PEER REVIEWED FEATURE 2 CPD POINTS Ankylosing spondylitis New insights into an old disease
LAURA J. ROSS MB BS RUSSELL R.C. BUCHANAN MB BS(Hons), MD, FRACP
Early recognition and treatment of patients with ankylosing spondylitis (AS) improves prognosis but is challenging. Suggestive symptoms include chronic back pain that worsens with rest and early morning axial pain and stiffness. NSAIDs and stretching exercises remain the mainstays of treatment. Tumour necrosis factor inhibitors improve quality of life for patients with refractory AS.
nkylosing spondylitis (AS) is the positivity and familial aggregation.2 prototypic form of spondylo In the past decade, major progress has arthritis (SpA). Historically, the been made in the understanding, recog term SpA has referred to a group nition and treatment of SpA. As a result, Aof chronic systemic, inflammatory diseases the Assessment of SpondyloArthritis Inter that include AS, psoriatic arthritis, arthritis national Society (ASAS) has developed related to inflammatory bowel disease, new classification criteria for SpA.3 The reactive arthritis, undifferentiated SpA and ASAS system characterises SpA as either a subgroup of juvenile idiopathic arthritis.1 axial (affecting the spine and sacroiliac These diseases share overlapping features, joints) or peripheral (affecting mainly such as sacroiliitis, extra-articular mani peripheral joints), according to the pre festations (e.g. acute anterior uveitis, dominant articular features at presenta psoriasis and inflammatory bowel disease), tion, although these groups overlap and includes AS and n onradiographic axial human leucocyte antigen (HLA)-B27 one may progress to the other. Axial SpA SpA (Box 1).4 A characteristic feature of SpA is enthesitis, defined as inflammation at the site of attachment of tendons, ligaments, 2 MedicineToday 2016; 17(1-2): 16-24 joint capsule or fascia to bone. The enthe sis is thought to be the major target of the Dr Ross is a Registrar in the Department of Rheumatology, Austin Health, Melbourne. immune response in SpA and thus the Professor Buchanan is Director of the Department of Rheumatology, Austin Health, Melbourne; and primary site for its immunopathology.2 Associate Professor in the Department of Medicine, University of Melbourne, Melbourne, Vic. The different forms of SpA are associated
16 MedicineToday ❙ JANUARY/FEBRUARY 2016, VOLUME 17, NUMBER 1-2 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2016. KEY POINTS • Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease characterised by sacroiliitis, extra-articular manifestations such as uveitis, human leucocyte antigen (HLA)-B27 positivity and familial aggregation. • Consider the diagnosis of AS in young patients with back pain and stiffness early in the morning and after prolonged sitting. • Appropriate initial investigations are a plain x-ray of the pelvis and blood tests for HLA-B27, erythrocyte sedimentation rate and C-reactive protein level. • MRI can identify early inflammatory bony changes not seen on x-ray and is prudent in patients with a clinical history consistent with AS but a normal x-ray appearance. • The mainstay of treatment for patients with AS remains NSAIDs and stretching exercises. • Tumour necrosis factor inhibitors are effective therapy for patients who fail to respond to first-line treatments.
bridging and fusion of joints and ankylosis of the spine. Characteristic extra-articular manifestations in AS include acute anterior uveitis (prevalence of 26%), psoriasis (9%) and inflammatory bowel disease (7%).5 The prevalence of acute anterior uveitis increases with longer disease duration.5 AS is a slowly progressive disease, and x-ray changes often do not appear until a decade after onset of symptoms.6 In some people who have a clinical history con sistent with AS but lack the characteristic x -ray changes, MRI can identify early inflammatory bony changes not seen on plain x-ray.7 Patients may be diagnosed with nonradiographic SpA when they have a history of inflammatory back pain and MRI changes of sacroiliitis with a normal appearance on plain x-rays. Clinical experience and limited data with characteristic extra-articular Definition of ankylosing suggest a sizeable proportion of patients manifestations, which can be useful to spondylitis with inflammation of sacroiliac joints on distinguish SpA from other types of AS is characterised by inflammatory back MRI will go on to develop x-ray changes.6 inflammatory arthritis and assist with pain that is typically subacute in onset and A review of the MRI changes associated prognostication.5 starts before the age of 45 years. Radio with axial SpA suggests that there is a win This article will address the contem graphic changes characteristically affect dow of six months to two years during porary definition of AS, early recognition the sacroiliac joints and may involve var which inflammatory changes seen on MRI in general practice of patients with AS iable levels of the spine. Inflammation at evolve into early structural changes associ and recent advances in diagnosis and these sites results in new bone formation ated with AS.8 Clinical symptoms among
© JOHN KARAPELOU, W. CMI management. leading to the typical AS features of patients with nonradiographic SpA are
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1. CLASSIFICATION OF THE 2. ASAS CLASSIFICATION CRITERIA FOR AXIAL SPONDYLOARTHRITIS* SPONDYLOARTHROPATHIES*
Predominantly axial SpA Patient has back pain • Ankylosing spondylitis • for three months or longer AND • Nonradiographic axial SpA • age of onset younger than 45 years Predominantly peripheral SpA • Arthritis with inflammatory bowel disease • Sacroiliitis on imaging AND • HLA-B27 positive AND • Psoriatic arthritis • One or more spondyloarthritis • Two or more spondyloarthritis • Reactive arthritis features features • Undifferentiated SpA
Abbreviation: SpA=spondyloarthritis. Sacroiliitis on imaging Spondyloarthritis features * Adapted from ASAS (Assessment of SpondyloArthritis • Active inflammation on MRI OR • Inflammatory back • Inflammatory International Society). Slide-educational kit. Available online at: http://www.asas-group.org • Definite radiographic pain bowel disease (accessed February 2016).4 sacroiliitis according to • Arthritis • Good response to modified New York criteria • Enthesitis (heel) NSAIDs comparable with those among patients with • Uveitis • Family history of spondyloarthritis x -ray-proven AS.1 Abbreviations: ASAS = Assessment of • Dactylitis SpondyloArthritis International Society; • HLA-B27 positive ASAS has validated classification cri CRP = C-reactive protein. • Psoriasis • Elevated CRP level teria for axial SpA, including AS and non * Modified from Sieper et al. Ann Rheum Dis radiographic axial SpA (Box 2).3 Criteria 2009; 68: ii1-ii44.3 include the presence of inflammatory back pain, extra-articular manifestations of History contrast, mechanical back pain is often SpA and HLA-B27 p ositivity, with or with Patients with AS account for 5% of patients intermittent, exacerbated by activity and out x-ray changes of sacroiliitis. with chronic low back pain.10 Identifying better with rest (Table). patients with inflammatory back pain is Important additional clues to identify Diagnosis the key to diagnosing AS and requires a ing patients with inflammatory back pain Early diagnosis of AS remains a challenge targeted history.7 Useful questions to ask include a history of peripheral inflamma and is typically delayed up to eight to patients are listed in Box 3.11 Important tory arthritis, a family history of AS and 10 years after symptom onset.9 AS remains features of inflammatory back pain include a good response of the pain to NSAIDs. a clinical diagnosis based on symptoms significant morning stiffness, gel phenom The presence of alternating buttock pain, and signs. Treatment response is generally enon (stiffness following sitting or other commonly radiating into the posterior better in patients with short disease dura inactivity) and awakening in the second thighs, is highly suggestive of sacroiliac tion and good functional status. half of the night with spinal stiffness. In joint pain.
