Elsevier

The Lancet

Volume 377, Issue 9783, 18–24 June 2011, Pages 2127-2137
The Lancet

Series
Spondyloarthritis

https://doi.org/10.1016/S0140-6736(11)60071-8Get rights and content

Summary

Spondyloarthritis is a group of several related but phenotypically distinct disorders: psoriatic arthritis, arthritis related to inflammatory bowel disease, reactive arthritis, a subgroup of juvenile idiopathic arthritis, and ankylosing spondylitis (the prototypic and best studied subtype). The past decade yielded major advances in the recognition of spondyloarthritis as an entity, the classification of the disease, and understanding of the genetic and pathophysiological mechanisms of disease-related inflammation and tissue damage. In parallel, new clinical and imaging outcomes have allowed the assessment of various therapeutic modalities. Blockers of tumour necrosis factor are a major therapeutic advance, but the exact roles of physiotherapy, and treatment with non-steroidal anti-inflammatory drugs and other biological treatments are unknown. The major challenges with direct relevance for clinical practice for the next decade are the development of techniques for early diagnosis, therapeutic modulation of structural damage, and, ultimately, induction of long-term, drug-free remission.

Introduction

In 1974, Moll and colleagues1 established the concept of a group of inter-related disorders originally termed seronegative spondarthritides. The group of diseases now called spondyloarthritis consists of psoriatic arthritis, reactive arthritis, arthritis related to inflammatory bowel disease, a subgroup of juvenile idiopathic arthritis, and ankylosing spondylitis—the prototype of spondyloarthritis.2 The various clinical forms include spinal (axial) features, peripheral arthritis, enthesopathy, and extra-articular features such as uveitis, psoriasis, and inflammatory bowel disease. The clinical rationale for grouping these diseases is that they are simultaneously or sequentially identified in the same patient or in a family member. Furthermore, clinical characteristics such as eye involvement and enthesopathy are similar whatever the diagnosis.1, 2 A strong argument, based on work in animals, in favour of grouping these diseases is that HLA-B27 transgenic rats develop the various clinical features that are noted in human beings with spondyloarthritis.3

One subject of debate at present is whether the clinical approach, including diagnosis, classification, and management, should be focused on a specific disease subtype (eg, ankylosing spondylitis) or on the overall group of spondyloarthritis. In the 1970s, several sets of criteria were proposed to classify patients with a specific spondyloarthritis subtype, such as the modified New York criteria for ankylosing spondylitis.4 These criteria have important restrictions in clinical practice: they focus exclusively on the axial features, omitting the other clinical features of the disease. In 1990, Amor and colleagues5 proposed the first set of classification criteria for the entire group of spondyloarthritis, allowing a patient to be classified as having spondyloarthritis whatever the presenting symptoms. A different set of criteria for the entire group of spondyloarthritis was developed by the European Spondyloarhropathy Study Group,6 with inflammatory back pain and peripheral arthritis as major entry criteria. Recognition of the drawbacks of criteria focused on a specific subtype, the Assessment of Spondyloarthritis International Society (ASAS) did a large cross-sectional study to propose new criteria on the basis of the two main clinical features identified in daily practice—eg, axial symptoms and peripheral involvement.

In the first set of criteria focusing on patients presenting with axial symptoms (panel),7 the term axial spondyloarthritis was proposed for the entire range of axial diseases irrespective of structural damage. These criteria emphasise three important points: the relevance of the clinical features identified whatever the presenting symptoms, the value of new imaging techniques to detect sacroiliac changes, and the contribution of HLA-B27 typing.

One important advance is the use of MRI to assess sacroiliac changes. Plain radiographs can detect only structural changes such as joint erosion and subchondral-bone sclerosis seen at the late stage of the disease; this restriction is also the case for CT, although with higher sensitivity and specificity but greater exposure to radiation. Unfortunately, the medical term used to describe such chronic changes focuses on inflammation—eg, sacroiliitis—despite the fact that plain radiographs cannot detect inflammation. By contrast, MRI allows the visualisation of synovial fluid, synovitis within the sacroiliac joint, and subchondral-bone oedema. The relevant abnormalities detected with MRI have been described and clearly defined,8 allowing inclusion of active inflammatory lesions of sacroiliac joints with definite bone-marrow oedema and osteitis on MRI in the new criteria for axial spondyloarthritis.7 Whether such a definition—eg, MRI findings at the sacroiliac joints—is optimum remains an open question since data suggest that inflammatory lesions of the posterior structures of the spine as well as the spinal fatty Romanus lesions (fatty changes at vertebral corners) are also suggestive of spondyloarthritis.9, 10 More importantly, however, these criteria were developed in a well defined cross-sectional study population (eg, age <45 years and with back pain for at least 3 months) and have not yet been validated for diagnostic use in prospective studies in clinical practice.

