Nearly all patients with systemic sclerosis (SSc) are negatively affected by dysfunction in the gastrointestinal tract, and the severity of gastrointestinal disease in SSc correlates with high mortality. The clinical complications of this dysfunction are heterogeneous and include gastro-oesophageal reflux disease, gastroparesis, small intestinal bacterial overgrowth, intestinal pseudo-obstruction, malabsorption and the requirement for total parenteral nutrition. The abnormal gastrointestinal physiology that promotes the clinical manifestations of SSc gastrointestinal disease throughout the gastrointestinal tract are diverse and present a range of therapeutic targets. Furthermore, the armamentarium of medications and non-pharmacological interventions that can benefit affected patients has substantially expanded in the past 10 years, and research is increasingly focused in this area. Here, we review the details of the gastrointestinal complications in SSc, tie physiological abnormalities to clinical manifestations, detail the roles of standard and novel therapies and lay a foundation for future investigative work.

Intervertebral disc degeneration (IDD) and osteoarthritis (OA) affecting the facet joint of the spine are biomechanically interdependent, typically occur in tandem, and have considerable epidemiological and pathophysiological overlap. Historically, the distinctions between these degenerative diseases have been emphasized. Therefore, research in the two fields often occurs independently without adequate consideration of the co-dependence of the two sites, which reside within the same functional spinal unit. Emerging evidence from animal models of spine degeneration highlight the interdependence of IDD and facet joint OA, warranting a review of the parallels between these two degenerative phenomena for the benefit of both clinicians and research scientists. This Review discusses the pathophysiological aspects of IDD and OA, with an emphasis on tissue, cellular and molecular pathways of degeneration. Although the intervertebral disc and synovial facet joint are biologically distinct structures that are amenable to reductive scientific consideration, substantial overlap exists between the molecular pathways and processes of degeneration (including cartilage destruction, extracellular matrix degeneration and osteophyte formation) that occur at these sites. Thus, researchers, clinicians, advocates and policy-makers should consider viewing the burden and management of spinal degeneration holistically as part of the OA disease continuum.

Giant cell arteritis (GCA) is a systemic vasculitis that affects large vessels. Cardiovascular complications that develop with GCA have high morbidity and can be fatal. The aim of this work was to discuss epidemiology, clinical picture, etiopathology and risk of development of cardiovascular complications in GCA.

Among the rheumatic diseases whose symptoms are more often associated with the possibility of cancer and other malignancies are systemic sclerosis, dermatomyositis and rheumatic polymyalgia. However, a differential diagnosis should be performed in each case of non-typical rheumatic disease and/or other neoplastic disease risk factors. The article's aim was based on a literature review of this subject and presentation own a case description and discussion about arthritis as a paraneoplastic syndrome. The conclusions of our analysis were as follows: more often paraneoplastic arthritis occurs in men, in ages higher than 50 years old, in patients who poorly respond to treatment of arthritis with polyarticular symmetrical involvement of the limbs, seronegative type of inflammatory joint disease. In this group of patients, complete remission after treatment of the primary tumor and recurrence of the symptoms in the presence of metastasis was observed.

A review of the literature from the last 10 years quite clearly shows that immobilization of the wrist in the splint (orthosis) is the most effective, initial method of conservative treatment of carpal tunnel syndrome (CTS). The particular advantages of the described method of treatment are: availability, low cost, good patient tolerance, simplicity and minimal incidence of complications.The aim of this study was to try to define the criteria of proceeding with the selection of the type of orthosis and the duration of its use depending on the clinical condition and the patient's expectations.

As clinical manifestations of systemic vasculitides share many common features with other conditions, the rate of diagnostic errors and delayed diagnoses is high. Hence we performed an analysis of the available data regarding misdiagnosis of vasculitis as lung cancer and vice versa, as well as coexistence of vasculitis and lung cancer. The present case-based review highlights the diagnostic challenges encountered when granulomatosis with polyangiitis (GPA) mimics lung cancer. The importance of a multidisciplinary team approach to patients with pulmonary involvement and multisystem manifestations is essential for appropriate planning of further diagnostic steps and for minimizing the delay in correct diagnosis and treatment. In the present case, although computed tomography raised suspicion for lung cancer, further biopsies and laboratory screening for systemic vasculitides rejected malignancy and confirmed the diagnosis of GPA.

