Ankylosing spondylitis Dr Chris Edwards Prevalence • Worldwide prevalence up to 0.9%1 • Prevalence varies by population and is closely correlated to prevalence of HLA-B272 • Prevalence also varies among ethnic groups • Male:Female – 5:1 g of onset: 15 – 35 yyears • Peak age 1. Braun et al. Arthritis Rheum 1998; 41: 58-67. 2. Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18. Co-morbidity & co-mortality • There may also be extra-articular manifestations of AS. • Spinal fracture - most serious complication encountered i AS in • Prostatitis is prevalent among men with AS • Long-term L t disease di iincreases risk i k off cardiovascular di l complications • Acute anterior uveitis occurs in 20% to 40% of cases cases. Other extra-articular manifestations include aortic regurgitation, pulmonary fibrosis, and, among male patients, prostatitis Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18. Disease burden – cost impact • Etanercept provides a rapid reduction in: • disease activity • Objective functional measures • Work instability This suggests that therapy may be cost effective in terms of work disability Barkham N et al Ann Rheum Dis 2008; 67 (suppl II) : 382 Productivity Costs of ankylosing spondylitis in the USA, The Netherlands, France and Belgium USA ((n=241) 241) Netherlands N th l d (n=130) F France (n= ( 53) B l i Belgium ((n= 26) Work disability (%) 12 41* 23* 9* Days sick leave pt/y; † mean (range) Not stated 19 (0–130) 6 (0–77) 9 (0–60) Friction costs/pt/y: † mean (range) ( ) Not applied €1257 (0–7356) €428 (0–5979) €476 (0–2354) Human capital costs/pt/y; mean (range) ( ) US $4945 (0–45800) €4227 (0–39145)‡ €8862 (0–46818) €3188 (0–43550) €3609 (0– 34320) *Adjusted for age and sex. Includes patients with partial work disability who continue in a part-time paid job in The Netherlands and France † in those with a paid job ‡ converted to Euros using 1998 purchasing power parities Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18. Disease burden – quality of life impact Understanding the burden of disease Quality of Life An individuals’ perception of their position in the context of the culture and value systems in which th lilive and they d iin relation l ti tto th their i goals, expectations, standards and concerns World Health Organisation (1995) Quality of Life • Ph i l ffunction Physical i • Employment, household management ADL, mobility, physical activity • Symptoms Pain, sleep, stiffness, fatigue • • Global health • Emotional well-being Anxiety, y control, self-esteem • Cognitive function Cognition, concentration Cognition concentration, memory Social well-being Relationships, opportunities, sexual activity and satisfaction R l activities Role ti iti • Personal constructs Life satisfaction, stigma, Bodily appearance, spirituality Work disability: AS-specific AS specific • Employment E l t rates t range 55–85% 55 85% • 50% of studies report < 70% • Work disability rates range 3–41% • 50% of studies report p > 20% • Risk factors: • • • • • • Age Disease duration Physical function** Pain Physically demanding jobs Lower education level Sieper et al, 2002; Boonen et al, 2001 Work disability: AS-specific AS specific • Workforce withdrawal • • • • • 1st year 5 years 10 years 15 years 20 years 5% 13% 21% 23% 31% • 3.1x higher g than g general p population p Sieper et al, 2002; Boonen et al, 2001 Social well well-being being • Old studies Older di suggest ffew problems bl • Intimate relationships • Men no problems; women less enjoyment • Few report marital strain / avoidance • 27% mild discomfort; 7% severe discomfort • (Elst et al, 1984) (Dalyan et al, 1999) (Wordsworth et al, 1986) Impact on daily life (n 129) - % reporting limitations: • • • • 1% social interactions 2% communication 3% normal role activities 6% leisure activities (Bakker et al, 1995) Social well well-being: being: AS and RA • Health status comparison: SF-36 generic health status • AS better Physical health • RA better Mental health • No g group p differences for: • SF-36: Pain, Physical or Emotional-Role functioning, Social Function, Vitality or General Health • Fatigue (MFI) or Behavioural Coping (CORS) • Work: +ve association with physical health in both groups Chorus et al, 2003 SF-36 scores for patients with RA and patients with AS 100 80 RA male 60 AS S male ae 40 RA female 20 AS female 0 Physical Component Summary Chorus et al, 2003 Mental Component Summary Immunology and pathogenesis Pathogenesis • Immune-mediated, involving: • • • • HLA-B27 Inflammatory cellular infiltrates Cytokines such as TNFα and IL-10 Genetic and environmental factors Sieper J et al. Ann Rheum Dis 2002; 61 (Suppl. III): iii8-18. Diagnosis AS/SpA: Characteristic Parameters Used for Early Diagnosis Symptoms IInflammatory fl t Back Pain Imaging Lab Patient’s history y HLA-B27 Good response to NSAIDs Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43 ESR/CRP Family history AS/Axial SpA: Typical Manifestations/Features Sensitivity Specificity LR+ LR- Inflammatory back pain 75% 76% 3.1 0.33 Enthesitis ((heel p pain)) 37% 89% 3.4 Peripheral arthritis 40% 90% 4.0 Dactylitis 18% 96% 4.5 Anterior uveitis 22% 97% 73 7.3 Positive family history for SpA 32% 95% 6.4 Psoriasis 10% 97% 3.3 Inflammatory bowel disease 4% 99% 4.0 Good response to NSAIDs 77% 85% 5.1 Elevated acute phase reactants 50% 80% 2.5 Positive likelihood ratio HLA-B27 (axial involvement) 0.29 0.27 (LR+) 90% = sensitivity/(100-specificity) 90% 9.0 0.11 Negative likelihood ratio (LR-) = (100-sensitivity/specificity) MRI ((STIR)) 90% 90% 9.0 0.11 Rudwaleit M, et al. Ann Rheum Dis. 2004;63:535-43 Rudwaleit M, Feldtkeller E. and Sieper J. Ann Rheum Dis 2007;. In press. Spondyloarthritis - main manifestations 1. Axial involvement/spinal inflammation 1 2. Peripheral arthritis 3 Peripheral enthesitis 3. SpA subtypes 1. Ankylosing spondylitis (AS) 2. Undifferentiated SpA 3. Psoriatic SpA p 4. Reactive SpA 5 5. SpA S A associated i t d with ith chronic h i inflammatory bowel diseases Axial SpA AS Ankylosing Spondylitis: a chronic inflammatory rheumatic h ti disease di with ith debilitating d bilit ti potential t ti l 24 years • main i affection ff i off the h spine, i entheses, h peripheral joints and the eye • main symptom: inflammatory back pain AS 49 years • 1/3 of patients with severe disease • overall prevalence high (0.5%) • etiology unknown • definite genetic load (new genes !) • strong HLA B27 association • l t diagnosis late di i (5-7 (5 7 years)) • reduced quality of life • increased risk of unemployment • direct/indirect costs Zink A et al, J Rheum 2000, 2001; Boonen A et al., Ann Rheum Dis 2001, 2002, Ward M et al. J Rheum 2001, A&R 2002 Possible Outcomes of Ankylosing Spondylitis Age at Onset of Symptoms and Age at Diagnosis in AS (DVMB) Time from first symptoms to diagnosis: 5–10 5 10 yrs 100 Age at onset of symptoms Pa atients (% %) 80 Age at diagnosis 60 40 n=1396 20 0 920 males 476 females Age (yrs) 0 10 20 Feldtkeller E, et al. Z Rheumatol. 1999;58:21-30. Feldtkeller E, et al. Rheumatol Int. 2003;23:61-6. 30 40 50 60 70 Differentiating clinical features of IBP in patients ti t < 45 years with ith chronic h i back b k pain i ( > 3 months ) • Morning stiffness > 30 min • Improvement with exercise, * not with rest * 2. half of the night because of pain • Awakening at • Alternating buttock pain * * Diagnosis of IBP if 2 / 4 criteria are fulfilled sensitivity iti it specificity 70 % 81 % (AS n = 101; non-AS back pain n = 112) Rudwaleit M et al. A&R 2006 Use of the new IBP criteria as diagnostic criteria it i iin individual i di id l patients ti t • Morning stifness > 30 min • Improvement p by y movement,, but not rest • Wakening up in the 2nd half of the night because of pain • Alternating buttock pain ≥ 2 out of 4 positive ≥ 3 out of 4 positive Sensitivity 70.3% Sensitivity 33.6% Specificityy 81.2% Specificityy 97.3% LR+ 3.7 LR+ 12.4 Rudwaleit et al. Arthritis Rheum 2006;54:678-81 X-ray evidence of sacroiliitis: a prerequisite for di diagnosing i AS (modified ( difi d NY criteria it i 1984) van der Linden Arthritis Rheum 1984 A role for magnetic resonance imaging in the diagnosis of early sacroiliitis in pondyloarthritides T1 T2 A ti sacroiliac Active ili inflammation i fl ti Braun J et al. A&R 1994 The diagnostic value of scintigraphy in assessing sacroiliitis in AS - a systematic literature research • Outt off a total O t t l off 99 articles ti l about b t scintigraphy i ti h ffound, d 25 were included into the analysis. • y for scintigraphy g p y to detect sacroiliitis was 52 % for Overall sensitivity patients with established AS (N= 361) and 49 % for patients with probable sacroiliitis (N= 255). • Sensitivity of scintigraphy in AS patients with inflammatory back pain (indicating ongoing inflammation) was 53 % (N= 112) and in patients with AS and suspected sacroiliitis with magnetic resonance imaging showing acute sacroiliitis (as a gold standard) was 53 % (N=62). (N 62). • In controls with MLBP specificity was 78 % (N= 60), resulting in LRs not higher than 2.5-3.0. • The