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Musculoskeletal Ultrasonography (US) is nowadays widely used for clinical grounds and for research purposes in rheumatology. US of the hand and wrist has recently developed due to the technological improvement and use of new, high resolution transducers. US is currently improving clinical examination of the rheumatic hand and wrist and it is commonly used as daily practice by many rheumatologists. The number of publications addressing this area of US scanning has grown exponentially over the last few years. The aim of this paper is to review the current literature on US of the hand and wrist in rheumatology, including US scanning techniques, as well as normal and pathological findings. [ABSTRACT FROM AUTHOR]

Background: Real-world evidence supporting a safe and effective transition from rituximab originator (RTX-O) to its biosimilars (RTX-B) in autoimmune rheumatic diseases (ARDs) is still limited., Objectives: The primary aims of this study were to evaluate the long-term persistence of RTX-B after the non-medical switch (NMS) from RTX-O in ARD patients, and to explore the RTX-B safety profile. The secondary aims were to evaluate the impact of different factors on RTX-B drug retention rate (DRR) and to identify any factors associated with RTX-B discontinuation., Design: Retrospective observational study., Methods: We included consecutive ARD patients undergoing NMS from RTX-O to GP2013 or CT-P10 from January 2018 to December 2020. RTX-B DRR was estimated by Kaplan-Meier plot analysis and compared according to different factors by the Log-rank test; the Cox proportional hazard model was used to detect factors associated with RTX-B discontinuation in the first 36 months., Results: We enrolled 181 patients switching to RTX-B: GP2013 in 143 (79.0%) cases and CT-P10 in 38 (21.0%). The estimated DRR for RTX-B was 81.5% at 12 months, 80.6% at 24 months, and 77.4% at 36 months. The incidence of adverse events with RTX-B was 12.6/100 patients/year. In the Log-rank test, no statistically significant differences were observed in the RTX-B DRR according to sex ( p  = 0.171), ARD diagnosis ( p  = 0.281), and concomitant immunosuppressive therapy ( p  = 0.054); on the contrary, patients on GP2013 showed a higher DRR than those on CT-P10 ( p  < 0.001). In the Cox proportional hazard analysis, the switch to CT-P10 was associated with a higher probability of stopping treatment (hazard ratio, 1.83 (confidence interval, 1.10-3.04), p  = 0.02)., Conclusion: NMS to RTX-B is associated with a high chance of retaining the drug for up to 36 months, irrespective of the diagnosis. GP2013 showed a higher retention rate than CT-P10., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objective: Patients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival., Methods: Patients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and ≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis., Results: Of 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations., Conclusion: We found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials., (© 2024. The Author(s).)

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research., Competing Interests: ST declares consultancy and speaker’s fees from Roche and Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tomassetti, Ciani, Luzzi, Gori, Trigiani, Giuntoli, Lavorini, Poletti, Ravaglia, Torrego, Maldonado, Lentz, Annunziato, Maggi, Rossolini, Pollini, Para, Ciurleo, Casini, Rasero, Bartoloni, Spinicci, Munavvar, Gasparini, Comin, Cerinic, Peired, Henket, Ernst, Louis, Corhay, Nardi and Guiot.)

