The burden of air pollution and temperature on Raynaud's phenomenon secondary to systemic sclerosis.

OBJECTIVES: to evaluate the effect of air pollution (ozone - O3 and particulate matter <=10 µm and <=2.5 µm - PM10 and PM2.5) on the severity of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). DESIGN: cross-sectional, observational, and single centre study. SETTING AND PARTICIPANTS: all consecutive SSc patients residing in Lombardy (Northern Italy) were enrolled. PM10, PM2.5, and O3 concentrations were calculated for each patient at municipality resolution in the week before the evaluation. Similar considerations were made for meteorological variables (temperature and humidity). MAIN OUTCOME MEASURES: patients were asked to assess RP severity during the week before the evaluation according to a visual analogue scale (VAS). Ordinal logistic regression models were fitted to evaluate the short-term effect of temperature and air pollution with respect to RP. A univariate linear regression model was created to consider the association between temperature and pollutants. RESULTS: in this study, 87 SSc patients were enrolled. Temperature was confirmed to strongly influence RP severity. PM10 and PM.5 were found to significantly worsen RP severity for the first four days before the evaluation, including the day of the visit, and as mean up to six days before the evaluation. O3 seemed to exert a protective effect on RP severity that was significant for the first four days before the evaluation, including the day of the visit, and as mean up to seven days before the evaluation. CONCLUSIONS: since the overwhelming effect of temperature on RP, final conclusions about the exact contribution of pollutants on RP severity cannot be drawn because of the strong inter-correlation between air pollution and temperature.

Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy.

OBJECTIVE: We aimed to study in SSc patients macrovascular involvement by using power Doppler ultrasound (PDUS) and microvascular one by PDUS and nailfold video-capillaroscopy (NVC) and to examine the association between history of digital ulcers (HDU) and imaging (PDUS and NVC) parameters. METHODS: NVC and PDUS were systematically performed in 106 consecutive SSc patients at the 3rd and 4th finger of the dominant hand after exclusion of ulnar artery occlusion (UAO). 22 MHz PDUS measurements included nailbed and fingertip qualitatively graded, and resistivity index (RI) of ulnar and radial proper digital arteries. Capillary number/mm was calculated by NVC on the same digits examined by PDUS. RESULTS: Vascularization at fingertip and nailbed showed a good correlation between them and to capillary number. RI, representative of macrovascular involvement, did not correlate to microvascular involvement as assessed by PDUS and NVC. RI and capillary number at NVC showed significant correlation to HDU while fingertip and nailbed vascularization as assessed by PDUS did not. As such, PDUS and NVC provide different and potentially complementary information on SSc-related peripheral macro- and micro-vascular involvement. CONCLUSION: Macro- and micro-vascular involvement in SSc patients are different processes and are not present at the same time in every patient. Thus, both these aspects should be carefully evaluated in SSc patients.

Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA).

OBJECTIVES: To define the correlation between joint ultrasonography and clinical examination in patients with juvenile idiopathic arthritis (JIA) and to assess whether synovitis detected by ultrasonography in clinically inactive patients predicts arthritis flares. METHODS: 88 consecutive patients with JIA-46 (52%) with persistent oligoarthritis, 15 (17%) with extended oligoarthritis, 15 (17%) with rheumatoid factor-negative polyarthritis and 12 (14%) with other forms of JIA, all clinically inactive for a minimum of 3 months-underwent ultrasound (US) assessment of 44 joints. Joints were scanned at study entry for synovial hyperplasia, joint effusion and power Doppler (PD) signal. Patients were followed clinically for 4 years. RESULTS: US was abnormal in 20/88 (22.7%) patients and in 38/3872 (0.98%) joints. Extended oligoarthritis and rheumatoid factor-negative polyarthritis were more frequent in US-positive than in US-negative patients (35.0% vs 11.8% and 30.0% vs 13.2%, respectively; P=0.005). During 4 years of follow-up, 41/88 (46.6%) patients displayed a flare; 26/68 (38.2%) were US-negative and 15/20 (75%) were US-positive at baseline. Abnormality on US examination, after correction for therapy modification, significantly increased the risk of flare (OR=3.8, 95% CI 1.2 to 11.5). The combination of grey scale and PD abnormalities displayed a much higher predictive value of relapse (65%, 13/20) than grey scale alone (33%, 6/18). CONCLUSIONS: US abnormalities are a strong predictor of relapse at individual patient level. Irrespective of treatment, the risk of flare in US-positive versus US-negative patients was almost four times higher. In case of US abnormalities, patients should be carefully followed regardless of both the International League of Associations for Rheumatology and Wallace categories.

