Association of anti-RNA polymerase III antibody with silicone breast implants rupture in a multicentre series of Italian patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune disease with distinct subsets identified by specific autoantibodies. Some environmental agents might play a role in SSc pathogenesis, including silicone breast implants (SBI). This association has been controversial in previous literature and only few studies reported the auto-antibody status in these SSc women. The objective of this study was to evaluate the association of SBI with SSc in a large cohort of Italian patients, classified according to their SSc-related autoantibodies and to their history of breast cancer. METHODS: Three Italian referral centres retrospectively collected clinical and laboratory data of consecutive SSc women, that were included when fulfilling the 2013 ACR/EULAR criteria and when SSc specific auto-antibodies status was available (anti-centromere (ACA), anti-Topoisomerase I (anti-Topo I) and anti-RNA Polymerase III antibodies (anti-RNAP3)). Data regarding history of SBI, SBI rupture and breast cancer were recorded. RESULTS: Among 742 SSc women, a history of SBI was recorded in 12 patients (1.6%); in only 1 case the implantation occurred after SSc diagnosis. In SSc patients with anti- RNAP3+ a significantly higher frequency of SBI rupture and SBI rupture without breast cancer were observed, as compared to anti-RNAP3-negative patients. No association was noted for SBI without rupture. CONCLUSIONS: In this study we demonstrated a link between SBI rupture and induction of anti-RNAP3+ SSc; further studies are needed to better define the characteristics of this syndrome and the possible effects of SBI removal and immunosuppressive treatment.

Effect of a tailored home-based exercise program in patients with systemic sclerosis: A randomized controlled trial.

OBJECTIVE: The aim was to evaluate the effect of a home-based exercise program on functional capacity, health-related quality of life (HRQoL), and disability, in patients with systemic sclerosis (SSc). METHODS: A 6-month randomized controlled trial was conducted on SSc patients by comparing a home-based minimally supervised exercise program (exercise on a stationary cycle and strengthening of upper limbs; stretching of the hands) with usual care. At baseline and after 3 and 6 months, the patients underwent: 6 minutes walking test; hand mobility in scleroderma test; maximal exercise test on an ergocycle; strength measures (handgrip, quadriceps, and biceps). HRQoL (short-form 36 [SF-36]) and disability (health assessment questionnaire disability index [HAQ-DI]) were measured at the same time. RESULTS: Forty-four patients participated in the study. Twenty-two were randomly assigned to the intervention group (IG, mean age 63.60 ± 10.40 years) and 22 to the control group (CG, 61.80 ± 14.40 years). At 6 months, the distance walked in 6 minutes increased by 46 m (baseline 486, 95% CI 458-513 m; 6 months 532, 95% CI 504-561 m) in IG, whereas it decreased by 5 m (baseline 464, 95% CI 431-497 m; 6 months 459, 95% CI 427-490 m) in CG with a significantly different temporal trend at the between-groups comparison (P < .001). An improvement was also observed for strength measures (handgrip, P = .003; quadriceps, P < .001; biceps, P < .001), for the SF-36 physical component score (P < .001) and for the HAQ-DI (P = .011). CONCLUSIONS: This study indicates that in SSc patients, a minimally supervised home-based exercise program improves physical performance, quality of life, and disability in comparison with usual care.

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study.

OBJECTIVE: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. METHODS: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. RESULTS: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). CONCLUSION: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Effects of biological and targeted synthetic DMARDs on bone loss in rheumatoid arthritis.

Bone loss is a typical consequence of Rheumatoid Arthritis (RA). It occurs not only locally, affecting the inflamed joints (erosions), but also systemically, leading to osteopenia and/or overt osteoporosis, with increased risk of fragility fractures. This complication, often underestimated, can worsen the burden of disability in RA patients. Moreover, systemic and local bone loss are closely intertwined as osteoporosis per se can facilitate the development of erosions. A fundamental role in this process is played by the osteoimmunologic dysregulation typical of RA and other chronic inflammatory conditions. The poor response to the DMARDs, in terms of progression of bone erosions, might depend on the concomitant osteoporosis and on other determinants of bone loss. Thus, we need a deeper investigation in RA patients of bone health and effects of DMARDs on it and, eventually, a specific anti-osteoporotic treatment, other than DMARDs, for the prevention of both fragility fractures and bone erosions. The present review summarizes the most relevant evidence on systemic bone loss of biological and targeted synthetic DMARDs.

