Current Rheumatology Reports最新文献

Purpose of review: Pathological roles of macrophage migration inhibitory factor (MIF) have recently been demonstrated in spondyloarthritis (SpA) preclinical models, identifying MIF as a new treatment target for SpA. However, the specific contribution of MIF and therapeutic potential of MIF-targeted therapies to various tissue types affected by SpA are not well delineated.

Recent findings: MIF and its cognate receptor CD74 are extensively involved in the pathogenesis of SpA including inflammation in the spine, joint, eyes, skin, and gut. The majority of the current evidence has consistently shown that MIF drives the inflammation in these distinct anatomical sites. In preclinical models, genetic deletion or blockade of MIF reduces the severity of inflammation. Although MIF is generally an upstream cytokine which regulates downstream effector cytokines, MIF also intensifies type 3 immunity by promoting helper T 17 (Th17) plasticity. MIF- or CD74-targeted therapies have also reported to be well tolerated in clinical trials for other diseases. Recent findings suggest that MIF-CD74 axis is a new therapeutic target for SpA to improve various clinical features. Clinical trials for MIF- or CD74-targeted therapies for SpA patients are warranted.

Purpose of review: This review aims to emphasize interesting and important new findings with a focus on the spectrum of spondyloarthritis (SpA) in China.

Recent findings: Over the past decade, significant advances have been made in the investigation of SpA epidemiology, the exploration of genetic and environmental risk factors, the identification of clinical features, and the updating of treatment protocols in the Chinese population. The prevalence of ankylosing spondylitis (AS) in China is 0.20-0.42%, and the prevalence of HLA-B27 in AS patients is 88.8-89.4%. HLA-B*2704 is the most common subtype in Chinese AS patients, followed by HLA-B*2705. HLA-A*01, more precisely HLA-A*01:01, may be associated with psoriatic arthritis (PsA). Tumor necrosis factor inhibitors and IL-17A inhibitors have been shown to be effective and safe for AS patients in China. Juvenile-onset AS is relatively rare, accounting for only 9.1% of the AS population. The prevalence of arthritis related to inflammatory bowel disease is 6.9 to 7.2%. A Chinese study showed that the most frequently prescribed medication was methotrexate (66.4%). Biological agents were prescribed in only16.4% of patients with PsA. This review summarizes the latest research in the epidemiology, pathogenesis, clinical manifestations, and management of SpA among Chinese populations. Multiple HLA associations with SpA have also been described, and it is hoped that discoveries of such ethnic-specific risk factor(s) and understanding of their pathological mechanisms may potentially lead to newer targeted therapies for the Chinese populations worldwide.

Purpose of review: This review provides an update on recent advances in the diagnosis, pathogenesis, clinical presentation, histopathological findings, and treatment approaches for antineutrophil cytoplasmic antibody (ANCA) vasculitis-associated interstitial lung disease (AAV-ILD) with a focus on literature published in the last 3 years.

Recent findings: Although there is no validated definition of AAV-ILD, which contributes to some of the heterogeneity seen in study results, there has been an increasing number of publications in recent years on this topic. Most patients with AAV-ILD have MPO-ANCA vasculitis, and this association appears to reduce their 5-year-survival to 60-66% (Sun et al. BMC Pulm Med 21(1), 2021, Maillet et al. J Autoimmun 106, 2020). Median age of diagnosis ranges from mid-60 s to mid-70 s (Ando et al. Respir Med 107(4), 2013), Kagiyama et al. BMJ Open Respir Res 2(1):1-9, 2015, Hozumi et al. Lung 194(2):235-42, 2016, Liu et al. Chest 156(4):715-23, 2019, Maillet et al. J Autoimmun 106, 2020, Wurmann et al. Sarcoidosis Vasc Diffuse Lung Dis 37(1):37-42, 2020, Watanabe et al. BMC Pulm Med 19(1), 2019). Computed tomography (CT) chest imaging for patients with AAV-ILD often shows a usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) pattern (12-58% and 13-61%, respectively) (Sun et al. BMC Pulm Med 21(1), 2021, Maillet et al. J Autoimmun 106, 2020, Wurmann et al. Sarcoidosis Vasc Diffuse Lung Dis 37(1):37-42, 2020, Watanabe et al. BMC Pulm Med 19(1), 2019, Baqir at al. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG 36(3):195-201, 2019). Additionally, lung biopsies typically do not demonstrate active inflammation, or capillaritis, questioning whether these patients should be treated with either immunotherapy or anti-fibrotic therapy, or both (Hozumi et al. Lung 194(2):235-42, 2016, Liu et al. Chest 156(4):715-23, 2019, Kitching at al. Nat Rev Dis Prim 6(1):71, 2020, Tanaka et al. Respir Med 106(12):1765-70, 2012). Besides immunosuppressive treatments, recent advances in anti-fibrotic therapy may offer patients with progressive AAV-ILD an alternative and/or more effective and individualized treatment option.

