Causes of Raynaud’s phenomenon and the predictive laboratory and capillaroscopy features for the evolution to a definite connective tissue disease

Objective In patients with RP, capillaroscopy is useful for discriminating primary from secondary causes. There are certain capillaroscopy and lab values as predictive factors leading to a known CTD. We conducted the present study to evaluate the causes of RP in our area and followed the studied subjects to find prognostic factors indicating a definite CTD or remaining a UCTD. Methods In this retrospective cohort study we included all adult patients with RP who were referred for capillaroscopy from 2010 to 2019. All the patients with primary and secondary RP with follow-up were evaluated for demography, laboratory results and capillaroscopy to find the risk factors of their progression to a CTD. Results A total of 760 of 776 patients were included, with 679 being female (89.3%) and 81 (10.7%) male. There were 660 subjects (90.8%) with secondary RP [mostly UCTD (48.2%) and then SSc (16.4%)] and 67 (9.2%) with primary RP; 109 patients were followed up and 42 (42%) of those with secondary RP developed a definite CTD. The scleroderma pattern and some capillary changes on capillaroscopy and/or positive ANA had statistically significant differences for CTD transition. Conclusion We had a small number of patients with primary RP. The most prevalent causes of secondary RP in our patients were UCTD and SSc. Some capillaroscopy and laboratory results alone or in combination could be used as a predictive marker for the transition of patients with UCTD to CTD.

Relation between nailfold capillaroscopic pattern (assessed using a dermoscope) and organ involvement in systemic sclerosis

Objectives: The objectives of the study were: (1) To document the nailfold capillary changes (using a dermoscope) in patients with systemic sclerosis attending a tertiary care center, (2) to study the relation between nailfold capillaroscopic pattern and skin sclerosis assessed by modified Rodnan skin score (mRSS), and (3) to study the relation between nailfold capillaroscopic pattern and organ involvement in systemic sclerosis. Materials and Methods: A cross-sectional study was conducted among 40 patients with systemic sclerosis who attended the dermatology outpatient department of a tertiary care center from January 1, 2018, to December 31, 2018. Nailfold capillaries were examined with the help of dinolite dermoscope AM4113ZT at 50× and 200× magnification, under polarized light. Results: Study participants included 34 (85%) females and 6 males (15%). The nailfold capillaroscopy showed “early scleroderma pattern” in 3 (7.5%) “active pattern” in 28 (70%) and “late pattern” in 9 (22.5%) patients. “Late scleroderma pattern” showed a significant association with disease duration, mRSS, and mean number of organs affected. Limitations: The study participants may be over-representing advanced cases since the study was conducted among patients attending a tertiary referral center. Conclusion: We found dermoscope to be a useful tool to study the nailfold capillary changes in patients with systemic sclerosis as reported by others. Late scleroderma pattern may serve as an indicator of high mRSS and involvement of more number of organs in systemic sclerosis.

