The concept of spondyloarthritis: Where are we now?

doi:10.1016/j.berh.2014.10.007

Best Practice & Research Clinical Rheumatology

Volume 28, Issue 5, October 2014, Pages 663-672

https://doi.org/10.1016/j.berh.2014.10.007 Get rights and content

Abstract

The term spondyloarthritis (SpA) encompasses a group of diseases characterized by inflammation in the spine and in the peripheral joints, and other clinical features such as uveitis, dactylitis, psoriasis, inflammatory bowel disease, and association with human leukocyte antigen (HLA) B27. The spectrum of SpA encompasses axial spondyloarthritis (axSpA) and peripheral spondyloarthritis including psoriatic arthritis (PsA), reactive arthritis (ReA), and inflammatory bowel disease-associated arthritis. In recent years, there has been tremendous progress in understanding the natural history and pathogenetic mechanisms underlying SpA leading to the development of effective treatments. It has become imperative to identify the disease early, and accurately, to avail patients of effective treatments in a safe manner. The development of the Assessment of SpondyloArthritis International Society (ASAS) classification criteria has been a welcome advance in this regard. This article provides a historical evolution of the concept of SpA, from the Rome Criteria to the ASAS criteria, current issues and barriers with the use of ASAS criteria, and the work that still needs to be done moving forward.

Introduction

The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory diseases that share common clinical and genetic features. These features include inflammation of the axial skeleton (sacroiliac (SI) joints and spine); peripheral arthritis commonly occurring in a characteristic pattern, that is, asymmetric, oligoarticular, and predominately in the lower extremities; enthesitis; dactylitis; uveitis; psoriasis; inflammatory bowel disease (IBD); and association with the HLA-B27 gene. While some diseases within the SpA group affect the axial skeleton predominantly, some conditions involve the peripheral skeleton primarily. In its current understanding, SpA encompasses axial spondyloarthritis (axSpA) including non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS), plus peripheral spondyloarthritis (pSpA) including psoriatic arthritis (PsA), reactive arthritis (ReA), and IBD-associated arthritis (Fig. 1). The past few years have witnessed considerable progress in advancing our understanding of the disease process and the natural history and genetics of patients with axial skeletal inflammation, some of whom may develop damage at the SI joints at a later stage. This led to defining axSpA as an umbrella term, which includes AS plus patients with axial inflammation who do not have the X-ray changes that currently define AS.

The estimated prevalence of SpA in Europe has been reported to be 1.2% and that of AS is 0.2–1.2% [1], [2], [3], [4], [5]. According to a recent National Health and Nutrition Examination Survey (NHANES), the age-adjusted prevalence of axSpA is estimated to be up to 1.4% in the USA [6], [7]. The onset of axSpA typically occurs at a young age (usually <45 years), but due to the lack of a pathognomonic clinical feature or laboratory test, early diagnosis is difficult. The average delay in diagnosis is estimated to be 8–11 years [8]. Without early diagnosis and with delayed treatment, axSpA imparts a tremendous symptomatic burden and loss of function during the productive years of life.

With limited treatment options in the past, the need for early diagnosis and treatment was less crucial, but with the availability of new effective treatment options (biologic agents blocking tumor necrosis factor alpha (TNF-α), and possibly interleukin (IL)-17, IL-12, and IL-23) [9] and with the evidence that early treatment may retard the radiological progression, it becomes imperative that we make efforts to identify these patients and institute treatments as early as possible after the onset of symptoms. The development of the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for both axSpA and pSpA has been a welcome advance in this regard after a long hiatus. This article provides a historical evolution of the concept of SpA, current issues and barriers with the use of ASAS criteria, and the work that still needs to be done moving forward.