Background: A subgroup of IPF patients can meet IPAF criteria (features suggesting an underlying autoimmune process without fulfilling established criteria for a CTD). This study was aimed to evaluate whether IPAF/IPF patients compared to IPF patients differ in clinical profile, prognosis and disease course., Methods: This is a retrospective, single center, case-control study. We evaluated 360 consecutive IPF patients (Forlì Hospital, between 1/1/2002 and 28/12/2016) and compared characteristics and outcome of IPAF/IPF to IPF., Results: Twenty-two (6%) patients met IPAF criteria. IPAF/IPF patients compared to IPF were more frequently females ( N = 9/22, 40.9% vs. N = 68/338, 20.1%, p = 0.02), suffered more frequently from gastroesophageal reflux (54.5% vs. 28.4%, p = 0.01), and showed a higher prevalence of arthralgias (86.4% vs. 4.8%, p < 0.0001), myalgias (14.3% vs. 0.3%, p = 0.001) and fever (18.2% vs. 1.9%, p = 0.002). The serologic domain was detected in all cases (the most frequent were ANA in 17 and RF in nine cases) and morphologic domain (histology features) was positive in 6 out of 10 lung biopsies (lymphoid aggregates). Only patients with IPAF/IPF evolved to CTD at follow-up (10/22, 45.5%; six rheumatoid arthritis, one Sjögren's and three scleroderma). The presence of IPAF was a positive prognostic determinant (HR 0.22, 95% CI 0.08-0.61, p = 0.003), whereas the isolated presence of circulating autoantibody did not impact prognosis (HR 1.00, 95% CI 0.67-1.49, p = 0.99)., Conclusion: The presence of IPAF criteria in IPF has a major clinical impact correlating with the risk of evolution to full blown-CTD during follow-up and identifying a subgroup of patients with a better prognosis., Competing Interests: ST declares speaker’s fee from Boehringer-Ingelheim, Roche, Erbe, PulmoniX; and VP declares speaker’s fees from Boehringer-inghelhem, Erbe, Ambu, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tomassetti, Ravaglia, Puglisi, Wells, Ryu, Bosi, Dubini, Piciucchi, Girelli, Parronchi, Lavorini, Rosi, Luzzi, Cerinic and Poletti.)

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination., Competing Interests: Conflict of interest: E.D. has received speaker fees or honoraria from Astra Zeneca, Pfizer, Bristol Myers Squibb, General Electric, and Abbott Vascular, and research funding from GE Healthcare. L.G. has received speaker fees or honoraria from GE Healthcare, Caption Health, Philips Healthcare, and EchoNous. J.A.C. Lima has received honoraria from Astra Zeneca. N.A.-M. has received speaker fees or honoraria from GE Healthcare and Abbott Vascular. M.M.-C. has received research funding from MSD. M.M. has received research funding from the National Scleroderma Foundation. R.N. has received speaker fees from Sanofi Genzyme, Bayer, and Boehringer-Ingelheim, and unrestricted research funding from Philips Volcano and Biotronik. N.A.B.N. has received speaker fees or honoraria from Novo Nordisk and Servier, research funding from GlaxoSmithKline, and royalties for intellectual property from UpToDate. S.E.P. provides consultancy to and is stockowner of Circle Cardiovascular Imaging. L.E.S. has received speaker fees or honoraria from Pfizer and Janssen. J.S. has received unrestricted research grant from Bayer. P.S. has received speaker fees or honoraria from Astra Zeneca, Boehringer-Ingelheim, Medtronic, Novartis, Servier, and Respicardia. L.M.S.-G. has received speaker fees or honoraria from Amgen. J.W. has received speaker fees or honoraria from Abbott Vascular and research funding form GE Healthcare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Bullous pemphigoid (BP) represents the most common autoimmune bullous disease and is characterized by IgG autoantibodies targeting collagen XVII (BP180). BP has reportedly been occurred in association with other inflammatory skin diseases. Here, we describe the unusual occurrence of BP in a female patient with a concomitant history of generalized morphea (localized scleroderma, LoS) and cutaneous and genital lichen sclerosus (LiS). The occurrence of BP was associated with elevated serum levels of anti-BP180 IgG autoantibodies, which decreased upon clinical remission. Autoimmune bullous diseases and sclerosing dermatitis are immunologically distinct entities, whose association has been rarely described. In this study, we provide a literature review on cases of BP developed in patients with either LoS or LiS. Further, we discussed immunological mechanisms which may have favored the emergence of BP in our patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maglie, Baffa, Montefusco, Pipitò, Senatore, Capassoni, Maio, Cerinic, Antiga and Guiducci.)

