Unmet Needs in Systemic Sclerosis Understanding and Treatment: the Knowledge Gaps from a Scientist's, Clinician's, and Patient's Perspective.

Systemic sclerosis (SSc) is a highly heterogeneous disease caused by a complex molecular circuitry. For decades, clinical and molecular research focused on understanding the primary process of fibrosis. More recently, the inflammatory, immunological and vascular components that precede the actual onset of fibrosis, have become a matter of increasing scientific scrutiny. As a consequence, the field has started to realize that the early identification of this syndrome is crucial for optimal clinical care as well as for understanding its pathology. The cause of SSc cannot be appointed to a single molecular pathway but to a multitude of molecular aberrances in a spatial and temporal matter and on the backbone of the patient's genetic predisposition. These alterations underlie the plethora of signs and symptoms which patients experience and clinicians look for, ultimately culminating in fibrotic features. To solve this complexity, a close interaction among the patient throughout its "journey," the clinician through its clinical assessments and the researcher with its experimental design, seems to be required. In this review, we aimed to highlight the features of SSc through the eyes of these three professionals, all with their own expertise and opinions. With this unique setup, we underscore the importance of investigating the role of environmental factors in the onset and perpetuation of SSc, of focusing on the earliest signs and symptoms preceding fibrosis and on the application of holistic research approaches that include a multitude of potential molecular alterations in time in an unbiased fashion, in the search for a patient-tailored cure.

Computerised versus conventional methodology of radiographic joint destruction assessment in early rheumatoid arthritis.

OBJECTIVES: To compare computerised and conventional methodology of radiographic joint destruction assessment in early rheumatoid arthritis (RA). METHODS: We investigated the contribution of the 3rd-to-5th carpometacarpal joints (CMC3-5, which are excluded in computerised assessment so far owing to bone overlapping) to total joint space narrowing (JSN) scores in two cohorts of patients with early RA (n=392). Next, we investigated agreement between JSN scoring using single time point individual joint-based method (individual joint of a single time point (IJSTP), reflecting computerised reading) and conventional JSN scoring using the Sharp-van der Heijde (SvdH) method in a cohort of patients with early RA (n=59). We used intraclass correlation coefficients (ICCs), Bland and Altman plots, and linear mixed modelling to analyse differences in progression between two methods. Radiographs were available at baseline, and at 1 and 2 years of follow-up. RESULTS: Of all joints affected by JSN at baseline or JSN progression during 2 years of follow-up, 3.9% and 6.6% concerned CMC3-5. Exclusion of CMC3-5 resulted in a decrease of 1.9-4.6% in JSN progression scores during 2 years of follow-up. The ICCs for JSN progression scores using IJSTP with or without CMC3-5 compared with SvdH were 0.71-0.81 and 0.69-0.78 at 1 and 2 years of follow-up. Signal-to-noise ratios for IJSTP-based and SvdH scoring were 0.51 and 0.58, respectively. The progression rate for each year was not statistically significantly different between two scoring methods (p=0.59 and 0.89). CONCLUSIONS: This study showed that excluding CMC3-5 has limited influence on JSN (progression) scores and showed the feasibility of using IJSTP-based reading for computerised scoring of JSN (progression) in RA.