Latest Reviews

  • Review Article |

    Hyperuricaemia is a risk factor for gout, and mouse models of this condition can help dissect the underlying regulatory mechanisms. However, these models come with both advantages and disadvantages, and interpreting and comparing data from these models can be challenging.

    • Jie Lu
    • , Nicola Dalbeth
    • , Huiyong Yin
    • , Changgui Li
    • , Tony R. Merriman
    •  & Wen-Hua Wei
  • Review Article |

    The HLA region is strongly associated with many rheumatic diseases, including inflammatory arthritis. In this Review, potential mechanisms underpinning these associations are discussed, as are the clinical implications of HLA associations for the diagnosis and treatment of these diseases.

    • Robert Busch
    • , Simon Kollnberger
    •  & Elizabeth D. Mellins
  • Review Article |

    Pain management is presently the focus of osteoarthritis (OA) therapy, but traditional pain-relieving drugs such as NSAIDs and glucocorticoids have limited utility. In this Review, the next generation of OA analgesics and their potential mechanisms of action are discussed.

    • Philip G. Conaghan
    • , Andrew D. Cook
    • , John A. Hamilton
    •  & Paul P. Tak
  • Review Article |

    Single-cell sequencing technologies enable transcriptomic, epigenomic and proteomic analysis of rare or heterogeneous populations of cells. In this Review, Kuo and colleagues discuss current and future uses of single-cell sequencing technologies for rheumatology research.

    • Peggie Cheung
    • , Purvesh Khatri
    • , Paul J. Utz
    •  & Alex J. Kuo
  • Review Article |

    Next-generation sequencing (NGS) technologies are being developed at a rapid pace. This Review highlights advances in our understanding of rheumatic diseases that have been gained from NGS and offers guidance to rheumatology researchers using these technologies.

    • Laura T. Donlin
    • , Sung-Ho Park
    • , Eugenia Giannopoulou
    • , Aleksandra Ivovic
    • , Kyung-Hyun Park-Min
    • , Richard M. Siegel
    •  & Lionel B. Ivashkiv
  • Review Article |

    B cells contribute to the pathogenesis of many rheumatic diseases. Targeting immune checkpoints that control the activation and effector function of B cells represents a promising therapeutic avenue.

    • Samuel J. S. Rubin
    • , Michelle S. Bloom
    •  & William H. Robinson
  • Review Article |

    Osteoarthritis occurs spontaneously in pet dogs, which often share environmental and lifestyle risk-factors with their owners. This Review aims to stimulate cooperation between medical and veterinary research under the One Medicine initiative to improve the welfare of dogs and humans.

    • Richard L. Meeson
    • , Rory J. Todhunter
    • , Gordon Blunn
    • , George Nuki
    •  & Andrew A. Pitsillides
  • Review Article |

    Inclusion body myositis (IBM) is a slowly progressive disease characterized by unique clinical and pathological features. This Review discusses the historical and clinical aspects of IBM and the mounting evidence arguing for the important pathogenic function of the immune system.

    • Steven A. Greenberg
  • Review Article |

    Platelets mediate inflammatory responses by facilitating immune cell crosstalk and participating in inflammatory signalling cascades. In this Review, the authors discuss the emerging role of platelet signalling pathways in the pathogenesis of rheumatoid arthritis.

    • Oore-ofe Olumuyiwa-Akeredolu
    • , Martin J. Page
    • , Prashilla Soma
    •  & Etheresia Pretorius
  • Review Article |

    Antibody therapeutics are a mainstay of treating patients with rheumatic diseases but are mostly basic monoclonal structures. What can the history of and modern developments in antibody technology tell us about the next generation of antibody-based therapeutics?

    • Anja S. Schmid
    •  & Dario Neri
  • Review Article |

    Many potentially disease-modifying therapies for systemic sclerosis (SSc) are under investigation in clinical and preclinical studies. Here, Volkman and Varga review the targets and purported mechanisms of action of these therapies in the context of our evolving understanding of SSc pathophysiology.

    • Elizabeth R. Volkmann
    •  & John Varga
  • Review Article |

    Bone turnover and risk of fracture are orchestrated by homeostatic functions of osteoclast–osteoblast bone remodelling units. Anabolic and antiresorptive drugs used to treat and prevent fractures have differing effects on remodelling defects, but which class of drug is the preferred front-line therapy?

    • Ego Seeman
    •  & T. J. Martin
  • Perspective |

    Treat-to-target has been a guiding principle for treatment in rheumatology for almost 10 years. This Perspectives article evaluates how well the idea of treat-to-target has translated into clinical practice.

    • Ronald van Vollenhoven
  • Review Article |

    Neuropsychiatric systemic lupus erythematosus (NPSLE) remains highly challenging to diagnose and treat. This Review describes current understanding of its pathogenesis, along with novel therapies and diagnostic tools that could eventually improve the management of NPSLE.