Acute and chronic effects of two different intravenous iloprost regimens in systemic sclerosis: a pragmatic non-randomized trial.

OBJECTIVES: I.v. iloprost (ILO) may be used in the treatment of refractory RP and digital ulcers. We aim to evaluate the acute and chronic effects of two different ILO regimens by power Doppler US (PDUS) and nailfold videocapillaroscopy. METHODS: In this 3-month single-centre pragmatic non-randomized trial, 96 SSc patients were included and stratified according to ILO treatment as: no ILO (group A), ILO once monthly (group B) and ILO for five consecutive days (group C). Resistivity index (RI), finger pulp blood flow and periungual vascularization by PDUS, and sum of capillaries apex width in 1 mm by nailfold videocapillaroscopy were evaluated. Results were adjusted for the average outdoor temperature at the place of residence. RESULTS: An acute ILO effect was observed for only finger pulp blood flow in groups B and C (P < 0.001 and P < 0.005, respectively). An acute effect was observed for RI and periungual vascularization only in group B. A progressive increase was observed for other parameters without statistical difference. ILO effects were not observed any longer before the following infusion. Some parameters (finger pulp blood flow in group B and RI in group C) showed a statistically higher increase the lower the outdoor temperature was. CONCLUSION: ILO had an acute effect as assessed by PDUS, especially in group B. By contrast, an ILO chronic effect was not detectable before the following infusion in both treatment groups. More studies are needed to define how often ILO should be administered.

Reliability and validity of the Italian version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument in patients with systemic sclerosis.

OBJECTIVES: To test the acceptability, feasibility, reliability and validity of the Italian translated version of the UCLA Scleroderma Clinical Trial Consortium GIT (UCLA-SCTC GIT) 2.0. Gastrointestinal tract (GIT) involvement is frequent in systemic sclerosis (SSc). The UCLA-SCTC GIT 2.0 is a validated instrument for measuring the presence and impact of GIT symptoms in SSc patients. METHODS: Acceptability and feasibility of the questionnaire were evaluated based on the input from the patients. Internal consistency was evaluated by Cronbach's alpha. External consistency was measured by comparing with the Short Form (SF)-36 and EQ-5D by Spearman's rho, meaningful if ≥0.30. RESULTS: Sixty-two consecutive SSc patients (mean age 60.6) were recruited, 88.5% were female. The UCLA-SCTC GIT 2.0 was well accepted. Percentage of missing data in UCLA-SCTC GIT total score was 2 %. Internal consistency was acceptable (alpha≥0.70) for all domains. Cronbach's alpha was ≥0.70 for all domains. UCLA-SCTC GIT 2.0 discriminated between patients with or without gastroesophageal reflux disease whether diagnosed clinically or by objective testing (p<0.01 for both). UCLA-SCTC GIT emotional well-being was correlated with the conceptually equivalent SF-36 mental health domains (correlation coefficient>0.35) and with the EQ-5D usual activities domain (0.38), thus reflecting the impact on everyday activities. The distention/bloating domain strongly correlated with the EQ-5D anxiety/depression domain (0.51) and reflux domain with role emotional of SF-36 (0.44). CONCLUSIONS: This is the first validation study of the Italian version of UCLA-SCTC GIT 2.0. Our data support its feasibility, reliability, and validity in Italian SSc patients.