Background: In women with rheumatic diseases (RDs) menstruation-related disorders have never been investigated. The aim of this study was to evaluate gynecological symptoms/disorders in fertile age women with RDs. Materials and methods: All patients (n = 200) filled up a self-administered questionnaire on their gynecological history, menstrual cycle pattern, menstrual-related symptoms, and quality of life (QoL). The RD group was then compared to a control group of 305 age-matched fertile age women. Results: Among patients with RDs, 58% had arthritis, 40% connective tissue diseases (CTDs), and 1.5% systemic vasculitis. No differences were observed between CTDs and arthritis, except for a family history of HMB which was more common among women with CTDs ( p < .01). When compared to controls, women with RDs reported more frequent heavy menstrual bleeding (HMB) during adolescence (51.7 and 25.4%, respectively; p = .0001) and adult life (37.7 and 25.9%, respectively; p = .0065). Also, dysmenorrhea in adolescence was significantly more common among cases (55.6 and 45.4%, respectively; p = .0338). Gynecological pain (dysmenorrhea, non-menstrual pelvic pain, dyspareunia, dysuria, and dyschezia) in patients with RDs was more frequent than in controls ( p = .0001, .0001, .0001, .0001, .0002, respectively). Considering women who reported moderate and severe symptoms in RDs, dysmenorrhea and dyspareunia remain significantly more frequent in women with RDs than in controls ( p = .0001; p = .0022; respectively). QoL scores were significantly reduced in women with RDs, either in physical ( p = .0001) and mental domains ( p = .0014) of short-form 12. Conclusion: Women affected by RDs frequently presented menstruation-related disorders; thus, female patients with RDs should be questioned about gynecological symptoms and referred to the gynecologist for an accurate evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Orlandi, Vannuccini, El Aoufy, Melis, Lepri, Sambataro, Bellando-Randone, Guiducci, Cerinic and Petraglia.)

➤: Bone marrow edema (BME) is a nonspecific but relevant finding, usually indicating the presence of an underlying pathology., ➤: The gold standard technique for detecting BME is magnetic resonance imaging (MRI), as it allows for a correct diagnosis to be made, which is extremely important given the heterogeneity of BME-related diseases., ➤: Depending on the severity of painful symptomatology and the MRI evidence, different treatment strategies can be followed: physical modalities, pharmacological options, and surgical therapy., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G779)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Cardiopulmonary complications are a leading cause of death in systemic sclerosis. Pulmonary hypertension in particular carries a high mortality and morbidity burden. Patients with systemic sclerosis can suffer from all of the clinical groups of pulmonary hypertension, particularly pulmonary arterial hypertension and pulmonary hypertension related to interstitial lung disease. Despite a similar pathogenetic background with idiopathic pulmonary arterial hypertension, different mechanisms determine a worse prognostic outcome for patients with systemic sclerosis. In this Viewpoint, we will consider the link between pathogenetic and potential therapeutic targets for the treatment of pulmonary hypertension in the context of systemic sclerosis, with a focus on the current unmet needs, such as the importance of early screening and detection, the absence of agreed criteria to distinguish pulmonary arterial hypertension with interstitial lung disease from pulmonary hypertension due to lung fibrosis, and the need for a holistic treatment approach to target all the vascular, immunological, and inflammatory components of the disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of children and adolescents. Autoimmune mechanisms are suspected to have a central role in its development. Vitamin D is an immuno-modulator in a variety of conditions, including autoimmune diseases. Low levels of vitamin D have commonly been found in JIA patients, but the influence of this hormone insufficiency in JIA pathogenesis is still unclear. Vitamin D receptor (VDR) mediates a great majority of vitamin D biological activities; specific polymorphisms of the VDR gene have been associated with different biologic responses to vitamin D. In this study, we analysed clinical characteristics of a cohort of 103 Italian JIA patients. The distribution of VDR polymorphisms in affected patients versus healthy controls was evaluated, as well as if and how these polymorphic variants associate with different disease presentations (active disease vs non-active disease), different JIA subtypes, serum levels of 25-hydroxy-vitamin D and parathyroid hormone (PTH), and lumbar spine Z-score values (osteopenia vs normal bone mineral density). A great majority of our JIA patients (84.5%) showed a suboptimal vitamin D status, in many cases (84.1%) not solved by vitamin D supplementation. Vitamin D status resulted to be independent of VDR genotypes. ApaI genotypes showed a highly significant different distribution between JIA patients and unaffected controls, with both the TT genotype and the T allele significantly more frequent in patient group.