Osteoporosis in Rheumatic Diseases.

Osteoporosis is a chronic disease characterized by an increased risk of fragility fracture. Patients affected by rheumatic diseases are at greater risk of developing osteoporosis. The purpose of the present review is to discuss the pathogenesis, epidemiology, and treatment of osteoporosis in patients affected by rheumatic diseases with special focus for rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, vasculitides, Sjogren syndrome, and crystal-induced arthritis.

Titer-Dependent Effect of Anti-Citrullinated Protein Antibodies On Systemic Bone Mass in Rheumatoid Arthritis Patients.

Bone loss in rheumatoid arthritis (RA) is a key feature both local and systemic. Anti-citrullinated protein antibodies (ACPA) have recently been found to directly induce differentiation and activation of osteoclasts and therefore contribute to periarticular bone loss. The aim of this study was to analyze the effect of ACPA on systemic bone mineral density (BMD) in patients with established RA. This is a cross-sectional study with a single-center RA population. BMD was measured with Dual X-ray absorptiometry at lumbar and femoral sites. ACPA were measured by EIA. Multivariate analysis was performed adjusting for the main confounding variables. One hundred twenty-seven RA patients were enrolled. In univariate analysis, ACPA-positive patients showed lower BMD Z-score (SD below the age- and gender-matched mean reference value) at femoral sites (p < 0.01). A negative correlation between ACPA titer and BMD Z-score at all sites was observed (p < 0.01). The multivariate analysis adjusted for the main confounding variables confirmed the negative effect of ACPA at femoral sites (p < 0.05), but not at lumbar spine BMD. No significant effect of rheumatoid factor has been observed. ACPA have a negative titer-dependent effect on BMD at femoral sites, mainly constituted by cortical bone. ACPA-positive patients, especially if at high titer, should undergo bone investigations and be treated with bone protecting agents. Disease-modifying anti-rheumatic drugs lowering ACPA titer might have positive effects on systemic bone mass.

Vitamin D levels strongly influence bone mineral density and bone turnover markers during weight gain in female patients with anorexia nervosa.

OBJECTIVE: The aim of the study was to investigate a potential role for vitamin D status on bone mineral density (BMD) during weight gain in patients with anorexia nervosa (AN). METHOD: Spine and hip BMD assessed by dual-energy X-ray absorptiometry (DXA), serum vitamin D (25-OH-D), N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), and intact parathyroid hormone (PTH) were measured before and after a 20-week intensive weight-restoration program in ninety-one female patients with AN and secondary amenorrhoea. RESULTS: Ninety-one consecutive female patients (age 13-45 years; weight 39.4 ± 5.6 kg, body mass index [BMI] 15.1 ± 1.6 kg m-2 ) were included in the study. Although weight and BMI significantly increased in all patients during treatment, mean BMD only significantly increased at the spine (1.0% ± 3.6%, p = .009). The increase in spine BMD was significantly higher only above post-treatment 25-OH-D levels of 30 ng mL-1 (2.5% vs. 0.5%, respectively, for 25-OH-D ≥ and < 30 ng mL-1 , p = .026). There was a significant decrease in bone resorption (CTX; p = .043) and increased bone formation (P1NP; p < .001) after weight restoration. Nevertheless, a significant increase in PTH was also found, which was inversely correlated with decreased post-treatment 25-OH-D levels (R2 = .153, p < .001). DISCUSSION: Hypovitaminosis D may counteract the efficacy of refeeding in AN through increased bone resorption mediated by secondary hyperparathyroidism, which strongly supports the use of vitamin D supplements for bone health in AN.

Bone Metabolism in a Large Cohort of Patients with Systemic Sclerosis.