Bone has a remarkable endogenous regenerative capacity that enables scarless healing and restoration of its prior mechanical function, even under challenging conditions such as advanced age and metabolic or immunological degenerative diseases. However - despite much progress - a high number of bone injuries still heal with unsatisfactory outcomes. The mechanisms leading to impaired healing are heterogeneous, and involve exuberant and non-resolving immune reactions or overstrained mechanical conditions that affect the delicate regulation of the early initiation of scar-free healing. Every healing process begins phylogenetically with an inflammatory reaction, but its spatial and temporal intensity must be tightly controlled. Dysregulation of this inflammatory cascade directly affects the subsequent healing phases and hinders the healing progression. This Review discusses the complex processes underlying bone regeneration, focusing on the early healing phase and its highly dynamic environment, where vibrant changes in cellular and tissue composition alter the mechanical environment and thus affect the signalling pathways that orchestrate the healing process. Essential to scar-free healing is the interplay of various dynamic cascades that control timely resolution of local inflammation and tissue self-organization, while also providing sufficient local stability to initiate endogenous restoration. Various immunotherapy and mechanobiology-based therapy options are under investigation for promoting bone regeneration.

Psoriatic arthritis (PsA) is a heterogeneous disease involving multiple potential tissue domains. Most outcome measures used so far in randomized clinical trials do not sufficiently reflect this domain heterogeneity. The concept that pathogenetic mechanisms might vary across tissues within a single disease, underpinning such phenotype diversity, could explain tissue-distinct levels of response to different therapies. In this Review, we discuss the tissue, cellular and molecular mechanisms that drive clinical heterogeneity in PsA phenotypes, and detail existing tissue-based research, including data generated using sophisticated interrogative technologies with single-cell precision. Finally, we discuss how these elements support the need for tissue-based therapy in PsA in the context of existing and new therapeutic modes of action, and the implications for future PsA trial outcomes and design.

There is no clear explanation for the availability of multiple sclerosis (MS) pharmacological treatment for patients in Greater Poland and it can be assumed that the same reason is common in most of the developed countries in the United Europe. As an autoimmune disease MS can overlap with other diseases especially rheumatic disease (RD) as well as some feature of RD may mimic MS, such as MS-like syndrome in the course of primary Sjögren's syndrome. Therefore proper diagnosis and sufficient treatment of MS is important not only for neurologists but also for other clinicians including rheumatologists.The study aims to provide insights that could help healthcare managers create more effective logistical guidelines to improve the timely initiation of pharmacological treatment for MS.

Renal failure in the course of rheumatoid arthritis (RA) is a consequence of many factors, including drug-induced nephrotoxicity, comorbidities and chronic inflammation. Contemporary treatment strategies have reduced the incidence of renal failure in the population of RA patients. However, it remains a problem for approximately 25% of patients. Therefore, special attention should be paid to the potential need for dosage modifications of administered medications. Many drugs used in the therapy of rheumatic diseases have not been thoroughly studied for their safety in patients with reduced glomerular filtration, resulting in limited data in this area. The establishment of precise, transparent, and consistent dosage recommendations for antirheumatic drugs in chronic kidney disease would significantly facilitate the care of patients with RA. The following review provides a general summary of the available knowledge regarding the dosage of rheumatic medications in renal insufficiency and aims to highlight the need for further research in this area.

Takayasu arteritis (TAK) is a granulomatous inflammation of vessels of large diameter, mainly affecting the aorta and its proximal branches, which is more common in young women. The incidence of coronary artery disease in TAK is unknown and not sufficiently studied.

The prevalence and severity of SLE have been found to vary across populations of different ancestries. This review explores whether these differences can be explained by the genetic aetiology of the condition. Large genetic studies suggest that populations of different ancestry share the same risk loci but individual risk alleles are more common in some, leading to a higher prevalence and severity and an earlier onset of the condition. Despite many of the loci being shared across populations, some have been found to be ancestry specific and these are hypothesized to have undergone differential selective pressure in recent human history. Additionally, the effectiveness of some of the drugs used in SLE has been found to vary across ancestries, which might affect progression of the disease, but it is unclear whether these differences are pharmacogenetic. We concluded that to understand the full role of genetics in the risk, presentation and response to treatment of SLE, larger studies including individuals from a wider representation of ancestries will be required.

Autoinflammatory diseases (AIDs) are defined as disorders of innate immunity. They were initially defined in contrast to autoimmune diseases because of the lack of involvement of the adaptive immune system and circulating autoantibodies. The four monogenic AIDs first described are called the 'historical' AIDs and include FMF (associated with MEFV mutations), cryopyrinopathies (associated with NLRP3 mutations), TNF receptor-associated periodic syndrome (associated with TNFRSF1A mutations) and mevalonate kinase deficiency (MKD; associated with MVK mutations). In the last 10 years, >50 new monogenic AIDs have been discovered due to genetic advances. The most important discovery for adult patients is VEXAS syndrome associated with somatic UBA1 mutations leading to an AID affecting mostly elderly men. Diagnosis of monogenic AIDs is based on personal and family history and detailed analysis of symptoms associated with febrile attacks in the context of elevated peripheral inflammatory markers. This review proposes a practical approach for the diagnosis of the main monogenic AIDs among adult patients.