Pleuroparenchymal fibroelastosis (PPFE) is a rare new interstitial lung disease (ILD) characterized by the fibrotic thickening of the visceral pleura and subadjacent parenchymal areas of the upper lobes This study reveals that patients with ILD-SSc associated with chest HRCT evidence of PPFE require close and recurrent follow-up with periodic evaluation of lung function parameters, DLCO and chest HRCT. Rheumatologists should be aware of this new radiological finding which is accompanied by a negative prognosis, especially when associated with a progressive course. Patients with this radiological pattern need to be monitored with particular attention.

Interstitial lung disease (ILD) is a major pulmonary manifestation of connective tissue disease (CTD), leading to significant morbidity and mortality. Chest high-resolution computed tomography (HRCT) is presently considered the diagnostic gold standard for pulmonary fibrosis diagnosis and quantification in the clinical arena. However, not negligible doses of ionizing radiation limit the use of HRCT, especially for serial follow-up in younger female patients. In the past decade, lung ultrasound (LUS) has been proposed to assess ILD by detecting and quantifying sonographic B-lines. Previous studies demonstrate that B-lines have a good diagnostic accuracy, especially high sensitivity, and correlate well with HRCT findings, suggesting LUS as a novel, non-invasive, and non-ionizing imaging method to be used in patients with CTD-ILD. Although preliminary data are promising, challenges and controversies still remain. For example, the mechanisms of B-line generation are not fully understood; the diagnostic accuracy and performance characteristics of LUS partially depend on the scanning scheme and scoring system used; and up-to-date B-lines cannot discriminate the early cellular inflammation from the chronic fibrotic phase in CTD-ILD. Therefore it is important for clinicians to understand the strengths and limitations of LUS in CTD-ILD patients, to maximize its value.

The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40 years. Knee pain in the absence of any recent trauma lasting for less than 6 months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.

Objective: In the last years, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) have been vastly studied and have generated considerable interest among clinicians. SYSADOA are generally used as a ground therapy with the main rationale to reduce the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and thus limit the related adverse events., Material and Methods: In this study, we evaluated the short-term effect of an oral combination of hyaluronic acid, chondroitin sulfate, and keratin matrix on early symptomatic knee osteoarthritis. Forty patients were treated for 1 month and were allowed to assume analgesics or NSAIDs if necessary., Results: At 2 months, the mean reduction of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 36% (p<0.001), and the mean reduction of the WOMAC pains score was 40% (p<0.001). Only two patients reported a sporadic need to assume analgesics; no patient reported any side effect during the study period., Conclusion: This data demonstrates that the oral combination of hyaluronic acid, chondroitin sulfate, and keratin matrix is safe, well tolerated, and shows a rapid action reducing pain and improving joint function and stiffness in early symptomatic knee osteoarthritis.