POS1409 AUTOMATED DETECTION OF SCLERODERMIFORM PATTERNS USING CAPILLARY.IO

Background:A nailfold capillaroscopy procedure is a non-invasive, low-cost, and well-established examination that can be used to diagnose several rheumatic autoimmune diseases and support the necessary follow-up of patients. While the clinical implications of the technique are known, a rigorous and in-depth examination of nailfold capillaries remains as one of the major challenges to produce new advances in research and diagnosis, due to practical limitations for analysing the whole nailfold area of each patient. The difference between the different patterns established by Maricq and Cutolo makes it possible to predict the evolution that the patient will present. We introduce Capillary.io, an automatic image reading system able to recognize capillaries in images obtained with any microscope, generate automatic measurements of each capillary and take advantage of this information to report capillary morphology and patterns.Objectives:to determine the ability to detect active and early scerodermiform patterns of Capillary.io.Methods:Forty-nine complete capillaroscopies, reported by expert capillaroscopists according to the different patterns manually (gold standard), were compared with the pattern detection capability of Capillary.io. A scoring system based on the algorithm of the Spanish Capillaroscopy Study Group (GREC) was performed and interpreted by capillary.io for the global interpretation of each of the capillaroscopies analyzed.Results:Overall, 37 of the 49 capillaroscopies reported agreed with the diagnosed pattern (75.51%). Separately, the early pattern presented a concordance of 77.27% and the active pattern of 74.07%. In reference to the findings detected by the Capillary.io system, the mean overall density was 5.01 capillaries/mm in the group with the active pattern compared to 6.46 capillaries/mm in the early pattern. The density of dilations and megacapillaries was 2.81/mm and 1.21/mm in the active pattern group versus 4.69/mm and 0.4/mm in the early pattern group. Global diameters were greater in the active pattern group with an apical mean of 37.3 μm compared to 28.5 μm in the early pattern subgroup.Conclusion:Capillary.io is a simple, easy-to-learn web system for interpreting capillaroscopic images of nail folds. It can be a very useful tool to standardize the interpretation of capillaroscopic images, not only individually for each capillary, but also jointly through the detection of different patterns.References:[1]Chen K, Wang J, Pang J, Cao Y, Xiong Y, Li X, et al. MMDetection: Open MMLab Detection Toolbox and Benchmark. arXiv preprint arXiv:190607155 2019;.[2]Cutolo M, Pizzorni C, Sulli A. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis - Reply. The Journal of Rheumatology 2000 11;27:2722–2723.[3]Cutolo M, Trombetta AC, Melsens K, Pizzorni C, Sulli A, Ruaro B, et al. Automated assessment of absolute nailfold capillary number on videocapillaroscopic images: Proof of principle and validation in systemic sclerosis. Microcirculation 2018 May;25(4):e12447.[4]Smith V, Vanhaecke A, Herrick AL, Distler O, Guerra MG, Denton CP, et al. Fast track algorithm: How to differentiate a “scleroderma pattern” from a “non-scleroderma pattern”. Autoimmu- nity Reviews 2019 nov;18(11):102394.[5]Tavakol ME, Fatemi A, Karbalaie A, Emrani Z, Erlandsson BE. Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be Evaluated? BioMed Research International 2015;2015:1–17.Disclosure of Interests:Eduardo Ramos Shareholder of: Co-founder and shareholder of Capillary.io, Alfredo Guillén-Del-Castillo: None declared, Carmen Pilar Simeón-Aznar: None declared, Borja Gracia Tello Shareholder of: Co-founder and shareholder of Capillary.io, Vicent Fonollosa Pla: None declared, Albert Selva-O’Callaghan: None declared, Luis Sáez-Comet: None declared, Elena Martínez Robles: None declared, Juan José Rios: None declared, Gerard Espinosa: None declared, Jose Antonio Todolí Parra: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Begoña Marí-Alfonso: None declared, Mayka Freire: None declared, Patricia Fanlo: None declared

POS0850 NAILFOLD CAPILLARY DILATIONS IN RAYNAUD’S PHENOMENON: QUANTIFYING A PREDICTIVE THRESHOLD FOR THE ‘SCLERODERMA PATTERN’

Background:Non-specific abnormalities could be detected by nailfold videocapillaroscopy (NVC) in subject with primary Raynaud’s Phenomenon (RP) several years before the clinical onset of connective tissue diseases (CTD)s [1]. Previous findings from our group proved that ≤30 μm capillary dilations in RP patients have a negative predictive value for developing the ‘scleroderma pattern’ during follow-up [2].Objectives:To investigate the role of NVC >30 μm capillary dilations as positive predictive factors of the ‘scleroderma pattern’ in RP patients later developing systemic sclerosis (SSc)-related RP.Methods:A 10-year retrospective NVC-based investigation evaluated the dataset of sequential NVCs of 18 RP patients later developing SSc (cases) and 19 sex- and age-matched RP patients later developing other CTDs (controls). Both cases and controls had ≥1 NVC performed before the ‘scleroderma pattern’/CTD diagnosis (basal NVC) showing >30 μm dilated capillaries. Each NVC was qualitatively and semi-quantitatively assessed, recording number of total capillaries, number and average/site-specific diameters (arterial, apical, venous) of >30 μm dilated capillaries [3]. Statistical analysis was performed to stratify the risk of developing the ‘scleroderma pattern’.Results:Significant differences of capillary diameters were observed between cases and controls both at basal NVC and during follow-up (p<0.001). The proportion of >30 μm dilated capillaries in basal NVC was the strongest predictor of ‘scleroderma pattern’ in a median 3-year time, with a 27% cut-off (PPV 0.79, 95%CI 0.54,0.94; p<0.001). Additional “Higher risk” NVC hallmarks for ‘scleroderma pattern’ development were apical diameter >40 μm (p<0.001), venous diameter >25 µm (p<0.05) and average diameter ≥35 µm (p<0.005). Conversely, CTDs patients showed a stable NVC ‘non-scleroderma pattern’ over a median 10-year time.Conclusion:This is the first study to show that NVC-detected homogeneous and progressive capillary loop dilations in RP patients significantly contribute to predict the ‘scleroderma pattern’ evolution within a median 3-year time, possibly providing a “very early” window of opportunity in SSc pre-clinical stages.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15(7):753–64. [2] Trombetta AC et al. J Rheumatol 2016;43:599–606. [3] Smith et al. Autoimmun Rev 2020; 19(3):102458.Disclosure of Interests:None declared

AB0439 CAPILLAROSCOPIC PATTERNS IN PATIENTS WITH SYSTEMIC SCLEROSIS-POLYMYOSITIS/DERMATOMYOSITIS (SSc-PM/DM) OVERLAP SYNDROME

Background:Impaired microcirculation is one of the leading factors in local and general pathogenesis of SSc. Widefield nail-fold video-capillaroscopy (NFVC) stands as the most informative and at the same time simple method used for evaluation of capillary circulation.Objectives:To identify characteristic and specific for SSc– PM/DM capillaroscopic features.Methods:Both hand II – V fingers of 68 pts with SSc-PM/DM were subjected to widefield NFC, evaluated using a binocular 20x magnification Olympus microscope and analyzed in view of specific skin lesions discriminating diffuse and limited SSc forms.Results:SSc-specific dilatations of capillary loops were the most common for SSc-PM/DM and were found in all pts; 50% of them had signs of active scleroderma pattern, such as capillary loss or “avascular areas” (50%) and hemorrhages (51.5%), associated with generalized microvascular spasm in early disease and capillary sclerosis in advanced disease. The morphological capillary abnormalities such as varying degrees of capillary loops tortuosity/vascular inhomogeneity were present in 63% of examined nailfolds, branching bushy behavior of capillary loops and mega-capillaries predominated; architectural disorientation/disarrangement of capillary loops with formation of subcutaneous plexus was seen in more than 50% of them. Capillaroscopic changes consistent with active scleroderma pattern were present in 54 % and were associated with lab signs of inflammatory muscle syndrome and immunological disorders: giant capillaries (p<0.02), disorientation of capillary loops (p<0.02) and ramified/bushy capillaries (p<0.04) were significantly more frequent in patients with severe muscle syndrome, increased CPK, ANF -positivity and hemorrhages (p<0.03).Conclusion:Thus, widefield NFVC revealed a “mixed” nature of capillaroscopic changes, combining features specific for SSc (capillary dilation, avascular areas, hemorrhages) and for PM/DM (bushy and giant capillaries, disorientation of capillary loops of the nailfold with formation of subcutaneous plexuses.)Disclosure of Interests:None declared

Nailfold capillaroscopy findings in cutaneous lupus erythematosus patients with or without digital lesions and comparison with dermatomyositis patients: A prospective study

Background Differential diagnosis between cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) may be challenging if digital lesions occur. Objectives To compare nailfold capillaroscopy (NFC) findings in CLE patients with or without digital involvement, and to compare capillaroscopic findings between CLE patients with digital lesions and DM patients. Methods Prospective monocentric study including CLE and DM patients. NFC was performed and standardized items were recorded. Results Fifty-one CLE patients and 10 DM patients with digital lesions were included. A scleroderma pattern was found in 6 patients (12%): in 5 out of 17 patients with digital lesions, compared with only 1 out of 34 patients without digital lesions (p = 0.01). In multivariate analysis, CLE digital lesions and digital ulcerations were statistically associated with scleroderma pattern. CLE digital lesions were significantly associated with architectural disorganization (p = 0.0003) and capillary rarefaction (p = 0.0038). A scleroderma pattern was significantly more frequent in DM patients (80%) than in CLE patients with digital lesions (30%, p = 0.018). Capillaroscopic findings were not significantly different between CLE patients with digital lesions and DM patients. Conclusion Although scleroderma pattern is more frequent in DM patients than in CLE patients with digital lesions, NFC cannot formally distinguish CLE from DM.

Nailfold capillary abnormalities in childhood-onset systemic lupus erythematosus: a cross-sectional study compared with healthy controls

