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Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTDs) characterised by increased pulmonary arterial pressure and pulmonary vascular resistance. CTD-PAH is the result of a complex interplay among endothelial dysfunction and vascular remodelling, autoimmunity and inflammatory changes, ultimately leading to right heart dysfunction and failure. Due to the non-specific nature of the early symptoms and the lack of consensus on screening strategies—except for systemic sclerosis, with a yearly transthoracic echocardiography as recommended—CTD-PAH is often diagnosed at an advanced stage, when the pulmonary vessels are irreversibly damaged. According to the current guidelines, right heart catheterisation is the gold standard for the diagnosis of PAH; however, this technique is invasive, and may not be available in non-referral centres. Hence, there is a need for non-invasive tools to improve the early diagnosis and disease monitoring of CTD-PAH. Novel serum biomarkers may be an effective solution to this issue, as their detection is non-invasive, has a low cost and is reproducible. Our review aims to describe some of the most promising circulating biomarkers of CTD-PAH, classified according to their role in the pathophysiology of the disease.

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BackgroundSystemic sclerosis (SSc) carries a significant burden of disease-related morbidity and life-threatening complications. Unlike other rheumatic disorders (e.g., systemic lupus erythematosus and rheumatoid arthritis), the concepts of “disease activity” and “damage” have only recently been defined in SSc.ObjectivesWe aimed to identify clinical and serological predictors of persistence of disease activity and remission in a monocentric prospective cohort of systemic sclerosis patients. Our second aim was to evaluate potential predictors of persistence or new onset of moderate-to-severe damage in our cohort.MethodsAdult patients fulfilling the ACR/EULAR 2013 classification criteria for SSc and referring to our center from 2013 to 2021 were enrolled. Clinical findings, serological indices and internal organ involvement (pulmonary, cardiac, gastrointestinal, renal and musculo-skeletal) at baseline and at each visit during follow-up were retrospectively analyzed. At least one follow-up visit was required to be included in the study. EUSTAR-AI (European Scleroderma Trials and Research group Activity Index)[1], Medsger severity scale (MSS)[2]and SCTC (Scleroderma Clinical Trials Consortium) damage index[3]were calculated at each visit, at baseline and during follow-up. Follow-up period was defined as the time between baseline and the last available visit. Active disease was defined as an EUSTAR-AI ≥ 2,5, while remission as an EUSTAR-AI <2,5; activity persistence was defined as an EUSTAR-AI ≥ 2,5 in more than 50% of follow-up visits. According to the literature, damage was classified as mild (SCTC damage index < 6) and moderate-severe (SCTC damage index ≥ 6).Results173 SSc patients (87,9% females) were enrolled in our study and followed up for a median time of 3,5 years. The median disease duration at baseline was 9 years while the median age at diagnosis was 45 years; 34,6% of patients had diffuse cutaneous SSc. Patients with persistently active disease during follow up (13,2%) had at baseline a significantly higher frequency of diffuse cutaneous subset (54% vs 17%, p<0,0001) and cardiac involvement (43,4% vs 20,7%, p=0,036) than persistently inactive patients; erythrocyte sedimentation rate (ESR) values were higher (p=0,002) and total lung capacity (TLC) values were lower (p=0,034) in persistently active patients. Positive anticentromere antibodies (ACA) were associated with persistent remission (p=0,042). Persistent disease activity was associated with higher disease severity [MSS 6,3 (±3) vs 3,5 (± 1,7)], p<0,0001] and more severe damage [SCTC-DI 3,7 (±4) vs 1,3 (±1,9), p<0,0001] at baseline. At the multivariate analysis, ESR values (OR 1,04 95% CI 1,01-1,07) and MSS values at baseline (OR 1,75, 95% CI 1,29-2,37) were independent predictors of activity persistence. Patients with persistent or new onset of moderate-severe SCTC at the end of the follow up (9%) had more frequently telangiectasia (81,3% vs. 