Aims: Systemic sclerosis (SSc) may induce cardiac fibrosis and systo-diastolic dysfunction. Cardiovascular magnetic resonance (CMR) can detect replacement myocardial fibrosis with late gadolinium enhancement (LGE) and interstitial myocardial fibrosis with T1 mapping techniques. The aim of the study was to detect subclinical cardiac involvement with CMR in paucisymptomatic SSc patients with no previous history of myocardial disease, comparing it with skeletal muscle remodelling., Methods and Results: Thirty consecutive SSc patients (mean age: 51 ± 12 years, all women) and 10 healthy controls (mean age: 48 ± 15 years, all women) underwent clinical, biohumoral assessment, and CMR. Extracellular volume fraction (ECV) was calculated from pre- and post-contrast T1 values in the myocardium and skeletal muscle. Seventeen patients (57%) were asymptomatic, 13 (43%) paucisymptomatic (effort dyspnoea). All patients had normal biventricular volumes and systolic function, while LGE was present in seven patients (23%). Myocardial ECV was significantly increased in patients with SSc (30 ± 4%) than controls (28 ± 4%, P = 0.03), as was skeletal muscle ECV (23 ± 6% vs. 18 ± 4%, P < 0.01). Myocardial ECV did not differ between patients with and without LGE (P = NS) and showed no significant correlations with clinical data, biventricular volumes, systolic, or diastolic function. Overall, myocardial ECV showed a significant correlation with skeletal muscle ECV (R = 0.58, P < 0.001)., Conclusion: SSc is associated not only with myocardial replacement fibrosis, as detected by LGE, but also with interstitial remodelling of the myocardium and skeletal muscles, as detected by an increased ECV also in patients with normal biventricular function, with potential diagnostic, prognostic, and therapeutic clinical implications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: SS and LC contributed equally to this manuscript. Hypovitaminosis D is common in the general population. Although many studies on 25-hydroxyvitamin D (25(OH)D) are available on systemic lupus erythematosus (SLE), few data are reported in juvenile-onset SLE (JSLE) patients., Design: This study aimed to assess serum 25(OH)D levels in JSLE patients and to identify risk factors for vitamin D deficiency in this population., Methods: Forty-five Caucasian JSLE patients (36 females, nine males; mean age 18.9±6.3 years) and 109 age- and sex-matched healthy controls entered the study. Dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine, serum calcium and phosphate, bone-specific alkaline phosphatase (BSAP), parathyroid hormone (PTH), and 25(OH)D were assessed. The data were compared with an age- and sex-matched control group including 109 Caucasian healthy subjects., Results: JSLE patients exhibited lower 25(OH)D levels than controls (p<0.005), with the lower values observed in patients with active vs. inactive disease (p<0.05). JSLE patients exhibited reduced total calcium levels (p<0.001) and higher phosphate levels (p<0.001), BSAP (p<0.001) and PTH (p<0.001) than controls. In addition, JSLE patients exhibited lower spine bone mineral apparent density (BMAD) SDS values than controls (p<0.001), with higher values in patients with 25(OH)D sufficiency and insufficiency than in those with 25(OH)D deficiency (p<0.001)., Conclusions: Patients with JSLE have significantly lower 25(OH)D levels than controls. Therefore, vitamin D supplementation may be useful to normalize bone mass and quality in subjects with JSLE., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Introduction: Our objective was to evaluate longitudinally the main bone-mass and quality predictors in young juvenile idiopathic arthritis (JIA) patients by using lumbar spine dual-energy X-ray absorptiometry (DXA) scan, radius peripheral quantitative computed tomography (pQCT), and phalangeal quantitative ultrasonography (QUS) at the same time., Methods: In total, 245 patients (172 females, 73 males; median age, 15.6 years: 148 oligoarticular, 55 polyarticular, 20 systemic, and 22 enthesitis-related-arthritis (ERA) onset) entered the study. Of these, 166 patients were evaluated longitudinally. Data were compared with two age- and sex-matched control groups., Results: In comparison with controls, JIA patients, but not with ERA, had a reduced spine bone-mineral apparent density (BMAD) standard deviation score (P < 0.001) and musculoskeletal deficits, with significantly lower levels of trabecular bone mineral density (TrabBMD) (P < 0.0001), muscle cross-sectional area (CSA) (P < 0.005), and density-weighted polar section modulus (SSIp) (P < 0.05). In contrast, JIA showed fat CSA significantly higher than controls (P < 0.0001). Finally, JIA patients had a significant reduced amplitude-dependent speed of sound (AD-SoS) (P < 0.001), and QUS z score (P < 0.005)., Conclusions: JIA patients have a low bone mass that, after a first increase due to the therapy, does not reach the normal condition over time. The pronounced bone deficits in JIA are greater than would be expected because of reduction in muscle cross-sectional area. Thus, bone alterations in JIA likely represent a mixed defect of bone accrual and lower muscle forces.