Purpose of review: The autonomic nervous system is an important regulator of stress responses and exhibits functional changes in chronic pain states. This review discusses potential overlap among autonomic dysregulation, osteoarthritis (OA) progression, and chronic pain. From this foundation, we then discuss preclinical to clinical research opportunities to close gaps in our knowledge of autonomic dysregulation and OA. Finally, we consider the potential to generate new therapies for OA pain via modulation of the autonomic nervous system.

Recent findings: Recent reviews provide a framework for the autonomic nervous system in OA progression; however, research is still limited on the topic. In other chronic pain states, functional overlaps between the central autonomic network and pain processing centers in the brain suggest relationships between concomitant dysregulation of the two systems. Non-pharmacological therapeutics, such as vagus nerve stimulation, mindfulness-based meditation, and exercise, have shown promise in alleviating painful symptoms of joint diseases, and these interventions may be partially mediated through the autonomic nervous system. The autonomic nervous system appears to be dysregulated in OA progression, and further research on rebalancing autonomic function may lead to novel therapeutic strategies for treating OA pain.

Purpose of review: This narrative review will focus on the role of the rheumatologist in evaluating patients with interstitial lung disease (ILD) without a defined rheumatic disease and will outline the current classification criteria for interstitial pneumonia with autoimmune features (IPAF) and describe what is known regarding IPAF pathobiology, natural history, prognosis, and treatment. Lastly, knowledge gaps and opportunities for future research will be discussed.

Recent findings: IPAF is a recently defined classification of ILD patients who have features suggesting an autoimmune-mediated process, but do not fulfill current rheumatic disease criteria. The goal of the IPAF criteria is to provide a uniform case definition for the study of autoimmune ILD patients who do not currently fit within standard ILD diagnostic categories, ultimately improving diagnosis and therapy. Many of these patients are referred for rheumatologic evaluation to aid the diagnostic process. The care of the IPAF patient is complex and is multidisciplinary with pulmonology, rheumatology, pathology, radiology, physical therapy, primary care, pulmonary transplant providers all serving vital roles. The rheumatologist has several roles which include classification, disease monitoring, and management.

Purpose of review: The effect of the transforming growth factor beta (TGFβ) signaling pathway on joint homeostasis is tissue-specific, non-linear, and context-dependent, representing a unique complexity in targeting TGFβ signaling in joint disease. Here we discuss the variety of mechanisms that TGFβ signaling employs in the synovial joint to maintain healthy joint crosstalk and the ways in which aberrant TGFβ signaling can result in joint degeneration.

Recent findings: Osteoarthritis (OA) epitomizes a condition of disordered joint crosstalk in which multiple joint tissues degenerate leading to overall joint deterioration. Synovial joint tissues, such as subchondral bone, articular cartilage, and synovium, as well as mesenchymal stem cells, each demonstrate aberrant TGFβ signaling during joint disease, whether by excessive or suppressed signaling, imbalance of canonical and non-canonical signaling, a perturbed mechanical microenvironment, or a distorted response to TGFβ signaling during aging. The synovial joint relies upon a sophisticated alliance among each joint tissue to maintain joint homeostasis. The TGFβ signaling pathway is a key regulator of the health of individual joint tissues, and the subsequent interaction among these different joint tissues, also known as joint crosstalk. Dissecting the sophisticated function of TGFβ signaling in the synovial joint is key to therapeutically interrogating the pathway to optimize overall joint health.

Purpose of review: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc). We explore the importance of early detection, monitoring, and management of SSc-ILD.

Recent findings: All patients with SSc are at risk of ILD and should be screened for ILD at diagnosis using a high-resolution computed tomography (HRCT) scan. Some patients with SSc-ILD develop a progressive phenotype characterized by worsening fibrosis on HRCT, decline in lung function, and early mortality. To evaluate progression and inform treatment decisions, regular monitoring is important and should include pulmonary function testing, evaluation of symptoms and quality of life, and, where indicated, repeat HRCT. Multidisciplinary discussion enables comprehensive evaluation of the available information and its implications for management. The first-line treatment for SSc-ILD is usually immunosuppression. The antifibrotic drug nintedanib has been approved for slowing lung function decline in patients with SSc-ILD. Optimal management of patients with SSc-ILD requires a multidisciplinary and patient-centered approach.