Objectives For selection of high-risk systemic lupus erythematosus (SLE) patients it is necessary to obtain indicators of disease severity that predict disease damage. As in systemic sclerosis, nailfold capillary abnormalities could be such a biomarker in SLE. The primary objective of this cross-sectional study is to describe capillary abnormalities in childhood-onset SLE (cSLE) cohort (onset < 18 years) and compare them with matched healthy controls. The secondary objective is to correlate the observed capillary abnormalities with demographical variables in both cohorts and with disease-specific variables in cSLE patients. Methods Healthy controls were matched for ethnic background, age and gender. Videocapillaroscopy was performed in eight fingers with 2-4 images per finger. Quantitative and qualitative assessments of nailfold capillaroscopy images were performed according to the definitions of the EULAR study group on microcirculation in Rheumatic Diseases. Results Both groups (n = 41 cSLE-patients and n = 41 healthy controls) were comparable for ethnic background (p = 0.317). Counted per mm, cSLE-patients showed significantly more ‘giants’ (p = 0.032), ‘abnormal capillary shapes’ (p = 0.003), ‘large capillary hemorrhages’ (p < 0.001) and ‘pericapillary extravasations’ (p < 0.001). Combined ‘abnormal capillary shapes and pericapillary extravasations’ (in the same finger) were detected in 78% (32/41 patients). By qualitative analysis, ‘microangiopathy’ was detected in 68.3% (28/41) and a ‘scleroderma pattern’ in 17.1% (7/41) of the cSLE-patients (without scleroderma symptoms). The difference of percentage positive anti-RNP antibodies in the group with or without a scleroderma pattern was not significant (p = 0.089). The number of ‘abnormal capillary shapes per mm’ was significantly correlated with treatment-naivety. The number of ‘large pathological hemorrhages per mm’ was significantly correlated with SLEDAI score and presence of nephritis. Compared to healthy controls, ‘pericapillary extravasations’ were found in significantly higher numbers per mm (p < 0.001) as well as in percentage of patients (p < 0.001). Conclusions Our observations confirm that giants, abnormal capillary morphology and capillary hemorrhages are also observed in cSLE, as was already known for adults with SLE. Number of capillary hemorrhages in cSLE was significantly correlated with disease activity. A high frequency and total amount of “pericapillary extravasations” was observed in cSLE patients, possibly revealing a new subtype of capillary hemorrhage that might reflect endothelial damage in these pediatric patients.

Coexistence of systemic and localized scleroderma: a systematic literature review and observational cohort study

Objective SSc and localized sclerosis (LoS) are considered clinically distinct entities. We describe herein the coexistence of SSc and LoS by both a systematic literature review and an observational cohort study of unselected SSc patients. Methods Original studies documenting the coexistence of SSc and LoS were identified in three electronic databases by means of a systematic literature search according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Additionally, the coexistence of SSc and LoS was studied in a prospective cohort of SSc patients visiting the Ghent University Scleroderma Unit for their yearly follow-up visit between January 2018 and January 2019. Results Five studies were finally included for quality appraisal and data extraction. The coexistence of SSc and LoS ranged between 2.4 and 7.4%. RP, scleroderma pattern on nailfold videocapillaroscopy (NVC) and the presence of SSc-specific antibodies were commonly observed in coexistent cases. Additionally, coexistence of SSc and LoS was found in 8/296 (2.7%) consecutive SSc patients of the Ghent University Scleroderma Unit. RP was present in 6/8 coexistent cases; a scleroderma pattern on NVC was observed in all coexistent cases, and SSc-specific antibodies (i.e. cenp-B) were found in 4/8 coexistent cases. Conclusion This is the first systematic literature review with additional cohort evaluation investigating the coexistence of SSc and LoS. A relatively high overlap of SSc and LoS was revealed, which is peculiar because both are rare diseases.

THU0529 CAPILLAROSCOPIC ALTERATIONS IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