The aim of this study was to evaluate in a large size cohort of SSc patients bone mineral density (BMD) and to analyze its possible determinants. 106 consecutive outpatients affected by SSc were enrolled and completely evaluated for bone metabolism and SSc characteristics. For the statistical analysis, we preferred Z score to BMD or T score since the population was composed of patients of different ages and of both sexes. Mean neck Z score was significantly lower than 0. No significant differences were found for other sites. Female patients were shown to have a total femur and neck Z score significantly lower than 0 (p = 0.028 and p < 0.001, respectively). 13 % of patients had at least one morphometric non-clinical vertebral fracture. In univariate analysis, total femur Z score was lower in female (p = 0.050) and positively correlates with BMI (p = 0.001), neck Z score positively correlates with age (p = 0.016), and whole body Z score positively correlates with BMI (p < 0.001). No correlations were found for lumbar Z score. The multivariate analysis confirmed the positive correlation between BMI and total femur and whole body Z score and between age and neck femur Z score (p = 0.005, p < 0.001 and p = 0.040, respectively). Lung involvement was shown to correlate with a lower whole body Z score in multivariate analysis (p = 0.037). We found a modest risk of low BMD in patients with SSc and the important protective role of BMI. Patients with lung involvement showed lower whole body Z score.

What lies beyond Asthma Control Test: Suggestions for clinical practice.

BACKGROUND: Asthma Control Test (ACT ™) validity relies on Global Initiative for Asthma (GINA) definition of control. It includes neither reversibility nor inflammation assessment despite their importance as hallmark of asthma, partially unrelated to symptoms. Furthermore though rhinitis may affect the patient's perception of asthma control, its impact on ACT accuracy has not been systematically evaluated. OBJECTIVE: To explore ACT validity according to a definition of control including: forced expiratory volume in 1 s (FEV1) ≥ 80%, negative reversibility test, exhaled nitric oxide at a flow rate of 50 ml/s (FeNO) < 50 ppb. RESULTS: 177 asthmatics referring to our Unit have been studied. ACT with cut-off score ≥20 showed a good positive predictive value (83.5%) but low sensitivity (47.8%), specificity (66.7%), and negative predictive value (26.5%). ROC curves analysis indicates that ACT in patients with mild intermittent rhinitis is more reliable (AUC: 0.714; p < 0.05) than in patients with nasal polyposis/chronic rhino-sinusitis (AUC: 0.176; p > 0.05). Considering asthma classification, the probability that ACT detects patients with uncontrolled asthma is significantly higher in moderate persistent asthma subgroup than in mild persistent asthma one (OR 5.464; IC 95%: 2.5-11,9; p < 0.05). CONCLUSIONS: As ACT mainly relies on patient's reported outcomes, it may not completely reflect the airways inflammation and airways obstruction. The presence and severity of rhinitis may affect ACT outcome. The awareness of the variables that could influence ACT evaluation is much more important in the primary care setting where ACT may often represent the only tool for asthma assessment.

Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels.

BACKGROUND: Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. OBJECTIVE: We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. METHODS: Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. RESULTS: In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004). CONCLUSIONS: The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

Prevalence and incidence of rheumatoid arthritis in Italy.

Aim of the study was to estimate the prevalence and incidence of rheumatoid arthritis (RA) from an administrative cohort consisting of 2,268,514 males and 2,446,769 females, aged ≥ 18 years, from 32 Italian Health Districts. The diagnosis of RA was certified by a qualified specialist and confirmed by ≥3 prescriptions of "specific drugs" (corticosteroids, DMARDs or "biological" agents) during 2011. Patients on "specific drugs" qualified as "active RA"; those who never had more than 4 prescriptions in the past were classified as "unlikely RA," and those previously on chronic treatment but who discontinued therapy for >1 year were classified as "remission RA." The patients with a diagnosis of RA were 22,801 (0.48 %) with a prevalence of "active RA," "remission RA" and "confirmed RA" (Active + Remission RA) of 0.32, 0.09 and 0.41 % (95 % CI 0.38-0.44), respectively. The classification criteria tested in a fifth of the study population by direct analysis yielded >90 % accuracy and precision. The yearly incidence of "active RA" per 100,000 subjects was 48 (95 % CI 40-57) and 20 (95 % CI 10-30) for women and men, respectively. The peak for both prevalence and incidence was around the eighth decade of life. The female/male ratios for both prevalence and incidence were ca. 2.6 before the fifth decade of life, but approached unity in the ninth decade of life. The overall prevalence and incidence of RA in a large sample of the Italian population is only marginally lower than that reported from a similar administrative database of Sweden. With advancing age, the female/male ratio declines to about one.

The co-occurrence of Hashimoto thyroiditis in primary Sjogren's syndrome defines a subset of patients with milder clinical phenotype.

To evaluate in a cohort of 100 consecutive patients affected by primary Sjogren's syndrome (pSS) the incidence of Hashimoto thyroiditis (HT) and to compare the clinical features and the laboratory parameters of patients affected by pSS with and without concomitant HT. In 100 consecutive patients affected by pSS, the occurrence of other autoimmune diseases was recorded and a full examination of thyroid function obtained. HT was associated with pSS in 27 cases. The comparison between pSS cases with and without HT showed that only patients with isolated pSS had low C4 level [p = 0.032, OR (IC 95 %) 230 (13.13-4,046)]. In addition, only patients affected by pSS without HT had evidence of cryoglobulins, cutaneous vasculitis with palpable purpura, peripheral neuropathy, and development of lymphoma, although all these manifestations were observed in a 4.1-8.2 % of the cases, without reaching statistical significance. The association of HT in patients suffering from pSS defines a subset of patients with milder disease and normal C4 levels.

The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.

OBJECTIVE: Dermatologists usually see patients with psoriasis before arthritis develops, making them well placed to diagnose early PsA (ePsA). This study aimed to develop a rapid and robust screening questionnaire for predicting PsA in patients with psoriasis referred to a specialized joint dermatology-rheumatology combined clinic. METHODS: In all, 228 psoriasis patients naïve to DMARD treatment were administered two screening questionnaire: the new Early ARthritis for Psoriatic patients (EARP) questionnaire and the existing Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. The diagnostic accuracy of the two questionnaires for the diagnosis of ePsA was compared by receiving operating characteristics curves. RESULTS: After psychometric analysis, a simplified questionnaire of 10 items was found to have good internal reliability (Cronbach's α = 0.83) and was much faster and simpler to administer than the PASE. Both the EARP and PASE questionnaires presented similar receiving operating characteristics curves (specificity 91.6 and 67.2 and sensitivity 85.2 and 90.7, respectively) in identifying ePsA patients by using the cut-off value of 3 for EARP-10 and the standard cut-off value of 44 for PASE. The CASPAR criteria for PsA were present in 61 (26.7%) of the patients at clinical presentation and in 32.9% at 1-year follow-up, and the EARP score of ≥3 correlated with clinically determined arthropathy by a rheumatologist. CONCLUSION: The EARP questionnaire is simple and fast to administer and proved robust for the identification of PsA in the dermatological setting. Dermatologists should consider the EARP for patients attending clinics, as it correlates well with early PsA diagnosis.

Sex-specific risk of anti-topoisomerase antibodies on mortality and disease severity in systemic sclerosis: 10-year analysis of the Leiden CCISS and EUSTAR cohorts.

BACKGROUND: We aimed to evaluate sex-specific risk of anti-topoisomerase I antibodies (ATA) on mortality, diffuse cutaneous systemic sclerosis, interstitial lung disease, and pulmonary hypertension in two cohorts of people with systemic sclerosis. METHODS: This study was a 10-year analysis of the prospective Leiden Combined Care in Systemic Sclerosis (CCISS) cohort in the Netherlands and the international European Scleroderma Trials and Research (EUSTAR) cohort. We included participants with systemic sclerosis according to the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification criteria; available autoantibody status; available skin subtyping; at least one available radiographic assessment of interstitial lung disease; and with a known date of disease onset. People with systemic sclerosis were categorised in six risk groups by sex and autoantibody status (anti-centromere antibody [ACA]-positive female, ACA-positive male, ACA and ATA-negative female, ACA and ATA-negative male, ATA-positive female, and ATA-positive male). We constructed Kaplan-Meier curves and Cox proportional hazard models, accounting for left-truncated survival to prevent bias because the date of disease onset (first non-Raynaud's symptom) preceded the date of cohort entry for all patients. The primary outcome was all-cause mortality and the secondary outcomes were diffuse cutaneous systemic sclerosis, interstitial lung disease, and pulmonary hypertension. FINDINGS: 445 (63%) of 708 participants between April 1, 2009, and Jan 1, 2022, in CCISS (101 [23%] male and 344 [77%] female) and 4263 (50%) of 8590 between June 1, 2004, and March 28, 2018, in EUSTAR (783 [18%] male and 3480 [82%] female) were eligible for this study. In both cohorts, ATA expression occurred significantly more often in males than in females (39 [39%] of 101 males vs 67 [19%] of 344 females in CCISS; p<0·0001 and 381 [49%] of 783 males vs 1323 [38%] of 3480 females in EUSTAR; p<0·0001). According to estimated survival rates, 30% of ATA-positive males versus 12% of ATA-positive females died in the CCISS cohort and 33% versus 15% died in the EUSTAR cohort within 10 years. After adjustment for age, race, and autoantibody status, male sex remained the most important risk factor for all-cause mortality (HR 2·9 [95% CI 1·5-5·5] in CCISS, p=0·0018; and HR 2·6 [2·0-3·4] in EUSTAR, p<0·0001). INTERPRETATION: We show that the association between male sex and increased mortality in systemic sclerosis cannot be explained by higher ATA prevalence. However, additional research on the effect of sex-specific characteristics on people with systemic sclerosis is required. FUNDING: None.

Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis.

INTRODUCTION: Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability. METHODS: This is a cross-sectional study enrolling 490 outpatients with RA (80% female, mean age 59.5). The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of depression with a cut-off of 11. We collected data about disease activity and disability with DAS28, TJC-68, PhGA, PGA, VAS, DAS28, SDAI, CDAI and HAQ. RESULTS: Prevalence of depression was 14.3% (95% CI: 11-17%). Depressed patients, when compared with not depressed ones, were found to have higher scores for TJC-68 (p = 0.011), PhGA (p = 0.001), PGA (p = 0.001), VAS (p = 0.001), DAS28 (p = 0.007), SDAI (p = 0.001), CDAI (p = 0.001) and HAQ (p = 0.001). Out of the 70 depressed patients, 30 subjects, already known to be depressed in the past, were still depressed at the time of the assessment, with only 11 (15.7%) under antidepressants. A multivariate analysis showed that male sex, higher PGA score, use of antidepressants and higher HAQ score were significantly associated with an increased risk of depression. CONCLUSIONS: Our study shows that depression is common in RA and may affect its activity mainly via an alteration in the perception of the disease. Although its important implications, depression is still under-diagnosed and its management is inadequate.

Pharmacokinetics of Oral Cholecalciferol in Healthy Subjects with Vitamin D Deficiency: A Randomized Open-Label Study.

BACKGROUND: the aim of this study was to investigate the pharmacokinetic (PK) and safety profile of high-dose vitamin D supplementation, comparing different schedules (daily, weekly, or bi-weekly) in an otherwise healthy vitamin D-deficient population. Methods: single-center, open-label study on healthy subjects deficient in vitamin D (25 (OH)D < 20 ng/mL), randomized to receive cholecalciferol (DIBASE®, Abiogen Pharma, Italy) using three different schedules: Group A: 10,000 IU/day for eight weeks followed by 1000 IU/day for four weeks; Group B: 50,000 IU/week for 12 weeks, Group C: 100,000 IU/every other week for 12 weeks. Total cumulative doses were: 588,000 IU, 600,000 IU, 600,000 IU. The treatment regimens corresponded to the highest doses allowed for cholecalciferol for the correction of vitamin D deficiency in adults in Italy. RESULTS: mean 25 (OH)D plasma levels significantly increased from baseline 13.5 ± 3.7 ng/mL to peak values of 81.0 ± 15.0 ng/mL in Group A, 63.6 ± 7.9 ng/mL in Group B and 59.4 ± 12 ng/mL in Group C. On day 28, all subjects showed 25 (OH)D levels ≥ 20 ng/mL and 93.1% had 25 (OH)D levels ≥ 30 ng/mL. On day 56 and 84, all subjects had 25 (OH)D levels ≥ 30 ng/mL. No serious adverse events occurred during the study. CONCLUSIONS: normalization of 25 (OH)D serum levels was quickly attained with all the studied regimens. A more refracted schedule provided a higher systemic 25 (OH)D exposure.