The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA.

Methotrexate is a key component of the treatment of inflammatory rheumatic diseases and the mainstay of therapy in rheumatoid arthritis. Hepatotoxicity has long been a concern for prescribers envisaging long-term treatment with methotrexate for their patients. However, the putative liver toxicity of methotrexate should be evaluated in the context of advances in our knowledge of the pathogenesis and natural history of liver disease, especially non-alcoholic fatty liver disease (NAFLD). Notably, patients with NAFLD are at increased risk for methotrexate hepatotoxicity, and methotrexate can worsen the course of NAFLD. Understanding the mechanisms of acute hepatotoxicity can facilitate the interpretation of elevated concentrations of liver enzymes in this context. Liver fibrosis and the mechanisms of fibrogenesis also need to be considered in relation to chronic exposure to methotrexate. A number of non-invasive tests for liver fibrosis are available for use in patients with rheumatic disease, in addition to liver biopsy, which can be appropriate for particular individuals. On the basis of the available evidence, practical suggestions for pretreatment screening and long-term monitoring of methotrexate therapy can be made for patients who have (or are at risk for) chronic liver disease.

Behçet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. Vascular involvement, most frequently superficial vein and deep vein thrombosis, can occur in up to 50% of patients with Behçet syndrome. Venous thrombosis at atypical sites (inferior and superior vena cava, suprahepatic veins with Budd-Chiari syndrome, portal vein, cerebral sinuses and right atrium and/or ventricle) and arterial involvement (mostly in situ thrombosis and aneurysms of the pulmonary arteries, as well as aneurysms of the abdominal aorta, and peripheral and visceral arteries) are also unique features of Behçet syndrome. Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome. This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. This Review discusses the main histopathological, pathogenetic and clinical aspects of vascular Behçet syndrome, addressing their implications for therapeutic management. Future perspectives in terms of pathogenetic studies, disease monitoring and treatment strategies are also discussed.

Pathological calcification of cartilage is a hallmark of osteoarthritis (OA). Calcification can be observed both at the cartilage surface and in its deeper layers. The formation of calcium-containing crystals, typically basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals, is an active, highly regulated and complex biological process that is initiated by chondrocytes and modified by genetic factors, dysregulated mitophagy or apoptosis, inflammation and the activation of specific cellular-signalling pathways. The links between OA and BCP deposition are stronger than those observed between OA and CPP deposition. Here, we review the molecular processes involved in cartilage calcification in OA and summarize the effects of calcium crystals on chondrocytes, synovial fibroblasts, macrophages and bone cells. Finally, we highlight therapeutic pathways leading to decreased joint calcification and potential new drugs that could treat not only OA but also other diseases associated with pathological calcification.

Previous systematic reviews focused on the evidence of common risk factors for knee OA (KOA); however, the effect and strength of association between risk factors and KOA might be different between the two sexes. The aim of the present systematic review was to determine the current evidence on sex differences in the association between risk factors and KOA and their prevalence.

'Non-inflammatory' pain, pain that is not associated with measures of inflammation, is common in patients with inflammatory arthritis including RA. One important cause of non-inflammatory pain is concomitant fibromyalgia. Systematic review has shown that fibromyalgia is common in inflammatory arthritis including RA affecting 1 in 5 patients and is associated with higher disease activity scores due to inflated tender joint count and patient global assessment. Consequently, many patients with RA and concomitant fibromyalgia may fail to reach treatment target and switch to alternate disease modifying drugs frequently. European Alliance of Association for Rheumatology has highlighted that concomitant fibromyalgia is an important consideration in assessing difficult-to-treat RA. The incidence and prevalence of fibromyalgia are higher in RA than the general population, raising the possibility that fibromyalgia may be 'secondary' to RA rather than a concomitant disease. The precise mechanisms whereby patients with RA develop fibromyalgia are unknown. In this review, we discussed fibromyalgia in RA, its clinical impact and epidemiology as well as data suggesting fibromyalgia might be 'secondary'. Lastly, we reviewed potential pathogenic mechanisms which included inflammatory cytokines sensitizing nociceptive neurones, temporal summation, also known as windup, from chronic pain and impaired coping from poor quality sleep and mental well-being. Deciphering the exact mechanisms may lead to treatment strategies that prevent development of secondary fibromyalgia and will address a common factor associated with difficult-to-treat RA.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.