Section snippets

Historical review

The term “ankylosing spondylitis” predates the term and concept of “spondyloarthritis.” The term is derived from the Greek words ankylosis (bent or crooked) and spondylos (vertebra). In 1912, Raymond described convincing illustrations of AS in mummies and graves of ancient Egypt [10]. Since then, various Egyptian, French, and Danish descriptions have been presented. This contrasts with the first accepted description of rheumatoid arthritis (RA) by Sydenham in 1848 [11]. Several separate

Evolution of the concept of SpA

The concept of SpA started with the understanding of AS as a separate disease, leading to the proposal of the first classification criteria for AS at the European Congress of Rheumatology in Rome, known as the “Rome criteria” in 1961 (Table 1). Soon after that, the New York (NY) criteria were published in 1966 [12] providing more specific definitions of AS and providing a grading method of sacroiliitis for the first time. Another seminal event occurred in 1974 when Moll and Wright identified

Evolution of the concept of axSpA and pSpA and development of ASAS classification criteria

The main limitation of mNY criteria, which mandate the presence of definite sacroiliitis, is their failure to identify early disease. With the knowledge that sacroiliitis typical of AS may take years to develop after the appearance of the initial symptoms of IBP or peripheral arthritis [21], ∗[22], as well as with the increasing use of new imaging modalities to diagnose sacroiliitis early, there has been a renewed interest in the development of new classification criteria for patients with

Advantages and drawbacks of the ASAS axSpA criteria

One major advantage of the ASAS criteria for axSpA is the identification of “non-radiographic” SpA patients so that the rheumatologist can institute treatment early. Inclusion of MRI to detect sacroiliitis early in the course has been a crucial advance. MRI is highly sensitive in detecting SI joint inflammation [36] and has been shown to predict the development of AS [38]. MRI also offers an advantage in distinguishing active inflammation (bone marrow edema) from chronic changes of previous

Advantages and drawbacks of the ASAS pSpA criteria

The ASAS pSpA criteria have several notable advantages. The inclusion of monoarthritis and polyarthritis in addition to oligoarthritis, requirement of fewer clinical features to fulfill the criteria, inclusion of enthesitis and dactylitis as entry criteria, and the addition of HLA-B27 are some obvious advantages increasing the sensitivity of the criteria. Clinical trials using new, targeted biologics for ReA or IBD-associated arthritis are unlikely to be carried out by the pharmaceutical

Summary

The concept of SpA is a work in progress. On the one hand, we would like to diagnose patients with SpA early, and, on the other, we would like to avoid overdiagnosis by erroneously including patients with mechanical back pain (or patients with fibromyalgia). ASAS criteria have been a major advance in furthering the understanding of SpA, paving the way for the highly needed research in this group of disorders. Several questions remain unanswered.

Future perspectives

The most appropriate terminology to describe the disease and its subsets continues to be debated. One could envision diagnosing patients as “SpA” alone with subsequent description of other characteristics such as predominantly axial or peripheral, presence or absence of structural changes on radiographs or MRI (for axial disease), and presence of psoriasis, uveitis, IBD or antecedent gastrointestinal or genitourinary infection, etc. The natural history of patients with inflammatory low back

Future research agenda

Modification of the current classification criteria to improve the specificity of axSpA, development of a consensus terminology for various subsets of spondyloarthritides, and conducting epidemiologic studies to assess the natural history of IBP and nr-axSpA are some of the important needs. These needs should be considered in any future research agenda on this topic.

Practice points:

1.
The average delay in the diagnosis of axial spondyloarthritis (axSpA) is estimated to be 8–11 years. Without early

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Cited by (84)