Duodenojejunal inflammation causing chronic vomiting in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease with a broad spectrum of clinical manifestations including fever, skin rash, arthralgia and neutrophilic leucocytosis. Small bowel inflammation in AOSD has been reported in association with Crohn's disease, coeliac disease and chronic intestinal pseudo-obstruction. We have here reported the first-time case of AOSD with small bowel involvement, presenting with chronic vomiting. Fluorodeoxyglucose total-body positron emission tomography/CT showed high uptake of the duodenum and first jejunal loop. Faecal calprotectin increased. Duodenal histology revealed neutrophilic infiltrate among duodenal enterocytes and severe chronic lymphoplasmacellular infiltrate of the lamina propria. Vomiting disappeared when duodenojejunal inflammation was controlled by immunomodulatory treatments for AOSD, suggesting a possible causal relation between duodenojejunal inflammation and the symptom.

Hyaluronic Acid Therapy in Hip OA Does Not Perform Equally in Osteoarthritis Secondary to Juvenile Idiopathic Arthritis When Compared to Primary Osteoarthritis: A 2-Year Preliminary Evaluation.

OBJECTIVE: Hip involvement in juvenile idiopathic arthritis (JIA) is one of most important causes of pain and disability. Total hip arthroplasty (THA) is considered the standard when medical approaches fail to relieve pain. However, THA is problematic for many reasons. As current literature lacks studies valuating medical management of osteoarthritis (OA) secondary to JIA, we assessed the long-term pain relief effect of US-guided intra-articular viscosupplementation in hip osteoarthritis secondary to JIA versus primary OA under different etiological conditions. METHODS: Patients in both groups received intra-articular Hylan G-F 20 2 ml once a month for 3 consecutive months and every 6 months for 2 years as maintenance. Effectiveness (VAS and WOMAC), NSAID/analgesic consumption, tolerability, withdrawals and reason for discontinuation were collected at each time point. An inverse probability weighting was used to balance the two groups. RESULTS: We retrospectively retrieved data of 14 JIA patients and 26 primary OA. Weighting successfully accounted for differences between the disease groups supporting the results. Viscosupplementation led to an early and significant improvement of pain and function and concomitant decrease in NSAIDs consumption, while the response diverged over 1 year with loss of benefits in JIA. The worst outcome was observed in active JIA. CONCLUSIONS: Duration of symptom relief after intra-articular injection of hyaluronic acid depends on the nature of arthritis. Multiple courses of viscosupplementation are required to maintain low-dose NSAIDs consumption in patients responsive to treatment while shortening the time between consecutive injections might provide persistent positive results in patients suffering from JIA.

A case report of monoarthritis in a COVID-19 patient and literature review: Simple actions for complex times.

RATIONALE: COVID-19 presentation is multifaceted and up to 44% of patients affected by COVID-19 experience musculoskeletal complaints, mostly in the form of diffuse aspecific arthromyalgias. Nevertheless, only a few cases of arthritis following SARS-CoV2 infection are reported. PATIENT CONCERNS: A 27-year-old man affected by nail psoriasis presented with monoarthritis 2 weeks after being diagnosed with COVID-19. DIAGNOSES: Diagnostic work-up and differential diagnosis were made difficult by patient isolation, absence of lab tests, and his visit via telemedicine, even though signs of first metacarpophalangeal joint involvement were clear. INTERVENTIONS: Due to the inefficacy of acetaminophen and nonsteroidal anti-inflammatory drugs, the patient was prescribed oral steroids with a rapid benefit. OUTCOMES: The patient's response to oral steroid was prompt and maintained even after therapy tapering. Even so, a formal diagnosis was not possible due to a difficult diagnostic work-up and lack of a long-term follow-up. LESSONS: Like many other viral diseases, SARS-CoV2 can play as a causative agent or as a trigger for inflammatory arthritis development in predisposed individuals.

Potential Short-Term Air Pollution Effects on Rheumatoid Arthritis Activity in Metropolitan Areas in the North of Italy: A Cross-Sectional Study.