Background: A high percentage of patients with systemic sclerosis (SSc) develop interstitial lung disease (ILD) during the course of the disease. Promising data have recently shown that lung ultrasound (LUS) is able to detect ILD by the evaluation of B-lines (previously called ultrasound lung comets), the sonographic marker of pulmonary interstitial syndrome., Objective: To evaluate whether LUS is reliable in the screening of ILD in patients with SSc., Methods: Fifty-eight consecutive patients with SSc (54 women, mean age 51±14 years) who underwent a high resolution CT (HRCT) scan of the chest were also evaluated by LUS for detection of B-lines. Of these, 32 patients (29 women, mean age 51±15 years) fulfilled the criteria for a diagnosis of very early SSc., Results: At HRCT, ILD was detected in 88% of the SSc population and in 41% of the very early SSc population. A significant difference in the number of B-lines was found in patients with and without ILD on HRCT (57±53 vs 9±9; p<0.0001), with a concordance rate of 83%. All discordant cases were false positive at LUS, providing a sensitivity and negative predictive value of 100% in both SSc and very early SSc., Conclusions: ILD may be detected in patients with very early SSc. The presence of B-lines at LUS examination correlates with ILD at HRCT. LUS is very sensitive for detecting ILD even in patients with a diagnosis of very early SSc. The use of LUS as a screening tool for ILD may be feasible to guide further investigation with HRCT.

Background: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation., Aim: The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc., Methods: We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively., Results: Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR., Conclusions: Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Dysfunctional angiogenesis is a pathogenetic marker of SSc. Circulating levels of endothelial progenitor cells are reduced, and mesenchymal stromal cells show a reduced differentiation into endothelial cells and capacity to form capillaries. This suggests that pathophysiologically relevant changes may already exist in SSc bone marrow (BM) stromal cells that may affect downstream angiogenesis. The aim of this study is to evaluate, in SSc BM, angiogenesis, cellular immune system and fibrosis., Methods: Eight SSc patients affected by a severe dcSSc and screened for autologous haematopoietic stem cells transplantation (HSCT) underwent a BM biopsy. BM biopsies were compared with six healthy controls. To evaluate angiogenesis and cellular immunity, the following antibodies were used: vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/flk-1), MMP-9 and CD34. To evaluate fibrosis, silver impregnation for reticulum was used. The number of vessels, the mean area of vascularization, the perimeter and microvessel density (MVD) were measured with a multiparametric computerized imaging analysis., Results: A significant reduction in BM vascularity was found, while VEGF expression was much higher in SSc BM samples. Two patients had a Grade 2, whereas another two had a Grade 1 fibrosis., Conclusion: In SSc, BM is characterized by a reduction of microvascular density and number of vessels and a significant increase of VEGF. This indicates that BM may be involved in the process of loss of angiogenesis, despite the presence of high local and systemic levels of VEGF.

Objective: In systemic sclerosis (SSc; scleroderma) patients in edematous phase, hand edema is often present. Manual lymph drainage (MLD) stimulates the lymphatic system and reduces edema. Our aim was to evaluate the efficacy of MLD in reducing edema and in improving functionality of the hands and perceived quality of life (QOL) in SSc patients in edematous phase., Methods: Of 35 SSc patients with edematous hands, 20 were treated with MLD according to the Vodder technique once a week for 5 weeks (intervention group), and 15 served as the observation group. Patients were evaluated at enrollment, at the end of treatment (T1), and after 9 weeks of followup (T2) by volumetric test (assessing hand volume), the Hand Mobility in Scleroderma (HAMIS) test, and 4 visual analog scales (VAS; scored 0-10) evaluating the perception of hand edema and pain and their interference on daily activities. QOL and disability were assessed by the physical synthetic index (PSI) and mental synthetic index (MSI) of the Short Form 36 (SF-36) and by the Health Assessment Questionnaire (HAQ)., Results: In the intervention group, hand volume, the HAMIS test, and the 4 VAS were improved significantly at the end of treatment (P < 0.001). The results were maintained at T2 (P < 0.001). The HAQ and the PSI and MSI of the SF-36 also improved significantly at T1 (P < 0.001), but only PSI improvement was maintained at T2 (P < 0.001). In the observation group, no improvement at T1 and at T2 was observed., Conclusion: In SSc, MLD significantly reduces hand edema and improves hand function and perceived QOL., (Copyright © 2011 by the American College of Rheumatology.)