiostatic factors with derangement of the microvasculature are hallmarks of systemic sclerosis (SSc). Raynaud's phenomenon in SSc probably is due to the impaired neuroendothelial control mechanisms between vasoconstriction and vasodilatation. The aim of this study is to evaluate autonomic nervous system function using heart rate variability (HRV) analysis and to correlate with vascular endothelial growth factor (VEGF). METHODS: Twenty-seven SSc patients were enrolled. HRV was measured and markers of global sympathetic and parasympathetic system, respectively standard deviation of normal-to-normal RR intervals (SDNN) and square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) were evaluated. Serum VEGF levels and nailfold videocapillaroscopy (NVC) were performed. RESULTS: A linear positive correlation was observed between RMSSD and VEGF (p<0.01, r=0.55), and RMSSD and disease duration (p< 0.01, r=0.54). The RMSSD median value was significantly increased (p< 0.05) with NVC damage progression. The RMSSD median value was significantly (p<0.05) higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [44 (39.4-60.2) vs 24.6 (23-37.1)]. CONCLUSIONS: In our study parasympathetic modulation increases in relation to VEGF. When microcirculation is modified with capillaroscopic pattern progression and DUs, autonomic system seems to stimulate vasodilatation trough parasympathetic system. We can conclude that parasympathetic activity increases with digital microvascular damage and promotes VEGF release.

Ultrasound detection of subclinical synovitis in rheumatoid arthritis patients in clinical remission: a new reduced-joint assessment in 3 target joints.

OBJECTIVES: The ability of ultrasound (US) to identify subclinical joint inflammation in rheumatoid arthritis (RA) patients in remission has been already reported. Nonetheless, current studies present a lack of homogeneity in patient's characteristics and number of joints assessed by US. The aim of this study was to identify a reduced set of target joints to be scanned in RA patients in clinical remission in order to detect subclinical synovitis. METHODS: Forty RA patients in clinical remission (DAS28 ≤2.6) for at least 3 months underwent an US examination of 18 joints: wrist, II-III-IV-V metacarpophalangeal (MCP) and II-III-IV-V metatarsophalangeal joints bilaterally. The presence of synovial hypertrophy (SH) and power-Doppler (PD) signal was registered following the OMERACT definitions and was graded according to a 4-point scale (0-3). Then, by applying a process of data reduction based on the frequency of joint involvement, a reduced assessment was obtained. RESULTS: Twenty (50%) subjects had at least one joint affected by active synovitis; 17.5% presented grade 1 PD and 32.5% grade 2 PD. The joints most frequently affected by active synovitis were the wrists (75%) and the II MCP joints (55%). After data reduction, the evaluation of 3 joints (both wrists and the II MCP of the dominant hand) obtained a sensitivity of 90% for the detection of subclinical synovitis. CONCLUSIONS: The US scan of 3 target joints showed a high sensitivity in detecting subclinical active synovitis in RA patients in clinical remission and can be feasible in the routine assessment of these patients.

Belimumab and low-doses of mycophenolate mofetil as induction therapy of class IV lupus nephritis: case series and literature review.

BACKGROUND: The treatment of Lupus Nephritis (LN) is an unmet need in the management of patients with Systemic Lupus Erythematosus (SLE). CASE PRESENTATION : We report two cases of women affected by Lupus Nephritis (LN) ISN/RNP Class IV with serological active disease, high disease activity and marked fatigue. In both cases, Mycophenolate mofetil (MMF), as induction therapy, was poorly tolerated because of gastrointestinal toxicity. Belimumab, together with low-doses of MMF, was effective as induction treatment leading to early achievement of complete renal response in these two selected cases of LN. CONCLUSIONS: We also report a literature review concerning the efficacy and safety of Belimumab in Lupus Nephritis. Further studies are needed to evaluate the use of Belimumab to manage the renal involvement in patients with Systemic Lupus Erythematosus, waiting for the results of ongoing randomized clinical trials.

Serum level of endostatin and digital ulcers in systemic sclerosis patients.

Patients with systemic sclerosis (SSc) are at a high risk of the development of ischaemic digital ulcers (DUs) that can be complicated with infections, gangrene, and osteomyelitis. The aim of this study is to evaluate the role of endostatin in scleroderma DUs.In total, 90 SSc patients were enrolled in this study. Serum endostatin levels and DU assessment were determined in all SSc patients. The serum levels of endostatin significantly increased with progression of capillaroscopic damage (P < .01). The serum levels of endostatin are significantly (P < .05) higher in SSc patients with new DUs than in SSc patients without new DUs (127 ± 31.1 ng/mL vs 116.3 ± 39.7 ng/mL). The Receiver Operating Characteristic (ROC) curves demonstrated good accuracy of new DU prediction for the serum level of endostatin (0.70, P < .01 [95% confidence interval (CI) 0.59-0.81]). Using a cut-off value of 116 ng/mL, the odds ratio was 2.609 (CI 1.075-6.330, P < .05). The serum levels of endostatin are significantly (P < .01) higher in SSc patients with infected DUs than in SSc patients without infected DUs (139.2 [114.6-340.91] ng/mL vs 117.5 [64.3-163.9] ng/mL). Serum levels of endostatin are higher in patients with DUs, especially in those with infected DUs.

Angiogenic and angiostatic factors in renal scleroderma-associated vasculopathy.

BACKGROUND: The angiogenesis in systemic sclerosis (SSc) is impaired. An imbalance of pro-angiogenic factors and angiogenesis inhibitors has been implicated in the progression of peripheral microvascular damage, defective vascular repair and fibrosis. Intrarenal resistance index are considered markers of renal vasculopathy. The aim of the study is to evaluate angiogenic and angiostatic factors (VEGF and endostatin) in SSc patients and to correlate with intrarenal hemodynamic parameters. METHODS: 91 SSc patients were enrolled in this study. Serum VEGF and endostatin levels were determined. All patients underwent a renal Doppler ultrasound RESULTS: A significant positive correlation was observed between endostatin and renal Doppler parameters (p<0.0001). A negative correlation was observed between serum levels of endostatin and eGFR (p<0.01). In SSc patients with high resistive index, serum levels of endostatin were significantly (p<0.01) higher than in SSc patients with normal resistive index. The serum levels of endostatin significantly increased with progression of nailfold videocapillaroscopy damage (p<0.01) and were significantly (p<0.05) higher in SSc patients with digital ulcers than in SSc patients without digital ulcers. CONCLUSION: This is the first study that assess in SSc patients intrarenal hemodynamic parameters and endostatin. In SSc patients, endostatin represents a marker of renal scleroderma-associated vasculopathy.