Current opinion in rheumatology最新文献

Purpose of review: Over the past several decades, the concept that the primary lesion accounting for the development of axSpA is an enthesopathy has been widely accepted. However, the hallmark abnormality of axSpA occurs in the sacroiliac joint at the interface of cartilage and bone at a location remote from any anatomical enthesis. Both imaging and histopathological data from the sacroiliac joint point to immunopathogenetic events in the bone marrow as being of primary importance. Here, we discuss new developments in our understanding of immune events in the bone marrow relevant to axSpA that reinforce the need for a change in our conceptual paradigm for the pathogenesis of axSpA.

Recent findings: Human spinal enthesis samples contain myeloperoxidase-expressing cells, a marker of neutrophils, and mucosal-associated invariant T cells in the perientheseal bone marrow, which may be activated by stromal cells and circulating microbial products to express IL-17A and IL-17F and tumor necrosis factor (TNF). Evaluation of transcriptomes of monocytes from patients with axSpA demonstrates a lipopolysaccharide/TNF signature characterized by the expression of genes associated with granulocytopoietic bone marrow cells. This neutrophil-like phenotype is more evident in established and more severe axSpA and may be activated by microbial products from the gut. A similar expansion of granulocyte-monocyte progenitor-driven hematopoiesis occurs in the SKG mouse driven by granulocyte-macrophage colony-stimulating factor. Mesenchymal stem cells (MSCs) from ankylosing spondylitis patients are more likely to exhibit osteogenic differentiation than MSCs from healthy donors, which may be mediated by the formation of specific clusters of transcriptional factors, super enhancers, regulated by axSpA-associated single nucleotide polymorphisms located mostly in noncoding regions. TNF-α may enhance directional migration of AS-MSC compared with MSC from healthy controls from the bone marrow to entheseal soft tissue, which is mediated by increased expression of engulfment and cell motility protein 1 (ELMO1). TNF and IL-17A display differential effects on adipogenesis and osteogenesis of MSC in perientheseal bone marrow and soft tissue.

Summary: Bone marrow has the capacity to undergo rapid adaptation in terms of cell composition, differentiation, and immune function, resulting in inflammation and osteogenesis in axSpA.

Purpose of review: Pelvic radiography in which structural lesions characteristic of sacroiliitis can be detected, is recommended as the first imaging modality when axial spondyloarthritis (axSpA) is suspected clinically. However, cross-sectional modalities like computed tomography (CT) and magnetic resonance imaging (MRI) are superior to radiographs for diagnosing sacroiliitis. Thus, we currently debate the role of radiography as first imaging modality in the diagnostic workup of axSpA.

Recent findings: Diagnosing sacroiliitis on pelvic radiographs is challenging with large interobserver and intraobserver variation. Low-dose CT (ldCT) of the sacroiliac joints (SIJs) was proved to be more sensitive and reliable than radiographs with comparable ionizing radiation exposure. MRI is the preferred modality for detecting early SIJ inflammation, well before structural lesions evolve. New, promising MRI sequences sensitive to cortical bone improve erosion detection, making MRI a one-stop shop for the diagnosis of sacroiliitis.

Summary: Given the debatable additive value of pelvic radiographs for the detection of sacroiliitis, and the presence of excellent alternatives for imaging the bony cortex of the SIJs such as ldCT and MRI with state-of-the-art sequences sensitive to cortical bone, it is high time to discuss the use of these more accurate modalities instead of radiographs.

Purpose of review: The association between human leucocyte antigen (HLA)-B27 and spondyloarthritis (SpA) was described half a century ago. New insights about pathophysiologic pathways and their role in bone formation were reported in recent years and will be discussed in this review.

Recent findings: There is a considerable variation in the association between HLA-B27 and SpA across the globe, with the strongest association reported in populations of Northern European and Asian descent and the lowest in the Middle East and Africa. Other genes are also involved in disease susceptibility, highlighting the importance of newly proposed weighted genetic scores to support the diagnosis. On the global level, the interaction between genetic background and gut dysbiosis seems critical for disease predisposition. As for the individual patient, the presence of HLA-B27 can have a significant influence on SpA diagnosis and disease phenotype. More importantly, new studies suggested a role for HLA-B27 in radiographic damage in the sacroiliac joints and the progression of bone formation in the spine.

Summary: Findings in recent years have enhanced our understanding of the role of HLA-B27 in the pathophysiology and in disease-related bone formation in SpA, which may pave the way for new therapeutic targets.

Purpose of review: Imaging is used in the diagnosis of peripheral and axial disease in juvenile spondyloarthritis (JSpA). Imaging of the joints and entheses in children and adolescents can be challenging for those unfamiliar with the appearance of the maturing skeleton. These differences are key for rheumatologists and radiologists to be aware of.

