Reviews & Analysis

Glucocorticoids are powerful and cost-effective drugs for the treatment of patients with rheumatic disease; however, currently available glucocorticoids have several adverse effects. This Review describes the genomic and nongenomic mechanisms of glucocorticoid action; detailed knowledge of these mechanisms is crucial for researchers to develop novel glucocorticoid receptor ligands and/or to further improve the use of currently available conventional glucocorticoids.

The introduction of mycophenolate mofetil to the treatment armamentarium for lupus nephritis raised the hope that the use of cyclophosphamide, with its toxic effects, would decrease. In this Review, the authors summarize the current knowledge of therapies for proliferative and membranous lupus nephritis and propose a treatment scheme, not of one therapy over another, but one that is tailored to the individual patient profile.

In this second in a series of three Reviews on Wnt–β-catenin signaling, Prof. Schett and colleagues discuss the molecular regulation of joint remodeling associated with chronic arthritis and the role of Wnt proteins in determining the differences in clinical presentation of inflammatory arthropathies, as well as implications for future therapy.

Although autoantibodies occur in healthy individuals, pathogenic autoantibodies are the key etiologic agent in many autoimmune diseases in humans, most notably lupus erythematosus. In this Review the authors explore how these autoantibodies become pathogenic, what accounts for their specificity, how they cause disease and whether they have a clinical role as biomarkers of disease.

MicroRNAs (miRNAs) have been implicated in the pathogenesis of rheumatic disease and are, therefore, a potential target for drug development. This Review describes the well-established roles of miRNAs in hematopoiesis and the immune response, the molecular action of miRNAs in the simultaneous post-transcriptional regulation of multiple targets, and the evidence for roles of specific miRNAs in rheumatic disease.

This Case Study illustrates the differential diagnosis and management of nephrogenic systemic fibrosis, a progressively debilitating fibrosing disorder. The authors describe the case of a 60-year-old woman with chronic renal disease who presented with progressive stiffness in her arms and legs following exposure to gadolinium-containing contrast media.

Guidelines for access to biologic therapies vary considerably between different nations. In this Viewpoint, Drs Deighton and Hyrich discuss the pros and cons of current guidelines for anti-tumor necrosis factor therapy in patients with rheumatoid arthritis, and recommend a number of elements that should be included in future guidelines.

Familial cold autoinflammatory syndrome, Muckle–Wells syndrome and chronic infantile neurologic cutaneous articular syndrome (also known as neonatal-onset multisystemic inflammatory disease) are rare autoinflammatory diseases classified as cryopyrin-associated periodic syndromes or cryopyrinopathies. Clinical characteristics, mechanisms of disease and new treatment options for these syndromes are outlined in this Review.

In this Case Study, Drs Flossmann and Jayne describe the treatment of a patient with refractory Wegener's granulomatosis and discuss the challenges associated with managing this disorder.

Although useful in clinical trials, current measures of RA activity have important limitations when used in clinical practice. In this Viewpoint, Drs Wolfe and Michaud discuss the limitations of these activity scales and indices, and recommend that clinicians use these measures in combination with longitudinal data and additional non-questionnaire information about the patient.

Central nervous system vasculitis can cause a wide spectrum of neurological deficits in children. In this Viewpoint, Drs Cantez and Benseler provide an overview of the field and highlight for rheumatologists the importance of recognizing and appropriately treating this disease.

Drs Asherson, Giampaolo and Strimling describe a middle-aged patient with total alopecia, muscular spasms, diarrhea and gastric ulceration. She is only the fifth reported case of adult-onset Satoyoshi syndrome (usual age of onset is 5–19 years), and the first person reported to have a combination of Satoyoshi syndrome, gastric ulceration, and eosinophilic enteritis.

In rheumatoid arthritis, bone involvement presents as generalized osteoporosis, periarticular osteoporosis and erosions. Prof. Haugeberg discusses evidence for all three features resulting from increased activation of the osteoclast, and suggests that potent anti-inflammatory treatment, or direct inhibition of the osteoclast, might protect against all of these types of bone damage seen in patients with rheumatoid arthritis.

The vitamin D system has both pathophysiological and therapeutic importance for autoimmune disease. In this Review, the authors discuss the role of the vitamin D system in autoimmunity, the mechanistic basis for this role, and present the potential of vitamin D receptor agonists to treat or prevent autoimmune diseases.

High concentrations of intact aggrecan are required for effective weight-bearing in healthy cartilage. Aggrecanases from the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzyme family, particularly ADAMTS-4 and ADAMTS-5, are thought to be involved in the pathogenesis of osteoarthritis. In this Review, Drs Fosang and Little discuss potential disease-modifying agents for osteoarthritis that could trigger the downregulation of ADAMTS enzymes.

The impact of the global HIV pandemic continues to grow and rheumatologists need to be aware of the spectrum of rheumatic diseases that occur in HIV-positive individuals, as outlined in this Review. Changes in the patterns of rheumatic diseases that have developed since the introduction of highly active antiretroviral therapy and the management of treatment of rheumatic diseases in HIV-positive patients are also discussed.

The canonical Wnt/β-catenin signaling pathway regulates multiple biological events, including embryonic bone development and fracture repair. In this Review, the authors discuss the role of this pathway in fracture repair at the molecular, cellular and physiological levels, and its potential as a therapeutic target.

Clinical trials in rheumatology, similar to other areas of research, are associated with a plethora of ethical issues. Relevant issues, depending on the type of trial (for example, early phase trials, prevention trials and postmarketing studies), are outlined in this article, along with issues related to the selection of control arms for clinical trials, the selection of relevant outcome measures and some of the challenges in obtaining informed consent.

Biologic agents that target tumor necrosis factor represent an attractive approach to the treatment of vasculitic diseases, especially those associated with granuloma formation. Available data on the use of these agents for individual vasculitic diseases, and the potential to apply these data to the care of vasculitis patients in clinical practice are discussed in this Review.

Optic neuritis and myelitis can occur as manifestations of idiopathic demyelinating syndromes, as well as of systemic rheumatic syndromes. In this Case Study, Drs Birnbaum and Kerr present a patient with systemic lupus erythematosus and concomitant neuromyelitis optica (also known as Devic's syndrome), and discuss the distinguishing clinical and radiographic features critical for an accurate diagnosis.