The concept of spondyloarthritis: Where are we now?




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.




Fig. 1


Current Concept of Spondyloarthritis. .


The estimated prevalence of SpA in Europe has been reported to be 1.2% and that of AS is 0.2–1.2% . 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 . 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 . 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) 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.




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 . 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 . Several separate descriptions at the end of the 19th century promoted the general recognition of AS.




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 . 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 . Several separate descriptions at the end of the 19th century promoted the general recognition of AS.




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 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 certain seronegative polyarthritides separate from RA with a relation to AS. These diseases with manifestations now known to be key for the pSpA spectrum included PsA, ReA (known as Reiter’s syndrome at the time), arthritis associated with uveitis, and IBD . Strong association with the HLA B27 gene was identified around the same time, providing a strong evidence for the unified concept . The concept of inflammatory back pain (IBP) evolved in 1977 to help differentiate it from the more common chronic low back pain and led to the modification of the NY criteria in 1984 . The criteria for IBP have also been revised since ( Table 1 ).



Table 1

Inflammatory back pain criteria .






















Feature Odds ratio
Age at onset <40 9.9
Insidious onset 12.7
Pain at night (with improvement upon getting up) 20.4
Improvement with exercise 23.1
No improvement with rest 7.7

Best trade-off if four or more of the above five parameters are fulfilled (sensitivity 79.6%; specificity 91.7%).

Positive likelihood ratio = 79.6/(100–72.4) = 2.9.


Radiographic sacroiliitis, still considered the hallmark of AS, remains an integral part of modified NY (mNY) criteria for the classification of AS. Radiographic sacroiliitis of grade 2 bilaterally or grade 3–4 unilaterally has been termed as “definite radiographic sacroiliitis.” For decades, sacroiliitis, as defined by the mNY criteria, has formed the backbone of defining AS and, by extension, the whole SpA spectrum ( Table 2 ). The Amor criteria and the European Spondyloarthropathy Study Group (ESSG) criteria were developed in the 1990s addressing for the first time the entire spectrum of SpA including undifferentiated SpA. The ESSG criteria have entry conditions requiring the presence of IBP or synovitis. The Amor criteria do not have mandatory features required for classification but provide different significance to various SpA features. The Amor criteria perform better than ESSG for early SpA, which may be attributable to the Amor inclusion of “response to NSAIDs” (NSAIDS, nonsteroidal anti-inflammatory drugs) and HLA-B27 typing .



Table 2

History of criteria developed for AS and SpA.












  • Rome criteria 1961



  • Clinical:



    • •

      Low back pain and stiffness for >3 months, which is not relieved by rest


    • •

      Pain and stiffness in the thoracic region


    • •

      Limited motion in the lumbar spine


    • •

      Limited chest expansion


    • •

      History or evidence of iritis or its sequelae




  • Radiological:



    • •

      X-ray showing bilateral sacroiliac changes characteristic of AS (this would exclude bilateral osteoarthritis of sacroiliac joints)





  • New York 1966



  • Clinical:



    • •

      Limitation of motion of lumbar spine in all three planes – anterior flexion, lateral flexion, and extension


    • •

      History or presence of pain at dorsolumbar junction or lumbar spine


    • •

      Limitation of chest expansion to ≤1 inch (2.5 cm), at fourth intercostal space




  • Radiological Grading:



  • Definite AS



    • •

      Grade 3–4 bilateral sacroiliitis with at least one clinical criterion


    • •

      Grade 3–4 unilateral or grade 2 bilateral sacroiliitis with clinical criterion 1 or with both clinical criteria 2 and 3




  • Probable AS



    • •

      Grade 3–4 bilateral sacroiliitis with no clinical criteria





  • Modified NY 1984



  • Clinical:



    • •

      Inflammatory low back pain for ≥3 months


    • •

      Limitation of lumbar motion


    • •

      Limitation of chest expansion




  • Plus



  • Radiographic:


  • •

    Sacroiliitis grade ≥2 bilaterally or ≥3 unilaterally




  • Amor criteria 1990



  • Diagnosis of an SpA requires a score of ≥ 6 .



  • Feature: Score



    • •

      Lumbar pain at night or lumbar morning stiffness: 1


    • •

      Asymmetric oligoarthritis: 2


    • •

      Buttock pain (or bilateral alternating buttock pain): 2


    • •

      Sausage-like toe or digit(s): 2


    • •

      Heel pain or other well-defined enthesities: 2


    • •

      Iritis: 2


    • •

      Nongonococcal urethritis/cervicitis within 1 month of onset: 1


    • •

      Acute diarrhea within 1 month of arthritis onset: 1


    • •

      Psoriasis, balanitis or inflammatory bowel disease (Crohn’s or ulcerative colitis): 2


    • •

      Sacroiliitis (bilateral grade 2 or unilateral grade 3): 2


    • •

      HLA-B27(+) or (+) family history of a spondyloarthropathy: 2


    • •

      Rapid (<48 h) response to NSAIDs: 2





  • ESSG criteria 1991



  • Inflammatory spinal pain or synovitis (asymmetric or predominantly in the lower limbs)



  • Plus



  • At least one of the following:



    • •

      Positive family history


    • •

      Psoriasis


    • •

      Inflammatory bowel disease


    • •

      Urethritis, or acute diarrhea


    • •

      Alternating buttock pain Enthesopathy


    • •

      Sacroiliitis as determined from radiography






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 , 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 axial inflammation.


In most early AS patients, SI joint inflammation can be detected by magnetic resonance imaging (MRI) scans, which marked an important advance in the diagnostic imaging of the pre-radiographic phase of AS . Studies show that up to 80% of such patients with no definitive changes of sacroiliitis on plain X-ray would progress to develop AS over the long term . It is also known that the sacroiliitis seen on plain radiographs does not fully explain the disease burden in these patients as assessed by disease activity measures, patient global assessments, or its impact on the quality of life . It was argued that “pre-radiographic” (or “non-radiographic”) and “radiographic” sacroiliitis were part of the same disease spectrum and that detection of sacroiliitis on plain radiographs should be taken as a measure of chronicity or severity and not as an essential part of the diagnosis . This concept is in line with the concept of early RA, in which the presence or absence of erosions is considered a measure of severity and not part of the diagnostic or classification criteria . As axSpA patients with or without radiographic sacroiliitis are considered to be part of a single disease entity, combined with the difficulties in grading sacroiliitis reliably, it was thought that distinguishing the lower grades (grade 1 and 2) from “definite” sacroiliitis (≥grade 3) was probably not important in the clinical practice . To address these issues, there was a strong need to develop new classification criteria to include such patients with early axial inflammation.


As there can be considerable overlap (and change over time) between axial and peripheral manifestations of SpA, a need was felt to develop new criteria for patients with predominantly peripheral manifestations of SpA, as the ESSG and Amor criteria were not developed specifically for pSpA but for the entire group .


These considerations were central in the development of the ASAS criteria for SpA, published in a series of papers from 2009 to 2011 ( Table 3 ) . The ASAS group proposed the term “axial spondyloarthritis” (axSpA) for the first time to describe the full spectrum of axial disease, and the term “peripheral spondyloarthritis” to describe the full spectrum of SpA diseases predominantly affecting the peripheral skeleton.


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Nov 10, 2017 | Posted by in RHEUMATOLOGY | Comments Off on The concept of spondyloarthritis: Where are we now?

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