Vitamin D level in ankylosing spondylitis male patients: A potential association with the functional status and platelet count
2023, Egyptian Rheumatologist
Ankylosing spondylitis (AS), spondyloarthritis (SpA) prototype characteristically involves the axial skeleton and enthesis. The pathogenesis of AS is multifactorial, however it has been reported that one important factor that might contribute is vitamin D deficiency. Vitamin D and platelets share specific roles in immune response, bone health and mineral metabolism.
To evaluate the serum vitamin D levels in AS patients and to study the relationship to clinical manifestations, disease activity, mobility and functionality.
The study included 33 male AS patients and 33 matched control. Bath AS metrology index (BASMI), Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) were evaluated. Serum 25-hydroxy vitamin D3 level was measured.
The 33 patients had a mean age of 37.2 ± 10.7 years, disease duration of 12.7 ± 6.8 years. 3 were ex-smokers, 15 currently and 15 never smoke. The mean BASDAI was 4.2 ± 2.1, 19 (57.6%) had BASDAI score ≥ 4 (active). The BASMI was 5.7 ± 1.4 and BASFI was 5.3 ± 2.6. Patient’s vitamin D level (7.2 ± 5.2 ng/ml) was lower significantly than in the control (21.3 ± 10.1 ng/ml) (p < 0.001). There were no differences in the level of vitamin D according to the smoking status (p = 0.9). A significant inverse relation was detected between vitamin D level and BASFI (r = -0.35, p = 0.045) and a significant correlation with the platelet level (r = 0.38, p = 0.027).
Low vitamin D level may contribute significantly to the pathogenesis of AS. It is significantly related to the impaired function in the disease and to low platelet count.
Sensitivity to the touch-Prevalence and effects of the fibromyalgia association and enthesitis in spondyloarthritis: Ancillary analysis of the ASAS-Perspa study
2022, Revue du Rhumatisme (Edition Francaise)
L’objectif principal était d’évaluer la coexistence de la fibromyalgie (FM) et de l’enthésite chez des patients atteints de spondyloarthrite (SpA). Les objectifs secondaires étaient l’identification des caractéristiques cliniques associées à la présence de FM dans l’enthésite et l’analyse des différences spécifiques au sexe.
Il s’agit d’une analyse ancillaire de l’étude ASAS-PerSpA (Assessment of SpondyloArthritis International Society Peripheral Involvement in SpA). L’enthésite a été définie comme la présence actuelle ou passée d’une enthésite. La FM clinique a été définie comme une FM confirmée par un rhumatologue. La FM selon les critères FiRST a été définie comme un score ≥ 5/6 au test de dépistage rapide FiRST (Fibromyalgia Rapid Screening Test).
Une enthésite actuelle ou passée et une FM concomitante (EFM) étaient présentes chez 10,3 % (n = 425) des patients du groupe sur la base des critères FiRST et chez 5,3 % sur la base du diagnostic clinique de FM. L’enthésite avait été confirmée par imagerie chez davantage de patients ayant une FM clinique que de patients ayant une FM selon les critères FiRST. Les femmes étaient plus nombreuses que les hommes à présenter l’association avec une FM clinique (76,9 % contre 23,1 %) ou une FM selon les critères FiRST (62,6 % contre 37,4 %). Dans les cas d’EFM, la maladie était plus sévère selon tous les indicateurs que dans les cas d’enthésite seule, sans différence significative entre les sexes. L’EFM a été significativement associée à l’âge, au sexe féminin, à l’IMC, au score BASDAI et à la région géographique.
La FM est une comorbidité importante dans le contexte de l’enthésite chez les patients atteints de SpA. Plus fréquente chez les femmes, l’EFM n’est cependant pas rare chez les hommes. Elle est associée à des indicateurs de sévérité de la SpA plus dégradés pour les deux sexes. Il est essentiel d’identifier la FM dans le contexte d’une enthésite afin de prévenir un surtraitement et d’optimiser les résultats des patients.
Tender to touch–Prevalence and impact of concomitant fibromyalgia and enthesitis in spondyloarthritis: An ancillary analysis of the ASAS PerSpA study
2022, Joint Bone Spine
Citation Excerpt :
Spondyloarthritis (SpA) is a chronic inflammatory arthritis predominantly involving the axial spine and sacroiliac joints (SIJs) [1]. The two most common forms of SpA are axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) [2]. Enthesitis is a characteristic feature, affecting up to 56% of patients with axSpA [3] and 30% of patients with PsA [4].
The primary objective was to evaluate the co-existence of fibromyalgia (FM) & enthesitis in individuals with spondyloarthritis (SpA). Secondary objectives were to identify clinical features associated with the presence of FM in enthesitis and analyse sex-specific differences.
This was an ancillary analysis of the Assessment of SpondyloArthritis International Society Peripheral Involvement in SpA (PerSpA) study. Enthesitis was defined as the presence of enthesitis ever. Clinical FM was defined as the rheumatologist's confirmation of the presence of FM. A score of ≥ 5/6 on the Fibromyalgia Rapid Screening Test (FiRST) defined a positive screening test for FM.