Ultrasonography involvement of carotid, upper and lower limb arteries in a large cohort of systemic sclerosis patients.

OBJECTIVES: Data on macrovascular involvement in systemic sclerosis (SSc) are still debatable. The aim of this study was to estimate its prevalence and possible determinants in a large cohort. METHODS: One hundred and fifty-five outpatients with SSc were enrolled. Data about disease characteristics and cardiovascular risk factors were collected and patients underwent ecocolor Doppler ultrasonography of arteries of the neck and lower (LL) and upper (UL) limbs. RESULTS: Mean age was 57.9 ± 14.5 years and most were female (88.4%) with a limited subset (63.2%). Mean disease duration was 11.4 ± 8.1 years. Twenty-three (14.8%) had hypertension, 7 (4.8%) diabetes, 64 (41.3%) hypercholesterolemia and 63 (40.6%) were active/past smokers. Seventy-nine (49%) patients had plaques at carotids, 49 (32.9%) at LL and 7 (4.9%) at UL. In multivariate analysis, patients with carotid plaques had more often a limited pattern (P = .001), patients with distal LL plaques pulmonary arterial hypertension (P = .006) and patients with proximal LL plaques lower diffusing capacity for carbon monoxide adjusted to hemoglobin and its ratio to alveolar volume (P = .004). In patients with UL plaques traditional cardiovascular risk factors were not more common, while forced vital capacity was lower (P = .023). Finally, upper limb and proximal LL plaques were as common in early disease patients as in longstanding ones, although the former were younger. CONCLUSIONS: This study shows that macrovascular involvement is quite common in SSc and that some disease characteristics linked to microvascular involvement are associated with atherosclerotic plaques, which can be present even in early disease. Our study suggests that a complete evaluation of macrocirculation is mandatory for rheumatologists treating SSc patients.

Vitamin D serum levels and the risk of digital ulcers in systemic sclerosis: A longitudinal study.

AIM: Low levels of vitamin D (25OHD) have been found to associated with digital ulcers (DUs) in systemic sclerosis (SSc), although only cross-sectional studies have been performed. We aimed to investigate if variations in vitamin D serum levels over time affect DU in SSc. METHODS: This is a retrospective study on 65 patients. 25OHD was measured in 2011 and 2016 and its variations correlated with DU. RESULTS: The mean age of our cohort was 58 (SD 12) years with a mean disease duration of 9.5 (5.3) years. Most of our patients had a limited SSc (69.2%). At baseline 50.8% and 41.5% after 5 years had 25OHD <30 ng/mL. Patients receiving supplementation (8750 IU/wk) at baseline numbered 39 (60.0%) and 45 (69.2%) at the end of follow up. Nevertheless, 31 (47.7%) had a decrease of 25OHD in 5 years. In univariate analysis, patients with incident DU had a decrease in 25OHD as compared to patients with no incident DU (-17.4 [37.0] vs 13.0 [89.5], P = 0.018). No differences in 25OHD variations were found for other disease characteristics. In multivariate analysis correcting for previous DU and modified Rodnan Skin Score at baseline, patients with a decrease in 25OHD had an increased risk of developing DU (odds ratio 16.6; 95% CI 1.7-164.5, P = 0.017). CONCLUSIONS: A decrease in 25OHD is associated with the risk of developing DUs. In addition, vitamin D supplementation with the doses currently recommended may be insufficient in SSc. Further studies in wider cohorts are needed to confirm these results.

Relationship Between Increased Fecal Calprotectin Levels and Interstitial Lung Disease in Systemic Sclerosis.

OBJECTIVE: To evaluate the relationship between fecal calprotectin (FC) and interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: The study enrolled 129 outpatients with SSc. Data about disease characteristics, in particular lung involvement, were collected and FC was measured. RESULTS: Patients with ILD (35, 27.1%) had higher values of FC (p < 0.001). In multivariate analysis, these variables were associated with increased risk of ILD: diffuse disease subset, higher modified Rodnan skin score, longer disease duration, higher severity scores, steroid treatment, and higher FC levels, while diverticulosis was protective. CONCLUSION: ILD is independently associated with increased FC levels in SSc.