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Inflammatory arthritis an overview


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an overview to diagnose RA, SpA and PsA with management principles

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Inflammatory arthritis an overview

  1. 1. Understanding inflammatory arthritis Evaluation and Management principles
  2. 2. CDC: Census Bureau 2004
  3. 3. 3 What is inflammation?  Normal body defence mechanism  Increased blood flow  Blood cells produce chemical messengers to continue the process  Heat, swelling, redness, pain, loss of function
  4. 4. Acute vs Chronic Inflammatory Arthritis Acute Arthritis Rapid onset (hours or days) Severe symptoms Mediated by components of innate immune response, especially neutrophils (proteases, leukotrienes, prostaglandins Can result in rapid joint destruction Can also evolve into chronic disease Examples: Gout and Infectious Arthritis Chronic Arthritis More gradual onset (days to weeks) Symptoms are more moderate, AM stiffness is a prominent symptom Mediated by the adaptive immune response, especially T cells and macrophages - a Th1 disease Cytokines and chronic inflammation lead to joint remodeling and destruction via erosions Examples: Rheumatoid Arthritis, Ankylosing Spondylitis, SLE, Lyme Disease
  5. 5. Diversity of Rheumatologic Diseases: Inflammatory and Immune Responses Inflammatory Diseases (innate immunity) Osteoarthritis Gout Pseudogout Immunologically-Mediated Diseases (adaptive immunity) Rheumatoid Arthritis* Systemic Lupus Erythematosus Spondyloarthropathies* Ankylosing spondylitis * Reactive Arthritis (Reiter’s Syndrome) Psoriatic Arthritis * Spondylitis associated with IBD Sjogren’s Syndrome Polymositis/Dematomyositis Lyme Disease Rheumatic Fever Behcet’s Syndrome Systemic Sclerosis (Scleroderma) Wegener’s Granulomatosis Giant Cell Arteritis * Diseases that will be covered in depth later in lecture of this course.
  6. 6. Pattern of Joint Involvement is Distinct in Different Diseases Monoarticular vs Polyarticular Mono Poly Gout RA Infection SLE Reactive Joint distribution PIPs and MCPs: RA, SLE DIPs: Osteoarthritis, Psoriatic MTP: Gout Symmetrical vs Asymmetrical Symmetrical: RA, SLE Asymmetrical: Psoriatic, Reactive
  7. 7. Multiple Factors Contribute to the Development of Arthritis Nature Reviews Immunology, 2007
  8. 8. Genetic Basis of Rheumatic Diseases: Genotype contributes to rheumatic disease susceptibility ________ Twin Studies____________ Monozygotic Dizygotic Genetic Component Disease Concordance (%) Concordance (%) Explained by HLA (%) Rheumatoid Arthritis 15-34 0-6 35 SLE 25-57 0-3 Ankylosing Spondylitis 50-75 13-18 37 ______________________________________________________________________________ Most often rheumatic diseases are polygenic. A certain genotype predisposes an individual to a disease, but does not make disease development a certainty.
  9. 9. October 2009: >30 RA Risk Loci Plenge RM, ACR Annual Meeting Presentation, October 2009 Together explain ~35% of the genetic burden of disease HLA DR4 “Shared epitope” hypothesis PADI4 PTPN22 CTLA 4 TNFAIP4 STAT4 TRAF1-C5 IL2-IL21 CD40 CCL21 CD244 IL2RB TNFRSF14 PRKCQ PIP4K2C IL2RA AFF3 REL BLK TAGAP CD28 TRAF0 PTPRC FCGR2A PRDM1 CD2-CD58 1978 1987 2003 20072004 2005 2008 2009
  10. 10. Oral Health and RA  Periodontal disease more common in people with RA than controls  Oral bacterium, Porphyromonas gingivalis, may be the connection x Associated with autoantibodies (CCP) x Could be part of causal pathway x Many ongoing studies of role in RA Rosenstein ED et al. Inflammation 2004;28:311-8