    • Noa Schwartz
    • , Ariel D. Stock
    •  & Chaim Putterman
  • Review Article |

    Improved understanding of cell migration in the synovial joint, including the associated cellular and environmental factors, might reveal new therapeutic strategies for joint diseases such as rheumatoid arthritis and osteoarthritis and have important implications for tissue engineering of the joint.

    • Feini Qu
    • , Farshid Guilak
    •  & Robert L. Mauck
  • Perspective |

    Dactylitis is diffuse inflammation of the digits and is so closely associated with psoriatic arthritis that it can be used as an outcome measure of it. In this Opinion article, the authors describe how imaging modalities and scoring systems combined with data from animal models can be used to understand the underlying anatomy and immunopathogenesis of dactylitis.

    • Dennis McGonagle
    • , Ai Lyn Tan
    • , Abdulla Watad
    •  & Philip Helliwell
  • Review Article |

    Nakazawa and colleagues describe advances in our understanding of anti-neutrophil cytoplasmic antibody-associated vasculitis. These insights have already generated promising new treatments that target B cells, T cells and cytokines; potential novel approaches targeting additional cells or molecules are also discussed.

    • Daigo Nakazawa
    • , Sakiko Masuda
    • , Utano Tomaru
    •  & Akihiro Ishizu
  • Review Article |

    The treatment of systemic lupus erythematosus involves a balance between control of disease activity and prevention of therapeutic harm that requires careful optimization. In this Review, the authors discuss available and emerging therapeutic strategies that exploit the current drug armamentarium.

    • Mariele Gatto
    • , Margherita Zen
    • , Luca Iaccarino
    •  & Andrea Doria
  • Perspective |

    In osteoarthritis, identifying those patients at most risk of disease progression and/or who might benefit the most from therapy is an important step. Incorporating machine-learning into the development of prediction models has great potential for moving towards precision medicine

    • Afshin Jamshidi
    • , Jean-Pierre Pelletier
    •  & Johanne Martel-Pelletier
  • Review Article |

    Gene therapy and tissue engineering strategies for the treatment of cartilage repair each pose unique challenges to clinical translation. Could combining the two approaches open new avenues for the treatment of articular cartilage defects in patients with osteoarthritis?

    • Magali Cucchiarini
    •  & Henning Madry
  • Review Article |

    Intra-articular therapies for knee osteoarthritis (OA) are causing excitement among clinicians and patients, but care should be taken when choosing which therapy to use. In this Review, Vangsness and colleagues critically appraise current and future intra-articular therapies for knee OA.

    • Ian A. Jones
    • , Ryan Togashi
    • , Melissa L. Wilson
    • , Nathanael Heckmann
    •  & C. Thomas Vangsness Jr
  • Review Article |

    Stromal cells of mesenchymal origin can help to sustain inflammation in the joint by various mechanisms; understanding these mechanisms could inform new therapeutic strategies and explain why joint inflammation persists in diseases of the joint such as arthritis, enthesopathy and tendinopathy.

    • Stephanie G. Dakin
    • , Mark Coles
    • , Jonathan P. Sherlock
    • , Fiona Powrie
    • , Andrew J. Carr
    •  & Christopher D. Buckley
  • Review Article |

    Hydroxychloroquine is a front-line treatment for systemic lupus erythematosus and other rheumatic diseases, but can cause retinopathy. Improved detection techniques for the early stages (pre-symptomatic) of retinopathy has led to recommendations for reduced dosing, but more data on the efficacy of low-dose hydroxychloroquine are needed.

    • April Jorge
    • , Cindy Ung
    • , Lucy H. Young
    • , Ronald B. Melles
    •  & Hyon K. Choi
  • Review Article |

    Nocebo effects can occur in patients with rheumatic and/or musculoskeletal diseases, and might result in suboptimal treatment outcomes or non-adherence. The consideration of nocebos is important in rheumatology practice and clinical trial design, including when switching patients to biosimilars.

    • Evrydiki Kravvariti
    • , George D. Kitas
    • , Dimos D. Mitsikostas
    •  & Petros P. Sfikakis
  • Review Article |

    The ability to resolve, rather than suppress, inflammation could enable new possibilities for the treatment of chronic diseases such as rheumatoid arthritis. Knowing more about the function of immune-regulatory cytokines is the first step towards realizing their therapeutic potential.

    • Zhu Chen
    • , Aline Bozec
    • , Andreas Ramming
    •  & Georg Schett
  • Review Article |

    Hand osteoarthritis (OA) is a heterogeneous and prevalent condition involving multiple joints. In this Review, the authors provide an update on the epidemiology, presentation and burden of hand OA, as well as on advances in imaging techniques, disease management and pathogenesis.

    • Michelle Marshall
    • , Fiona E. Watt
    • , Tonia L. Vincent
    •  & Krysia Dziedzic
  • Review Article |

    Our ability to interrogate the genetic and epigenetic processes that underpin disease are advancing rapidly. In this Review, Radstake and colleagues highlight insights gained into the pathogenesis of systemic sclerosis from the past 4 years of genetic and epigenetic research.

