Ankylosing Spondylitis Level Basic Version No Version Date

Ankylosing Spondylitis Level: Basic Version No: Version Date: May 2012 L. I. T. Reviews Author(s): Charles A. Withers, MD Affiliation(s): Duke University Medical Center Department of Internal Medicine Division of Rheumatology, Fellow

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Learning Objectives • To review the classic clinical features of ankylosing spondylitis • To outline a diagnostic approach for patients with suspected ankylosing spondylitis • To discuss treatment options for patients with ankylosing spondylitis L. I. T. Reviews

Outline • • • What are spondyloarthropathies, particularly ankylosing spondylitis (AS)? Epidemiology Pathogenesis and Genetics Clinical Features Extra articular Involvement Radiographic Findings Diagnostic Criteria Exam “Pearls” Treatment L. I. T. Reviews

Spondyloarthritis Clinical Features History • Group of interrelated inflammatory disorders with similar clinical features and overlapping genetic markers • Clinical descriptions date to the 16 th century • Clinical Features: – – – Inflammatory back pain Peripheral arthritis Enthesitis Dactylitis Uveitis L. I. T. Reviews • Current concept dates to the 1970 s: – seronegative spondylarthritides – Sacroiliac joint involvement on X -ray – Examples: ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis with Ulcerative Colitis or Crohn's disease, Whipple’s disease and Behçet’s syndrome

Epidemiology – AS • Ankylosing Spondylitis (AS): chronic inflammatory disease of the axial skeleton manifested by back pain and progressive spinal stiffness • Prevalence: 0. 1 to 0. 14 %: Varies with ethnic group and prevalence of HLA-B 27 – – Nearly absent in sub-Saharan Africa Low in Japan Higher in Norway Highest in arctic regions of Eurasia and North America • Gender: – Historically, male: female = 9: 1 – Recent Studies, 2 to 3: 1 – Females: • slightly younger at disease onset by 1 to 2 years, but diagnosis 1 to 2 years later • Less ankylosis on radiographs • Milder disease L. I. T. Reviews

Genetics – AS • Two-hit hypothesis for disease onset • Heritability – Twin studies confirm high heritability – First degree relatives of AS patients have a 5 to 16 x greater risk for disease than the general population (HLA-B 27 positive) • Human Leukocyte Antigen(HLA) - B 27 – Major Histocompatibility Complex (MHC) on chromosome 6 p – Less than 50% of overall genetic risk – Approx. 8% white Europeans carry HLA-B 27 – Approx. 5% of Chinese carry HLA-B 27 – 10 to 20% HLA-B 27 positive patients with a first degree relative with AS develop disease L. I. T. Reviews

Clinical Features - AS • “Inflammatory” back pain – Insidious onset, often buttocks or hips – Before the age of 40 (often early adulthood) – Lack of improvement at rest (night pain) – Improvement with increased activity (improvement with arising) – Morning stiffness (>30 min) – Improvement with NSAIDs L. I. T. Reviews Image: www. ccfc. ca

Clinical Features - AS • Sacroiliac Joint Tenderness • Enthesitis: inflammation of tendon/ligament insertions • Hips and shoulders – 50 % of patients – Loss of joint space – Hip disease is often a marker for severe AS activity • Peripheral Arthritis: – Rare, more common in women – Asymmetric, oligoarticular arthritis, lower extremities – Marker for severe disease L. I. T. Reviews

Extra-articular Involvement - AS • Ocular: 25 to 40% of AS patients develop anterior uveitis (iritis) • GI : 50% of AS patients have microscopic or macroscopic cecal inflammation; related to Crohn’s Disease • Osteoporosis: up to 50% of AS patients; dual-energy x-ray absorptiometry (DEXA) values can be falsely elevated from syndesmophytes • Cardiac: 1 to 9% of patients can experience aortitis, aortic regurgitation, pericarditis, or complete heart block • Pulmonary: approx 1% of patients experience upper lobe fibrosis or apical pleural thickening • Renal: 4 to 9% of patients experience secondary renal amyloidosis and Ig. A nephropathy L. I. T. Reviews