38,6%, p=0,001) and ILD (62,5% vs. 31,6%, p=0,013) at baseline than patients with mild damage; they also showed lower DLCO values (p=0,047) and lower TLC values (p<0,0001), as well as higher systolic pulmonary arterial pressure (sPAP) on transthoracic echocardiography (p< 0,0001) at baseline. Multivariate analysis showed that TLC values (OR 0,95, 95% CI 0,92-0,98) and telangiectasia (OR 4,7, 95% CI 1,18-18,54) were independent predictors of moderate-severe damage. An association was found between persistence of disease activity and moderate-severe damage at the end of follow-up (p=0,003).ConclusionIdentifying predictors of disease activity persistence and damage accrual at baseline may help to improve the risk stratification of SSc patients, through the identification of those patients who require prompt treatment and a more thorough clinical follow-up.References[1]Valentini G et al., Annals of the Rheumatic Diseases. 2017;76(1):270-6.[2]Medsger TA et al., Journal of Rheumatology. 1999 Oct 1;26(10):2159–67.[3]Ferdowsi N et al., Annals of the Rheumatic Diseases. 2019 Jun 1;78(6):807–16.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundSubclinical primary muscular involvement and malnutrition may occur in a significant percentage of patients with systemic sclerosis (SSc), and they are potential risk factors for the development of sarcopenia [1]. Sarcopenia is defined as age-associated loss of muscle mass, strength, and function, and unlike other chronic rheumatic inflammatory disorders, it has been poorly investigated in SSc patients. In recent years, some imaging methods have emerged for the identification of sarcopenic markers such as altered muscle composition and fat infiltration (myosteatosis).ObjectivesTo evaluate the occurrence of myosteatosis and the prognostic role of body composition, assessed by computed tomography, in patients affected with SSc.MethodsPatients affected with SSc (2013 EULAR/ACR criteria) referring to our tertiary center from 2015 to 2021 who underwent chest computed tomography to assess pulmonary involvement were included. A semi-automatic segmentation of the subcutaneous fat and paravertebral muscle was performed at the level of the 12thdorsal vertebra using a software and the following body composition variables (BCV) were collected: subcutaneous fat area, subcutaneous fat Hu, paravertebral muscle area, paravertebral muscle Hu. Myosteatosis was considered as Hu values <30. The Student’s t-test was used to evaluate if any difference regarding BCV occurred between males and females. Logistic regression analysis was applied to assess the role of the BCV on the overall survival while the Spearman correlation coefficient was used to evaluate the relationship between the BCV and the skin score. For all the analyses the applied significance level was p<0.05.ResultsSixty SSc patients were included (51 females; mean age 55.63±14 years). Most patients were positive for anti-nuclear antibodies (ANA, 90%), with anti-topoisomerase I specificity in 61.6% of them; twenty-nine patients (48.3%) were affected by the diffuse cutaneous form. At baseline, the mean modified Rodnan skin score (mRSS) was 10.22 (±8.8) and the mean revised EUSTAR activity index was 2.08 (±1.4). Signs of myosteatosis were detected in forty-seven (78.3%) SSc patients. Males showed significantly greater muscle areas (males 9732±3019 vs. females 6599±1328 mm2; p<0.001) and less hypodense subcutaneous fat (males 76±18 vs. females 88±16 Hu; p=0.027). Overall, seven patients deceased at a 5-year follow-up. No correlation was found between BCV and the mRSS. None of the radiological variables emerged as a predictor of survival.ConclusionMost patients with SSc are affected by myosteatosis, even those without symptoms of muscle involvement, while overall body composition does not appear to predict survival. The results of our pilot study may open the door to evaluating the role of body composition in SSc patients: larger longitudinal studies looking at different time-points in the disease course may provide further insights.Reference[1]Paik JJ, Mammen AL, Wigley FM, Gelber AC. Myopathy in scleroderma, its identification, prevalence, and treatment: lessons learned from cohort studies. Curr Opin Rheumatol 2014; 26:124–30.Acknowledgements:NIL.Disclosure of InterestsNone Declared.