Objective Body mapping of normal values of skin thickness and hardness may be a useful aid in daily practice. By employing non-invasive techniques, our pilot study provides these values in healthy individuals using high frequency ultrasound (HFUS) and durometry in areas used to evaluate the modified Rodnan skin score (mRSS). Methods One-hundred-fifty-two healthy volunteers from Ghent and Genova University Hospitals (mean ages 31.2, 35.5, and 64.9 years), were evaluated to exclude rheumatologic diseases. HFUS and durometry were used to assess the dermal status in mRSS areas. Exploratory analyses were performed to assess the impact of demographic and anthropometric characteristics on intra-subject skin measurements. Statistical analysis was performed with Datatab (R). Results The upper and lower arms exhibited significantly higher durometry values and lower dermal thickness compared to the trunk regions, underscoring distinct variations across these areas (all p<0.05). The hardest skin was found on the finger, while the thickest dermal measurements were at the abdomen and thighs. Dermal thickness was higher in men in multiple areas in the three cohorts, albeit with relatively modest effect sizes (r coefficients ranging between 0.02 and 0.6). Despite the presence of significant inter-group differences in dermal thickness, HFUS mapping showed similar topographical distributions in both centres. Conclusion Our study offers a comprehensive skin mapping status in healthy individuals. Key findings indicate lower dermal thickness in the upper arms, legs, and feet, and higher skin hardness in peripheral areas like fingers, compared to truncal regions.This skin mapping pilot study might provide the normal distribution values in outpatient clinics for physicians to be used when comparing the same areas in pathological conditions like systemic sclerosis-related skin.

Background: Systemic sclerosis (SSc) is a complex systemic disease featured by immune dysregulation, vasculopathy and fibrosis. The identification of disease phenotypes through the clinical, autoantibody and microvascular profiles might help stratifying patients and target treatment. From a vascular perspective, the involvement of the ocular microcirculation has been described in SSc but its correlations with clinical clusters and peripheral microcirculation, assessed with nailfold capillaroscopy (NVC) and laser speckle contrast analysis (LASCA), has been minimally explored [1]. Objectives: We compared Optical Coherence Tomography Angiography (OCTA) variables in SSc vs age- and sex- matched healthy controls (HCs).OCTA data were correlated with the clinical phenotype of patients with SSc and with the morphological peripheral microvascular status, assessed by NVC, and the functional perfusion, analysed by LASCA.We aimed also to evaluate the performance degree of the combination of OCTA +/- LASCA as classifiers to distinguish patients with limited (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc), subdivided as per Leroy’s criteria [2]. Methods: We included 35 SSc patients (mean age 62.4 ± 11.7 years, mean disease duration 8.4 ± 5 years) and 35 HCs in a single centre from March to October 2022. The patients were classified by the ACR/EULAR 2013 criteria, and the assessments were performed, at the same day, including ophthalmological examinations, OCTA, NVC and LASCA. Patients were under standard treatment for SSc and those requiring endovenous prostanoids were evaluated for the study assessment at least one month after the last infusion. Results: DcSSc patients exhibited a lower choroidal perfusion (p=0.03) but an increased choroidal thickness (CT) than lcSSc (306 ± 43 µm vs 172 ± 63 µm, p < 0.001, Figure 1). CT was increased also in patients with positive Scl70 antibodies (p = 0.001) and with a history of digital ulcers (p = 0.03) directly correlating with disease duration (r = 0.72, p = 0.001).Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p < 0.05). Additionally, a significantly reduced retinal and choroidal perfusion was detected in SSc patients versus controls (all p < 0.05).Interestingly, there were no significant differences between the ocular variables of SSc patients compared to HCs, except for a significantly higher intra-ocular pressure observed in SSc patients (p = 0.006). This increase, however, did not correspond with any change in the thickness of the retinal nerve fiber layer, which remained similar between SSc patients and HCs (p = 0.7).In the context of discerning between patients with dcSSc and lcSSc, only the measurement of the CT exhibited a noteworthy area under the curve (AUC) value of 0.84. A threshold value of 211 μm in CT was identified as the optimal point of demarcation, yielding sensitivity and specificity values of 85% and 69%, respectively, in the differentiation of dcSSc from lcSSc (Figure 2). Conclusion: The increased CT, limited to dcSSc and more frequent with longstanding disease, Scl70 positivity and a history of digital ulcers, might be related to the more intense fibrotic process, observed in several tissues of such patients.The altered morphological and functional microvascular status at nailfold correlate with an impairment of the retinal and choriocapillaris microvasculature in SSc patients. This suggests that the ocular microvascular alterations observed in SSc patients mirror the peripheral microvascular involvement, even though these changes may not present with overt clinical symptoms. REFERENCES: [1] Kreps et al. Semin Arthr Rheum 2019. [2] LeRoy et al. J. Rheumatol 1988. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1Differences in choroidal thickness between a patient with diffuse cutaneous SSc (upper panel) and a limited cutaneous SSc patient (lower panel). Figure 2ROC analysis between lcSSc vs dcSSc patients assessing the mean peripheral perfusion detected by LASCA, OCTA parameters, combined variables and choroidal thickness.