Examination 3. QUESTIONS TO HELP IDENTIFY PATIENTS WITH INFLAMMATORY BACK PAIN* The characteristic examination finding in patients with AS is a reduced range of In patients with back pain of three months’ duration or longer: spinal movement. Lateral spinal flexion • Did your back pain start when you were younger than 40 years? is often the first movement to be affected. • Did your back pain develop gradually? Important objective measures of spinal • Does your back pain improve with movement? mobility are described in Box 4 and • Do you find your back pain worsens when you rest? Figure 1. • Do you have back pain that worsens overnight and then improves when you get up? • Do you ever have back pain that radiates into your buttocks? Extra-articular manifestations A ‘yes’ answer to four or more of these questions usually indicates inflammatory back Extra -articular manifestations that sup pain requiring further investigation. port the diagnosis of AS or other forms of * Adapted from Sieper et al. Ann Rheum Dis 2009; 68: 784-788.11 SpA include anterior uveitis, psoriasis and inflammatory bowel disease. Around
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TABLE. COMPARISON OF INFLAMMATORY AND MECHANICAL BACK PAIN 4. OBJECTIVE MEASURES OF SPINAL MOBILITY Inflammatory back pain Mechanical back pain Modified Schober’s test (Figure 1) Morning stiffness for longer than 30 minutes Minimal morning stiffness • Place a mark on the patient's back in Back pain improves with exercise Back pain improves with rest the midline between the lumbosacral junctions (dimples of Venus) Awakening with back pain during the night Back pain exacerbated by activity • Mark a point 10 cm above • Ask the patient to bend forward to try Alternating buttock pain Intermittent in nature to touch the floor • Measure the distance between the 9 to 11% of patients diagnosed with pso Pulmonary dysfunction may occur as marks at full forward flexion riasis and 1.8 to 2.6% of those diagnosed the result of interstitial lung disease or • N ormal increase in distance between with inflammatory bowel disease have restriction caused by diminished chest wall the two marks ≥5 cm SpA at diagnosis.6 and spinal mobility. Upper lobe fibrosis Lateral spinal flexion The presence of dactylitis or enthesitis occurs in 1 to 2% of patients with AS and • Have the patient stand with their back supports a diagnosis of SpA. It has been is typically asymptomatic and associated against a wall and feet 30 cm apart reported that 39% patients with AS have with long disease duration.14 High resolu • Measure fingertip to floor distance on enthesitis and 6% have dactylitis at tion CT of the chest has shown that AS can each side diagnosis.6 Enthesitis often manifests as also cause a range of other lung pathologies, • Ask the patient to bend laterally as recurrent heel pain, indicating inflam including interstitial lung disease, bron far as possible mation of the plantar fascia ligament or chiectasis, emphysema, septal thickening • M easure fingertip to floor distance in full lateral flexion on each side swelling of the Achilles tendon near its and pleural thickening. Of these changes, • N ormal change in fingertip to floor insertion. septal and pleural thickening can be seen distance between standing upright AS can be associated with aortic early in the disease course. and laterally flexed ≥10 cm regurgitation, caused by thickening of the Occiput to wall distance aortic valvular cusps and dilation of the Investigations • Have the patient stand with heels aortic root.12 Aortic regurgitation occurs Radiography and buttocks against a wall in approximately 10% of patients with Plain x-ray remains the best investigation • Ask the patient to extend their head AS, an incidence slightly higher than to diagnose AS and then to monitor for back as far as possible in the the general population. Patients with disease progression. Plain x-ray films are horizontal plane long -standing AS have also been found to more sensitive than MRI for detecting new • Measure the distance between the wall and occiput have a higher rate of left ventricular s ystolic bone formation, including ankylosis and • Normal occiput to wall distance, 0 cm dysfunction, but it is unclear whether this syndesmophytes.15 is the result of underlying inflammatory All patients with possible SpA should Chest expansion (a late sign) disease or comorbidities such as hyper undergo a single anteroposterior x-ray of • Normal chest expansion >4 cm tension and advancing age.13 the pelvis with the sacroiliac joints centred
Figure 1. Modified Schober’s test. a (far left). With the patient standing upright, two marks are placed over the spine, one midway between the lumbosacral junctions and the other 10 cm above. b (left). The patient is asked to bend forward 10 cm to try to touch the floor and the distance between the marks is remeasured. A normal value is ≥15 cm.