Patient Evaluation - AS Exam Labs and Imaging • Chief finding is loss of spinal mobility • HLA-B 27 • Schober’s Test: • Inflammatory Markers – C-reactive Protein (CRP) – Sedimentation Rate (ESR) • Other labs: – Comprehensive Metabolic Panel – Complete Blood Count Radiographs: sacroiliitis, bridging syndesmophytes, and “bamboo spine” • – – Occiput-to-wall: – – • Mark midpoint between iliac crests Measure 10 cm up and mark this point Have the patient bend forward to touch toes The distance should increase from 10 cm to >15 cm in healthy individuals; <15 indicates fusion Patient stands with heels and buttocks against the wall They should be able to tilt their head back and touch the occiput to the wall Chest Expansion: normal > 5 cm L. I. T. Reviews • • MRI: increased sensitivity – should be considered in early disease Image: www. jaaos. org

Diagnostic Criteria - AS Modified New York Criteria Patients are considered to have AS if they meet at least 1 clinical and 1 radiologic parameter: • Clinical Parameters: ASAS Criteria In patients with > 3 months of back pain and age of onset under 45 yrs: • • – Lower back pain for > 3 months that improves with exercise but not relieved with rest – Limited motion of the lumbar spine in both sagittal and frontal planes – Limited chest expansion relative to norms for age and sex • Radiologic Parameters: – Sacroiliitis grade > 2 bilaterally – Sacroiliitis grade 3 or 4 unilaterally – – – – – Inflammatory back pain Arthritis Enthesitis (Achilles) Dactylitis Psoriasis Crohn’s/colitis Good response to NSAIDs Family history of Sp. A HLA-B 27 Elevated CRP OR • L. I. T. Reviews Sacroiliitis on imaging plus >1 feature of spondyloarthritis (Sp. A) Sp. A features: HLA-B 27 plus > 2 other Sp. A features

Treatment – AS • NSAIDs: – 70 -80% of pts report substantial benefit – Only 15% pts with mechanical back pain report a benefit • TNF-a inhibitors: infliximab, etanercept, adalimumab, golimumab – Concomitant Disease Modifying Anti-Rheumatic Drugs (DMARDs, e. g. methotrexate) are not required – Effects are usually seen quickly – No evidence that disease progression is interrupted • Others: – Sulfasalazine: less commonly used since introduction of TNF-a inhibitors – Opioids: rarely effective when used alone – Glucocorticoids: long term use for AS is usually avoided (also, bone loss can be exacerbated) L. I. T. Reviews

Summary • Ankylosing Spondylitis is a chronic systemic inflammatory disease with a predilection for the axial skeleton • Strong association with HLA-B 27 • Clinical features include inflammatory back pain. Peripheral arthritis, uveitis, enthesitis and other systemic manifestations can be seen. • Perform Schober’s, occiput-to-wall test chest expansion measurement during exam • Look for sacroiliitis and bridging syndesmophytes on Xray • Patients frequently respond to NSAIDs. Consider TNF-a inhibitors for refractory or systemic disease. L. I. T. Reviews

Key References 1. 2. 3. 4. Hochberg, MC, et. al. Rheumatology. 5 th Edition. 2011 van der Berg, R. et. al. First update of the current evidence for the management of ankylosing spondylitis with non-pharmacological treatment and non-biologic drugs: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Rheumatology. 2012 Aug; 51(8): 1388 -96. Weber, U, Lambert, RG, Ostergaard, M et. al. The diagnostic utility of magnetic resonance imaging in spondylarthritics: an international multicenter evaluation of one hundred and eighty seven subjects. Arthritis Rheum 2010; 62: 304858. Zeidler, H and Amor, B. The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress. Ann Rheum Dis. 2011 Jan; 70(1): 1 -3. L. I. T. Reviews

Acknowledgements • Lisa Criscione-Schreiber, MD L. I. T. Reviews