Long-Term Data on Efficacy and Safety of Selexipag for Digital Systemic Sclerosis Vasculopathy.

OBJECTIVE: Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy. METHODS: Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed. RESULTS: Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration (P < 0.001 and P = 0.01, respectively). All patients achieved a complete healing of their DUs (P = 0.03) within 6 months. A progressive reduction of fingers skin score was observed (P = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion (P = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature. CONCLUSION: We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy.

Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case-control study from the Italian national multicenter "SPRING" (Systemic Sclerosis Progression InvestiGation) Registry.

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data. Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group). Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, "late" scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis. Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets.

Lung ultrasound and high-resolution computed tomography quantitative variations during nintedanib treatment for systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: Lung ultrasound (LUS) and high-resolution computed tomography (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a one-year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes. METHODS: SSc-ILD patients who started NIN were enrolled and followed for twelve months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after one year and quantitatively analysed with CALIPER software. RESULTS: Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after twelve months (from 175.1 ± 66.7-120.8 ± 70.3 for BL, p= 0.005 and from 50.6 ± 32.5-37.2 ± 22.4 for PLI, p= 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction of both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (p= 0.016 and p= 0.04, respectively) and Saint George's Respiratory Questionnaire (p= 0.006 and p= 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after twelve months of NIN, thus paralleling the stabilization obtained at pulmonary function tests. CONCLUSIONS: We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects.

OBJECTIVE: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects. METHODS: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them. RESULTS: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN. CONCLUSION: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

Multiparametric Skin Assessment in a Monocentric Cohort of Systemic Sclerosis Patients: Is There a Role for Ultra-High Frequency Ultrasound?

Background: To assess skin involvement in a cohort of patients with systemic sclerosis (SSc) by comparing results obtained from modified Rodnan skin score (mRSS), durometry and ultra-high frequency ultrasound (UHFUS). Methods: SSc patients were enrolled along with healthy controls (HC), assessing disease-specific characteristics. Five regions of interest were investigated in the non-dominant upper limb. Each patient underwent a rheumatological evaluation of the mRSS, dermatological measurement with a durometer, and radiological UHFUS assessment with a 70 MHz probe calculating the mean grayscale value (MGV). Results: Forty-seven SSc patients (87.2% female, mean age 56.4 years) and 15 HC comparable for age and sex were enrolled. Durometry showed a positive correlation with mRSS in most regions of interest (p = 0.025, ρ = 0.34 in mean). When performing UHFUS, SSc patients had a significantly thicker epidermal layer (p < 0.001) and lower epidermal MGV (p = 0.01) than HC in almost all the different regions of interest. Lower values of dermal MGV were found at the distal and intermediate phalanx (p < 0.01). No relationships were found between UHFUS results either with mRSS or durometry. Conclusions: UHFUS is an emergent tool for skin assessment in SSc, showing significant alterations concerning skin thickness and echogenicity when compared with HC. The lack of correlations between UHFUS and both mRSS and durometry suggests that these are not equivalent techniques but may represent complementary methods for a full non-invasive skin evaluation in SSc.

Systemic sclerosis: one year in review 2023.

Systemic sclerosis is a rare and chronic connective tissue disease resulting from an intricate pathogenesis and is expressed in very heterogeneous clinical manifestations. Every year many studies try to unravel and shed new insight into the pathogenesis, organ involvement and treatment of this complex and severe disease. We herein provide an overview of the most relevant studies published in the literature in 2022.

Preliminary Clinical and Laser Speckle Contrast Analysis Data on Selexipag Efficacy for the Treatment of Digital Vasculopathy in Systemic Sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is burdened by Raynaud phenomenon (RP) and digital ulcers (DUs), and sometimes standard vasoactive therapies are ineffective or contraindicated. Selexipag is an oral selective IP prostacyclin receptor agonist approved for the treatment of SSc-related pulmonary arterial hypertension. We aimed to evaluate the clinical and instrumental efficacy of selexipag in SSc digital vasculopathy. METHODS: Patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies were administered selexipag. RP- and DU-related clinical outcomes were evaluated, and digital perfusion was assessed by laser speckle contrast analysis (LASCA), all at baseline and after 3 months. RESULTS: Selexipag was administered to 9 patients with SSc (66.6% female, mean age 52.3 [SD 16.6] yrs). One patient had to stop the drug because of adverse effects. After 3 months of selexipag administration, there was a significant reduction in RP daily episodes (P = 0.01) and RP mean duration (P = 0.04). The number of DUs decreased from 10 to 4 without reaching statistical significance. A significant improvement in mean perfusion of the fingers (P = 0.02) was observed with LASCA. CONCLUSION: Selexipag showed good potential for the treatment of SSc digital vasculopathy. Our results are certainly preliminary, yet quite encouraging. New trials for the evaluation of selexipag efficacy in SSc digital vasculopathy are needed.

Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology.

OBJECTIVE: To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. METHODS: Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. RESULTS: Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). CONCLUSION: The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

Is oropharyngoesophageal scintigraphy the method of choice for assessing dysphagia in systemic sclerosis? A single center experience.

OBJECTIVES: To evaluate the performance of oropharyngoesophageal scintigraphy (OPES) in the assessment of dysphagia in patients with systemic sclerosis (SSc), and to compare OPES results with those of barium esophagogram. METHODS: Adult SSc patients who underwent OPES for the assessment of dysphagia were enrolled. OPES was performed with both liquid and semisolid boluses and provided information regarding oropharyngeal transit time, esophageal transit time (ETT), oropharyngeal retention index (OPRI), esophageal retention index (ERI), and site of bolus retention. Barium esophagogram results were also collected. RESULTS: Fifty-seven SSc patients (87.7% female, mean age 57.7 years) with dysphagia were enrolled. OPES identified at least one alteration in each patient and findings were generally worse for the semisolid bolus. Esophageal motility was widely impaired with 89.5% of patients with an increased semisolid ERI, and middle-lower esophagus was the most frequent site of bolus retention. However, oropharyngeal impairment was highlighted by widespread increased OPRI, especially in anti-topoisomerase I positivity. Older patients and with longer disease duration presented slower semisolid ETT (p = 0.029 and p = 0.002, respectively). Eleven patients with dysphagia had a negative barium esophagogram: all of them presented some alterations in OPES parameters. CONCLUSION: OPES revealed a marked SSc esophageal impairment, in terms of both slowed transit time and increased bolus retention, but also shed light on oropharyngeal swallowing alterations. OPES showed high sensitivity, being able to detect swallowing alterations in dysphagic patients with negative barium esophagogram. Therefore, the use of OPES for the assessment of SSc-related dysphagia in clinical practice should be promoted.

Comparison of different forms of Raynaud's phenomenon by LASCA proximal-distal gradient perfusion.

OBJECTIVE: To evaluate finger proximal-distal gradient (PDG) perfusion in subjects with primary Raynaud's phenomenon (PRP), then making comparisons with systemic sclerosis (SSc) patients and healthy controls (HC). METHODS: Consecutive adult PRP subjects were enrolled, along with an equal number of SSc and HC. Peripheral blood perfusion of the hands was assessed by laser speckle contrast analysis (LASCA). PDG was then calculated applying a generalizable formula independent of both intra- and inter-personal factors. Non-specific anti-nuclear autoantibody (ANA) isolated positivity was assessed. RESULTS: Fifty PRP patients (88 % female, mean age 45 ± 17.9 years) were enrolled, along with 50 SSc patients and 50 HC. After adjusting mean PDG results for age and sex, no significant differences emerged between PRP and SSc (1.80 ± 0.43 vs 1.76 ± 0.53; p = 0.294). Conversely, PRP values were significantly reduced when compared to HC (2.72 ± 0.37; p < 0.001). Among PRP subjects, no significant differences were found regarding isolated ANA positivity (1.86 ± 0.44 vs 1.74 ± 0.44; p = 0.42). CONCLUSION: PRP and SSc seems to share the same basal PDG perfusion impairment assessed by LASCA. Isolated ANA positivity, in the absence of clinical and capillaroscopic suspicion for secondary causes, should not be considered an exclusion criterion for PRP classification.

Ultra-high frequency ultrasound for digital arteries: improving the characterization of vasculopathy in systemic sclerosis.

OBJECTIVES: To provide a full characterization of proper palmar digital arteries (PPDA) in systemic sclerosis (SSc) with ultra-high frequency ultrasound (UHFUS), and to investigate possible relationships between digital macroangiopathy and microangiopathy. METHODS: SSc patients without active digital ulcers and healthy controls (HC) were enrolled. Each subject underwent UHFUS 70 MHz evaluation of PPDA from II to V fingers bilaterally, searching for vessel occlusion and measuring the thickness of the three arterial layers and the systolic-diastolic excursion range. Microcirculation was investigated with capillaroscopy and laser speckle contrast analysis (LASCA). RESULTS: Forty-six SSc patients (87% female, mean age 55.5 years) and 15 HC comparable for age and sex were enrolled. UHFUS in SSc revealed the occlusion of 124 (16.8%) PPDA, whereas in HC they were all patent. Considering a finger with at least one PPDA occluded as ultrasonographically pathological, 67.4% patients presented ≥1 pathological fingers. All three arterial layers were significantly thicker and excursion range significantly reduced in SSc than in HC (p<0.001 for all). Seventy-three percent of fingers previously affected by digital ulcers, were ultrasonographically pathological. Disease duration was directly correlated to the thickness of all three arterial layers. No significant correlations emerged between capillaroscopy or LASCA findings and UHFUS features. CONCLUSION: UHFUS allows the characterization of vasculopathic involvement of PPDA in SSc, also showing subclinical vasculopathy. The lack of correlations between UHFUS and capillaroscopy or LASCA likely mirrors non-overlapping vasculopathic processes. UHFUS evaluation of PPDA emerges as complementary to microcirculation assessment for a more accurate and complete characterization of SSc vasculopathy.

Systemic sclerosis: one year in review 2022.

Systemic sclerosis (SSc) is an autoimmune disease characterised by microvasculopathy, immune dysregulation, and skin and visceral organ fibrosis. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published in the scientific community.In this review we report an overview of some of the most relevant contributions published in 2021.

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature.

INTRODUCTION: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. MATERIALS AND METHODS: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. RESULTS: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. CONCLUSION: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Definition and application of proximal-distal gradient finger perfusion in systemic sclerosis by laser speckle contrast analysis.

OBJECTIVE: In patients with systemic sclerosis (SSc) the perfusion of the fingers shows an alteration of the physiological proximal-distal gradient (PDG). The aim of this study is to provide a generalizable definition of PDG, applying it in a cohort of SSc patients and healthy controls (HC) using laser speckle contrast analysis (LASCA). METHODS: Adult consecutive SSc patients and HC were enrolled. Peripheral blood perfusion of the hands was evaluated by LASCA, subsequently obtaining 3 different regions of interest: from the distal interphalangeal joint to the fingertip (DIST), from the metacarpophalangeal joint to the distal interphalangeal joint (PROX), and of the whole finger (TOT). A PDG formula independent of both intra- and inter-personal factors was then built. The PDG formula so obtained was: [(DIST × 2.63) - PROX]/TOT. RESULTS: Ninety-four SSc patients (79.8% female, mean age 58.7 years) were enrolled. Applying the PDG formula, SSc patients revealed mean PDG values significantly lower than HC (1.82 ± 0.44 PU vs 2.70 ± 0.38 PU; p < 0.0001). Patients with a previous history of digital ulcers presented significant lower PDG values (p = 0.002). The ROC curve analysis identified in 2.28 PU the best PDG cut-off value between SSc and HC, with 86% sensibility and 90% specificity. CONCLUSION: This study provided a PDG formula generalizable to all kind of subjects, applying it in SSc with great sensibility and specificity using LASCA, the best non-invasive imaging technique for the dynamical evaluation of peripheral perfusion. LASCA-PDG appears also as a tool able to identify a subclinical microangiopathic impairment.

Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology.

OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Cardiovascular burden in systemic sclerosis: QRISK3 versus Framingham for risk estimation.

OBJECTIVES: To compare two algorithms for cardiovascular (CV) risk estimation in systemic sclerosis (SSc) patients, investigating correlations with disease characteristics. METHODS: Traditional CV risk factors and SSc-specific characteristics were assessed in a cohort of SSc patients. Framingham and QRISK3 algorithms were used to estimate the risk of developing a CV disease over the next 10 years. RESULTS: Seventy-two SSc patients were enrolled. Among those 56 without previous CV events, Framingham reported a median risk score of 9.6%, classifying 24 (42.9%) subjects at high risk. QRISK3 showed a median risk score of 15.8%, with 36 (64.3%) patients considered at high risk. Both algorithms revealed a significant role of some traditional risk factors and a noteworthy potential protective role of endothelin receptor antagonists (p = .003). QRISK3 was also significantly influenced by some SSc-specific characteristics, such as limited cutaneous subset (p = .01), interstitial lung disease (p = .04), and non-ischemic heart involvement (p = .03), with the first two maintaining statistical significance in the multivariate analysis (p = .02). CONCLUSIONS: QRISK3 classifies more SSc patients at high risk to develop CV diseases than Framingham, reflecting the influence of some SSc-specific characteristics. If its predictive accuracy were prospectively verified, the use of QRISK3 as a tool in the early detection of SSc patients at high CV risk should be recommended.

One year in review 2021: systemic sclerosis.

Systemic sclerosis is a rare and chronic connective tissue disease with a multifaceted pathogenesis characterised by heterogeneous multi-organ clinical manifestations. Every year, many studies contribute to enrich the knowledge on the pathogenesis, organ involvement and treatment of this complex and severe disease. We herein provide an overview on the most relevant contributions published in the literature in 2020.

Bioelectrical Impedance Vector Analysis for Nutritional Status Assessment in Systemic Sclerosis and Association With Disease Characteristics.

OBJECTIVE: To use bioelectrical impedance vector analysis (BIVA) in a cohort of patients with systemic sclerosis (SSc) in order to assess their nutritional status in comparison to other groups of patients and to find any correlation with clinical characteristics and outcome of the disease. METHODS: We retrospectively collected data from 50 SSc patients who underwent BIVA for clinical suspicion of malnutrition and compared them with patients affected by other chronic autoimmune rheumatic diseases (OCAD, n = 27) and those who were only symptomatic of malnutrition but without autoimmune features (n = 15), and with 50 healthy controls (HC). RESULTS: Patients with SSc presented significantly lower values of phase angle (PhA), basal metabolic rate (BMR), and body cellular mass (BCM), and an increase in extracellular water (ECW; P < 0.01 for all) than HC; instead, there were no significant differences for BMI. No significant differences were found between SSc and OCAD. Among patients with SSc, age directly correlated with ECW (ρ = 0.342, P = 0.015) and inversely with PhA (ρ = -0.366, P = 0.009). Female sex, anemia, hypoalbuminemia, reflux, and early satiety/abdominal distension associated with relevant alterations in BIVA results. BIVA variables were significantly different when cardiopulmonary and microvascular involvement was present. Four patients died during the study: they had significantly (P ≤ 0.01) lower PhA, BMR, and BCM, with an increased ECW. CONCLUSION: BIVA, unlike BMI, allowed an accurate characterization of SSc patients at risk of malnutrition, correlating with serological malnutrition markers, with SSc-specific organ manifestations (cardiopulmonary involvement and microvascular damage), and with mortality. BIVA variables might represent a surrogate marker of damage accrual that leads to malnutrition, thus playing a leading role in the prognostic stratification of SSc patients.

The impact of skin calcinosis on digital ulcers in patients with SSc: clinical and prognostic stratification using the "wound bed score".

Digital ulcers (DUs) represent one of the major burdens for patients with systemic sclerosis (SSc), especially when associated with skin calcinosis (SC). The aim of this work is to evaluate the impact of SC in DUs of patients with SSc for clinical characteristics and prognosis assessed by the wound bed score (WBS). We prospectively enrolled 55 patients with DUs and SSc followed in our dedicated wound care clinic. For all the patients we collected clinical and anthropometric data and characteristics of the DU, and we calculated the WBS for each DU. Ninety-nine DUs were evaluated (24 with SC). SC was prevalent in limited cutaneous SSc (75%) and in patients with longer disease duration (P = 0.02). SC-DUs were prevalent at the fingertip (P = 0.04). The healing time was significantly higher in patients with SC (10.4 ± 7.9 weeks) compared with non-SC (7.0 ± 5.7 weeks) P = 0.03. The WBS negatively correlated with the time to achieve complete healing (r = -0.237 P = 0.023) and the correlation was maintained in the non-SC (r = -0.46, P = 0.033). DUs in SSc patients with SC are common and difficult to heal. When DUs are treated in dedicated centres, the prognosis is good. The WBS is fast and easy and maybe commonly applied in clinical practice.

One year in review 2020: systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterised by diffuse microangiopathy and immune dysregulation which ultimately results in widespread fibrosis of the skin and internal organs. This complex autoimmune disease is characterised by heterogeneous clinical manifestations and variable disease course in which the severity of pathology dictates the disease prognosis and course. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published. Herewith, we provide an overview of the most significant literature contributions published last year, with the aim of helping the clinician in the understanding and management of SSc patients.