7Spondyloarthritides
Introduction
Ankylosing spondylitis (AS) is the major subtype and a major outcome of an interrelated group of rheumatic diseases named ‘spondyloarthritides (SpA)’. The most important clinical features of this group are inflammatory back pain (IBP), asymmetric peripheral oligoarthritis, predominantly of the lower limbs, enthesitis and specific organ involvement, most frequently as anterior uveitis, and there are close associations with psoriasis and chronic inflammatory bowel disease (IBD) [1]. For clinical purposes, two forms related to the predominant clinical manifestation – axial and peripheral SpA – and five subgroups – AS, SpA associated with psoriasis and IBD, reactive arthritis and undifferentiated SpA – are differentiated. Axial SpA including AS is the most frequent subtype of SpA, followed by psoriatic arthritis and undifferentiated SpA, while reactive arthritis and IBD-related SpA are less frequent.
The clinical symptoms of the SpA are characteristically similar and there is some evidence of genetic similarities, association and linkage but there is also heterogeneity. The strongest known contributing factor for AS, the major histocompatibility complex (MHC) class I molecule human leukocyte antigen (HLA)-B27, is known since 1973, while others such as endoplasmic reticulum aminopeptidase 1 (ERAP-1) and the interleukin (IL)-23R have only recently been identified [1]. Of interest, IL23R gene polymorphisms have also been identified in psoriasis and IBD [2], [3]. However, the pathogenesis of the SpA is still largely obscure.
The SpA belongs to the most common rheumatic diseases with a prevalence of 0.5–1.9% – this is similar to rheumatoid arthritis (RA) [4], [5], [6], [7]. AS and PsA are the SpA subsets with the potentially most severe course of disease. The outcome is mainly influenced by the degree of disease activity over time and the loss of function and mobility, part of which is caused by inflammation, while the other part is due to radiographic damage of the spine and of peripheral joints [8]. Male patients who are slightly more frequently affected than females have more radiographic progression [9]. The degree of pain and disability of AS patients was found to be similar to RA [10]. The quality of life of patients with AS is decreased in comparison to the normal population [11]. The socio-economic burden due to AS has been studied in some detail [12], [13], [14], [15], [16], [17], [18] pointing out that absence from work and work disability is threefold increased in AS patients [12], [13], [14] – this leads to substantial direct and indirect costs. Worse physical function [17] and high-disease activity have been identified as important determinants of costs. AS patients themselves also have substantial out-of-pocket costs [16], [17].
Therapeutic options for patients suffering from the more severe forms of SpA have been limited during the last decades. Conventional disease-controlling anti-rheumatic therapy (DCART) has some efficacy in PsA and other SpA but only for peripheral and not for axial disease manifestations. However, data are limited. By contrast, symptom-modifying anti-rheumatic drugs (SMARDs) such as non-steroidal anti-inflammatory agents (NSAIDs) are currently considered the first choice of medical therapy. NSAIDs are widely used to ameliorate spinal pain in AS [19], [20], [21]. Recent data have suggested that they may also have a DCART effect [22]. Corticosteroids work mainly when given locally. Furthermore, there is a clear role for regular physiotherapy in AS to prevent loss of spinal mobility [23], [24], [25].
Taken together, before the introduction of anti-tumour necrosis factor (TNF) therapy about 12 years ago, there has been a clear need for more effective treatments in the SpA [25]. Now there are four anti-TNF agents approved for the treatment of patients with active AS who have insufficiently responded to conventional therapies: infliximab, etanercept, adalimumab and golimumab. As far as it stands now, TNF blockers seem to have no influence on new bone formation in AS but they do inhibit radiographic damage in PsA. Other biologic agents have not been tested in AS, have had negative results or have only been tested in small open pilot studies [26], [27], [28], [29], [30].
Section snippets
Pathogenesis of SpA
Based on large family and genome-wide association studies, the susceptibility to AS has been estimated to be 80–90% genetically determined [31]. On this basis, it seems more likely that ubiquitous environmental factors, such as many different bacteria, may be involved. By far, the strongest genetic association is with HLA-B27. More than 60 HLA-B27 subtypes have been described so far. Some of them, such as HLA-B*2706 and HLA-B*2709, are not associated with the disease suggesting that the minor
How can we diagnose SpA early?
A major challenge in the management of patients with axial spondyloarthritis (SpA) is the substantial delay in diagnosis, which consistently averages 7–9 years [36], [37], [38]. This reflects the lack of specificity of presenting clinical features of the disease, particularly in the setting of a much higher prevalence of mechanical back pain, the lack of sensitivity of laboratory markers and the slow rate of radiographic progression in the SIJs over 5–10 years despite ongoing symptoms of IBP
Recommendations for the management of SpA
Treatment recommendations for the management of AS were first published in 2006 as a result of collaboration between ASAS and European League Against Rheumatism (EULAR) [65]. The recommendations were based on a systematic literature search until 2005. However, the research in this field has rapidly evolved making an update of the recommendations necessary – this was published very recently [66].
Treatment of SpA is mainly based on non-pharmacological and pharmacological treatment, including the
Treatment with biologics
It seems likely that the current view on the long-term efficacy and safety of anti-TNF agents in patients with AS will not dramatically change. The future perspective in the field of SpA will focus on diagnosis and treatment of patients in early disease stages such as non-radiographic axial SpA. Three TNF blockers have already shown efficacy in such patients in placebo-controlled randomised clinical trials. In the first trial [146] on adalimumab, patients with non-radiographic axial SpA who had
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Wnt5a is expressed in spondyloarthritis and exerts opposite effects on enthesis and bone in murine organ and cell cultures
2015, Translational ResearchCitation Excerpt :In many patients, the pain can be relieved by treatments with nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-tumor necrosis factor α (anti–TNF-α) therapy for NSAID-resistant patients. Anti-TNF agents have dramatic beneficial effects on active inflammatory lesions and result in improvements in functional outcomes.5 However, TNF-blockers are not really effective in retarding structural progression in SpA, as they do not seem to stop bone erosion or bony ankylosis.6,7
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2015, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :Other SpA characteristics are enthesitis, which involves inflammation on attachment sites of ligaments [90] and new bone synthesis advancing towards ankylosis or enthesophyte development [91]. SpA is the second most frequent inflammatory rheumatic disease following RA [92]. Recent studies have provided strong evidence that mechanical strain results in entheseal inflammation as well as new bone synthesis in SpA.
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2014, Forensic Science InternationalCitation Excerpt :It is the major subtype of an interrelated group of inflammatory diseases named spondyloarthritides. The most important clinical features of this group include inflammatory back pain, asymmetric peripheral oligoarthritis, enthesitis and specific organ involvement [1]. Historically, the Rome criteria of 1961 were the first to be developed for the classification of AS [2].
How good is the agreement between clinical diagnoses and classification criteria fulfilment in axial spondyloarthritis? Results from the SPARTAKUS cohort
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