Background: Juvenile Sjögren’s syndrome (jSjS) is a rare autoimmune disease, primarily marked by the involvement of exocrine glands and a range of systemic symptoms, including small vessel vasculitis and Raynaud’s phenomenon (RP). Objectives: Our study focused on investigating the microvascular status in jSjS patients by nailfold videocapillaroscopy (NVC) correlating it with clinical and serological features. Methods: Clinical information was gathered from thirteen consecutive jSjS patients (11 females and 2 males). The average age was 16 ± 4 years and participants were diagnosed before 16 years of age (mean age at diagnosis 12 ± 3) according to the 2016 American College of Rheumatology/EULAR criteria for adult SjS [1]. Thirteen healthy controls (HCs) were age- and sex-matched. Clinical, laboratory, and instrumental data were collected, together with NVC examination. According to recently published standardised definitions in capillaroscopy, non-specific and specific NVC parameters were investigated [2]. These included capillary density, capillary dilations, giant capillaries, microhaemorrhages and abnormal shapes. Associations between NVC findings and clinical/serological features were explored and analysed using parametrical and non-parametrical tests. Results: RP was present in 8% of jSjS patients (Table 1). No specific NVC pattern for jSjS was identified, whereas the occurrence of abnormal capillary shapes were significantly greater in jSjS patients compared with HCs (p = 0.005, Figure 1). The reduction of capillary density correlated significantly with articular involvement, in particularly with arthralgias (p = 0.024). Microhaemorrhages correlated with lower C3 serum concentrations (p = 0.034). NVC abnormalities were not associated with SjS-specific instrumental tests (biopsy findings, imaging, Schirmer’s test). Conclusion: The reduction of capillary density, as well as microhaemorrhages at NVC analysis, are significantly associated with some clinical aspects like articular involvement and serum biomarkers (C3 reduction). The NVC is suggested as safe and further analysis in jSjS patients. REFERENCES: [1] Shiboski et al. Arthritis Rheumatol 2018.[2] Smith V et al. Aut Rev 2020. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1NVC pictures of three juvenile jSjS patients (magnification 200×); (a) microhaemorrhages (*); (b) abnormal shapes (arrowheads) in a patient with overall reduced capillary density (6.3 capillaries/mm); (c) normal count of the capillaries of the first row, with two dilated capillaries (arrows). All the patients presented non-specific alterations. Table 1Descriptive analysis of the features of the jSjS patients’ cohort.DEMOGRAPHIC FEATURESCLINICAL AND IMAGING FEATURESTotal patients, n13Raynaud’s phenomenon, n (%)1 (8%)Sex, F (%)11 (84%)Parotid swelling, n (%)8 (62%)Age at diagnosis, years ± SD12±3Xerostomia, n (%)8 (62%)Age at NVC, years ± SD16±4Xerophthalmia, n (%)7 (54%)Disease duration, years ± SD4±5Arthralgia, n (%)7 (54%)LABORATORY FEATURESArthritis, n (%)3 (23%)ANA positivity, n (%)10 (77%)Nervous system involvement, n (%)1 (8%)Anti-SSa +, n (%)10 (77%)Lung involvement, n (%)2 (15%)Anti-SSb +, n (%)9 (69%)Cytopenias, n (%)4 (31%)Rheumatoid factor +, n (%)7 (54%)Vasculitis involvement, n (%)1 (8%)CRP, mg/l0.3±1.1Muscular involvement, n (%)1 (8%)ESR, mm/h27±19Adenopathy, n (%)2 (15%)C3, mg/dl120±21Parotid US, abnormal (%)10 (77%)C4, mg/dl19±3Schirmer’s test, abnormal (%)7 (54%)Hb, g/dl12.6±1.6Salivary gland biopsy, abnormal (%)9 (69%)WBC, *109/L5.0±1.8Treatment with HCQ, n (%)9 (69%)Neutrophils, *109/L2.9±1.6Treatment with sirolimus, n (%)3 (23%)Lymphocytes, *109/L1.7±0.4Treatment with PDN, n (%)5 (38%)PLT, *109/L240±50Overlap with MTCD2 (15%)ESSDAI6±5Overlap with SLE1 (8%)Legend. F=female; SD=standard deviation; NVC=nailfold videocapillaroscopy; CRP=C-reactive protein; ESR=erythrocyte sedimentation rate; Hb=haemoglobin; WBC=white blood cells; PLT=platelets; ESSDAI=EULAR Sjögren’s Syndrome Disease Activity Index; US=ultrasound; HCQ=hydroxychloroquine; PDN=prednisone; MCTD= mixed connective tissue disease; SLE= systemic lupus erythematosus.

Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by endothelial dysfunction and progressive fibrosis leading to organ failure. The increasing endothelial damage is one of the hallmarks of the disease [1]. Aminaphtone is a synthetic molecule registered to treat microvascular disorders that interferes with the expression of vasoactive mediators released by activated endothelial cells [2,3]. Nailfold videocapillaroscopy (NVC) is the standardized tool to assess microvascular damage and may be considered a morphological biomarker for detection of SSc diagnosis and progression [4]. Objectives: The aim of our study was to evaluate the safety and the possible effects of aminaphtone on microvascular morphology when added to standard treatment (ST) in SSc patients in a time frame of five years. Methods: Seventy-six SSc patients (68 females and 8 males, mean age 69–15 years) according to 2013 ACR/EULAR criteria with active secondary Raynaud's phenomenon started aminaphtone treatment (75 mg BID) in addition to stable ST for SSc. As control group we used a cohort of forty-two age and sex matched SSc patients treated only with ST. All patients provided written informed consent to manage their clinical data. Possible side effects related to aminaphtone treatment were carefully checked every six months. NVC was assessed at baseline, after 1 and 5 years of treatment, adopting the SSc-pattern classification ("Early", "Active", "Late") [4,5]. The timing of transition of the scleroderma-pattern was compared between patients treated with aminaphtone and patients only treated with ST. Results: In our cohort of patients no serious side-effect has been reported during the observational time frame of 5 years. Nevertheless, 10% of SSc patients presented mild intolerance due to well-known reversable adverse events (headache 2.7%, itching 1.3%, others 6%) leading to aminaphtone discontinuation. NVC patterns in SSc patients treated with aminaphtone remained stable during the observational time frame in 91% of cases; in 9% of patients was observed a transition from "Early" to "Active" or from "Active" to "Late" SSc-pattern (6.6% and 3.4%, respectively). Of note, SSc patients treated with aminaphtone showed a significantly slower time of transition between NVC patterns compared to the control group of patients treated with ST alone (from "Active" to "Late" 120±64 months vs 50±26 months, p=0.05), while a similar transition time from "Early" to "Active" (36±30 months vs 36±42 months; p>0.05) was observed in both groups. Conclusion: Aminaphtone was shown to be safe and well tolerated in SSc patients with secondary RP during long term treatment (5 years). The scleroderma-pattern stability over five years follow-up, observed at NVC examination, suggests the potential supplementary therapeutic effect by aminaphtone when used alongside standard therapy in SSc patients, at least on vascular tissue damage. Further investigations to confirm this outcome are ongoing. REFERENCES: [1] Sulli A et al. Rheumatology (Oxford) 2020 1;59(5):1051-1058. [2] Gotelli E et al. Pharmaceuticals (Basel) 2023;16(4):569. [3] Ruaro B et al. Front Pharmacol 2019;10:293. [4] Cutolo M et al. Nat Rev Rheumatol 2010;6, 578–87. [5] Smith V et al. Autoimmun Rev. 2020;19(3):102458. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Aminaphtone (3-Methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-y4-amino-benzoate) is a chemical vasoactive compound licensed to treat microvascular disorders [1]. The drug has been proved to play a role in the management of both primary and secondary Raynaud's phenomenon (RP), with a good safety profile, being able to reduce RP clinical symptoms and increase peripheral blood perfusion [1,2]. In-vitro clinical studies reported the downregulation by aminaphtone of adhesion molecules, vasoconstrictor peptides and pro-inflammatory cytokine expression, including transforming growth factor beta (TGF-beta) [3]. This latter is a growth factor playing a crucial role in fibrotic processes. Objectives: The aim of the study was to investigate the effect of aminaphtone short-term treatment (3 months) on TGF-beta plasma levels in systemic sclerosis (SSc) patients with secondary RP. Methods: 26 patients affected by SSc according to the EULAR/ACR 2013 criteria (4 males and 22 females, mean age 63±17 years; mean disease duration 11±5 years), who complained of secondary RP, started treatment with aminaphtone (75 mg BID) in addition to their stable therapies. All patients provided written informed consent to enter the study and for the management of their clinical data. Blood samples were collected at baseline (W0), after 3 (W3) and 12 weeks (W12), and were frozen (-80 °C) until assayed by ELISA (Ella automated immunoassay system) in triplicate to measure the endogenous level of the active form of TGF-beta. Median values were reported as pg/ml. Laser speckle contrast analysis (LASCA) was also performed at week 0, 3 and 12 to measure digital blood perfusion (2). Statistical analysis was carried out by non-parametric tests. Results: TGF-beta plasma levels progressively decreased from W0 to W12 in aminaphtone treated patients (Freedman test p=0.05; median 7942 [IQR 13411], 7050 [7655], 5154 [3985] pg/ml, respectively at W0, W3 and W12). In particular, the Wilcoxon signed rank test confirmed a strong statistical significance (p=0.007) comparing TGF-beta levels between W3 and W12. Interestingly, at all times, TGF-beta levels were found lower in SSc patients with better clinical response to aminaphtone treatment, as assessed by LASCA (increase of peripheral blood perfusion) than in those with poorer response, even if this difference was not statistically significant (median and [IQR] respectively at W0, W3 and W12 for higher vs poorer-responders: 6137 [14253] vs 10491 [29400], 5940 [13632] vs 10430 [25054], 4861 [7353] vs 5447 [3185] pg/ml). Results are limited by large biological variability of TGF-beta levels since evaluated in a small cohort of patients. No serious side effects were observed during the follow-up, and one patients had to discontinue the treatment due to head ache. Conclusion: Aminaphtone seems to reduce TGF-beta plasma levels in SSc patients when added to their ongoing standard treatment. The reduction of TGF-beta levels as profibrotic mediator might explain, at least partially, the beneficial clinical effects observed in SSc patients treated with aminaphtone. Indeed, TGF-beta might be considered a serum biomarker to assess aminaphtone clinical response in SSc patients in presence of secondary RP, at least within 12 weeks. REFERENCES: [1] Gotelli E et al. Pharmaceuticals (Basel) 2023;16(4):569. [2] Ruaro B et al. Front Pharmacol 2019;10:293. [3] Salazar Get al. Eur. J. Pharmacol. 2016;782:59–69. Acknowledgements: NIL. Disclosure of Interests: Alberto Sulli Laboratori Baldacci, Stefano Soldano: None declared, Emanuele Gotelli: None declared, Andrea Cere: None declared, Rosanna Campitiello: None declared, Elvis Hysa: None declared, Tamara Vojinovic: None declared, Sabrina Paolino: None declared, Maurizio Cutolo Laboratori Baldacci.

The temporomandibular disorders (TMDs) encompass a heterogenous group of inflammatory and degenerative diseases which impair the masticatory function causing local pain and dysfunctional consequences of the temporomandibular joint (TMJ) [1].To systematically review the literature concerning TMDs in immune-mediated rheumatic diseases (IMRDs) of the adult and synthetize their burden in multiple domains of clinical interest: patient-reported outcomes (PROs), frequencies of signs on physical examination, imaging features, histological findings, and risk factors for their development in patients with IMRDs.A literature search on PubMed Central, Embase and Cochrane Library databases was performed, until June 2022, for studies including TMJ outcomes in IMRDs patients compared with healthy controls, other rheumatic diseases or in the assessed IMRDs patients after follow-up and treatment.Among the IMRDs of the adult, original articles investigating TMJ involvement in inflammatory polyarthritides and/or autoimmune connective tissue diseases were considered.The TMJ outcomes used in clinical studies, the prevalence of TMDs in IMRDs and the risk factors for their development were qualitatively synthetized.The quality of the studies was scored using the Newcastle-Ottawa scale (NOS).Of the 3259 screened abstracts, 56 papers were included in the systematic review. All of them were evaluated as of fair quality, at least.Most of the papers (77%) investigated TMDs in rheumatoid arthritis (RA) with a prevalence of signs and symptoms varying from 8% to 70%(Table 1).The risk factors for TMDs development in RA were female sex, younger age, anti-citrulline peptide antibodies (ACPA) positivity, higher disease activity, cervical spine involvement, cardiovascular and neuropsychiatric comorbidities(Figure 1).Ten papers (18 %) evaluated TMDs in spondylarthritides (SpA) reporting a prevalence of symptoms and signs in 12%-80% of patients with higher TMDs prevalence in patients with radiographic spine involvement, skin psoriasis and HLADRB1*01 positivity.Among autoimmune connective tissue diseases (CTDs), systemic sclerosis (SSc) displayed the highest evidence of TMDs PROs and clinical findings (20-93%), followed by systemic lupus erythematosus (SLE) in 18-85%, mixed connective tissue disease (MCTD) in 31-63%, primary Sjögren’s syndrome (pSS) in 24-54% and idiopathic inflammatory myopathies (IIMs) in 4-26%.In SSc and SLE, TMDs were more frequent in patients with higher disease activity and duration, correlating with the extent of skin fibrosis in SSc and with renal involvement in SLE.TMDs in IMRDs display a significant relevance in the rheumatological clinical practice even if they are often overlooked.This burden is epidemiologically important in terms of PROs and clinical findings which correlate with disease activity in RA, SpA, SSc and SLE.The early recognition and multidisciplinary management of TMDs is warranted and should be aimed at hindering the TMJ structural damage maximizing the quality of life of patients.[1]Covert et al. Diagnostics 2021Table 1.Prevalence of TMJ findings across multiple clinical domains in different IMRDs.IMRD Domains of TMJ involvementRASpASScSLEpSSMCTDIIMsNumber of studies investigating TMJ involvement43/56(77%)10/56(18%)5/56(9%)4/56(7%)4/56(7%)3/56(5%)1/56(2%)Prevalence of TMJ PROs8-70%12-80%20-93%31-66%24-54%31%17-26%Prevalence of TMJ signs on physical examination(i.e., reduced mouth opening)30-54%17-68%44-71%41-85%24-44%50-63%4-13%Imaging findings on X-ray of TMJ50-66%30-38%NA22%NA19%NAImaging findings on computerized tomography of TMJ61-76%NANANANANANAImaging findings on magnetic resonance imaging of TMJ11-95%6-67%67-94%NANA13-93%NAHistological findings of TMJSynovitis and degenerative changesNANANANANANALegenda.NA: not assessed. See the text for the other abbreviations.Figure 1.Risk factors for TMJ involvement in RA, SpA, SSc and SLE (created with biorender.com)NIL.None Declared.