Rheumatoid arthritis (RA) flare is related to increased joint damage, disability, and healthcare use. The impact of short-term air pollution exposure on RA disease activity is still a matter of debate. In this cross-sectional study, we investigated whether short-term exposure to particulate matter (PM)10, PM2.5, nitrogen dioxide (NO2), and ozone (O3) affected RA disease activity (DAS28 and SDAI) in 422 consecutive RA residents in Lombardy, North of Italy. Air pollutant concentrations, estimated by Regional Environmental Protection Agency (Lombardy-Italy) at the municipality level, were used to assign short-term exposure from the day of enrolment, back to seven days. Some significant negative associations emerged between RA disease activity, PM10, and NO2, whereas some positive associations were observed for O3. Patients were also stratified according to their ongoing Disease-Modifying anti-Rheumatic Drugs (DMARDs) treatment: no DMARDs (n = 25), conventional synthetic DMARDs (n = 108), and biological or targeted synthetic DMARDs (n = 289). Therapy interaction seemed partially able to influence the relationship between short-term air pollution exposure and RA disease activity (PM2.5 levels and DAS28 at the day of the visit-O3 levels and disease activity scores for the seven days before the evaluation). According to our results, the impact of short-term air pollution exposure (seven days) minimally impacts disease activity. Moreover, our study suggests therapy could alter the response to environmental factors. Further evidence is needed to elucidate determinants of RA flare and its management.

Adherence to Mediterranean diet and patient perception of rheumatoid arthritis.

OBJECTIVE: To evaluate the association between the adherence to Mediterranean diet (MD) and disease impact, activity, and comorbidities in patients with rheumatoid arthritis (RA). DESIGN: Consecutive patients with RA were enrolled in this cross-sectional study. For each patient, Disease Activity Score on 28 joints (DAS28), Simple Disease Activity Index (SDAI), RA Impact of Disease (RAID), Health Assessment Questionnaire (HAQ), patient global assessment (PGA) and general health (GH) and a self-reported questionnaire called MD score were recorded. RESULTS: 205 RA patients (median age 53 years, female 80.49 %) were enrolled. An association between MD score and HAQ (p-value = 0.033), PGA and GH (p-value 0.023 both) was observed. RAID total score had a statistically significant negative relationship with MD score (p-value = 0.016). A statistically significant negative association was found for pain (p-value = 0.025), functional disability (p-value<0.001), sleep (p-value = 0.041), physical well-being (p-value = 0.027) and coping (p-value = 0.008). Multiple regression analysis to evaluate the relationship between significant RAID items and MD score did not show any statistical significance as all items are strongly related to each other. A negative trend, although not statistically significant was found for DAS28 and SDAI. The only comorbidity associated with MD score was arterial hypertension (OR = 0.94). CONCLUSIONS: In this Italian RA cohort, the adherence to MD was significantly associated with a better RAID, PGA and GH, but higher MD score was not significantly associated with lower disease activity. Our study suggests an overall potential beneficial effect of MD in RA patients.

Hyaluronic Acid Injections in the Treatment of Osteoarthritis Secondary to Primary Inflammatory Rheumatic Diseases: A Systematic Review and Qualitative Synthesis.

The purpose of this study is to review the current literature on the use of hyaluronic acid (HA) specifically applied to the treatment of osteoarthritis (OA) secondary to primary inflammatory rheumatic diseases. Osteoarthritis should be carefully considered because it has potentially devastating effects on health-related quality of life. Locally injected HA seems to be an effective treatment for OA but it is not clear how to place this treatment in the context of inflammatory rheumatic disorders. To retrieve relevant articles, we conducted the search through MEDLINE, EMBASE and Cochrane Databases performing the PICO strategy. We finally selected four randomized clinical trials and six observational studies and grouped them in accordance with its main objective within three focuses: the clinical effect of HA therapy in joints without any signs of inflammation, the clinical effects of HA therapy in joints with active synovitis, and the involvement and changes of synovial fluid in the treatment of secondary OA. Our qualitative analysis clearly showed that the current literature is marked by high levels of heterogeneity and therefore difficult to interpret. Therefore, our hypothesis that viscosupplementation should be considered as a treatment for chronic moderate symptomatic OA secondary to inflammatory rheumatic diseases, and not for flares with joint swelling, cannot be definitely supported. Well-designed studies are necessary to definitively clarify the range of application of intra-articular HA injections in the treatment of inflammatory rheumatic disorders.

Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis.

BACKGROUND: Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis. METHODS: The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated. RESULTS: The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04-1.44] to 3.20 [1.97-5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18-1.21] to 0.47 [0.46-0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed. CONCLUSIONS: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection. TRIAL REGISTRATION: Retrospectively registered. Not applicable.

Personalized medicine in rheumatoid arthritis: How immunogenicity impacts use of TNF inhibitors.

Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay - RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

Ultrasonographic detection, definition and quantification of soft tissue oedema in psoriatic dactylitis.

AIM: To define and score finger soft tissue oedema in psoriatic dactylitis by ultrasound. MATERIAL AND METHODS: A systematic literature review (SLR) on ultrasound-detected finger soft tissue oedema was performed. Subsequently, based on the SLR, a Delphi survey was developed and circulated among a group of 13 expert sonographers, in order to obtain agreement on detection, definition and scoring of finger oedema by B-mode and power Doppler ultrasound. Agreement was considered achieved when each statement was approved by >75% of participants. RESULTS: At the first Delphi round, 91 % agreement was obtained for the scanning technique to adopt, including the most appropriate area to evaluate. At the second round, 76% agreement was achieved on the definition of soft tissue finger oedema. At the third round, 76% agreement was obtained for B-mode and power Doppler scores. The volar aspect of the finger and comparisons with the contralateral side were agreed to be the most appropriate in terms of scanning technique. Agreed ultrasound definition of finger soft tissue oedema was "abnormal hypoechoic/anechoic areas, diffused or localized within the subcutaneous tissue between the epidermidis and the tendon-related anatomic structures (i.e. flexor tendon sheath, peritenonium, tendon pulleys), with local thickening, with or without local abnormal Doppler signal, visualised in two perpendicular planes and not evident on the contralateral side". Semiquantitative (0-3) scores for both B-mode and power Doppler were agreed to be the most appropriate to be used. CONCLUSION: Our work produced, for the first time, technical indications, definition and scoring for the ultrasound assessment of soft tissue oedema in psoriatic dactylitis.

Effectiveness and Tolerability of Repeated Courses of Viscosupplementation in Symptomatic Hip Osteoarthritis: A Retrospective Observational Cohort Study of High Molecular Weight vs. Medium Molecular Weight Hyaluronic Acid vs. No Viscosupplementation.

Background: Nonsurgical management of symptomatic hip osteoarthritis needs real-world evidence. We evaluated the effectiveness and tolerability of US-guided intra-articular treatment of two hyaluronic acids (HAs) commercially available in Italy and investigated predictors of response. Methods: Outpatient records including three cohorts: 122 subjects treated with medium (1,500-3,200 kDa; Hyalubrix®) molecular weight (MW) or high (hylan G-F20; Synvisc®) MW HAs and 20 controls taking NSAIDs/analgesics on demand were retrospectively analyzed. Pain VAS score, WOMAC, NSAID/analgesic consumption, and causes of suspension were available at 1, 6, 12, and 24 months after first administration. As selection bias usually affects observational retrospective studies, a quasi-randomization process was attained by performing propensity score approach. Results: Propensity score adjustment successfully allowed comparisons among balanced groups of treatments. VAS and WOMAC considerably decreased over time in treated groups independently of the radiological grade (p<0.001). On the other hand, the control group showed only a slight and rather uneven variation in VAS. Mean score changes were comparable in both HA cohorts from the earliest stages (ΔVAS(HA1,500-3,200kDa)T1vsT0 = -20%; ΔVAS(hylan G-F20)T1vsT0 = -23%/ΔWOMAC(HA1,500-3,200kDa)T1vsT0 = -17%; ΔWOMAC(hylan G-F20)T1vsT0 = -19%), reaching a further substantial reduction after 12 months (ΔVAS(HA1,500-3,200kDa)T12vsT0 = -52%; ΔVAS(hylan G-F20)T12vsT0 = -53%/ΔWOMAC(HA1,500-3,200kDa)T12vsT0 = -45%; and ΔWOMAC(hylan G-F20)T12vsT0 = -47%). Almost 11% (=13/122) of ineffectiveness and few moderate local side effects 3% (=4/122) were detected. Conclusions: Viscosupplementation in a real-life setting seems to provide a sound alternative in pain management in comparison to oral NSAIDs/analgesics, guaranteeing a reduced intake of pain killer medications. Analgesic effectiveness, functional recovery, and reduced joint stiffness extend and improve over 12 and 24 months, suggesting that repeated administrations achieve an additive effect.