The second set of criteria proposed by ASAS is focused on patients presenting with peripheral rheumatological involvement (eg, peripheral arthritis, enthesopathy, dactylitis) without axial symptoms.11 These criteria (figure 1) also emphasise the importance of the different clinical features, HLA-B27 typing, and imaging of sacroiliac joints despite the absence of spinal symptoms. Sacroiliac abnormalities at imaging raise the question of which of the investigations should be done when spondyloarthritis is suspected, whatever the presenting symptoms. Clinicians agree on the use of HLA-B27 typing, although it is only useful in cases with an a-priori high suspicion, and a negative result does not preclude the presence of spondyloarthritis. The findings of the study12 used to develop the criteria also suggest that in a case of peripheral rheumatological presentation, the systematic radiological (eg, plain radiographs and MRI) assessment of the sacroiliac joints might be of interest even in the absence of any axial features. Similarly, a systematic assessment of different entheses allows differentiation between spondyloarthritis patients and controls even in the absence of clinical enthesopathy.13, 14, 15

Enthesopathy, inflammation at the bone insertion sites of ligaments and tendons, is an important ASAS criterion. The main peripheral clinical location is the heel (inferior part at the insertion of plantar fascia on the calcaneus and posterior part at the insertion of Achilles tendon on the calcaneus). The recognition of spondyloarthritis and the use of these new criteria should allow clinical trials in patients with early disease and thereby the assessment of treatments to alter the course of the disease. Whether these criteria will also shorten the diagnostic delay remains to be investigated prospectively. Another interesting approach to reduce the diagnostic delay is the development of early referral strategies, since patients with back pain are usually first seen by primary care physicians.16 Defining better strategies and techniques for early diagnosis remains one of the major challenges in spondyloarthritis for the next decade.

Section snippets

Pathophysiology

Advances in the classification of spondyloarthritis show that progress in the understanding of genetics (eg, the gene for HLA-B27), the pathophysiology of inflammation (eg, lesions on MRI), and structural damage (eg, sacroiliitis on plain radiographs) affect clinical practice in the context of classification and diagnosis. Basic understanding of the pathophysiology of the disease is even more relevant for outcome measurement and targeted treatment.

Through familial aggregation studies17

Outcome assessment

The optimum management of patients necessitates systematically addressing five points related to the possible clinical presentations (axial, peripheral, enthesopathy, and extra-articular): does the patient really have the disease, is the disease active, is the disease severe, is the disease potentially severe, and is the disease refractory? One of the major challenges in spondyloarthritis remains the development of sensitive and specific imaging or biological markers for early diagnosis.

Treatment

The objectives of treatment of spondyloarthritis are to improve the condition of the patient (eg, pain, functional disability) as well as to prevent subsequent clinical deterioration. ASAS has provided recommendations for both the management of spondyloarthritis in general90 and the use of TNF blockers in particular.92

A recent Cochrane systematic review of published work93 concluded that an individual home-based or supervised exercise programme is better than no intervention, that supervised

Future prospects

From the present state of the art in spondyloarthritis, several important clinical and pathophysiological issues seem unsolved: the development and validation of better clinical or biological markers for early diagnosis and for prognosis, clarification whether the subtypes of spondyloarthritis are driven by different pathophysiological processes or rather represent different phenotypes of a single pathological entity, deciphering the functional role and the interaction of genes emerging from

Search strategy and selection criteria

We searched The Cochrane Library and Medline for work published in the past 5 years (2005–10), as well as the abstracts of the American (American College of Rheumatology) and European (European League Against Rheumatism) congresses of Rheumatology published during the past 2 years (2009–10). We used the search terms “spondyloarthropathy”, “spondylarthropaty”, “spondyloarthritis”, “spondylarthritis”, “ankylosing spondylitis”, and “psoriatic arthritis”. We limited our search to published

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