Enthesitis ever and FM (EFM) co-existed in 10.3% (n = 425) of the cohort using FiRST criteria and 5.3% using clinical diagnosis of FM. More individuals with FM by clinical diagnosis had imaging-confirmed enthesitis ever than by FiRST criteria. More females had EFM than males, defined clinically (76.9% vs 23.1%) or by FiRST criteria (62.6% vs 37.4%). Individuals with EFM had more severe disease across all measures compared to those with enthesitis only, with no significant difference between sexes. EFM was significantly associated with age, female sex, BMI, BASDAI and region.
FM is an important comorbidity in the setting of enthesitis in SpA. While EFM is more common in females, it is not a rare condition in males. EFM is associated with worse disease severity measures in SpA in both males and females. Recognition of FM in the setting of enthesitis is essential to prevent overtreatment and optimise patient outcomes.
Axial spondyloarthritis
2022, Medicine (United Kingdom)
Citation Excerpt :
It encompasses radiographic (r-axSpA, or AS) and non-radiographic axSpA (nr-axSpA); the nr-axSpA category was created because of the recognition of early axial disease, characterized by a constellation of signs, symptoms, laboratory and imaging features that allow the diagnosis of axSpA to be made in the absence of definite SIJ changes on radiographs. These patients often have evidence of SIJ changes on magnetic resonance imaging (MRI), particularly bone marrow oedema (BMO)/osteitis (Figure 34).5 axSpa can lead to chronic pain, structural damage and progressive spinal stiffness.
Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that predominantly involves the axial skeleton. The term describes a disease spectrum including patients with radiographic axSpA (also called ankylosing spondylitis), which have established (chronic) sacroiliitis on radiographs, and a further subgroup of ‘non-radiographic axSpA’, which typically shows evidence of active sacroiliitis on magnetic resonance imaging (MRI) in the absence of definite radiographic changes. The association between axSpA and HLA-B27 has been known for some time, and newer genetic links have been found with IL23R and ERAP1. Animal studies also support a link between the gut microbiome, gut inflammation and axSpA, and biomechanical stress may play a role. Chronic back pain, often with inflammatory features, is the cardinal manifestation, with enthesitis being the key pathological lesion. Many patients develop peripheral features such as enthesitis, arthritis or dactylitis, and some develop extra-articular manifestations (also called extra-musculoskeletal manifestations), namely uveitis, psoriasis or inflammatory bowel disease. Diagnosis of early-stage disease can be challenging, and MRI plays a key role in detecting inflammatory changes. Non-steroidal anti-inflammatory drugs and physical therapy are cornerstones of management, with tumour necrosis factor and interleukin (IL)-17 inhibitors vastly improving clinical outcomes. Newer treatments include new IL-17 inhibitors and JAK inhibitors.
A Road Map of the Axial Spondyloarthritis Continuum
2022, Mayo Clinic Proceedings
Citation Excerpt :
No differences in response to treatment with NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, biologics, or systemic glucocorticoids were identified between groups (P>.05 for all comparisons).71 The clinical course of axSpA may be nonlinear and unique to individual patients (Figure).11 Only a subset of patients with nr-axSpA may eventually have radiographic damage.11,12
Axial spondyloarthritis (axSpA) is a chronic, immune-mediated inflammatory disease characterized by inflammatory low back pain, inflammation in peripheral joints and entheses, and other extra-articular or systemic manifestations. Although our understanding of the natural history of axSpA has been limited by incomplete knowledge of disease pathogenesis, axSpA is increasingly understood as a spectrum of axial, peripheral, and extra-articular inflammatory conditions that includes nonradiographic axSpA and radiographic axSpA, also known as ankylosing spondylitis. In this narrative review, we present a road map of this axSpA continuum, highlighting genetic risk factors for the development of axSpA, triggers of disease, and reasons for and implications of diagnostic delay. We present a detailed overview of the spectrum of axSpA clinical manifestations and highlight factors known to influence the risk of disease progression. Finally, we provide some expert commentary on the practical use of this road map to assist health care providers in the identification of axSpA in clinical practice.
Beyond the sacro-Iliac joints: Vertebral involvement in axial spondylarthritis
2021, European Journal of Radiology
Citation Excerpt :
Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic diseases, often associated with the HLA-B27 gene [1].
Imaging plays a central role in the diagnosis of axial spondylarthritis (axSpA). Commonly the sacroiliac joints are involved but vertebral involvement can occur in isolation in 1 out of 4 patients. Recognizing vertebral involvement patterns in axSpA can help establishing a diagnosis early and initiate therapy before irreversible changes have occurred. Magnetic resonance imaging (MRI) is considered the reference standard for early detection of inflammatory changes of the disease. Aims of this review are to present an overview of the imaging findings of vertebral involvement in axSpA, and to detail the current recommendations on the role of imaging in the diagnosis of axSpA in patients with isolated vertebral involvement.

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1The concept of spondyloarthritis: Where are we now?

Abstract

Introduction

Section snippets

Historical review

Evolution of the concept of SpA

Evolution of the concept of axSpA and pSpA and development of ASAS classification criteria

Advantages and drawbacks of the ASAS axSpA criteria

Advantages and drawbacks of the ASAS pSpA criteria

Summary

Future perspectives

Future research agenda

Practice points:

Rheum Dis Clin North Am

The risk of developing ankylosing spondylitis in HLA–B27 positive individuals: a comparison of relatives of spondylitis patients with the general population

Arthritis Rheum

Prevalence of ankylosing spondylitis in males and females in a young middle-aged population in Tromsø, northern Norway

Ann Rheum Dis

Prevalence of spondylarthropathies in HLA–B27 positive and negative blood donors

Arthritis Rheum

Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France

J Rheumatol

Estimates of the prevalence of arthritis and other rheumatic conditions in the United States

Part I. Arthritis Rheum

The prevalence of axial spondyloarthritis in the United States: estimates from the U.S. national health and nutrition examination survey, 2009–10

Arthritis Care Res (Hoboken)

Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis

Rheumatol Int

Update on spondyloarthropathies

Ann Intern. Med

Les maladies de nosanc eancetres a l’age de la pietre (The diseases of our ancestors in stone age)

Aeschlape

Medical observations concerning the history and cure of acute diseases. translated by RG Latham

Population studies of the rheumatic diseases

Associations between ankylosing spondylitis, psoriatic arthritis, Reiter's disease, the intestinal arthropathies, and Behcet's syndrome

Med (Baltimore)

Seronegative polyarthritis: a unified concept

Arthritis Rheum

Clinical history as a screening test for ankylosing spondylitis

JAMA

Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria

Arthritis Rheum

New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from Assessment of Spondyloarthritis International Society (ASAS)

Ann Rheum Dis

The European Spondyloarthritis Study Group preliminary criteria for the classification of Spondyloarthropathy

Arthritis Rheum

Criteria for classification of spondyloarthropathies

Rev Rhum Osteoartic

The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral arthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress

Ann Rheum Dis

Clinical features and prognosis of patients with possible ankylosing spondylitis: results of a 10-year followup

J Rheumatol

The challenge of diagnosis and classification in early ankylosing spondylitis. Do we need new criteria?

Arth Rheum

Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography: a prospective, longitudinal study

J Rheumatol

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The concept of spondyloarthritis: Where are we now?