Use of antibodies recognizing cyclic citrullinated peptide in the differential diagnosis of joint involvement in systemic sclerosis.

OBJECTIVE: To determine the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, and clinical manifestations. MATERIALS AND METHODS: Anti-CCP antibodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24-85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radiographs of the hands and wrists were examined in each patient. RESULTS: The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p<0.0001) and marginal erosions (p=0.001). CONCLUSION: Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment.

Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis.

BACKGROUND: The aim was to investigate CD4+T-cell subsets, immune cells and their cytokine profiles in blood and synovial compartments in rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) to define specific immune signatures. METHODS: Peripheral blood, synovial fluid (SF) and synovial membranes (SM) of RA and OA patients were analyzed. CD4+T-cell subset frequencies were determined by flow cytometry, and cytokine concentrations in serum and SF were measured by ELISA. RESULTS: In peripheral blood, OA patients had altered frequencies of regulatory T-cell subsets, and higher frequencies of Th17 and of Th1/17 cells than RA patients. In the synovial compartment of OA patients, conventional Th17 cells were largely excluded, while Th1/17 cells were enriched and more frequent than in RA patients. Conversely, in the synovial compartment of RA patients, regulatory T cells and Tfh cells were enriched and more frequent then in OA patients. IL-17 and Blys were increased both in serum and SF of RA patients, and correlated with autoantibodies and disease activity. Notably, Blys levels were already significantly elevated in RA patients with low disease activity score in 28 joints (DAS28) and without autoantibody positivity. CONCLUSIONS: Although patients with inflammatory OA have immune activation in the synovial compartment, they display different T-cell subset frequencies and cytokine profiles. Soluble mediators such as Blys might help to discriminate mild clinical forms of RA from inflammatory OA particularly at the onset of the disease.

N-TproBNP as biomarker in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue fibrosis affecting the skin and internal organs, fibroproliferative vasculopathy, and autoimmune activation. SSc still heralds a poor prognosis with significant morbidity and mortality. Early detection of organ involvement is critical as currently available treatments are most effective when started early. Many candidate biomarkers have been investigated in the past two decades. However, despite the enormous efforts, no accurate tool to predict the pattern of organ involvement and to assess disease activity has been yet identified. The N-terminal fragment of probrain natriuretic peptide (N-TproBNP) is a neurohormone released by ventricular myocytes in response to pressure overload. N-TproBNP is highly relevant for diagnosis, prognosis, and prediction of pulmonary arterial hypertension in SSc. Moreover, several studies support its potential benefit for cardiac assessment of scleroderma patients. Conversely, the role of N-TproBNP as surrogate marker of pulmonary fibrosis and skin involvement is much less clear. We provide an extensive review of the studies that have previously investigated the role of N-TproBNP as candidate biomarker in scleroderma manifestations, presenting also the findings of a recent study we conducted in a cohort of 87 SSc patients.