Classification, Diagnosis, and Referral of Patients with Axial Spondyloarthritis




The concepts for classification, diagnosis and referral of patients with axial spondyloarthitis differ, although they of course basically relate to the same disease. While classification criteria and referral strategies concentrate largely on patients with chronic back pain with an age at onset before 45 years, the rheumatologist can make a diagnosis of axial SpA in patients with late onset or in patients with back pain for only some weeks if other items are fulfilled. Early recognition of patients with axial SpA is important to establish the diagnosis, potentially start therapeutic interventions and avoid unnecessary health care procedures.








  • The concepts for classification, diagnosis and referral of patients with axial spondyloarthitis differ, although they of course basically relate to the same disease. While classification criteria and referral strategies concentrate largely on patients with chronic back pain with an age at onset before 45 years, the rheumatologist can make a diagnosis of axial SpA in patients with late onset or in patients with back pain for only some weeks if other items are fulfilled.



  • Early recognition of patients with axial SpA is important to establish the diagnosis, potentially start therapeutic interventions and avoid unnecessary health care procedures.



Key Points
axSpA, including ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA), is a chronic inflammatory rheumatic disease that predominantly affects the axial skeleton. It typically starts in young adulthood, at between 20 and 30 years of age, and more than 90% of patients are younger than 45 years when the first symptoms appear. Men are slightly more affected than women. Several recent clinical trials have shown that anti-inflammatory therapy with anti–TNF-directed biologics is effective, especially in patients with axSpA who had a short disease duration, which may reach Assessment of SpondyloArthritis International Society (ASAS) partial remission in approximately 50% of patients treated. In line with that, young age is predictive of response to therapy. Although it is unclear whether (early) treatment is able to prevent structural changes (early) at all, consequent inhibition of sacroiliac and spinal inflammation seems, at present, the only intervention that may have this effect. In addition, NSAIDs seem to have an influence on new bone formation in established disease but recent data have suggested that this may be different in early disease.


Early recognition of axSpA is not an easy challenge. There is a well-reported delay between the first onset of symptoms—usually IBP (discussed later) —and the diagnosis of AS, which is frequently reported to be between 5 and 10 years. The main reasons for this are (1) the high prevalence of back pain in the population, (2) the lack of knowledge in a substantial proportion of general practitioners and orthopedic surgeons, and (3) the requirement of structural changes in the sacroiliac joints, which may last several years to become visible on conventional radiographs.


The process of development of structural changes may take many years in some patients but this may be different in others: in one study, approximately 20% of patients with IBP for less than 2 years already had structural changes. To clarify one issue of terminology: due to the known limitations of conventional radiography the term radiographic sacroiliitis reflects structural damage as the consequence of inflammation rather than active ongoing inflammation. Patients who do not (yet) fulfill this criterion have recently been named as having, non-radiographic axSpA ( nr-axSpA ) —this is included in the ASAS classification criteria of axSpA ( Box 1 ), which addresses both patients with radiographic axSpA (AS) and those with nr-axSpA and in combination with peripheral SpA (perSpA) ( Box 2 ), which includes both patients with radiographic axSpA (AS) and those with nr-axSpA. These criteria for the first time allow patients with early and also with abortive forms of the disease to be classified.



Box 1




  • 1.

    Patients must have had ≥3 months of back pain (with/without peripheral manifestations) and age at onset should have been <45 years.


  • 2.

    In addition, there should be either sacroiliitis a on imaging plus ≥1 SpA feature or HLA-B27 needs to be positive plus ≥2 other SpA features




  • SpA features



  • Iflammatory back pain (IBP)



  • Arthritis



  • Enthesitis (heel)



  • Uveitis



  • Dactylitis



  • Psoriasis



  • Crohn disease/ulcerative colitis



  • Good response to non-steroidal anti-inflammatory drugs (NSAIDs)



  • Family history for SpA



  • HLA-B27



  • Elevated C-reactive protein (CRP)



a Either by conventional radiographs according to the New York criteria or by MRI according to the ASAS definition.


ASAS classification criteria for axial spondyloarthritis (SpA, )


Box 2




  • 1.

    Patients with peripheral manifestations only who have


  • 2.

    Arthritis, a and/or enthesitis and/or dactylitis and in addition either


  • a.

    1 of these SpA features



    • i.

      (Anterior) uveitis


    • ii.

      Psoriasis


    • iii.

      Crohn disease/ulcerative colitis


    • iv.

      Preceding infection


    • v.

      HLA-B27


    • vi.

      Sacroiliitis on imaging




  • or


  • b.

    2 of these SpA features



    • i.

      Arthritis


    • ii.

      Enthesitis


    • iii.

      Dactylitis


    • iv.

      Inflammatory back pain (IBP) ever


    • v.

      Family history of SpA




a Usually lower limb and/or asymmetric arthritis.


ASAS classification criteria for peripheral spondyloarthritis (SpA, )


Since the first definition of the leading clinical symptom in AS, IBP, in 1977, it has been regarded as the most important clinical sign for the identification of patients with axSpA. Different sets of criteria have been proposed that have comparable sensitivity and specificity of approximately 80%. They include morning stiffness, wakening up in the second half of the night because of back pain, and improvement by exercise but not by rest. Differences between the items may be relevant for referral because items behave differently when used in primary versus tertiary care.


Diagnosis and classification


The concept of SpA has been discussed since the publication by Moll and colleagues in 1974, which appeared a year after the discovery of the association of AS with HLA-B27. Thereafter, more proposals for classification have widened the spectrum of SpA. The performance of the new classification criteria for SpA has recently been intensively discussed. This article focuses on the consequences for the nomenclature and the diagnosis of SpA. Terminology and placement of the main groups and the subgroups are as follows:




  • (Predominant) axSpA



  • nr-axSpA



  • AS = radiographic axSpA



  • Both can be associated with psoriasis and/or inflammatory bowel disease (IBD)




  • (Predominant) perSpA



  • Psoriatic arthritis (PsA) and/or perSpA associated with psoriasis



  • perSpA associated with IBD: type I and type II



  • Reactive arthritis



  • Undifferentiated perSpA



This proposal is further defined by the following statements and definitions:




  • The term, axSpA, covers both AS as defined by the 1984 New York criteria and nr-axSpA as defined by the ASAS criteria.



  • axSpA can be subdivided into 3 stages: nonradiographic stage I, stage II as defined by structural changes in the sacroiliac joints but no structural changes in the spine, and stage III as defined by structural changes in the spine. There is, however, no international agreement on this. The role of inflammatory changes in the spine requires further study. Late onset of SpA has been reported.



  • The term, undifferentiated , is no longer used for SpA patients with predominant axial involvement who have no structural changes in the axial skeleton. This subgroup is now named nr-axSpA. The authors believe this should also mean that there are no definite structural changes in the spine (syndesmophytes). There is currently no agreement, however, on this and patients with syndesmophytes are allowed to be included in trials with nr-axSpA patients (if they have no definite changes in the sacroiliac joints).



  • No further differentiation is made between primary axSpA and secondary axSpA, including AS. Cases of axSpA with concomitant psoriasis and/or chronic IBD are described as “in association with.”



  • All patients with peripheral arthritis who have present or past psoriasis are named as having PsA, according to the Classification Criteria for Psoriatic Arthritis (CASPAR) —unless their clinical presentation is typical for SpA. Formally, the 2 definitions of PsA and/or perSpA associated with psoriasis could be differentiated by the ASAS explanation of arthritis, usually lower limb and/or asymmetric arthritis , versus the CASPAR definition , that a patient must have inflammatory articular disease (joint, spine, or entheseal). This should be handled liberally, however, because a precise definition of a cutoff does not seem to work practically. Therefore, the authors propose leaving the decision of terminology to rheumatologists, knowing that PsA is the most frequently used term. This term could be preferentially used for the patients with a clinical picture that is more reminiscent of rheumatoid arthritis. If arthritis of the lower limbs and/or enthesitis is the predominant feature, the term, perSpA associated with psoriasis , may be preferred. In patients with peripheral symptoms suggestive of SpA who have a history of psoriasis, the term, perSpA associated with psoriasis , may be preferred. In cases of definite erosive or osteoproliferative changes, the old term, PsA sine psoriase , also seems ok. The authors also would not change the terminology for the synovitis, acne, pustolosis, hyperostosis, and osteitis (SAPHO) syndrome.



  • Osteodestructive changes in peripheral joints occur mainly in PsA and AS but also may rarely occur in other subtypes.



  • Peripheral arthritis associated with IBD can be subdivided into types I and II, as proposed several years ago.



  • Reactive arthritis is diagnosed mainly in patients with a clinically convincing preceding infection in the urogenital tract, enteral tract, or respiratory tract—unless a significant change in antibody titers or a positive polymerase chain reaction result for Chlamydia is available either from synovial fluid or a smear from the urogenital tract. IBP may occur after reactive arthritis but is a rare event.



  • In cases of joint pain and/or entheseal pain in patients with a suspicion of SpA based on clinical symptoms laboratory assessments, CRP and HLA-B27 should be performed, and imaging results, obtained by MRI, ultrasound, or, in special cases, scintigraphy, may be needed to make a diagnosis. In case of positive findings these patients can be classified as (undifferentiated) perSpA.



Which patients could potentially be diagnosed as axSpA who do not fulfill the ASAS classification criteria for axSpA?




  • Patients with predominant axial symptoms



  • With <3 months back pain



  • With an age at onset >45 years



  • With evidence of sacroiliitis on imaging but without ≥1 SpA feature



  • Without evidence of sacroiliitis on imaging but with ≥1 SpA feature



  • With HLA-B27+ but with <2 other SpA features



  • Without HLA-B27+ but with ≥2 other SpA features



  • Without




    • IBP



    • Arthritis



    • Heel enthesitis



    • (Anterior) uveitis



    • Dactylitis



    • Psoriasis



    • Crohn disease/colitis



    • Good response to NSAIDs



    • Family history of SpA



    • HLA-B27



    • Elevated CRP




  • With evidence of spondylitis (MRI)



  • With evidence of structural changes in the spine (syndesmophytes or ankylosis)



  • With a preceding infection



Which patients could potentially be diagnosed as perSpA who do not fulfill the ASAS classification criteria for perSpA?





  • Patients with peripheral manifestations only



  • With arthritis and/or enthesitis and/or dactylitis but not ≥1 SpA features (uveitis, psoriasis, Crohn disease/colitis, preceding infection, HLA-B27)



  • With arthritis, enthesitis, or dactylitis but not ≥2 SpA features (arthritis, enthesitis, dactylitis, family history for SpA, sacroiliitis on imaging)



  • Without arthritis, enthesitis, or dactylitis but ≥1 SpA features (uveitis, psoriasis, Crohn disease/colitis, preceding infection, HLA-B27)



  • Without arthritis but enthesitis or dactylitis plus ≥1 SpA features (uveitis, psoriasis, Crohn disease/colitis, preceding infection, HLA-B27)



  • Without enthesitis arthritis or dactylitis plus ≥1 SpA features (uveitis, psoriasis, Crohn disease/colitis, preceding infection, HLA-B27)



  • Without dactylitis but arthritis or enthesitis plus ≥2 SpA features (arthritis, enthesitis, dactylitis, family history for SpA, sacroiliitis on imaging)



  • With pain at/around joints and/or entheses plus any signs of SpA



  • With spondylitis on imaging (MRI) only



  • With definite structural changes in peripheral joints



  • With definite structural changes in the spine



These lists may be incomplete but presumably they cover the spectrum of SpA. They mark the difference between classification and diagnostic criteria in SpA. Because the classification criteria have been extensively tested, approximately 20% of the patients who have undergone the process of classification for SpA have either false-positive or false-negative results. Thus, the best strategy in daily clinical practice is to work on the basis of classification criteria but to give a reason when a diagnosis of SpA is made when the classification criteria are not fulfilled.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Oct 1, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Classification, Diagnosis, and Referral of Patients with Axial Spondyloarthritis

Full access? Get Clinical Tree

Get Clinical Tree app for offline access