Objective: Vitamin D has pleiotropic effects including immunomodulatory, cardioprotective, and antifibrotic properties and is thus able to modulate the three main links in scleroderma pathogenesis. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis and to analyze the associations between the concentration of vitamin D and the features of systemic sclerosis.Material and Methods: Fifty-one consecutive patients were evaluated for visceral involvement, immunological profile, activity, severity scores, and quality of life. The vitamin D status was evaluated by measuring the 25hydroxy-hydroxyvitamin D serum levels. Results:The mean vitamin D level was 17.06±9.13 ng/dL. Only 9.8% of the patients had optimal vitamin D levels; 66.66% of them had insufficient 25(OH)D levels, while 23.52% had deficient levels. No correlation was found between vitamin D concentration and age, sex, autoantibody profile, extent of skin involvement, or vitamin D supplementation. Vitamin D levels were correlated with the diffusing capacity of the lung for carbon monoxide (p=0.019, r=0.353), diastolic dysfunction (p=0.033, r=−0.318), digital contractures (p=0.036, r=−0.298), and muscle weakness (p=0.015, r=−0.377) and had a trend for negative correlation with pulmonary hypertension (p=0.053, r=−0.29).Conclusion: Low levels of vitamin D are very common in systemic sclerosis. Poor vitamin status seems to be related with a more aggressive disease with multivisceral and severe organ involvement, especially pulmonary and cardiac involvement.

BackgroundAssessment of synovitis in Rheumatoid Arthritis (RA) is a major issue for a proper treatment administration; it has been proven that ultrasound (US) examination could be of valuable help and it is currently being investigated as a possible outcome measure for the disease. It is, though, of greatest importance to accurately establish the place of US scores among the already validated outcome measures, according to Outcome Measures for Rheumatoid Arthritis in Clinical Trials (OMERACT) filter. The present study is designed to compare the results of gray-scale ultrasound (GSUS) and Power Doppler ultrasound (PDUS) additive scores, separately calculated for volar and dorsal aspects of the hand, with physical examination, patient's evaluation of disease pain and global activity on Visual Analogic Scale (VAS) and traditional scores for disease activity assessment (DAS28, CDAI, SDAI, HAQ). The final aim is to prove the advantages of volar US evaluation in RA patients.Methods42 RA patients have been clinically evaluated for pain and swelling of their hand joints, completed VAS and HAQ questionnaires and underwent both volar and dorsal sonography of the hands during the same day. The US examiner was blinded to clinical assessments and lab results. For each patient 20 joints were assessed by sonography (radiocarpal, intercarpal, metacarpophalangeal (MCP) 2-5, proximal interphalangeal (PIP) 2-5). Carpal joints were only evaluated from dorsal view, while MCPs and PIPs were evaluated both from dorsal and volar aspect resulting a total of 36 distinct evaluations for each patient. GSUS synovial hypertrophy was assessed both by quantitative measurement and semiquantitative scale (0-3 grades); Doppler signal (PDUS) was recorded on a semiquantitative scale (0-3 grades). The semiquantitative grades for both GSUS and PDUS evaluation of each joint were added and the sum was defined as the Echographic Score (ES) of each patient. Separately, we added the semiquantitative grades for volar and dorsal side, resulting in Volar ES (VES) and Dorsal ES (DES) of each patient.ResultsWe found ESs correlated with other activity scores: DAS28, CDAI, SDAI, HAQ. Correlations with clinical indices as CDAI and SDAI were stronger for VES than for DES. US discovered more synovitis than clinical examination.ConclusionVES is a suitable reflection of RA activity and volar US examination should accompany the dorsal one both in clinical practice and in clinical trials.

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.

Psoriatic arthritis (PsA) is a chronic inflammatory disorder that belongs to the group of spondyloarthritis (SpA). It was found that single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase (ERAP1 and ERAP2) genes influence the risk of ankylosing spondylitis, the most common form of SpA and the risk of psoriasis. Our purpose was to investigate the possible association of ERAP1 and ERAP2 gene SNPs with psoriatic arthritis susceptibility in Romanian population. Subsequent analyses included patients' subgroups according to HLA-B27 status. Psoriatic arthritis patients (N = 98) and random healthy controls (N = 139) were genotyped for ERAP1/2 genes SNPs rs30187, rs27044, rs2910686, and rs2248374 by TaqMan Allelic Discrimination Assays. An additional control group (N = 108; 100% HLA-B27 positive) was used for subsequent analyses. The results showed the association of rs2248374 SNP of ERAP2 gene with the risk of PsA, especially for HLA-B27 negative disease (p = 0.02; OR 1.59). ERAP2 haplotype GT (rs2248374/rs2910686) was significantly under-represented in PsA patients than in controls (43 vs. 55%; p = 0.02). The analysis of ERAP1 SNPs in HLA-B27 positive controls and PsA subgroup showed strong evidence of association for rs30187 (p = 0.005; OR 2.73) and for CC rs30187/rs27044 haplotype (47% in patients vs. 70.5% in controls; p = 0.006). In conclusion, we found a significant association of ERAP2 with PsA and HLA-B27 negative PsA, while ERAP1 association was restricted only to HLA-B27 positive disease. To our knowledge, this is the first study that investigated ERAP2 polymorphisms in relation to PsA susceptibility.

We investigated two nonsynonymous variants (rs30187 and rs27044) of ERAP1 gene in HLA-B27 positive individuals (150 spondyloarthritis and 108 controls) and in general ankylosing spondylitis (AS) patients (n = 137) vs random controls (n = 139). Both single nucleotide polymorphisms (SNPs) were associated with the risk of spondyloarthritis [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.24-2.62, P = 0.001 for rs30187, OR 1.58, 95% CI 1.07-2.34, P = 0.02 for rs27044]. The CC haplotype was a protective factor (P = 0.002), while the TG haplotype was a risk factor (P = 0.01) for spondyloarthritis. The SNP rs30187 was also associated with the risk of HLA-B27+ AS. For the general group of AS, the carriers of minor alleles showed an increased risk for the disease (OR 1.92, 95% CI 1.17-3.13 for rs30187, OR 1.74, 95% CI 1.08-2.80 for rs27044). This is the first study that shows the association of ERAP1 gene variants and haplotypes with HLA-B27 positive spondyloarthritis.