Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

ObjectiveTo identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6‐month period in patients with systemic sclerosis (SSc).MethodsIn this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses.ResultsOf the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow‐up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756).ConclusionThis international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.

Cystoid macular edema (CME) is a leading cause of blindness. In this study we assessed the efficacy and safety of Tocilizumab (TCZ) in refractory CME. DESIGN: Retrospective case series. METHODS: Patients with CME secondary to non-infectious uveitis who had inadequate response to corticosteroids and at least one conventional immunosuppressive drug, and in most cases to other biological agents were studied. CME was defined as central retinal thickness greater than 300 µm. The primary outcome measure was macular thickness. Intraocular inflammation, best corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. RESULTS: A total of 25 patients (mean± SD age 33.6±18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n=9), Behçet's disease (n=7), birdshot retinochoroidopathy (n=4), idiopathic (n=4), and sarcoidosis (n=1). The ocular patterns were panuveitis (n=9), anterior uveitis (n=7), posterior uveitis (n=5) and intermediate uveitis (n=4). Most patients had CME in both eyes (n=24). TCZ was used in monotherapy (n=11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7±177.2 vs 259.1±499.5 microns; p=0.00009) and BCVA (0.39±0.31 vs 0.54±0.33; p =0.0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9±13.6 mg/day vs 3.1±2.3 p=0.002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow up of 12.7±8.34 months. CONCLUSION: Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.

Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.