Background Nailfold videocapillaroscopy (NVC) safely allows the detection of microvascular damage which can vary in terms of extent and severity (validated NVC patterns) in patients with Raynaud's phenomenon (RP) secondary to autoimmune connective tissue diseases (CTDs). Objectives The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of patients with RP secondary to a CTD at the time of the first single NVC analysis, independently from their current treatment, autoantibody profile and comorbidities. Methods One-thousand-one-hundred-eighty-one (1181) patients affected by CTDs (1065 females, mean age 54.1 ± 16.2, mean disease duration 4.5 years ± 3) were analysed from 2001 to 2021. The considered CTDs, diagnosed through the classification criteria available at the time of the enrollment, included: systemic sclerosis (SSc, 51%), undifferentiated connective tissue disease (UCTD, 26%), mixed connective tissue disease (MCTD, 6%), dermatomyositis (DM, 3%), systemic lupus erythematosus (SLE, 9 %), Sjögren's syndrome (SS, 3%) and primary anti-phospholipid syndrome (aPS, 2%). The capillaroscopic parameters were classified according to the CAP Fast Track Algorithm and distinguished between scleroderma-pattern (specific NVC alterations) and non-scleroderma patterns (non-specific NVC alterations) [1]. The presence of specific NVC findings detectable with a progressive microangiopathy in SSc patients (“early”, “active”, “late” patterns) have been searched also in other CTDs, beyond SSc. The “scleroderma-like pattern” was defined when a concomitant mix of the specific abnormalities of the SSc-patterns (namely: giant capillaries, loss of capillaries, capillary dilations, microhaemorrhages, abnormal shapes) was detected without fitting the single definition of “Early”, “Active” or “Late” pattern [2]. Results Among CTDs, the mean capillary density (1 linear mm) was significantly lower in SSc, DM and MCTD (respectively, 7.04 ± 0.18 vs 6.5 ± 0.75 vs 7.7 ± 0.48) compared with other CTDs. “Early”, “Active” and “Late” NVC scleroderma patterns were detected in 34%, 38% and 16% of SSc patients, whereas the scleroderma-like pattern was found significantly more frequent in DM (63 %) and MCTD (37%).Giant capillaries, capillary dilations and microhaemorrages were significantly more frequent in SSc and DM compared with other CTDs (respectively in 73%, 99% and 70% of SSc patients e in 73%, 96% e 70% of DM patients, Figure 1). The non-specific abnormalities of capillary morphology, such as the ramifications (abnormal shapes as expression of neoangiogenesis) were significantly more frequent in SSc, MCTD and APS among all the CTDs (respectively, in 48%, 41% and 36% of cases). Moreover, giant capillaries and abnormal shapes were detected in 61% and 41% of MCTD patients. In APS, the most significant prevalence of microhaemorrages (50%) was observed compared with other CTDs, to the exclusion of SSc and DM being detectable in 70% of cases. No significant damages were observed in SS and SLE patients (Figure 1). Conclusion This large sample size of CTDs patients, collected over 20 years of analysis, confirms the highest specificity and severity of the NVC microvascular damage respectively in SSc and DM patients, when compared to other CTDs. Those data will be used to implement easy algorithms to distinguish scleroderma patterns, from non-scleroderma and scleroderma-like patterns. Reference [1]Smith V et al. Autoimmun Rev 2019 [2] Cutolo M et al. Nature Rev Rheumatol 2021 Acknowledgements Elvis Hysa, Silvia Sammorì and Carmen Pizzorni equally contributed to this work. Disclosure of Interests None Declared.Figure 1Frequency of capillary density, giant capillaries, abnormal shapes and microhemorrhages across different CTDs (see text)

Background Connective tissue diseases (CTDs) are a heterogeneous group of autoimmune disorders and, among them, mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease (UCTD) show overlap symptoms with other CTDs, but share secondary Raynaud's Phenomenon (sRP) as a typical vascular symptom[1,2].Laser speckle contrast analysis (LASCA) is a reliable tool to measure the peripheral blood perfusion (PBP) and has already demonstrated to be useful in detecting the peripheral microcirculation status of SSc patients and severe sRP[3]. Objectives To measure hand PBP in patients with sRP in CTDs (MCTD, UCTD) and to compare it with healthy controls (HCs). Methods Twenty-four CTDs patients with sRP (7 with MCTD, 17 with UCTD) and 28 age- and sex-matched HCs were evaluated during standard follow-up assessments. CTDs diagnoses were set up according to the international classification criteria[4,5]. Patients had a stable therapy (mainly glucocorticoids and conventional disease modifying anti-rheumatic drugs) and had not had intravenous vasodilator treatments for the previous three months at least.All subjects underwent a LASCA registration (Laser Speckle Contrast Analysis - Pericam PSI, Perimed, Jarfalla) after acclimatization of 15 minutes at 20-22°C. After recording, PBP was quantified (perfusion units, P.U.) in the following region of interests (ROIs): fingertips (with and without thumbs) and periungual areas (with and without thumbs).Statistical analysis was performed using DATATab®, with parametric tests in case of normally distributed data and non-parametric tests in case of non-symmetrically distributed data. Results Although not statistically significant, a trend to a lower PBP was found when comparing MCTD LASCA values versus UCTD LASCA values, particularly for ROIs of periungual areas (see Table 1). In addition, PBP was found significantly lower in MCTD and UCTD when individually compared with HCs. This result was confirmed for all four ROIs (p<0,02; see Table 1). Conclusion To our knowledge, no evaluations of PBP by LASCA are available in literature in other CTDs other than SSc[6]. This preliminary study showed, using the LASCA methodology, that the PBP in MCTD and UCTD patients affected by sRP is significantly lower than in age- and sex-matched HCs. A trend with a lower PBP in MCTD patients than UCTD patients was observed but did not reach a statistical significance due to the small sample size.These results may demonstrate a potential role of LASCA in assessing the vascular involvement of CTDs other than SSc. Further investigations on a larger and more homogeneous sample size and a focus on the possible correlations between PBP and the morphological microvascular damage assessed by nailfold videocapillaroscopy have been planned. References [1]Pauling, J. D. et al., Clin. Rheumatol., 2019.[2]Hirschl, M. et al., Arthritis Rheum., 2006.[3]Cutolo, M. et al., Autoimmun. Rev., 2018.[4]Tani, C. et al., J. Autoimmun., 2014.[5]Antunes, M. et al., RMD Open, 2019.[6]Ruaro, B. et al., Ann. Rheum. Dis., 2014. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Mean age and mean PBP in MCTD, UCTD and HCs, as measured by laser speckle contrast analysis (LASCA). PBP: peripheral blood perfusion; MCTD: mixed connective tissue disease; UCTD: undifferentiated connective tissue disease; HCs: healthy controls; P.U.: perfusion units.MCTDUCTDHCsp-valuesAge (years)Mean ± SD59.8±14.251.2±15.957.6±11.7n.s.Mean fingertips perfusion (P.U.)132.3±78.2138.7±87.5202.8±59.3MCTD vs HCs: p=0.013 UCTD vs HCs: p=0.005MCTD vs UCTD: n.s.Mean fingertips perfusion (thumbs excluded) (P.U.)131.5±80.1139.2±90.7203.9±60.9MCTD vs HCs: p=0.013 UCTD vs HCs: p=0.006MCTD vs UCTD: n.s.Mean periungual perfusion (P.U.)85.4±51100±55.5146.9±44.3MCTD vs HCs: p=0.003 UCTD vs HCs: p=0.003MCTD vs UCTD: n.s.Mean periungual perfusion (thumbs excluded) (P.U.)85.3±51.199.2±55.7145.4±45.9MCTD vs HCs: p=0.005 UCTD vs HCs: p=0.004MCTD vs UCTD: n.s.

Background Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease characterized by the presence of systemic inflammation, vasculitis, early-onset stroke, and hematologic manifestations such as cytopenia and immunodeficiency. Mucocutaneous and peripheral microvascular manifestations, such as livedo racemosa, cutaneous ulcers and Raynaud’s phenomenon (RP), can occur, in up to 50%, 22% and 8 % of DADA2 patients respectively [1]. Objectives To investigate the microvascular architecture in nailfold capillaries of DADA2 patients comparing them with adequate healthy controls (HCs) and primary RP individuals. Methods The data of 9 patients with DADA2 followed at Istituto Gaslini were retrospectively retrieved and compared to 11 HCs and 7 RP. Clinical and genetic data were collected for DADA2 patients. Nailfold videocapillaroscopy (NVC) findings were collected in the whole cohort, independently from their current treatment. The capillaroscopic parameters were classified according to the Fast Track Algorithm and distinguished between scleroderma-pattern (encompassing specific NVC alteration, such as the presence of giant capillaries and/or loss of capillaries combined with abnormally shaped capillaries) and non-scleroderma patterns (non-specific NVC alterations) [2]. A validated semiquantitative scale (score 0–3 for each NVC parameter) was used to compare microvascular findings in the three groups [3] Results The patients with DADA2 were diagnosed according to genetic testing. The disease onset was in early infancy, while the mean age at NVC was of 18.8 years. Livedo racemosa was present in 7 patients (78%), digital ulcers in 1 patient, and an ischemic stroke was reported in 5 patients (55%). None of the patients had RP (0%). The NVC showed the presence of non-specific alterations in all DADA2 patients (capillary dilations in 100%, abnormally shaped capillaries and haemorrages in 23% of patients). The capillary density was normal (median = 9) and no scleroderma-like pattern was found. No significant differences in the rates of each microvascular finding were detected between DADA2, RP patients and HCs. Conclusion This is the first report investigating the NVC findings in DADA2 patients. Microvascular damage in DADA2 does not show a specific capillaroscopic alteration but the presence of non-specific findings might suggest a disease-related endothelial damage. References [1] Meyts I et al. J Clin Immunol 2018 [2] Smith V et al. Autoimmun Rev 2019 [3] Sulli A et al. Ann Rheum Dis. 2008 Acknowledgements: NIL. Disclosure of Interests None Declared.

