G Model BONSOI-4195; No. of Pages 3
ARTICLE IN PRESS Joint Bone Spine xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Editorial
Spondyloarthritis: A concept or a disease?
a r t i c l e
i n f o
Keywords: Spondyloarthritis Phenotype Patient profile
1. Is spondyloarthritis a group of distinct but related entities or a single disease that can produce various phenotypes? 1.1. From nosology to phenotype The development of new classification criteria has led not only to terminological changes [1], with “spondyloarthritis” now being used instead of “spondyloarthropathy”; but also to a shift in the nosological perspective, with individualized entities (e.g., psoriatic arthritis or enteropathic arthropathy) being replaced by clinical presentations (e.g., axial involvement or entheseal involvement) (Table 1). These changes are reflected in the current classification criteria developed by the ASAS, which distinguish axial and peripheral disease [2]. For classification as axial spondyloarthritis, patients must meet either an imaging criterion (sacroiliitis by radiography or MRI) plus at least one SpA feature or a clinical criterion (presence of the HLA-B27 antigen) plus at least two SpA features (Fig. 1). New terms have been suggested to describe the clinical phenotypes of patients with spondyloarthritis [1] (Table 2). 1.2. Evidence supporting phenotypic diversity Whether distinguishing different phenotypes of spondyloarthritis is useful in everyday practice needs to be discussed. Benefits might consist in additional information on the disease and its course, improved management, and/or better knowledge of factors that predict the outcome or treatment response. The many factors included in classification criteria sets could serve to define a potentially large number of disease phenotypes or expression patterns. Thus, clusters of selected factors might identify specific patient subgroups. A decade ago, the group led by Breban identified two major phenotypes that were independent from disease duration, based on a cluster analysis of 540 spondyloarthritis patients belonging to 190 different families [3]. The group with phenotype A had a predominance of women and the group with phenotype B a predominance of men. The two groups were similar for axial
Table 1 Changes in the classification of spondyloarthritis. Subgroup (nosology) Spondyloarthritis Ankylosing spondylitis Psoriatic arthritis Reactive arthritis Enteropathic arthropathies Undifferentiated spondyloarthritis
Clinical presentation (phenotype) Axial Arthritis Enthesopathy Dactylitis Extra-rheumatic involvement
Table 2 Suggested terminology for describing the clinical phenotype of patients with spondyloarthritis [1]. Axial spondyloarthritis Radiographica Nonradiographica Peripheral spondyloarthritis involving the joints Erosivea Nonerosivea Peripheral spondyloarthritis involving the enthesesa a Add any concomitant extraarticular manifestations to better characterize the phenotype (e.g., with psoriasis, Crohn’s disease, ulcerative colitis, or anterior uveitis).
symptoms, radiographic sacroiliitis, and the frequency of uveitis. Compared to phenotype A, phenotype B was characterized by onset at a younger age and higher frequencies of clinical enthesitis, peripheral arthritis, dactylitis, psoriasis, and inflammatory bowel disease. Some degree of familial aggregation was noted in both groups. More recently, studies of prospective cohorts such as DESIR [4] provided information about the impact of specific manifestations on the clinical presentation at study inclusion. In the DESIR cohort, the presence of HLA-B27 was associated with onset of inflammatory back pain at a younger age, a shorter time to diagnosis, MRI evidence of axial inflammation, radiographic sacroiliitis, a lower level of disease activity, and a lower frequency of psoriasis [5]. Females in the DESIR cohort had a higher degree of disease activity (as assessed using the BASDAI) and higher scores for fatigue and functional impairment, despite lesser severity of radiographic sacroiliitis and MRI inflammation of the spine and sacroiliac joints, compared to males. Women with radiographic sacroiliitis more often had peripheral involvement and a family history of spondyloarthritis. Features associated with male gender were presence of
http://dx.doi.org/10.1016/j.jbspin.2015.06.006 1297-319X/© 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Wendling D, et al. Spondyloarthritis: A concept or a disease? Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.006
G Model BONSOI-4195; No. of Pages 3
ARTICLE IN PRESS Editorial / Joint Bone Spine xxx (2015) xxx–xxx
2
Fig. 1. ASAS classification criteria for spondyloarthritis (SpA). From Rudwaleit et al. Ann Rheum Dis 2011;70:25–31.