data suggest that scintigraphy of the sacroiliac joints is at the most of limited diagnostic value for the diagnosis of established AS including the early diagnosis of probable / suspected sacroiliitis. Song I et al. Ann Rheum Dis. 2008 Jan 29 [Epub ahead of print] Early back pain cohort: clinical items vs. i imaging i for f the th diagnosis di i off spondyloarthritis d l th iti 84 90 n = 69 with IBP < 2 years 80 70 60 X-rays X rays MRI ESSG criteria 50 33 40 30 21 20 10 0 X X-rays MRI ESSG criteria Heuft-Dorenbosch L et al. Ann Rheum Dis. 2006 Jun;65(6):804-8. Epub 2005 Oct 11 What is helpful for an early diagnosis of AS ? • Screen young patients ( < 45 y) with back pain > 3 months • Ask for inflammatory back pain • Ask for other signs of spondyloarthritis (uveitis, enthesitis) • Do the HLA B27 test • Add imaging when necessary (MRI, X-rays) AS assessment tools AS Measures of Disease Outcome • Bath B th A Ankylosing k l i S Spondylitis d liti (BAS) scales l • • • • BASDAI – Disease Activity Index BASFI – Functional F ti l Index I d BASGI – Global Index BASMI – Metrology Index • BASRI – Radiographic Index • Other measurement indexes • SF-36 – 36-Item Medical Outcomes Study Short-Form Health Survey • ASAS – Assessments in Ankylosing Spondylitis Working Group Improvement Criteria Disease Activity Assessment Index Metric BASFI Di bilit L Disability Levell BASDAI Disease Activity y Level BASMI Spinal Mobility ASAS - IC Composite Sum of Disease Activity BASFI = Bath Ankylosing Spondylitis Functional Index BASDAI = Bath Ankylosing Spondylitis Disease Activity Index BASMI = Bath Ankylosing Spondylitis Metrology Index ASAS - IC = ASsessment in Ankylosing Spondylitis Improvement Criteria Bath Ankylosing Spondylitis Functional Index (BASFI) • Vi Visual l analogue l scale l • • Easy (1) – impossible (10) Mean (VAS) of 10 questions: 1. 1 2. 3. 4. 5. 5 6. 7. 8. 9. 10 10. Putting on your socks or tights without help or aids Bending forward from the waist to pick up a pen from the floor without an aid Reaching up to a high shelf without help or aids (e.g helping hand) Getting up out of an armless dining room chair without using your hands or other help Getting up off the floor without help from lying on your back Standing unsupported for ten minutes without discomfort? Climbing 12-15 steps without using a handrail or walking aid (one foot on each step)? Looking over your shoulder without turning your body? Doing physically demanding activities (eg physio exercises, gardening, sport)? Doing a full day day’s s activities at home or at work? relate to the functional anatomy of subjects relate to a subject’s ability to cope with everyday life Calin, J Rheumatol 1994;21:2281-85. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Visual analogue scale (0 – 10 cm) • None (1) – Very severe (10) 1. Fatigue - How would you describe the overall level of fatigue/tiredness you have experienced? p 2. Spinal pain - How would you describe the overall level of AS neck, back or hip pain you have had? 3. Joint pain - How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 4. Enthesitis - How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure? 5. Inflammation: 1. Duration morning stiffness - How would you describe the overall level of morning stiffness you have had from the time you wake up? 2 Severity 2. S it morning i stiffness tiff - How H llong d does your morning i stiffness tiff llastt from the time you wake up? (scale of 0 to >2 hrs) BASDAI = 0 2 [F + S + J + E + 0.5 0.2 0 5 (Duration + Severity Morning Stiffness)] • Range 0 – 10 Garrett, J Rheumatol 1994;21:2286-91. Bath Ankylosing Spondylitis Metrology Index (BASMI) • Represented R d as aggregate score (ranging ( i from f 0 to 10) using i the variables below Score Measurement 0 1 2 Tragus-to-wall < 15 cm 15 to 30 cm >30 cm Lumbar flexion (modified Schober test) > 4 cm 2 to 4 cm < 4 cm > 70º 20 to 70º < 20º Lumbar side flexion > 10 cm 5 to 10 cm < 5 cm Intermalleolar distance > 100 cm 70 to 100 cm < 70 cm Cervical rotation Jenkinson, J Rheumatol 1994;21:1694-98. Objectives of disease management • R d Reduce and/or d/ prevent deleterious d l i effects ff of: f • Inflammation • Ankylosis y • Abnormal posture • Aim for: • • • • • • No or llow di N disease activity ti it ((pain, i stiffness, tiff MRI, MRI CRP) Good function, no disability No structural damage g ((no g growth of syndesmophytes) y y ) Good quality of life No increased cardiovascular morbidity Normal life expectancy Dougados M et al. J.Rheumatol 2001;28-62:16-20