Background:Nailfold capillaroscopy (NFC) is a useful, noninvasive, widely available diagnostic tool in rheumatology practice. We commonly use it to describe patterns of abnormalities in systemic sclerosis however we have enough data which proves NFC usefulness for monitoring idiopathic inflammatory myopathies (IIM) considering it as diagnostic tool, monitoring of disease activity and treatment efficiency. Despite evident clinical relevance of NFC in IIM patients we still do not have clear capillaroscopic images for IIM definition.Objectives:That’s why, the goal of our research was aimed to analyze capillaroscopic peculiarities among IIM patients and find possible associations with clinical and activity data.Methods:69 patients with IIM were examined and 47 IIM patients with capillaroscopic alterations were included in the study, 26 patients with dermatomyositis (DM) and 21 patients with polymyositis (PM) according to the Targoff Criteria (1997). NFC we performed usingDino-Lite CapillaryScope with 200 magnification. We assessed nailfold capillary density (NCD), presence of microhemorrhages, giant, dilated and ramified capillaries, scleroderma patterns (defined as an early, active or late pattern) and neovascular pattern (defined as an active and late scleroderma patterns). To asses disease activity we use Manual Muscle Testing 8 (MMT8), Health Assessment Questionnaire (HAQ), Myositis Disease Activity Assessment Tool (MDAAT), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), physician’s VAS, patient’s VAS, serum muscle enzymes levels. We divided patients into 4 groups: 1stgroup – 17 DM patients with active disease (8 of them with newly onset disease), 2ndgroup included 9 DM patients with inactive disease, 3rdgroup – 11 PM patients with active disease (5 of them with newly onset disease) and 4thgroup included 10 PM patients with inactive disease.Results:The most common finding was low NCD, 70% of all patients had NCD lower than 6 per 1 mm. NCD for the 1stgroup was 4,4±1,12, 2ndgroup – 6,0±1,0, 3rdgroup – 5,8±1,1, 4thgroup – 9,2±2,1 (F=26,27, p<0,001). Hemorrhages were significantly more common among DM patients and active disease and were observed among 47,1% (p=0,036,χ2=8,574) with no significant difference with regard to the disease onset. Analyzing scleroderma patterns, among 1stgroup of patients – 17,6% had early, 47,1% – active, 35,3% – late pattern, in the 2ndgroup – 66,7% had early pattern, in the 3rdgroup – 27,3% patients with early and 18,2% with active pattern and in the 4thgroup – 50% of patients presented with early pattern (p=0,001,χ2=31,87). Neovascular pattern was found significantly more often among patients with active DM (p=0,001) with no regard to the disease onset. No statistically significant difference in giant and ramified capillaries distribution was found.Conclusion:According to our results, we can admit that the most common capillaroscopic finding was decreased NCD, which were significantly lower among patients with active DM, the same as microhemorrhages and neovascular scleroderma pattern. This data suggests that NCD, microhemorrhages and neovascular scleroderma pattern could be consider as biomarkers of DM activity but not PM, therefore more detailed research with larger numbers of patients are required.Disclosure of Interests:None declared

FRI0257 CAPILLAROSCOPIC VERY EARLY MORPHOLOGICAL AND QUANTITATIVE SPECIFIC ABNORMALITIES ANTICIPATE THE DEVELOPMENT OF THE “SCLERODERMA PATTERN” IN PATIENTS WITH RAYNAUD’S PHENOMENON

Background:Nailfold videocapillaroscopy (NVC) abnormalities in subjects with isolated Raynaud’s phenomenon (RP) may be present before transition to secondary RP(SRP) and development of a NVC “scleroderma pattern” and are known to predict for evolution to a connective tissue disease (CTD) within few years [1]. In a previous study, we have demonstrated that the very early increase of capillary diameter over 30 μm is an independent predictor for development of Systemic Sclerosis (SSc) associated SRP [2].Objectives:Present pilot retrospective study aimed to investigate in a cohort of patients affected by CTD–related RP the presence of very early capillaroscopic morphological and quantitative abnormalities in the acquired pictures of NVC performed before the development of the NVC scleroderma-pattern. In particular, the study was addressed to identify a “very early”scleroderma pattern, in order to intercept patients with RP at high risk of evolution in a CTD, specifically SSc.Methods:We selected the NVCs of 273 SSc patients presenting one of the validated NVC “scleroderma patterns”. We enrolled 26 SSc patients having a NVC analysis performed before the development ofthe “very early”NVC pattern. As controls, we evaluated 26 patients affected by other CTDs with stable non-scleroderma pattern over time. The 16 images per patient obtained by NVC examination were analyzed for total number of capillaries, number and the limbs diameters of capillaries with a diameter >30 μm, and microhemorrhages. Statistical analysis was performed using non-parametric tests.Results:All 26 SSc patients showed dilated capillaries with a diameter >30 μm in their previous NVC. Patients later developing scleroderma pattern had statically higher number and percentage of capillaries with a diameter >30 μm (p=0.0004 and p=0.0005), as well as a larger apical dilatation >40 μm (p=0.002). A progressive and significant increase in all capillary diameters were only detected in patients later diagnosed for SSc (apical p=0.006, venous p=0.02, arterial p=0.03). A significant homogeneous and progressive dilation was observed from the apical region and then involving both venous and arterial branches, only in SSc patients (p=0.002).Conclusion:Present pilot study demonstrates, for the first time that, before to develop a validated NVC scleroderma-pattern, all potential SSc patients present significant very early morphological and quantitative NVC changes. In particular, the progressive and homogeneous capillary loop dilation over 40 μm in over 40% of total number capillaries significantly could contribute to identify RP patients who will develop a SSc pattern after 4-5 years.References:[1]Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27:155-60.[2]Trombetta AC, et al. J Rheumatol 2016;43:599-606.Disclosure of Interests:Monica Pendolino: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Emanuele Gotelli: None declared, Carlotta Schenone: None declared, Francesco Cattelan: None declared, Massimo Patanè: None declared, Elisa Alessandri: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha