Family history of rheumatoid arthritis (RA) is a proxy for an individual's genetic and, in part, environmental risk of developing RA, and is a well-recognized predictor of disease onset. Although family history of RA is an old concept, the degree of familial aggregation of RA, whether it differs by age, sex, or serology, and what value it has for clinical decisions once a diagnosis of RA has been made remain unclear. New data have been emerging in parallel to substantial progress made in genetic association studies. In this Review, we describe the various ways that familial aggregation has been measured, and how the findings from these studies, whether they are based on twins, cohorts of first-degree relatives, or genetic data, correspond to each other and aid understanding of the aetiology of RA. In addition, we review the potential usefulness of family history of RA from a clinical point of view, demonstrating that, in the era of big data and genomics, family history still has a role in directing clinical decision-making and research.

Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of RA patients-and even more in early disease-present without RF or ACPA. The aim of this study was to confirm the presence of previously identified autoantibodies to novel Hasselt University (UH) peptides in early and seronegative RA.

Digital ulcers (DUs) are a common visible manifestation of the progressive vascular disease that characterizes the SSc disease process. DUs not only impact significantly on patients' quality of life and hand function, but are also a biomarker of internal organ involvement and of disease severity. The aetiology of (digital) vascular disease in SSc is multifactorial, and many of these factors are potentially amenable to therapeutic intervention. The management of DU disease in SSc is multifaceted. Patient education and non-pharmacological interventions (e.g. smoking cessation) should not be neglected. There are a number of drug therapies available to prevent (e.g. phosphodiesterase type-5 inhibitors and ET receptor-1 antagonists) and treat (e.g. i.v. iloprost) DUs. DUs are also important for two other reasons: firstly, as a primary end point in SSc-related clinical trials; and secondly, DUs are included in the ACR/EULAR SSc classification criteria. However, the reliability of rheumatologists to grade DUs is poor to moderate at best, and this poses challenges in both clinical practice and research. The purpose of this review is to provide the reader with a description of the spectrum of DU disease in SSc including pathophysiology, epidemiology and clinical burden, all of which inform the multifaceted approach to management.

B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanized anti-CD20 mAb that has shown efficacy in the treatment of haematological malignancy and RA. The use of ofatumumab in the treatment of AAV has not previously been reported.

Inflammation and oxidative stress are closely related. Further, oxidative stress plays an important role in the pathology of inflammation-based Kawasaki disease. An excessive in vivo production of reactive oxygen species increases oxidative stress in the body, which triggers an endless vicious spiral of inflammation reactions and reactive oxygen metabolites. This presumably forms diffuse vasculitis in the acute phase. Acute inflammation and oxidative stress can be rapidly controlled by treatments; however, they may remain for a long time. This has recently been identified as a problem in the chronic phase of Kawasaki disease. Generally, the presence of vascular inflammation and oxidative stress impairs blood vessels, leading to the onset of atherosclerosis, which is a widely recognized risk. The current discussion focuses on whether the same is valid for blood vessels in the chronic phase of Kawasaki disease.

To investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobility type (EDS-HT).

Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout.

Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies.

To investigate the prevalence and significance of the autoantibodies against complement component 1 q subcomponent (C1q) in patients with APS.

Comparative effectiveness research (CER) enables the comparison of different treatments in the real-world setting to inform clinical decision-making. Rheumatoid arthritis (RA) has been identified as a high priority area for CER. Administrative health databases, which generally consist of physician billing claims, hospital discharge summaries and prescription drug records, have been widely used to conduct observational research in RA. These data are accurate and complete records of health-care use unaffected by recall bias, and provide large, general population samples and information on long-term follow-up. However, administrative health data pose unique methodological challenges for CER in the field of RA. Here, we discuss the challenges of studying treatment effectiveness with CER (as distinct from harms and costs), in particular, issues relating to the identification and definition of RA cases, timing of disease onset and determination of disease severity. We also discuss an algorithm developed to measure effectiveness outcomes of RA treatments in administrative data, and potential sources of bias that might affect the validity of results. Finally, we explore opportunities for use of administrative data in CER, such as comparisons between reference drugs and biosimilars.

Adipose tissue secretes highly bioactive factors, the adipokines. Systemic levels of adipokines are often altered in the presence of inflammation. In turn, adipokines affect different tissues and cells systemically as well as locally, contributing to immunomodulatory and bone remodelling mechanisms. The role of adipokines has been evaluated in chronic inflammatory diseases, such as rheumatoid arthritis, as well as in primarily degenerative joint diseases, such as osteoarthritis, particularly with regard to their levels of expression and their effects on joint tissues including synovial membrane, cartilage and bone. Distinct adipokines have been found to modulate matrix remodelling as well as inflammatory responses. In this Review, we summarize current knowledge relating to adipokines in rheumatic diseases, with a particular focus on the effects of adipokines on bone remodelling.

Researchers continue to gather evidence that transient receptor potential vanilloid (TRPV) channels contribute towards pain signalling pathways. However, it is unknown whether polymorphisms of the TRPV gene are associated with FM. For the first time, we investigated the association between the polymorphisms of the TRPV2 and TRPV3 genes, FM susceptibility and the severity of the symptoms.

Autophagy may represent a functional processing event that creates a substrate for autoreactivity. In particular, autophagy may play a role in the pathogenesis of RA, since autophagy is a key cellular event involved in the generation of citrullinated peptides, with consequent breakage of tolerance. Thus, in RA, autophagy may be the common feature in several situations (including smoking, joint injury and infection) that may drive the adaptive responses to citrullinated self-proteins. The aim of this study was the analysis, in vitro, of the role of autophagy in the generation of citrullinated peptides and, in vivo, of the relationship between autophagy and the production of anti-CCP antibodies (Abs).

The aim was to assess the validity and responsiveness of the Michigan Hand Questionnaire (MHQ) in patients with SSc.