Rheumatology

An Update on Diagnosis and Classification of Axial Spondyloarthritis Abstract Purpose of Review To summarize the most relevant recent progress to diagnose and classify patients with axial spondyloarthritis (axSpA). Recent Findings A substantial proportion of new studies focused on the diagnosis and classification of patients with axSpA. Efforts have been concentrated on setting the best strategy to refer patients with suspected axSpA and evaluating the utility of different tools during the diagnostic work-up, especially of imaging techniques. On top of this, researchers have worked on addressing some concerns raised about the employment of the Assessment of SpondyloArthritis international Society classification criteria, especially those related to the validity and misuse of the criteria, providing valuable data on this regard. Summary Recent findings emphasize that classification should serve a completely different purpose than diagnosis. In addition, they highlight the importance to consider the limitations for imaging acquisition, the appropriate context, and differential diagnosis when interpreting imaging findings during the diagnostic work-up of patients with suspected axSpA.

Skeletal Muscle Wasting and Its Relationship With Osteoarthritis: a Mini-Review of Mechanisms and Current Interventions Abstract Purpose of Review Osteoarthritis (OA) is a subset of joint disorders resulting in degeneration of synovial joints. This leads to pain, disability and loss of independence. Knee and hip OA are extremely prevalent, and their occurrence increases with ageing. Similarly, loss of muscle mass and function, sarcopenia, occurs during ageing. Recent Findings Little is known about the impact of muscle wasting on OA progression; nevertheless, it has been suggested that muscle wasting directly affects the stability of the joints and loss of mobility leads to gradual degeneration of articular cartilage. The molecular mechanisms underlying muscle wasting in OA are not well understood; however, these are probably related to changes in gene expression, as well as epigenetic modifications. Summary It is becoming clear that skeletal muscle wasting plays an important role in OA development and/or progression. Here, we discuss mechanisms, current interventions, such as exercise, and potentially novel approaches, such as modulation of microRNAs, aiming at ameliorating OA symptoms through maintaining muscle mass and function.

The Role of Chondrocyte Morphology and Volume in Controlling Phenotype—Implications for Osteoarthritis, Cartilage Repair, and Cartilage Engineering Abstract Purpose of Review Articular chondrocytes are exclusively responsible for the turnover of the extracellular matrix (ECM) of hyaline cartilage. However, chondrocytes are phenotypically unstable and, if they de-differentiate into hypertrophic or fibroblastic forms, will produce a defective and weak matrix. Chondrocyte volume and morphology exert a strong influence over phenotype and a full appreciation of the factors controlling chondrocyte phenotype stability is central to understanding (a) the mechanisms underlying the cartilage failure in osteoarthritis (OA), (b) the rationale for hyaline cartilage repair, and (c) the strategies for improving the engineering of resilient cartilage. The focus of this review is on the factors involved in, and the importance of regulating, chondrocyte morphology and volume as key controllers of chondrocyte phenotype. Recent Findings The visualisation of fluorescently-labelled in situ chondrocytes within non-degenerate and mildly degenerate cartilage, by confocal scanning laser microscopy (CLSM) and imaging software, has identified the marked heterogeneity of chondrocyte volume and morphology. The presence of chondrocytes with cytoplasmic processes, increased volume, and clustering suggests important early changes to their phenotype. Results from experiments more closely aligned to the normal physico-chemical environment of in situ chondrocytes are emphasising the importance of understanding the factors controlling chondrocyte morphology and volume that ultimately affect phenotype. Summary An appreciation of the importance of chondrocyte volume and morphology for controlling the chondrocyte phenotype is advancing at a rapid pace and holds particular promise for developing strategies for protecting the chondrocytes against deleterious changes and thereby maintaining healthy and resilient cartilage.

ILC3 in Axial Spondyloarthritis: the Gut Angle Abstract Purpose of Review A growing body of evidence supports the relevance of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway for the pathogenesis of axial spondyloarthritis (axSpA) and its treatment. Recently, innate lymphoid cells (ILC), a heterogeneous family of immune effector cells, have been identified as a relevant contributor in tissue homeostasis, partially via IL-23/IL-17 axis. This review describes the biology and the origins of the group 3 ILCs (ILC3s) in humans, focusing on their role in the pathogenesis of axSpA. Recent Findings Clinical trials showed the effectiveness of IL23/IL-17 axis inhibition in both spondyloarthritis (SpA) and Inflammatory Bowel Disease (IBD). Recent findings confirm the high prevalence of subclinical gut inflammation in patients with SpA. Translational data in humans have demonstrated an increase in the number of ILC3s responsive to IL-23 and producing either IL-22 or IL-17 in the gut of SpA patients. The observation of gut-derived ILC3s in circulation and at inflamed tissues in patients with SpA suggest a recirculation of ILCs from mucosal site to lymphoid tissues and possibly enthesis and joints. Summary Multiple observations demonstrate the expansion of IL-17- and IL-22-producing ILC3 in the subclinically inflamed gut of SpA patients. These innate immune cells, also observed in normal entheses, seem to be able to re-circulate from the gut to inflamed tissues of SpA patients, thus contributing to the disease perpetuation. The development of tools that can provide access to diseased tissue from sacroiliac joint and spinal entheses will provide valuable knowledge on the role of ILC3 in axSpA pathogenesis.

Emerging Immunomodulatory Therapies and New Treatment Paradigms for Axial Spondyloarthritis Abstract Purpose of Review The purpose of this review is to educate the reader about the evolving classification of axial spondyloarthritis (AxSpA) and describe recent treatment data from clinical trials of medications with mechanisms of action other than TNF inhibition. The review will also address emerging treatment strategies for AxSpA. Recent Findings New and more sensitive classification schema for AxSpA find that the prevalence of the disease is more than twice that of the historic definition of ankylosing spondylitis (AS), when patients without radiographically observable damage to the sacroiliac joints are included. TNF inhibitors have shown efficacy in the full spectrum of disease. IL-17 inhibitors, e.g., secukinumab and ixekizumab and janus kinase (JAK) inhibitors, have shown good efficacy and relatively good safety in radiographically defined AxSpA and are being tested in non-radiographic (nr) AxSpA. Several immunomodulatory medicines approved for psoriasis, psoriatic arthritis, and rheumatoid arthritis have not shown efficacy in AxSpA, highlighting the importance of conducting good-quality, placebo-controlled trials in this condition. Treatment strategies such as "treat to target" and tapering therapy are being studied. Summary There remains a large unmet need to identify and adequately treat the full spectrum of AxSpA. The use of TNF inhibitors has improved our ability to achieve remission or low disease activity in AxSpA. Newer medicines with different mechanisms of action, e.g., IL-17 or JAK inhibition, are also showing similar ability. Continued research, including identification of new targets of treatment, is critical.

In the Real World: Infections Associated with Biologic and Small Molecule Therapies in Psoriatic Arthritis and Psoriasis Abstract Purpose of Review To summarize our most current understanding of the real world risk of infections associated with biologic and small molecule therapies in the setting of psoriatic disease. Recent Findings Patients with psoriasis or psoriatic arthritis are at increased risk for infection from both their disease and some of their therapies. There is little real world data for biologic and small molecule therapies; however, ustekinumab and biologics inhibiting IL-17 or IL-23 appear to have reduced risk estimates compared to anti-TNF therapies. Apremilast seems to have little infectious signal with limited real world data, and for JAK inhibitors, limited real world data suggest a higher risk of herpes zoster. Summary Recently approved targeted and small molecule therapies for psoriasis carry infectious risks for patients, although they appear to vary across mechanism of action. As these treatments become more widespread, and additional therapies are approved, it will be imperative to evaluate their safety in the context of real world data.

Correction to: Cell Senescence in Lupus The original version of this article unfortunately contained mistakes.

Treatment Strategies in ANCA-Associated Vasculitis Abstract Purpose of Review The long-term survival of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) has improved dramatically as a direct result of evolving therapy. This review summarizes evidence-based treatment strategies with currently approved immunosuppressive medications to serve as a guide for practitioners in the management of patients with AAV. Recent Findings Targeted therapy aimed at minimizing treatment-related adverse effects while optimizing effectiveness is a propagated approach. Such tailored therapy considers disease severity and is especially warranted in those at high risk for relapsing vasculitis. Summary As treatment options for AAV become available, the need to tailor therapy has become increasingly relevant to optimize patient outcomes.

Emotional Awareness and Expression Therapy for Chronic Pain: Rationale, Principles and Techniques, Evidence, and Critical Review Abstract Purpose of Review Patients with chronic pain, especially primary or centralized pain, have elevated rates of psychosocial trauma and intrapersonal or intrapsychic conflict. To address these risk factors and potentially reduce pain, the authors developed emotional awareness and expression therapy (EAET). This article presents the rationale for EAET, describes its principles and techniques, reviews its development and early testing as well as recent clinical trials, and critically analyzes the evidence base. Recent Findings Four initial trials (between 2006 and 2011) demonstrated the efficacy of earlier versions of EAET. Four recent randomized, controlled trials of different EAET durations (1 to 8 sessions) and formats (individual or group) in patients with fibromyalgia, irritable bowel syndrome, pelvic pain, or medically unexplained symptoms support the earlier findings. EAET reliably reduces pain and interference, although improvements in anxiety and depression are less reliably achieved and may be delayed. The largest and best conducted trial found superiority of EAET over cognitive-behavioral therapy for fibromyalgia. Patient retention in EAET is high, and adverse events are rare. Summary EAET merits inclusion as a treatment option for primary pain conditions, and it may be the preferred treatment for some patients. Research is needed on EAET with other pain conditions and samples, using better controls and comparison conditions, and on additional ways to motivate and help patients engage in successful emotional processing.

Osteoporosis Pathophysiology, Epidemiology, and Screening in Rheumatoid Arthritis Abstract Purpose of Review To review the burden of osteoporosis (OP) in rheumatoid arthritis (RA) and to describe the OP screening strategies applied in RA. Recent Findings RA is an inflammatory condition that predisposes patients to development of OP. OP in RA has a multifactorial pathogenesis with systemic inflammation and glucocorticoid use playing major roles. Newer studies have reported an intriguing association between RA autoantibodies and the development of OP. OP screening strategies in RA patients include clinical and vitamin D assessment, biochemical markers of bone remodeling, and bone imaging evaluations, particularly dual-energy X-ray absorptiometry (DXA). Summary Fragility fractures are an important comorbidity of RA. OP screening strategies are both feasible and effective in RA patients and recommended by most specialty organizations. Given the considerable exposure to factors related to OP development, such as pro-inflammatory cytokines and glucocorticoid treatment, special attention should be directed to biochemical and DXA results in RA patients.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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alsfakia@gmail.com