Early Diagnosis of Rheumatoid Arthritis & Axial Spondyloarthritis

Transcription

1 Early Diagnosis of Rheumatoid Arthritis & Axial Spondyloarthritis 奇 美 醫 院 過 敏 免 疫 風 濕 科 陳 宏 安

2 Rheumatoid arthritis Most common chronic inflammatory joint disease Multisystem autoimmune disease of unknown etiology

3 Prevalence of approximately 1% in adult population Age of onset usually between years Female to male ratio of 3:1 Chronic, progressive and disabling

4 47 normal rheumatoid arthritis Synovitis,, the inflammation of a synovial (joint-lining) membrane

5 2010 ACR/EULAR classification criteria for rheumatoid arthritis Target population (Who should be tested?): Patient who (1) have at least 1 joint with definite clinical synovitis (swelling). (2) with the synovitis not better explained by another disease.

6 Early-stage RA with swelling of the proximal interphalanegeal (PIP) joints

7 2010 Rheumatoid arthritis classification criteria: An American College C of Rheumatology/European League Against Rheumatism collaborative initiative itiative Arthritis & Rheumatism Volume 62, Issue 9, pages , 10 AUG 2010 DOI: /art

8 2010 ACR/EULAR classification criteria Synovitis plus score of 6/10 needed for the classification of definite RA Joint involvement 1 large joint large joints small joints* small joints* 3 >10 joints (at least one small joint) 5 Serology # RF- and ACPA- 0 Low RF+ or low ACPA/anti-CCP+ 2 High RF+ or high ACPA/anti-CCP+ 3 Acute-phase reactants # Normal CRP and normal ESR 0 Abnormal CRP or abnormal ESR 1 Duration of symptoms <6 weeks 0 6 weeks 1 *With or without involvement of large joints. # at least one test result needed for classification. ACPA: Anti-citrullinated protein/peptide antibodies; anti-ccp: Anti-citrullinated peptide; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate Aletaha et al. Ann Rheum Dis 2010;69:

9 2010 ACR/EULAR classification criteria for rheumatoid arthritis Differential diagnoses: lupus, psoriatic arthritis, gout, & Lyme disease. Joint involvement: 1. Any swollen or tender joint, 2. May be confirmed by imaging evidence of synovitis.

10 Ultrasonography & MRI in second metacarpophalangeal joint. Thin arrows indicate an erosive change; thick arrows indicate synovitis.

11 Small joints in rheumatoid arthritis Hand 1. Metacarpophalangeal joints (MCP) 2. Proximal interphalangeal joints (PIP) 3. Thumb interphalangeal joints 4. Wrists Foot 1. 2 nd -5 th metatarsophalangeal joints (MTP).

12 Large joints in rheumatoid arthritis Shoulders Elbows Hips Knees Ankles

13 Rheumatoid arthritis vs. Osteoarthritis Joints typically involved in osteoarthritis are excluded: 1. Distal interphalangeal joints (DIP) 2. First carpometacarpal joints (1 st CMC) 3. First metatarsophalangeal joints (1 st MTP)

14 Validation of a prediction rule for disease outcome in patients with recent onset undifferentiated arthritis Arthritis & Rheumatism Volume 58, Issue 8, pages , 30 JUL 2008 DOI: /art.23681

15 Curve plotted of subjects prediction scores versus the predicted risk to develop RA

16 Laboratory markers Serology: 1. RF: rheumatoid factor 2. ACPA/anti-CCP: CCP: anti-citrullinated peptide antibodies 3. High-positive RF or ACPA: >3 times the upper limit of normal. Acute-phase reactants: 1. CRP: C-reactive C protein 2. ESR: Erythrocyte sedimentation rate

17 Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors 50 percentage of positive patients CCP and/or IgM-RF CCP IgM-RF years before start of symptoms Arthritis & Rheumatism Volume 50, Issue 2, pages , 5 FEB 2004 DOI: /art

18 ACPA/anti-CCP: CCP: anti-citrullinated peptide antibodies

19 The median time from the first IgM-RF or anti-ccp positivity to development of symptoms was 2.0 years and 4.8 years, respectively Arthritis & Rheumatism Volume 50, Issue 2, pages , 5 FEB 2004 DOI: /art

20 Accumulated percentage positive samples of IgA, IgG and IgM isotypes.

21 Concentrations, in percentage of cut off value of anti-ccp2 antibody isotypes before and at disease onset. Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthritis Res Ther Feb 3;13(1):R13.

22 The concentrations and frequencies of all anti-ccp and RF isotypes were increased in first- degree relatives and patients with RA compared with healthy controls. Ann Rheum Dis Jun;71(6):825-9.

23 Radiological destruction in patients with and without anti-cyclic cycliccitrullinated peptide antibodies. Arthritis Res Ther. 2005;7(5):R

24 Rheumatoid factor

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26 Take home message RA should be considered in any patient with clinical synovitis in at least one joint. Number of involved joints and acute-phase reactants express the level of inflammation. ACPA/anti-CCP CCP and RF can be present years before clinical synovitis. Not only the presence but also the level of auto-antibodies antibodies is of predictive relevance.