HLA-B27, C-reactive protein (CRP) elevation, and MRI evidence of spinal inflammation [6]. Psoriasis was associated with enthesitis; higher BASDAI and BASFI values; and higher serum levels of CRP, cholesterol, and triglycerides compared to patients without psoriasis; in contrast, radiographic and MRI findings were similar in the two groups [7]. Among patients included in the ASSERT trial who had advanced spondyloarthritis meeting modified New York criteria, the only difference between the groups with and without skin psoriasis was the number of peripheral joints with synovitis [8]. Factors independently associated with uveitis by multivariate analysis were clinical involvement of the cervical spine, a history of infection preceding the onset of the inflammatory disease, and concomitant Crohn’s disease [9]. In this cohort of patients with recent-onset disease, anterior chest wall pain, which is an axial manifestation of spondyloarthritis, was associated with greater disease severity and activity, involvement of the peripheral entheses and thoracic spine, and radiographic sacroiliitis, independently from symptom duration [10]. Molto et al. analyzed clinical features depending on whether patients met the ASAS classification criteria based on sacroiliitis (imaging arm) or HLA-B27 (clinical arm) [11]. Few differences were found, although the imaging arm was characterized by a younger mean age, larger proportion of males, and higher CRP value. Similarly, in another study of the DESIR cohort of patients with recent-onset axial symptoms, Blachier et al. [12] found that, compared to patients without radiographic sacroiliac and/or spinal abnormalities, those with such abnormalities exhibited few specific characteristics (higher CRP levels, poorer responsiveness to nonsteroidal antiinflammatory drugs, and MRI inflammation at the sacroiliac joints and spine). These findings suggest that some phenotypic characteristics may identify patient subgroups, whereas
others (e.g., radiographic sacroiliitis) may be equally distributed across all phenotypes or subgroups. Using multiple correspondence analysis, d’Agostino et al. [13] classified 688 patients from the DESIR cohort into three main groups: group A had a predominance of males and higher proportions of isolated axial manifestations, uveitis, and HLA-B27; group B had a predominance of females, higher proportions of peripheral involvement (including entheseal vascularization detected by power Doppler) and psoriasis, and a younger age at symptom onset; and group C had equal proportions of males and females, a predominance of axial symptoms, and higher proportions of patients with the HLA-B27 antigen and/or with sacroiliitis by radiography or MRI. These data show clearly that the various spondyloarthritis features tend to cluster, thereby defining different phenotypic profiles. Future studies on the outcomes of DESIR-cohort patients will determine whether specific phenotypes are associated with disease outcomes. 1.3. From pathophysiology to clinical practice A major issue is whether the different patient profiles stem from one or from several different pathogenic mechanisms, that is, whether spondyloarthritis is a group of distinct but interrelated diseases or a single disease with a range of phenotypic expressions [14]. International experts have examined this issue based on evidence from family aggregation studies, animal models, immunopathological studies, structural outcomes, and therapeutic responses. They found no fundamental pathophysiological difference across the various spondyloarthritis phenotypes. Thus, spondyloarthritis seems to be a single disease with a heterogeneous phenotype.
Please cite this article in press as: Wendling D, et al. Spondyloarthritis: A concept or a disease? Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.006
G Model BONSOI-4195; No. of Pages 3
ARTICLE IN PRESS Editorial / Joint Bone Spine xxx (2015) xxx–xxx
Recognition of spondyloarthritis phenotypes may have implications, not only for evaluating and monitoring the disease, but also for making therapeutic decisions. Thus, the response to medications may vary across phenotypes. For instance, some of the TNF␣ antagonists may be particularly effective in nonradiographic axial spondyloarthritis [15], and specific phenotypic features may be associated with a good therapeutic response (e.g., younger age, CRP elevation, and short disease duration predict a good response to TNF␣ antagonists) [16]. This view of spondyloarthritis is already reflected in recent recommendations [17], which include adjusting the follow-up and treatment strategies to the phenotypic profile. The identification of new markers for spondyloarthritis, such as anti-CD74 autoantibodies for instance [18], will help to further refine the definition and implications of specific subgroups. 2. Conclusion Spondyloarthritis is not a concept encompassing various distinct rheumatic conditions but, instead, a single disease with heterogeneous phenotypic profiles that should be taken into account in clinical practice. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Claudepierre P, Wendling D, Breban M, et al. Ankylosing spondylitis, spondyloarthropathy, spondyloarthritis, or spondylarthritis: what’s in a name? Joint Bone Spine 2012;79:534–5. [2] Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011;70:25–31. [3] Porcher R, Said-Nahal R, D’Agostino MA, et al. Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families. Arthritis Rheum 2005;53:263–71. [4] Dougados M, d’Agostino MA, Benessiano J, et al. The DESIR cohort: a 10year follow-up of early inflammatory back pain in France: study design and baseline characteristics of the 708 recruited patients. Joint Bone Spine 2011;78:598–603. [5] Chung HY, Machado P, van der Heijde D, et al. HLA-B27 positive patients differ from HLA-B27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis. Ann Rheum Dis 2011;70:1930–6. [6] Tournadre A, Pereira B, Lhoste A, et al. Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort. Arthritis Care Res (Hoboken) 2013;65:1482–9. [7] Richette P, Tubach F, Breban M, et al. Psoriasis and phenotype of patients with early inflammatory back pain. Ann Rheum Dis 2013;72:566–71. [8] Machado P, Landewe R, Braun J, et al. Ankylosing spondylitis patients with and without psoriasis do not differ in disease phenotype. Ann Rheum Dis 2013;72:1104–7.
3
[9] Wendling D, Prati C, Demattei C, et al. Impact of uveitis on the phenotype of patients with recent inflammatory back pain: data from a prospective multicenter French cohort. Arthritis Care Res (Hoboken) 2012;64: 1089–93. [10] Wendling D, Prati C, Demattei C, et al. Anterior chest wall pain in recent inflammatory back pain suggestive of spondyloarthritis. Data from the DESIR cohort. J Rheumatol 2013;40:1148–52. [11] Moltó A, Paternotte S, van der Heijde D, et al. Evaluation of the validity of the different arms of the ASAS set of criteria for axial spondyloarthritis and description of the different imaging abnormalities suggestive of spondyloarthritis: data from the DESIR cohort. Ann Rheum Dis 2014, http://dx.doi.org/10.1136/annrheumdis-2013-204262. [12] Blachier M, Canouï-Poitrine F, Dougados M, et al. Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort. Rheumatology (Oxford) 2013;52:1686–93. [13] D’Agostino MA, Aegerter P, Dougados M, et al. Three phenotype profiles are revealed by cluster analysis in early inflammatory back pain suggestive of spondyloarthritis (spa). Results from the devenir des spondyloarthropathies indifferenciees recentes (DESIR) cohort. Ann Rheum Dis 2012;71: 411. [14] Baeten D, Breban M, Lories R, et al. Are spondylarthritides related but distinct conditions or a single disease with a heterogeneous phenotype? Arthritis Rheum 2013;65:12–20. [15] Wendling D, Prati C, Claudepierre P, et al. Non-radiographic spondyloarthritis: a theoretical concept or a real entity? Joint Bone Spine 2012;79: 531–3. [16] Arends S, van der Veer E, Kallenberg CG, et al. Baseline predictors of response to TNF-␣ blocking therapy in ankylosing spondylitis. Curr Opin Rheumatol 2012;24:290–8. [17] Wendling D, Lukas C, Paccou J, et al. Recommendations of the French Society for Rheumatology (SFR) on the everyday management of patients with spondyloarthritis. Joint Bone Spine 2014;81:6–14. [18] Meyer O. CD74: a diagnostic key for spondyloarthritis? Joint Bone Spine 2014, http://dx.doi.org/10.1016/j.jbspin.2014.07.005.
Daniel Wendling a,∗ Pascal Claudepierre b Clément Prati a Maxime Dougados c a Service de rhumatologie, université de Franche-Comté, CHRU de Besanc¸on, boulevard Fleming, 25030 Besanc¸on, France b Service de rhumatologie, laboratoire d’investigation clinique (LIC) EA4393, université Paris Est Créteil, hôpital Henri-Mondor, AP–HP, 94000 Créteil, France c Inserm U1153, Department of Rheumatology, Clinical Epidemiology and Biostatistics, Paris Descartes University, hôpital Cochin, PRES Sorbonne Paris-Cité, AP–HP, Paris, France ∗ Corresponding author. E-mail address: [email protected] (D. Wendling)
Accepted 24 November 2014 Available online xxx
Please cite this article in press as: Wendling D, et al. Spondyloarthritis: A concept or a disease? Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.006
ARTICLE IN PRESS Joint Bone Spine xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Editorial
Spondyloarthritis: A concept or a disease?
a r t i c l e
i n f o
Keywords: Spondyloarthritis Phenotype Patient profile
1. Is spondyloarthritis a group of distinct but related entities or a single disease that can produce various phenotypes? 1.1. From nosology to phenotype The development of new classification criteria has led not only to terminological changes [1], with “spondyloarthritis” now being used instead of “spondyloarthropathy”; but also to a shift in the nosological perspective, with individualized entities (e.g., psoriatic arthritis or enteropathic arthropathy) being replaced by clinical presentations (e.g., axial involvement or entheseal involvement) (Table 1). These changes are reflected in the current classification criteria developed by the ASAS, which distinguish axial and peripheral disease [2]. For classification as axial spondyloarthritis, patients must meet either an imaging criterion (sacroiliitis by radiography or MRI) plus at least one SpA feature or a clinical criterion (presence of the HLA-B27 antigen) plus at least two SpA features (Fig. 1). New terms have been suggested to describe the clinical phenotypes of patients with spondyloarthritis [1] (Table 2). 1.2. Evidence supporting phenotypic diversity Whether distinguishing different phenotypes of spondyloarthritis is useful in everyday practice needs to be discussed. Benefits might consist in additional information on the disease and its course, improved management, and/or better knowledge of factors that predict the outcome or treatment response. The many factors included in classification criteria sets could serve to define a potentially large number of disease phenotypes or expression patterns. Thus, clusters of selected factors might identify specific patient subgroups. A decade ago, the group led by Breban identified two major phenotypes that were independent from disease duration, based on a cluster analysis of 540 spondyloarthritis patients belonging to 190 different families [3]. The group with phenotype A had a predominance of women and the group with phenotype B a predominance of men. The two groups were similar for axial
Table 1 Changes in the classification of spondyloarthritis. Subgroup (nosology) Spondyloarthritis Ankylosing spondylitis Psoriatic arthritis Reactive arthritis Enteropathic arthropathies Undifferentiated spondyloarthritis
Clinical presentation (phenotype) Axial Arthritis Enthesopathy Dactylitis Extra-rheumatic involvement
Table 2 Suggested terminology for describing the clinical phenotype of patients with spondyloarthritis [1]. Axial spondyloarthritis Radiographica Nonradiographica Peripheral spondyloarthritis involving the joints Erosivea Nonerosivea Peripheral spondyloarthritis involving the enthesesa a Add any concomitant extraarticular manifestations to better characterize the phenotype (e.g., with psoriasis, Crohn’s disease, ulcerative colitis, or anterior uveitis).
symptoms, radiographic sacroiliitis, and the frequency of uveitis. Compared to phenotype A, phenotype B was characterized by onset at a younger age and higher frequencies of clinical enthesitis, peripheral arthritis, dactylitis, psoriasis, and inflammatory bowel disease. Some degree of familial aggregation was noted in both groups. More recently, studies of prospective cohorts such as DESIR [4] provided information about the impact of specific manifestations on the clinical presentation at study inclusion. In the DESIR cohort, the presence of HLA-B27 was associated with onset of inflammatory back pain at a younger age, a shorter time to diagnosis, MRI evidence of axial inflammation, radiographic sacroiliitis, a lower level of disease activity, and a lower frequency of psoriasis [5]. Females in the DESIR cohort had a higher degree of disease activity (as assessed using the BASDAI) and higher scores for fatigue and functional impairment, despite lesser severity of radiographic sacroiliitis and MRI inflammation of the spine and sacroiliac joints, compared to males. Women with radiographic sacroiliitis more often had peripheral involvement and a family history of spondyloarthritis. Features associated with male gender were presence of
http://dx.doi.org/10.1016/j.jbspin.2015.06.006 1297-319X/© 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Wendling D, et al. Spondyloarthritis: A concept or a disease? Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.006
G Model BONSOI-4195; No. of Pages 3
ARTICLE IN PRESS Editorial / Joint Bone Spine xxx (2015) xxx–xxx
2
Fig. 1. ASAS classification criteria for spondyloarthritis (SpA). From Rudwaleit et al. Ann Rheum Dis 2011;70:25–31.
HLA-B27, C-reactive protein (CRP) elevation, and MRI evidence of spinal inflammation [6]. Psoriasis was associated with enthesitis; higher BASDAI and BASFI values; and higher serum levels of CRP, cholesterol, and triglycerides compared to patients without psoriasis; in contrast, radiographic and MRI findings were similar in the two groups [7]. Among patients included in the ASSERT trial who had advanced spondyloarthritis meeting modified New York criteria, the only difference between the groups with and without skin psoriasis was the number of peripheral joints with synovitis [8]. Factors independently associated with uveitis by multivariate analysis were clinical involvement of the cervical spine, a history of infection preceding the onset of the inflammatory disease, and concomitant Crohn’s disease [9]. In this cohort of patients with recent-onset disease, anterior chest wall pain, which is an axial manifestation of spondyloarthritis, was associated with greater disease severity and activity, involvement of the peripheral entheses and thoracic spine, and radiographic sacroiliitis, independently from symptom duration [10]. Molto et al. analyzed clinical features depending on whether patients met the ASAS classification criteria based on sacroiliitis (imaging arm) or HLA-B27 (clinical arm) [11]. Few differences were found, although the imaging arm was characterized by a younger mean age, larger proportion of males, and higher CRP value. Similarly, in another study of the DESIR cohort of patients with recent-onset axial symptoms, Blachier et al. [12] found that, compared to patients without radiographic sacroiliac and/or spinal abnormalities, those with such abnormalities exhibited few specific characteristics (higher CRP levels, poorer responsiveness to nonsteroidal antiinflammatory drugs, and MRI inflammation at the sacroiliac joints and spine). These findings suggest that some phenotypic characteristics may identify patient subgroups, whereas
others (e.g., radiographic sacroiliitis) may be equally distributed across all phenotypes or subgroups. Using multiple correspondence analysis, d’Agostino et al. [13] classified 688 patients from the DESIR cohort into three main groups: group A had a predominance of males and higher proportions of isolated axial manifestations, uveitis, and HLA-B27; group B had a predominance of females, higher proportions of peripheral involvement (including entheseal vascularization detected by power Doppler) and psoriasis, and a younger age at symptom onset; and group C had equal proportions of males and females, a predominance of axial symptoms, and higher proportions of patients with the HLA-B27 antigen and/or with sacroiliitis by radiography or MRI. These data show clearly that the various spondyloarthritis features tend to cluster, thereby defining different phenotypic profiles. Future studies on the outcomes of DESIR-cohort patients will determine whether specific phenotypes are associated with disease outcomes. 1.3. From pathophysiology to clinical practice A major issue is whether the different patient profiles stem from one or from several different pathogenic mechanisms, that is, whether spondyloarthritis is a group of distinct but interrelated diseases or a single disease with a range of phenotypic expressions [14]. International experts have examined this issue based on evidence from family aggregation studies, animal models, immunopathological studies, structural outcomes, and therapeutic responses. They found no fundamental pathophysiological difference across the various spondyloarthritis phenotypes. Thus, spondyloarthritis seems to be a single disease with a heterogeneous phenotype.
Please cite this article in press as: Wendling D, et al. Spondyloarthritis: A concept or a disease? Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.006
G Model BONSOI-4195; No. of Pages 3
ARTICLE IN PRESS Editorial / Joint Bone Spine xxx (2015) xxx–xxx
Recognition of spondyloarthritis phenotypes may have implications, not only for evaluating and monitoring the disease, but also for making therapeutic decisions. Thus, the response to medications may vary across phenotypes. For instance, some of the TNF␣ antagonists may be particularly effective in nonradiographic axial spondyloarthritis [15], and specific phenotypic features may be associated with a good therapeutic response (e.g., younger age, CRP elevation, and short disease duration predict a good response to TNF␣ antagonists) [16]. This view of spondyloarthritis is already reflected in recent recommendations [17], which include adjusting the follow-up and treatment strategies to the phenotypic profile. The identification of new markers for spondyloarthritis, such as anti-CD74 autoantibodies for instance [18], will help to further refine the definition and implications of specific subgroups. 2. Conclusion Spondyloarthritis is not a concept encompassing various distinct rheumatic conditions but, instead, a single disease with heterogeneous phenotypic profiles that should be taken into account in clinical practice. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Claudepierre P, Wendling D, Breban M, et al. Ankylosing spondylitis, spondyloarthropathy, spondyloarthritis, or spondylarthritis: what’s in a name? Joint Bone Spine 2012;79:534–5. [2] Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011;70:25–31. [3] Porcher R, Said-Nahal R, D’Agostino MA, et al. Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families. Arthritis Rheum 2005;53:263–71. [4] Dougados M, d’Agostino MA, Benessiano J, et al. The DESIR cohort: a 10year follow-up of early inflammatory back pain in France: study design and baseline characteristics of the 708 recruited patients. Joint Bone Spine 2011;78:598–603. [5] Chung HY, Machado P, van der Heijde D, et al. HLA-B27 positive patients differ from HLA-B27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis. Ann Rheum Dis 2011;70:1930–6. [6] Tournadre A, Pereira B, Lhoste A, et al. Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort. Arthritis Care Res (Hoboken) 2013;65:1482–9. [7] Richette P, Tubach F, Breban M, et al. Psoriasis and phenotype of patients with early inflammatory back pain. Ann Rheum Dis 2013;72:566–71. [8] Machado P, Landewe R, Braun J, et al. Ankylosing spondylitis patients with and without psoriasis do not differ in disease phenotype. Ann Rheum Dis 2013;72:1104–7.
3
[9] Wendling D, Prati C, Demattei C, et al. Impact of uveitis on the phenotype of patients with recent inflammatory back pain: data from a prospective multicenter French cohort. Arthritis Care Res (Hoboken) 2012;64: 1089–93. [10] Wendling D, Prati C, Demattei C, et al. Anterior chest wall pain in recent inflammatory back pain suggestive of spondyloarthritis. Data from the DESIR cohort. J Rheumatol 2013;40:1148–52. [11] Moltó A, Paternotte S, van der Heijde D, et al. Evaluation of the validity of the different arms of the ASAS set of criteria for axial spondyloarthritis and description of the different imaging abnormalities suggestive of spondyloarthritis: data from the DESIR cohort. Ann Rheum Dis 2014, http://dx.doi.org/10.1136/annrheumdis-2013-204262. [12] Blachier M, Canouï-Poitrine F, Dougados M, et al. Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort. Rheumatology (Oxford) 2013;52:1686–93. [13] D’Agostino MA, Aegerter P, Dougados M, et al. Three phenotype profiles are revealed by cluster analysis in early inflammatory back pain suggestive of spondyloarthritis (spa). Results from the devenir des spondyloarthropathies indifferenciees recentes (DESIR) cohort. Ann Rheum Dis 2012;71: 411. [14] Baeten D, Breban M, Lories R, et al. Are spondylarthritides related but distinct conditions or a single disease with a heterogeneous phenotype? Arthritis Rheum 2013;65:12–20. [15] Wendling D, Prati C, Claudepierre P, et al. Non-radiographic spondyloarthritis: a theoretical concept or a real entity? Joint Bone Spine 2012;79: 531–3. [16] Arends S, van der Veer E, Kallenberg CG, et al. Baseline predictors of response to TNF-␣ blocking therapy in ankylosing spondylitis. Curr Opin Rheumatol 2012;24:290–8. [17] Wendling D, Lukas C, Paccou J, et al. Recommendations of the French Society for Rheumatology (SFR) on the everyday management of patients with spondyloarthritis. Joint Bone Spine 2014;81:6–14. [18] Meyer O. CD74: a diagnostic key for spondyloarthritis? Joint Bone Spine 2014, http://dx.doi.org/10.1016/j.jbspin.2014.07.005.
Daniel Wendling a,∗ Pascal Claudepierre b Clément Prati a Maxime Dougados c a Service de rhumatologie, université de Franche-Comté, CHRU de Besanc¸on, boulevard Fleming, 25030 Besanc¸on, France b Service de rhumatologie, laboratoire d’investigation clinique (LIC) EA4393, université Paris Est Créteil, hôpital Henri-Mondor, AP–HP, 94000 Créteil, France c Inserm U1153, Department of Rheumatology, Clinical Epidemiology and Biostatistics, Paris Descartes University, hôpital Cochin, PRES Sorbonne Paris-Cité, AP–HP, Paris, France ∗ Corresponding author. E-mail address: [email protected] (D. Wendling)
Accepted 24 November 2014 Available online xxx
Please cite this article in press as: Wendling D, et al. Spondyloarthritis: A concept or a disease? Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.06.006