    • Chiara Angiolilli
    • , Wioleta Marut
    • , Maarten van der Kroef
    • , Eleni Chouri
    • , Kris A. Reedquist
    •  & Timothy R. D. J. Radstake
  • Review Article |

    Both spondyloarthritis and uveitis are associated with HLA-B27 positivity. This Review discusses this overlap and how the intestinal microbiome and dysbiosis might contribute to the development of both diseases.

    • James T. Rosenbaum
    •  & Mark Asquith
  • Review Article |

    The IL-23–IL-17 signalling pathway has paradoxical effects on bone remodelling in psoriatic arthritis and ankylosing spondylitis. In this Review, Gravallese and Schett examine the evidence for and outline the reasons behind this paradox.

    • Ellen M. Gravallese
    •  & Georg Schett
  • Review Article |

    Adult-onset Still’s disease (AoSD) is not easily diagnosed, and treatment options are limited. This Review provides an overview of the disease and its pathogenesis, clinical trial results, therapeutic options and a plan to diagnose and clinically manage these patients.

    • Eugen Feist
    • , Stéphane Mitrovic
    •  & Bruno Fautrel
  • Perspective |

    Environmental changes can sometimes be too rapid for genetic adaptation and result in a mismatch between our genetics and the environment. Osteoarthritis should be considered a mismatch disease owing to a rapid increase in prevalence that is associated with the modern lifestyle, diet and patterns of physical activity.

    • Francis Berenbaum
    • , Ian J. Wallace
    • , Daniel E. Lieberman
    •  & David T. Felson
  • Review Article |

    The deposition of calcium-containing crystals can result in various acute and chronic arthropathies. Understanding the biological effects of these crystals and underlying pathogenic mechanisms might inform on the development of future therapeutic strategies for these conditions.

    • Geraldine M. McCarthy
    •  & Aisling Dunne
  • Review Article |

    Cancer immunotherapies that function as checkpoint inhibitors are an exciting development but are associated with immune-related adverse events that can occur in almost any organ. Among these events are complications that mirror established rheumatic diseases, so oncologists and rheumatologists must work together.

    • Leonard H. Calabrese
    • , Cassandra Calabrese
    •  & Laura C. Cappelli
  • Review Article |

    Preclinical rheumatoid arthritis (RA) is characterized by the presence of RA-related autoantibodies in the serum in the absence of clinical symptoms. This Review discusses the relationships during this period between mucosal alterations and the initiation of local and systemic anti-citrullinated protein antibody production.

    • V. Michael Holers
    • , M. Kristen Demoruelle
    • , Kristine A. Kuhn
    • , Jane H. Buckner
    • , William H. Robinson
    • , Yuko Okamoto
    • , Jill M. Norris
    •  & Kevin D. Deane
  • Review Article |

    The two major lung complications in systemic sclerosis, lung fibrosis and pulmonary arterial hypertension, share some pathogenic mechanisms. Strategies for managing patients with these complications have greatly advanced in the past decade, and many tools and treatments are now available.

    • Christopher P. Denton
    • , Athol U. Wells
    •  & John G. Coghlan
  • Review Article |

    B cell depletion has become standard-of-care for the treatment of ANCA-associated vasculitis, but can more be done to target B cells? In this Review, the authors look beyond rituximab to alternative B cell-targeting therapies and novel therapeutic combinations.

    • Mark McClure
    • , Seerapani Gopaluni
    • , David Jayne
    •  & Rachel Jones
  • Review Article |

    S100 proteins have many intracellular functions, as well as being extracellular signalling molecules in inflammation. A deeper understanding of this family of proteins could lead the way to diagnostic and prognostic biomarkers and novel therapeutic strategies.

    • Judith Austermann
    • , Christoph Spiekermann
    •  & Johannes Roth
  • Review Article |

    Evidence from genetic, experimental and clinical studies has accumulated to indicate a role for the IL-17 pathway in the pathogenesis of spondyloarthritis. This Review discusses how IL-17A and IL-17F and their cellular sources contribute to the immunopathology of these diseases.

    • Leonie S. Taams
    • , Kathryn J. A. Steel
    • , Ushani Srenathan
    • , Lachrissa A. Burns
    •  & Bruce W. Kirkham
  • Review Article |

    Leukocytes travel through many different tissues during their lifetime, being educated by the cells and environments they encounter. An increased understanding of this journey in the context of rheumatoid arthritis offers hope for the development of future therapies.

    • Christopher D. Buckley
    •  & Helen M. McGettrick
  • Review Article |

    A growing body of evidence indicates that neutrophils and neutrophil extracellular traps (NETs) are involved in the progression of rheumatic diseases. This Review focuses on the role of NETs in systemic lupus erythematosus, vasculitis, rheumatoid arthritis and gout.

    • Falko Apel
    • , Arturo Zychlinsky
    •  & Elaine F. Kenny