Recent findings: In youth, skeletal variation during maturation makes the identification of arthritis, enthesitis, and sacroiliitis difficult. A great effort has been put forward to define imaging characteristics seen in healthy children in order to more accurately identify disease. Additionally, there are novel imaging modalities on the horizon that are promising to further differentiate normal physiologic changes versus disease.

Summary: This review describes the current state of imaging, limitations, and future imaging modalities in youth, with key attention to differences in imaging interpretation of the peripheral joints, entheses, and sacroiliac joint in youth and adults.

Purpose of review: To summarize recently discovered novel cell states in rheumatoid arthritis (RA) synovium that could have important implications for disease treatment.

Recent findings: The use of multiomic technologies, including single-cell and spatial transcriptomics and mass cytometry, has led to the discovery of several novel cell states, which could have important implications for the treatment of RA. These cells can be found in patient blood, synovial fluid, or synovial tissue and span several immune cell subsets as well as stromal cell types. These diverse cell states may represent the targets of current or future therapeutics, while their fluctuations may inform the ideal timing for therapy. Future efforts are needed to implicate how each cell state functions in the pathophysiologic network within affected joints and how medications perturb each cell state and ultimately the tissue.

Summary: Multiomic molecular technologies have afforded the discovery of numerous novel cellular states in RA synovium; the next challenge will be to link these states to pathophysiology and treatment response.

Purpose of review: This review provides a framework for understanding inflammatory eye disease diagnosis, differential diagnosis, and management for rheumatologists. Uveitis, scleritis, episcleritis, peripheral ulcerative keratitis, and orbital inflammation are all discussed. The goal is to facilitate the development of approaches to inflammatory eye diseases that will help rheumatologists co-manage these patients with eye care providers specializing in ocular inflammation.

Recent findings: In recent years, studies have aimed to advance biologic treatments and define standard-of-care therapy. Inflammatory eye diseases are highly heterogeneous and often rare, which poses significant challenges to their research and the interpretation of existing data. To date, glucocorticoids, mycophenolate, methotrexate, and TNF inhibitors remain the mainstay of treatment options for many of these diseases.

Summary: Patients with inflammatory eye diseases require multidisciplinary care for best outcomes, frequently including rheumatologists. Understanding the differentials, diagnostics, and treatment are essential to preserving vision in these patients. The diverse nature of the disease processes within this field requires focusing on specific disease phenotypes and endotypes in research and clinical practice.

Purpose of review: To summarize the findings of studies investigating patients with rheumatoid arthritis (RA) and risk of acute and postacute COVID-19 outcomes 3 years into the pandemic.

Recent findings: Most studies early in the pandemic included all patients with systemic autoimmune rheumatic diseases (SARDs), not only those with RA, due to limited sample size. Many of these studies found that patients with SARDs were at higher risk of COVID-19 infection and severe outcomes, including hospitalization, hyperinflammation, mechanical ventilation, and death. Studies performed later were able to focus on RA and found similar associations, while also identifying RA-specific factors such as immunosuppressive medications, disease activity/severity, and interstitial lung disease as risk factors for severe COVID-19. After COVID-19 vaccination, the risks for COVID-19 infection and severity were reduced for patients with RA, but a gap between the general population persisted, and some patients with RA are susceptible to breakthrough infection after vaccination. Preexposure prophylaxis, effective treatments, and changes in viral variants have also contributed to improved COVID-19 outcomes throughout the pandemic. Emerging data suggest that patients with RA may be at risk for postacute sequelae of COVID-19 (PASC).

Summary: Although COVID-19 outcomes have improved over the pandemic for patients with RA, some experience poor acute and postacute outcomes after COVID-19. Clinicians and patients should remain vigilant about risk mitigation for infection and consider early treatment for RA patients with COVID-19. Future studies are needed to investigate clinical outcomes and mechanisms of PASC among patients with RA.

Purpose of review: This review seeks to summarize the literature relevant to the treatment of glucocorticoid-induced osteoporosis in premenopausal women; an issue commonly encountered by rheumatologists and yet lacking good clinical practice guidelines.

Recent findings: Although most of the relevant literature on osteoporosis includes postmenopausal women only, data from both randomized controlled trials and case reports suggest bisphosphonates can be an effective and well tolerated treatment for premenopausal patients. Data for other medications to treat premenopausal osteoporosis is less robust.

Summary: The use of bisphosphonates in young women may be safer than initially thought and should likely be used for the treatment of glucocorticoid-induced osteoporosis in rheumatology clinics. Further research is needed to continue to understand long-term risk.