The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research (EUSTAR) group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis, and gastrointestinal involvement. Compared with the 2009 recommendations, the 2015 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressing SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

Active rheumatoid arthritis is characterized by originating from few but affecting subsequently the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) are key players in joint destruction and migrate in vitro, the current study evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, healthy human cartilage was co-implanted subcutaneously into SCID mice together with RASFs. At the contralateral flank, healthy cartilage was implanted without cells. RASFs showed an active movement to the naïve cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a strong destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.

Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. The involvement of immune cells is a general hallmark of autoimmune-related disorders. In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA. However, the notion that RA is a primarily T-cell-dependent disease has been strongly challenged during recent years. Rather, it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. A number of studies have demonstrated that RASFs show alterations in morphology and behaviour, including molecular changes in signalling cascades, apoptosis responses and in the expression of adhesion molecules as well as matrix-degrading enzymes. These changes appear to reflect a stable activation of RASFs, which occurs independently of continuous exogenous stimulation. As a consequence, RASFs are no longer considered passive bystanders but active players in the complex intercellular network of RA.

Articular adipose tissue is a ubiquitous component of human joints, but its local functions are largely unknown. Because recent studies revealed several links between adipose tissue, adipocytokines, and arthritis, we investigated the expression of the adipocytokine adiponectin and its functional role in articular adipose tissue and synovium of patients with different arthritides. In contrast to its protective role in endocrinological and vascular diseases, adiponectin was found to be involved in key pathways of inflammation and matrix degradation in the human joint. The effects of adiponectin in human synovial fibroblasts appear to be highly selective by inducing only two of the main mediators of rheumatoid arthritis pathophysiology, IL-6 and matrix metalloproteinase-1, via the p38 MAPK pathway. Owing to the observation that these effects could be inhibited by different TNF-α inhibitors, adipocytokines such as adiponectin may also be key targets for therapeutic strategies in inflammatory joint diseases. In summary, articular adipose tissue and adipocytokines cannot be regarded as innocent bystanders any more in chronic inflammatory diseases such as arthritis.