BackgroundDescription of flow, measured by laser speckle contrast analysis (LASCA), in ‘early’ systemic sclerosis (SSc) versus ‘clinically overt’ SSc (diffuse cutaneous SSc [DcSSc] and limited cutaneous SSc [LcSSc]) has not yet been described [1].ObjectivesTo investigate in an unselected, SSc cohort if baseline LASCA PBP-measurements differ between ‘early’ SSc and ‘clinically overt’ SSc.MethodsBetween September 2019 and December 2022, patients with SSc (as defined by the 2013 ACR/EULAR criteria and/or the 2001 LeRoy and Medsger criteria) were included [1,2]. A group of 20 consecutive ‘early’ SSc, LcSSc and DcSSc patients were recruited. Vasoactive medication was continued. LASCA was performed at baseline in standardized instrumental and environmental conditions [3]. PBP was assessed by marking regions of interest (ROI’s) with fixed 1 cm diameters at the fingertips of the 2nd through 5th digit volary bilaterally. The adjusted mean PBP was calculated (expressed in perfusion units [PU]). A linear mixed model was fit with a random intercept per patient, together with a linear covariance structure to capture the residual correlations between fingers. Fixed effect terms included subset, side, finger, vasoactive medication, active smoking, history or presence of digital trophic lesions (DTL), and disease duration. Significance level was set at 0.05 and no correction for multiple testing was applied.ResultsSixty patients with SSc (75% female, mean age 53 years, mean disease duration 73.1 months) were enrolled (table 1). Comparing the adjusted mean PBP at baseline in ‘early’ versus ‘clinically overt’ SSc, no statistical significant difference was found (144 vs. 150 PU, p=0.77) (figure 1A). Additionally within the ‘clinically overt’ group no significant difference was perceived between DcSSc and LcSSc (157 vs. 141, p=0.53). A wide variability was noted when observing the individual measurements of each subset (figure 1B).ConclusionThis study with an unselected day-to-day SSc population, where patients were allowed to continue their vasoactive medication, showed there was no difference in PBP at baseline between ‘early’ SSc and ‘clinically overt SSc’ when corrected for subset, vasoactive medication, active smoking, history or presence of DTL and disease duration. Interestingly a wide variation of individual datapoints was noted in each subset, which emphasizes the heterogeneity of SSc. In conclusion, there is no inter-individual variation between the different subsets of SSc, as measured with LASCA. Future investigation is needed to enlighten us about the intra-individual changes over time.References[1]E.C. LeRoy, T.A. Medsger Jr. J Rheumatol. 2001; 28(7):1573-1576. [2]van den Hoogen F, Khanna D, et al. Arthritis Rheum. 2013;65(11):2737–47. [3]Cutolo M, Vanhaecke A, et al. Autoimmun Rev. 2018;17(8):775-80.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Objective: To systematically review the literature concerning temporomandibular disorders (TMDs) in immunemediated rheumatic diseases (IMRDs) of the adult. The temporomandibular joint (TMJ) outcomes used in clinical studies, the prevalence of TMDs in IMRDs and the risk factors for their development were qualitatively synthetized.Methods: A literature search on PubMed Central, Embase and Cochrane Library databases was performed for studies including TMJ outcomes in IMRDs patients compared with healthy controls, other rheumatic diseases or in the assessed IMRDs patients after follow-up and treatment. Among the IMRDs of the adult, original articles investigating TMJ involvement in inflammatory polyarthritides and/or autoimmune connective tissue diseases were considered. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS).Results: Of the 3259 screened abstracts, 56 papers were included in the systematic review. Most of the papers (77%) investigated TMDs in rheumatoid arthritis (RA) with a prevalence of signs and symptoms varying from 8% to 70%. The risk factors for TMDs development in RA were female sex, younger age, anti-citrulline peptide autoantibodies (ACPA) positivity, higher disease activity, cervical spine involvement, cardiovascular and neuropsychiatric comorbidities. Ten papers (18%) evaluated TMDs in spondylarthritides (SpA) reporting a prevalence of symptoms and signs in 12%-80% of patients with higher TMDs prevalence in patients with radiographic spine involvement, skin psoriasis and HLADRB1x01 positivity. Among autoimmune connective tissue diseases (CTDs), systemic sclerosis (SSc) displayed the highest evidence of TMDs patient-reported outcomes (PROs) and clinical findings (20-93%), followed by systemic lupus erythematosus (SLE) in 18-85%, primary Sjogren's syndrome (24-54%) and idiopathic inflammatory myopathies (4-26%). In SSc and SLE, TMDs were more frequent in patients with higher disease activity and duration, correlating with the extent of skin fibrosis in SSc and with renal involvement in SLE.Conclusion: TMDs in IMRDs display a significant relevance in the rheumatological clinical practice even if often misdiagnosed. This burden is epidemiologically important in terms of PROs and clinical findings which correlate with disease activity in RA, SpA, SSc and SLE. The early recognition and multidisciplinary management of TMDs is warranted and should be aimed at hindering the TMJ structural damage maximizing the quality of life of patients.

Background Hypermobile Ehlers Danlos syndrome (hEDS) is the most common subtype among the EDS syndromes and is a rare inherited connective tissue disease characterized mostly by hyperextensible skin and generalized joint hypermobility. Microvascular assessment has been documented only by one case report in the “vascular type” of EDS, despite vascular manifestations may occur also in other EDS subtypes [1,2]. A reduced skin thickness has been previously reported in hEDS patients [3]. Objectives To investigate, for the first time, nailfold microvascular status in hEDS patients in comparison with healthy controls (HCs). Peripheral blood perfusion (PBP) and dermal thickness (DT) were also assessed. Methods Twelve hEDS patients (75% females, mean age 41±16, classified with the 2017 International Classification Criteria of EDS [4]) and twelve age- and sex-matched HCs were observed from 2018 to 2022. Beighton score was calculated for both patients and HCs. Main nailfold videocapillaroscopy (NVC) parameters (dilated capillaries, giant capillaries, microhemorrhages, abnormal shapes and number of capillaries) were analysed and compared between the two groups to assess morphological features [5]. To assess the microvascular functional status, laser speckled contrast analysis (LASCA) was used to measure PBP in several region of interests. DT was also measured by cross-sectional B-mode scans obtained by a high-frequency 22 MHz ultrasound probe in 17 different areas of the body (including upper arms, lower arms, trunk and forehead). Results No statistically significant differences were observed in this small cohort between hEDS and HCs concerning the microvascular findings detected by NVC, even if microhemorrages were more prevalent in hEDS patients (33% vs 0 %) (see Table 1). Also, PBP assessed by LASCA was found similar in hEDS patients and HCs (178.12 ± 49.76 perfusional units vs 157.81 ± 67.15 at fingertips, p = 0.43). The mean DT did not significantly differ from hEDS patients and HCs in all skin areas (mean total DT of 18.44 ± 2.21 mm in hEDS patients vs 18.49 ± 2.13 mm in HCs, p = 0.96). As expected, the mean Beighton score was significantly higher in hEDS patients than in HCs (5.54±1.75 vs 1.25±1.58), but no significant correlation was detected between DT and Beighton score (r = 0.1, p = 0.76). Conclusion Microhemorrages seem more prevalent in hEDS patients than in ECs, suggesting a subclinical microvascular fragilility also in this subgroup of EDS patients. Skin ultrasound and PBP findings did not detect significant differences between hEDS patients and HCs, which might be due to the small sample size. These findings will be followed by further research including cases of the vascular EDS phenotype [6]. References [1]D'hondt S et al. Genet Med 2018.[2]Superti-Furga A et al. Int J Microcirc Clin Exp 1992.[3]Eisenbeiss C et al. Br J Dermatol 2003.[4]Malfait F et al. Am J Med Genet C Semin Med Genet 2017.[5]Sulli A et al. Ann Rheum Dis 2014.[6]Sulli A et al. RMD Open. 2018. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1NVC in hEDS vs HCs. See text for abbreviationsNVC findingshEDS (n = 12)HCs (n = 12)p -valuesMean capillary number9.4±0.88.8±0.480.08Dilations n (%)10 (83%)10 (83%)0.97Giant capillaries n (%)001Microhaemorrages n (%)4 (33%)00.09Abnormal shapes n (%)3 (25%)4 (33%)0.65