27 Axial Spondyloarthritis (SpA) Ankylosing spondylitis Reactive arthritis (Reiter's syndrome) Psoriatic arthritis Enteropathic spondylitis (Crohn's disease & ulcerative colitis) Undifferentiated spondyloarthropathy

28 Figure 1 The concept of axial SpA Definite evidence of sacroiliitis on plain radiographs is delayed by 6-8 years. Rudwaleit, M. & Sieper, J. (2012) Referral strategies for early diagnosis of axial spondyloarthritis Nat. Rev. Rheumatol. doi: /nrrheum

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30 Rudwaleit M et al. Ann Rheum Dis 2009;68(6):770-6 ASAS Classification Criteria for Axial SpA In patients with back pain 3 months and age at onset <45 years Sacroiliitis* on imaging plus OR HLA-B27 plus 1SpA feature** *Sacroiliitis on imaging: Active (acute) inflammation on MRI highly suggestive of sacroiliitis associated with SpA or Definite radiographic sacroiliitis according to modified New York criteria 2 other SpA features** **SpA features: Inflammatory back pain Arthritis Enthesitis (heel) Uveitis Dactylitis Psoriasis Crohn s disease/ulcerative colitis Good response to NSAIDs Family history for SpA HLA-B27 Elevated CRP

31 Ankylosis Sacroiliitis Hip arthritis

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33 (A) MRI image showing corner- related osteitis (white arrows) at T12 to L3. (B) There is fatty marrow infiltration at the upper endplate of T12 (white arrowhead).

34 Human Leukocyte Antigen (HLA-B27) A A class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6.

35 Khan MA. Ann Intern Med 2002;136(12): SpA and HLA-B27 Disease Approximate Prevalence of HLA-B27 (%) AS 90 Reactive arthritis (ReA) Juvenile spondyloarthropathy 70 Enteropathic spondyloarthropathy Psoriatic arthritis Undifferentiated spondyloarthropathy 70 Acute anterior uveitis 50 Aortic incompetence with heart block 80

36 The early disease stage in axial spondylarthritis: : Results from the german spondyloarthritis inception cohort Arthritis & Rheumatism Volume 60, Issue 3, pages , 26 FEB 2009 DOI: /art

37 Onset age in patients with ankylosing spondylitis Age at onset (years) N= 385 HLA-B27 (+) Men 47 HLA-B27 (-) Men 93 HLA-B27 (+) Women 21 HLA-B27 (-) Women Chen HA, Chou CT. J Rheumatol May;39(5):

38 Table 1 Comparison of clinical and laboratory SpA features relevant for axial SpA Rudwaleit, M. & Sieper, J. (2012) Referral strategies for early diagnosis of axial spondyloarthritis Nat. Rev. Rheumatol. doi: /nrrheum

39 Inflammatory back pain Four out of 5 must be present: Age at onset <40 years Insidious onset Improvement with exercise No improvement with rest Pain at night (with improvement upon getting up)

40 Mechanical back pain Any type of back pain caused by placing abnormal stress and strain on muscles of the vertebral column. Poor posture, poorly-designed seating and incorrect bending and lifting motions.

41 Dactylitis and Enthesitis Dactylitis or sausage digit: inflammation of an entire digit (a finger or toe) Heel enthesitis: pain or tenderness of the site of the insertion of Achilles tendon or plantar fascia at the calcaneus

42 Family history of SpA Presence in first-degree or second-degree degree relatives of any of the following: AS 1. AS 2. Psoriasis 3. Acute uveitis 4. Reactive arthritis 5. IBD

43 Pedigree of patients with ankylosing spondylitis (AS) extending over 10 generations. Geirsson A J et al. Ann Rheum Dis doi: /ard by BMJ Publishing Group Ltd and European League Against Rheumatism

44 Ankylosing spondylitis (AS) Prototype of axial SpA Main clinical manifestations: 1. Sacroiliitis 2. Spondylitis 3. Hip or peripheral joint arthritis/enthesitis 4. Uveitis Juvenile-onset AS (JoAS( JoAS): symptom onset occurs in patients aged 16 or less

45 Table 1 Comparison of clinical, laboratory, and radiographic data among AS patients based on the onset age of disease Juvenile-onset Adult-onset Late-onset p (n =67) (n = 460) (n =19) Initial symptoms/signs Back pain, % 49/67 (73.1) 392/460 (85.2) 12/19 (63.2) 0.003* Peripheral arthritis, % 25/67 (37.3) 99/460 (21.5) 4/19 (21.1) 0.017* Enthesitis, % 9/67 (13.4) 47/460 (10.2) 3/19 (15.8) Uveitis, % 7/67 (10.4) 44/460 (9.6) 4/19 (21.1) Peripheral arthritis/enthesitis only, % 11/67 (16.4) 35/460 (7.6) 1/19 (5.3) 0.049* Chen HA, Chou CT. J Rheumatol May;39(5):

46 Decision tree on diagnosing axial SpA. Rudwaleit M et al. Ann Rheum Dis 2004;63: by BMJ Publishing Group Ltd and European League Against Rheumatism

47 Approach to the diagnosis of axial SpA in daily practice for the physician less experienced (GP) in dealing with patients with rheumatic disease. Rudwaleit M et al. Ann Rheum Dis 2004;63: by BMJ Publishing Group Ltd and European League Against Rheumatism

48 Figure 2 Proposed referral strategy for axial spondyloarthritis for primary care physicians Rudwaleit, M. & Sieper, J. (2012) Referral strategies for early diagnosis of axial spondyloarthritis Nat. Rev. Rheumatol. doi: /nrrheum

49 Take home message Target population for axial SpA: 1. Chronic back pain > 3 months 2. Age at onset of < 45 years Inflammatory back pain is the key clinical symptoms. HLA-B27 is the key laboratory marker. Definite sacroiliitis on plain radiographs requires years to develop.

50 Thank you for your attention