No abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints, though a consistent proportion of patients may also display extra articular manifestations (EAMs). From rheumatoid nodules to interstitial lung disease, from cardiovascular events to vasculitis, the spectrum of EAMs encompasses various conditions with different prognoses. EAMs may also occur as first RA manifestation, therefore the coordination with other health professionals, including general practitioners, is needed. The aim of this article is to provide an overview on EAMs in RA with particular focus on the recognised risk factors and the available recommendations for managing them, as well as comorbidities in RA patients.

Sjögren's syndrome (SS) is a systemic autoimmune disease mainly characterized by inflammatory involvement of exocrine gland. Atherosclerosis is a complex process leading to plaque formation in arterial wall with subsequent cardiovascular (CV) events. Recently, numerous studies demonstrated that SS patients bear an increased CV risk. Since activation of immune system is a key element in atherosclerosis, it is interesting to analyze whether and how the autoimmune and inflammatory events characterizing SS pathogenesis directly or indirectly contribute to atherosclerosis risk in these patients. An increase in circulating endothelial microparticles and integrins, which may be a consequence of endothelial damage and impaired repair mechanisms, has been demonstrated in SS. Increased endothelial expression of adhesion molecules with subsequent infiltration of inflammatory cells into arterial wall is also a critical event in atherosclerosis. The early inflammatory events taking place in the atherosclerotic plaque cause an increase in alarmins, such as S100A8/A9, which seems to be associated with SS disease activity and, in turn, induce up-regulation of interleukin (IL)-1β and other pro-atherogenic cytokines. Interestingly, increased IL-1β levels were also detected in tertiary lymphoid structures developing in vessel adventitia adjacent to the atherosclerotic plaque, suggesting a direct role of IL-1β in this process. Similar to these structures, germinal center-like structures arising in SS exocrine glands are also tertiary lymphoid systems where T-helper (Th) cell subsets govern the adaptive immune response. Th1 cells are the most prevalent subtype and have been shown to be strongly involved in both SS pathogenesis and atherosclerosis. Th17 cells are attracting great interest and few studies showed its importance in SS development. Albeit in low amounts, a Th17 signature was also detected in atherosclerotic plaques and some animal models demonstrated a significant pro-atherogenic role and positive effects of IL-17A blockade. Despite the fact that T cells have a pivotal role in the inflammatory process that ultimately leads to atherosclerosis, B cells have also been detected in atherosclerotic plaques, although their exact role is still mostly unknown with studies showing contrasting results. In this scenario, the role of inflammation in atherosclerosis pathogenesis in patients with SS needs to be further explored.

Rheumatoid factor and antibodies against cyclic citrullinated peptides represent a diagnostic hallmark in rheumatoid arthritis (RA). However, over the last decades many other autoantibodies have been identified. Several proteins can trigger an aberrant autoimmune response in their native form while others acquire this feature after post-translational modifications such as citrullination, carbamylation or acetylation. It is of interest that also the enzymes catalyzing such post-translational modifications (e.g. the protein arginine deiminases) can transform themselves into autoantibodies in RA. The purpose of this review article is to provide an overview of relevant literature published over the last years regarding novel autoantibodies and their possible diagnostic and prognostic significance in RA.

Management of rheumatoid arthritis (RA) has evolved over the years as a result of better understanding of the role of different therapeutic strategies, as well as following an increasing availability of new disease-modifying antirheumatic drugs. However, the role of patients in sharing decisions, as well as the rules informing precision medicine or the principles to follow in case of specific comorbidities or extra-articular manifestations are still areas for improvement. Moreover, in 2020, the novel Coronavirus disease-19 outbreak has completely changed many attitudes in terms of assessment and treatment paradigms in most clinical diseases, including RA. In this narrative review, the authors report their specific point of view on the management of RA, based on a critical revision of literature published in 2020, focusing on relevant novelties and future research directions.