BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain.
OBJECTIVE: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort.
METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms \"systemic sclerosis\" and \"NOR90\" across three databases: Medline via PubMed, Scopus, and Thomson Reuters\' Web of Science Core Collection, from inception to November 1st, 2023.
RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %.
CONCLUSIONS: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

OBJECTIVE: Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary Raynaud\'s phenomenon due to systemic sclerosis (SSc). However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time.
METHODS: Follow-up data from 334 SSc patients (265 women; 18 LSSc/203 LcSSc/113 DcSSc) registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardised definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed.
RESULTS: 257/334 (76.9%) patients developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less frequent novel overall severe organ involvement/progression (OR = 0.77, p < 0.001) and novel peripheral vascular involvement (OR = 0.79, p = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, p = 0.029); and a \"severe\" (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, p = 0.002) and skin progression (OR = 1.70, p = 0.049).
CONCLUSIONS: Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardised way, we were underpowered to detect associations with infrequent severe organ involvement/progression.

OBJECTIVE: Study aim was to evaluate estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with mortality in systemic sclerosis (SSc) patients from the European Scleroderma Trials and Research Group (EUSTAR) database.
METHODS: SSc patients from the EUSTAR database with available items for calculation of eGFR at baseline visit and with a second follow-up visit were included. A cut-off of 60 ml/min was chosen for all SSc patients and 30 ml/min for scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the role of eGFR as predictive factor of mortality.
RESULTS: 3650 SSc patients were included. Mean serum level of creatinine and eGFR were 0.8 mg/dl (IQR 0.6-0.9) and 86.6 ± 23.7 ml/min. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR <60 ml/min respect to patients with eGFR ≥ 60 ml/min [OS at five years 0.763 (CI 95%: 0.700-0.814) vs 0.903 (CI 95%: 0.883-0.919 p< 0.001)]. In multivariable analysis, OS was associate with male gender (p< 0.01), systolic pulmonary arterial pressure (sPAP) (p< 0.001) and eGFR (p< 0.001). Cumulative incidence of deaths due to SSc was associate with increased sPAP (p< 0.001) and reduced eGFR (p< 0.05). OS at five years of 53 SRC patients was not significantly different in SSc patients with eGFR > 30 ml/min or eGFR < 30 ml/min.
CONCLUSIONS: eGFR represents a predictive risk factor of overall survival in SSc. The eGFR is not a risk factor for death in SRC.

The rarity of systemic sclerosis (SSc) and its widely heterogeneous presentation and disease course are the main limitations for clinical research. The European Scleroderma Trials and Research group (EUSTAR) was launchegd in 2004, aiming to unify research efforts in the field of SSc. The central EUSTAR database has grown exponentially over the years, promoting new research and clinical trials, shedding new light on SSc diagnosis, its clinical course and providing new ideas for state-of-the-art therapy.Areas covered: The authors summarized the key findings of the main EUSTAR studies by reviewing PubMed and Web-of-Science databases through July 2020. The authors focused on the very early diagnosis of SSc, the prediction of disease course and mortality, the evaluation of disease activity and quality of life, the general management and therapy.
The findings elucidated in EUSTAR studies have substantially improved the diagnostic and therapeutic approach to SSc in the last 15 years. Further efforts are warranted to identify early prognostic markers of the disease and stratify patients who may benefit most from vasoactive, immunosuppressive, and/or antifibrotic therapy. This will be particularly important in leading the future of SSc toward precision medicine and to promote more targeted clinical trials.

OBJECTIVE: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database.
METHODS: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile.
RESULTS: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56.
CONCLUSIONS: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue.