'My back is killing me' - managing ankylosing spondylitis

Case

A 28 year old woman presented to her GP with worsening longstanding lower back pain. The patient reported onset of back pain at age 21. The nature of the back pain was mechanical and of sudden onset, needing treatment with physiotherapy and microsurgery (for a disc prolapse) a few years later. Her back symptoms did not improve, however, with a constant severity of 4/10 on a pain visual analogue scale. In the last year, her worsening symptoms were attributed to some home improvements. The pain had recently spread to her thoracic spine (with some pleuritic features) and left buttock. Exercise appeared to improve her symptoms and so she swam regularly.

Her GP screened her for spondyloarthritis features and the patient denied any personal or family history of arthritis, enthesitis, dactylitis, uveitis or inflammatory bowel disease. She worked as a chef and did not smoke. There was no other significant history. A musculoskeletal screen, showed some minor reduction in forward lumbar flexion (due to pain rather than true spinal restriction) but no other overt musculoskeletal signs. General examination was within normal limits.

Blood tests showed normal results for renal profile, liver profile, bone profile, FBC and CRP. HLA-B27 was positive.

She was referred for a rheumatology opinion after imaging, where a diagnosis of axial spondyloarthritis was confirmed and a trial of anti-inflammatories (NSAIDs) was started alongside specialised physiotherapy. At her three month review her disease activity, measured via a composite outcome measure (e.g. Bath Ankylosing Spondylitis Disease Activity Index) was still high, so she was worked up for biologics therapy. Her symptoms improved shortly after the start of therapy and she was able to continue her work and enjoy her social life.

The problem

Axial spondyloarthritis is a chronic inflammatory condition predominantly involving the spine and sacroiliac joints. Other musculoskeletal manifestations include peripheral arthritis, enthesitis and dactylitis. Associated extra-articular manifestations such as anterior uveitis, psoriasis and IBD may also be present.⁵ Axial spondyloarthritis has a disease spectrum and this includes non-radiographic axial spondyloarthritis – individuals with axial spondyloarthritis features but without established radiographic changes and ankylosing spondylitis– individuals with axial spondyloarthritis features and radiographic sacroiliitis.⁶

Axial spondyloarthritis typically begins in the second and third decade.⁷ Delayed diagnosis is a major problem, with an average delay of between eight and 10 years. This means that patients often endure intolerable symptoms, which are linked to worse outcomes despite the availability of effective new therapies.⁸ Early treatment offers the best chance of drug-free remission and early disease responds best to TNF inhibitors.^9,10 Research into delayed diagnoses concluded that there is still a need for further targeted education of healthcare professionals in order to address the issue.¹¹

In an attempt to address the problem of the delay to diagnosis, the National Ankylosing Spondylitis Society (NASS) have worked in partnership with the British Society for SpondyloArthritis (BRITSpA) to sponsor an RCGP eLearning course² on axial spondyloarthritis which is available on the RCGP website. The course aims to educate primary care practitioners about axial spondyloarthritis. In addition, NICE has recently published a clinical guideline – NG65 Spondyloarthritis in over 16s: diagnosis and management. A BMJ infographic on ‘How to assess people with suspected spondyloarthritis’ has also been produced to summarise the NICE guideline on diagnosing and managing spondyloarthritis.³

Clinical Features

Axial spondyloarthritis has a disease spectrum and the clinical presentation can be insidious at onset. There needs to be a high index of suspicion by GPs armed with knowledge of axial spondyloarthritis features (see box 1) to detect early axial spondyloarthritis in a young adult presenting with chronic back pain. Axial spondyloarthritis typically presents with inflammatory back pain (see box 2) with or without other musculoskeletal complaints such as peripheral arthritis, enthesitis or dactylitis. Axial spondyloarthritis is commonly associated with extra-articular manifestations such as acute anterior uveitis, IBD and psoriasis, with a reported prevalence of 16-26%, 4-7% and 10-11% respectively.^12,13 The risk of developing acute anterior uveitis, IBD and psoriasis in patients with ankylosing spondylitis compared with the general population is increased by 16-fold, 3.3-fold and 1.5-fold respectively. The risk for acute anterior uveitis remains throughout the course of the disease, whereas the excessive risk for psoriasis and IBD reduces after the first year following diagnosis. These features are often present before the diagnosis of ankylosing spondylitis.

Box 1 – features suggestive of early axial spondyloarthritis^19,20

Main features:

Inflammatory type back pain (see box 2).
Family history of axial spondyloarthritis, reactive arthritis, psoriasis, IBD, anterior uveitis.
Good response to NSAIDs.
Raised acute-phase reactants (CRP).
HLA-B27 positivity.
Sacroiliitis on MRI.

Other features*:

Acute anterior uveitis.
Inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
Peripheral arthritis, enthesitis (heel), dactylitis.
Psoriasis.

Be aware that axial spondyloarthritis³:

Affects a similar number of women as men.
Can occur in people who are HLA-B27 negative.
May be present despite no evidence of sacroiliitis on a plain film X-ray.

*These features should be considered in all patients but may not be present in early disease. They are helpful in increasing axial spondyloarthritis probability if present at assessment, but should not be ignored if absent.

Box 2 – features of back pain that suggest axial spondyloarthritis^24-32

Pre-test characteristics (before applying to features below):

Chronic back pain (>3 months).
Age of onset of back pain (<45 years old).
Clinical exclusion of red flag features (of malignancy and infection) and entrapment neuropathies.

Features that increase the probability of an inflammatory back pain^32-35:

Age of onset <40 years old.
Pain improves with exercise.
Pain does not improve with rest.
Insidious onset; less likely to be acute.
Awakening in second half of the night because of pain, with improvement upon getting up.
Morning stiffness (lasting more the 30 minutes after waking up).

Diagnosis

Axial spondyloarthritis is diagnosed clinically based on suspicious clinical features with supportive laboratory tests, such as HLA-B27 and raised CRP, and imaging (MRI or X-ray). Advances in MRI have enabled earlier diagnosis of axial spondyloarthritis via the identification of bone marrow oedema in the sacroiliac joints or spine prior to the development of structural changes on radiograph.^16-18 As there are many clinical features to consider, the clinician may use the web-based SPADE tool²², which uses probability estimation to determine the likelihood that the patient has axial spondyloarthritis based on their symptoms, as an adjunct to their clinical reasoning during the diagnostic process.

It is important to note that classification criteria are not intended to be used as diagnostic criteria. A physician-verified clinical diagnosis of axial spondyloarthritis must be ascertained before the application of any classification criteria.²³ The contemporary classification criteria for axial spondyloarthritis (see box 3), based on a combination of imaging or clinical criteria in patients with chronic back pain with onset before 45 years of age, have been established by the Assessment of SpondyloArthritis international Society.^24,25

Box 3 – ASAS classification criteria for axial spondyloarthritis²⁵

In patients with >3 months of back pain and age at onset < 45 years old
Sacroiliitis on imaging* AND ≥1 SpA feature** OR HLA-B27 AND ≥2 other SpA features *
** SpA features:
- Inflammatory back pain.
- Arthritis.
- Enthesitis (heel).
- Uveitis.
- Dactylitis.
- Psoriasis.
- Crohn’s/colitis.
- Good response to NSAIDs.
- Family history for SpA.
- HLA-B27.
- Elevated CRP.
*Sacroiliitis on imaging
- Active acute inflammation on MRI highly suggestive of sacroiliitis associated with SpA.
- Definite radiographic sacroiliitis according to modified New York criteria.

Management^{3, 26}

Axial spondyloarthritis should be managed with appropriate specialist input with prompt referral to rheumatology as recommended by NICE and ASAS-EULAR.^{3, 26} The primary aim of treating the patient with axial spondyloarthritis is to maximise their quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation or normalisation of function and social participation. This is achieved via a combination of non-pharmacological and pharmacological treatments based on shared decision making between the patient and the rheumatologist.

Patients should be educated about axial spondyloarthritis and encouraged to exercise on a regular basis and stop smoking – known factors for poor disease prognosis.^{27, 28} NASS provides patient education through their interactive website and membership events. Physiotherapy (including access to hydrotherapy) via a specialist therapist should be considered initially following diagnosis and also as an adjunct to long-term management.

The treatment of patients with axial spondyloarthritis should be individualised according to the signs and symptoms of the disease (axial, peripheral and extra-articular manifestations) and the patient characteristics, including comorbidities and psychosocial factors. Patients suffering from pain and stiffness should use an NSAID as the first-line drug treatment at the lowest effective dose, taking risks and benefits into account. If NSAIDs taken at the maximum tolerated dose for 2-4 week do not provide adequate pain relief, consider switching to another NSAID. Targeted glucocorticoid injections and DMARDS may be considered in a subset of patients with associated peripheral arthritis, enthesitis or dactylitis.

Biological treatments^29,30 are recommended for patients with persistently high disease activity despite conventional treatments. The impact of these treatments, which target pro-inflammatory cytokines, is impressive and provides sustained efficacy with a favourable adverse effect profile. Treatment options for axial spondyloarthritis are likely to increase in the future³¹ but the main issue now is to identify and diagnose axial spondyloarthritis patients early so that they can benefit from existing treatments.

Dr Karl Gaffney is a consultant rheumatologist and Dr Chong Seng Edwin Lim is a rheumatology research fellow, both at Norfolk and Norwich University Hospital

References

1. Back Pain Plus [Internet]. NASS. [cited 2017 Sep 24]. Available from: https://nass.co.uk/get-involved/campaigning/back-pain-plus/

2. Summary of Axial Spondyloarthritis [Internet]. [cited 2017 Oct 31]. Available from: http://elearning.rcgp.org.uk/course/info.php?id=229

3. McAllister K, Goodson N, Warburton L, Rogers G. Spondyloarthritis: diagnosis and management: summary of NICE guidance. BMJ. 2017 Mar 1;356:j839.

4. The musculoskeletal examination: GALS Arthritis Research UK [Internet]. [cited 2017 Oct 31]. Available from: http://www.arthritisresearchuk.org/health-professionals-and-students/student-handbook/the-msk-examination-gals.aspx

5. Hamilton L, Barkham N, Bhalla A, Brittain R, Cook D, Jones G, et al. BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics. Rheumatology. 2017 Feb 1;56(2):313–6.

6. Keat A, Bennett AN, Gaffney K, Marzo-Ortega H, Sengupta R, Everiss T. Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents? Rheumatol Int. 2017 Mar;37(3):327–36.

7. Zink A, Listing J, Klindworth C, Zeidler H. The national database of the German Collaborative Arthritis Centres: I. Structure, aims, and patients. Ann Rheum Dis. 2001 Mar;60(3):199–206.

8. Seo MR, Baek HL, Yoon HH, Ryu HJ, Choi H-J, Baek HJ, et al. Delayed diagnosis is linked to worse outcomes and unfavourable treatment responses in patients with axial spondyloarthritis. Clin Rheumatol. 2015 Aug;34(8):1397–405.

9. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Märker-Hermann E, Zeidler H, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum. 2009 Mar;60(3):717–27.

10. Sieper J, Heijde D van der, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013 Jun 1;72(6):815–22.

11. Sykes MP, Doll H, Sengupta R, Gaffney K. Delay to diagnosis in axial spondyloarthritis: are we improving in the UK? Rheumatol Oxf Engl. 2015 Dec;54(12):2283–4.

12. de Winter JJ, van Mens LJ, van der Heijde D, Landewé R, Baeten DL. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis. Arthritis Res Ther. 2016 Sep 1;18:196.

13. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis. 2015 Jan;74(1):65–73.

16. Sieper J, Rudwaleit M, Khan MA, Braun J. Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol. 2006 Jun;20(3):401–17.

17. Rudwaleit M, Sieper J. Referral strategies for early diagnosis of axial spondyloarthritis. Nat Rev Rheumatol. 2012 May;8(5):262–8.

18. Slobodin G, Eshed I. Non-Radiographic Axial Spondyloarthritis. Isr Med Assoc J IMAJ. 2015 Dec;17(12):770–6.

22. SPADE Tool [Internet]. [cited 2017 Nov 5]. Available from: http://www.spadetool.co.uk/

23. Braun J, Baraliakos X, Kiltz U, Heldmann F, Sieper J. Classification and diagnosis of axial spondyloarthritis–what is the clinically relevant difference? J Rheumatol. 2015 Jan;42(1):31–8.

24. Rudwaleit M, Landewé R, Heijde D van der, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis. 2009 Jun 1;68(6):770–6.

25. Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009 Jun;68(6):777–83.

26. Heijde D van der, Ramiro S, Landewé R, Baraliakos X, Bosch FV den, Sepriano A, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017 Jun 1;76(6):978–91.

27. Poddubnyy D, Haibel H, Listing J, Märker-Hermann E, Zeidler H, Braun J, et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 2012 May;64(5):1388–98.

28. Zhao S, Challoner B, Khattak M, Moots RJ, Goodson NJ. Increasing smoking intensity is associated with increased disease activity in axial spondyloarthritis. Rheumatol Int. 2017;37(2):239–44.

29. TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis Guidance and guidelines NICE [Internet]. [cited 2017 Nov 14]. Available from: https://www.nice.org.uk/guidance/ta383

30. Secukinumab for active ankylosing spondylitis after treatment with non-steroidal anti-inflammatory drugs or TNF-alpha inhibitors Guidance and guidelines NICE [Internet]. [cited 2017 Nov 14]. Available from: https://www.nice.org.uk/guidance/ta407

31. Clavel G, Boissier M-C, Sigaux J, Semerano L. Developments with experimental and investigational drugs for axial spondyloarthritis. Expert Opin Investig Drugs. 2017 Jul;26(7):833–42.

32. Health Professional Resources [Internet]. NASS. [cited 2017 Nov 2]. Available from: https://nass.co.uk/nass/en/healthcare-professionals/resources-for-health-professionals/health-professional-resources/

33. Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a screening test for ankylosing spondylitis. JAMA. 1977 Jun 13;237(24):2613–4.

34. Rudwaleit M, Metter A, Listing J, Sieper J, Braun J. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum. 2006 Feb;54(2):569–78.

35. Sieper J, van der Heijde D, Landewé R, Brandt J, Burgos-Vagas R, Collantes-Estevez E, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009 Jun;68(6):784–8.