BackgroundRecent studies show that Aminaphtone is effective in the treatment of Raynaud’s phenomenon (RP) symptoms in patients with systemic sclerosis (SSc), and an increase in peripheral blood perfusion was demonstrated by Laser speckle contrast analysis in treated patients (1,2). Unfortunately, the drug is only available in a few countries.ObjectivesTo evaluate long-term tolerability and safety of Aminaphtone in SSc patients with secondary RP.MethodsSeventy SSc patients (EULAR/ACR criteria) (mean disease duration 8±7 years, mean age 61±10 years) who started Aminaphtone treatment due to active RP were enrolled and followed for at least 4 years. Patients were also taking various concomitant treatments, including immunomodulators, cyclic intravenous iloprost, endothelin receptor antagonists and aspirin. None was taking sildenafil or selexipag. Survival of Aminaphtone in therapy was assessed along with possible drug-related side effect. The Raynaud condition score (RCS) to asses disease severity and blood examinations were routinely performed.ResultsThe mean follow-up of patients was 49±11 months. Aminaphtone was orally administered at 75 mg twice daily, as standard initial posology in our clinical practice. During the follow-up, six patients (8,6%) referred headache as side effect and had to reduce Aminaphtone posology to 75 mg per day, while maintaining clinical benefits. No other side effect related to the drug was observed during the follow-up. Seven patients increased the posology to 75 mg three times daily due to poor effectiveness, and further seven patients increased the posology to 75 mg three times daily only during the colder months of the year. Conversely, thirty-five patients reduced the dosage to 75 mg once daily only during the hottest months of the year, due to partial remission of the RP. During follow-up, blood tests did not reveal any significant alteration ascribable to Aminaphtone. A subjective improvement of Raynaud’s symptoms (assessed by the RCS) was already evident after 1-2 months of treatment in fifty-six patients (80%). Globally, the patients referred a sustained improvement followed by stabilization of Raynaud’s symptoms during the follow-up.ConclusionDuring an average observation period of four years, Aminaphtone showed a good tolerability and safety profile along with sustained efficacy in patients with SSc-related RP, without disabling or serious side effects. A randomized controlled trial for Aminaphtone use in the management of SSc-related RP is desirable to better assess the clinical efficacy of the drug over time.References[1]Parisi S, et al. Am J Int Med. 2015;3:204–209. 2. Ruaro B et al. 2019. Front Pharmacol 10:293.Disclosure of InterestsANDREA CERE: None declared, Emanuele Gotelli: None declared, Adriano Lercara: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Elisa Alessandri: None declared, Maurizio Cutolo Grant/research support from: Bristol Myers Squibb, Celgene, Pfizer, Boehringer Ingelheim, Alberto Sulli: None declared

OBJECTIVESWe aimed to investigate the clinical off-label use of mycophenolate mofetil (MMF), including its safety and efficacy in patients with rare and complex rheumatic connective tissue diseases (rCTDs).METHODSA survey was distributed across experts from ERN-ReCONNET reference centres in order to assess the experience with MMF off-label use. Patient-level data of patients with rCTDs under treatment with MMF was also collected for analysis of safety and efficacy.RESULTSTwelve experts from eleven centres distributed throughout Europe (7 countries) answered the survey. The experience was concordant in that, despite of its off-label use, experts reported opting frequently for this therapeutic alternative with robust confidence on its efficacy and safety. The analysis of 108 patients with rCTDs under MMF revealed a good safety profile, as well as good clinical outcomes, especially for systemic lupus erythematosus and idiopathic inflammatory myopathies. The presence of interstitial lung disease was, as expected, associated with a worse clinical outcome despite use of MMF.CONCLUSIONSMMF is widely used in reference centres for rCTDs. Its safety profile and efficacy seem to be recognised by experts and demonstrated with patient-level analysis. While selected rCTDs will likely remain an off-label indication for MMF, robust data seem to support this therapy as an appropriate alternative for safely and effectively treating many manifestations of rCTDs.

Background The pathogenesis of systemic sclerosis (SSc) is thought to result from interactions between epigenetic features and environmental factors, leading to the onset and progression of the disease in genetically susceptible patients (1). Case reports of women with silicone breast implants who developed SSc have been published, but case-control and prospective studies in connective tissue diseases often failed to find an increased risk of SSc associated with silicone cosmetic surgery (2,3). These studies have several limitations, including heterogeneous cohorts of enrolled patients not selective for SSc, non-homogeneous disease duration or disease stage at study entry. For these reasons, the possible effect of silicone implants as immune adjuvants is highly suspected but remains unclear (4). Objectives Retrospective study of SSc patients, to find out who developed SSc after silicone cosmetic surgery. Methods The clinical files of 140 female patients with systemic sclerosis were retrospectively evaluated and clinical data collected. Results Five patients showing a history of silicone cosmetic surgery (3.6%) before SSc development were identified. The brief clinical histories of the five patients are below reported, showing very similar outcomes after silicone implant. 1. TC 47-year-old female underwent cosmetic breast prosthesis: twelve months later she experienced Raynaud’s phenomenon (RP) and diffuse cutaneous SSc after 10 further months; antinuclear antibodies were positive with a speckled and nucleolar pattern, but specific SSc-related autoantibodies negative. 2. LS 28-year-old female underwent cosmetic breast prosthesis: twenty-two months later RP appeared and anticentromere antibodies (ACA) positive aggressive diffuse SSc was diagnosed one year later. 3. PJ 38-year-old female underwent cosmetic breast prosthesis: eleven months later she experienced RP and after 10 further months, aggressive diffuse cutaneous SSc; antinuclear antibodies were positive with a speckled patter, but specific SSc-related autoantibodies were negative. 4. CM 58-year-old female who underwent cosmetic lip silicone application: one year later she complained of simultaneous onset of RP and very aggressive diffuse cutaneous SSc with anti-topoisomerase positivity; she died during follow-up. 5. BS 33-year-old female who underwent cosmetic breast prosthesis: twenty months later she complained of RP and after ten further months, limited cutaneous SSc with ACA positivity; SSc clinical condition partially improved and its progression stopped after prosthesis removal. Globally, after silicone implant, RP occurred in a mean time of 15±5 months and SSc in 23±8 months. Conclusion This study reports a prevalence of 3.6% of silicone cosmetic surgery before SSc onset, interestingly with a close and similar temporal association between silicone implant and disease development. This finding suggests a possible role of silicone in SSc pathogenesis (ASIA syndrome). Specifically addressed large clinical studies or big-data studies need to rule out this matter. References [1]Denton C, et al. Lancet 2017; 390: 1685–99. [2]Marie I et al. Semin Immunopathol 2015; 37:463–473. [3]Coroneos CJ et al. Ann Surg. 2019 Jan;269(1):30-36. [4]Watad A et al. Lupus. 2017; 26:675-681. Disclosure of Interests Adriano Lercara: None declared, Alberto Sulli: None declared, Carmen Pizzorni: None declared, Emanuele Gotelli: None declared, Sabrina Paolino: None declared, ANDREA CERE: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Celgene, Pfizer, Boehringer-Ingelheim

Background:Aminaphtone has been used since many years to treat microvascular disorders. Aminaphtone seems to improve clinical symptoms of Raynaud’s phenomenon (RP), either primary or secondary to systemic sclerosis (SSc) by increasing peripheral blood perfusion as assessed by Laser speckle contrast analysis (1).Objectives:To evaluate long-term survival and tolerability of Aminaphtone in SSc patients with secondary RP.Methods:Eighty SSc patients (mean age 64±12 years; mean disease duration 9±8 years) treated with Aminaphtone due to active RP were enrolled (ACR/EULAR 2013 criteria). Patients were taking also various concomitant treatments, including aspirin, cyclic intravenous iloprost, immunomodulators, endothelin receptor antagonists. SSc patients performed periodic clinical and laboratory assessments on average every four months per our clinical practice. Duration of Aminaphtone administration, side effects, and self-assessment of Raynaud Condition Score (RCS) with a scale from 0 (absence of pain) to 10 (maximal pain) were retrospectively assessed.Results:The observation period was between twelve and seventy months (mean 36±19 months). Aminaphtone was administered at 75 mg twice daily, as standard initial posology per our clinical practice. During the follow-up, five patients (6.2%) referred headache as side effect: three of them had to reduce Aminaphtone posology to 75 mg per day, while maintaining clinical benefits; two patients had to stop the treatment. No other side effects related to the drug appeared during the treatment period, and repeated blood tests did not reveal any significant alteration ascribable to Aminaphtone. After 3 months of treatment sixty-six patients (83%) referred a subjective improvement of RP (RCS 3.6±0.8, vs baseline RCS 7.4±0.8, p=0.032), whereas fourteen patients (17%) were clinically unsatisfied (RCS 6.1±0.4, p=0.12). In this last group of patients, Aminaphtone posology was increased to 75 mg three times a day with a satisfactory amelioration in further nine patients (94% of total) (RCS 4.0±0.6, p=0.04), while five patients (6.2%) definitively discontinued therapy for subjective ineffectiveness within six months. Patients referred a sustained improvement of RCS along the observational period (36±19 months) (last RCS 3.6±0.7 vs baseline, p=0.031).Conclusion:During an average observation period of three years, Aminaphtone showed a good tolerability profile along with sustained efficacy in 94% of patients with SSc-related RP, without disabling side effects. The absence of a placebo-control group, the retrospective design limit the results, and a randomized controlled trial for Aminaphtone use in the management of SSc-related RP is needed.References:[1]Ruaro B et al. 2019. Front Pharmacol 10:293.Disclosure of Interests:Alberto Sulli: None declared, Emanuele Gotelli: None declared, ANDREA CERE: None declared, Elvis Hysa: None declared, Greta Pacini: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Maurizio Cutolo Grant/research support from: Laboratori Baldacci s.p.a.

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by self-amplifying microvascular damage sustained by autoimmune response and progressive skin and visceral fibrosis. Besides, SSc patients show higher incidence of bone micro/macroarchitectural damages and bone fractures. Emerging data demonstrate that high serum levels of homocysteine (Hcy) could modulate osteoclastogenesis and are recognized as risk factors for osteoporosis (2). Furthermore, serum levels of Hcy were found to be higher in SSc patients than in healthy controls (3).Objectives:to evaluate the bone status according to HCy serum levels in a cohort of SSc patients.Methods:20 female patients fulfilling ACR 2013 criteria for SSc underwent a dual-energy X-ray absorptiometry scan (DXA) (Lunar Prodigy) to evaluate bone status. We analysed bone quantity and quality respectively by bone mineral density (BMD) and trabecular bone score (TBS). According to the WHO criteria, osteoporosis was defined as a bone density of 2.5 standard deviations below that of a young adult (T-Score). Fasting blood samples were obtained from all patients in order to test serum Hcy level and bone turnover markers after obtaining the informed consent. All subjects underwent morphometric spine X-Ray to evaluate vertebral fractures. Statistical analysis was performed using non-parametric tests.Results:The mean age of patients was 64.15 ± 10.8 years with a mean disease duration of 9.1 ± 2.3 years. The mean modified Rodnan Skin Score (mRSS) was 10.7 ± 8.5. All patients showed a “scleroderma pattern” at nailfold Videocapillaroscopy (NVC): in particular, 7 patients showed the “Late” pattern, 9 patients the “Active” pattern and 4 patients the “Early” NVC pattern. Hyperomocisteinemia (HHcy) was found in 25% of patients. Interestingly, SSc patients with the “Late” NVC pattern showed a significantly higher serum level of Hcy compared to the “Early/Active” group (11.15 ± 4.4 vs 17.17 ± 6.4, p=0.03). No significant differences were observed in relation to the autoantibody profiles. Of note, 60% of patients with HHcy were found osteoporotic and 40% had bone fractures.Considering the bone status, patients with Hcy showed a significantly lower TBS (p=0.03); the average values of BMD on the lumbar spine (p=0.79) and femoral neck (p=0.13) were found lower compared to, but without any statistical significance. Furthermore, no significant differences were observed in bone turnover markers according to Hcy levels.Conclusion:The study demonstrates a relationship between higher levels of Hcy and lower TBS values within SSc patients, particularly in those with most severe microvascular damage al NVC (“Late” SSc pattern). Therefore it is concluded that higher serum levels of Hcy associate to both bone microarchitectural and microvascular damage in SSc.References:[1]Cutolo M et al Expert Rev Clin Immunol 2019; 15: 753-64[2]Behera J et al. J Cell Physiol 2017;232(10):2704-2709[3]Yan-lie Zhang et al. Rheumatol 2018; 28(4):681-689Disclosure of Interests:None declared