  11. 11. 11 Symptoms  Joint pain  Joint swelling  Morning stiffness  Fatigue  Weight loss  Flu-like symptoms
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  14. 14. Rheumatoid Arthritis: PIP Swelling  Swelling is confined to the area of the joint capsule  Synovial thickening feels like a firm sponge
  15. 15. Rheumatoid Arthritis: Ulnar Deviation and MCP Swelling  An across-the-room diagnosis  Prominent ulnar deviation in the right hand  MCP and PIP swelling in both hands  Synovitis of left wrist
  16. 16. Rheumatoid Arthritis Early erosion at the tip of the ulnar styloid
  17. 17. 2010 ACR/EULAR Classification Criteria for RA JOINT DISTRIBUTION (0-5) 1 large joint 0 2-10 large joints 1 1-3 small joints (large joints not counted) 2 4-10 small joints (large joints not counted) 3 >10 joints (at least one small joint) 5 SEROLOGY (0-3) Negative RF AND negative ACPA 0 Low positive RF OR low positive ACPA 2 High positive RF OR high positive ACPA 3 SYMPTOM DURATION (0-1) <6 weeks 0 ≥6 weeks 1 ACUTE PHASE REACTANTS (0-1) Normal CRP AND normal ESR 0 Abnormal CRP OR abnormal ESR 1 ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past
  18. 18. 18 Extraarticular ?  Eyes: dryness, inflammation, uveitis  Lungs: fluid, inflammation, nodules  Skin: nodules, ulcers, psoriasis, balanitis, keratoderma blenorhagia  Heart: fluid, inflammation, ischaemic heart disease  Blood: anaemia, low counts
  19. 19. Spondyloarthritis, Psoriasis and PsA Spondyloarthritis (SpA)  The prevalence of SpA is comparable to that of RA (0.5–1.9%)1,2 Psoriasis (Pso)  Psoriasis affects 2% of population  7% to 42% of patients with Pso will develop arthritis3 Psoriatic Arthritis  A chronic and inflammatory arthritis in association with skin psoriasis4  Usually rheumatoid factor (RF) negative and ACPA negative5 x Distinct from RA  Psoriatic Arthritis is classified as one of the subtypes of spondyloarthropathies x Characterized by synovitis, enthesitis, dactylitis, spondylitis, skin and nail psoriasis4 1 Rudwaleit M et al. Ann Rheum Dis 2004;63:535-543; 2 Braun J et al. Scand J Rheumatol 2005;34:178-90; 3 Fitzgerald “Psoriatic Arthritis” in Kelley’s Textbook of Rheumatology, 2009; 4 Mease et al. Ann Rheum Dis 2011;70(Suppl 1):i77–i84. doi:10.1136/ard.2010.140582; 5 Pasquetti et al. Rheumatology 2009;48:315–325 Juvenile SpA Reactive arthritis Arthritis associated with IBD PsA Undifferentiated SpA (uSpA) Ankylosing spondylitis (AS) RA: Rheumatoid arthritis
  20. 20. AS: A Debilitating Rheumatic DiseaseAS: A Debilitating Rheumatic Disease 1 Linden VD et al. Chapter 10. In: Firestein, Budd, Harris, McInnes, Ruddy and Sergent, eds. Kelley’s Textbook of Rheumatology: Spondyloarthropathies. 8th ed. Saunders Elsevier;2009:p.1171 2 Braun J & Sieper. J Rheumatology 2008;47:1738-40
  21. 21. Ankylosing Spondylitis “Bamboo Spine” Repeated process of healing and bone formation leads to formation of syndesmophytes ‘bone bridges’ ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994.
  22. 22. • Mortality figures parallel RAMortality figures parallel RA6,7,86,7,8  ““Rare”Rare”  ““Not” a serious disease, functional limitation isNot” a serious disease, functional limitation is mildmild  ““Rarely shortens life”Rarely shortens life” AS (“Mis-”) Perceptions • Burden of disease significant in pain, sick leave, earlyBurden of disease significant in pain, sick leave, early retirementretirement3,4,53,4,5 • 0.1-0.9%0.1-0.9%1,21,2 11 Sieper J et al.Sieper J et al. Ann Rheum Dis.Ann Rheum Dis. 2002; 61 (suppl 3);iii8-18.2002; 61 (suppl 3);iii8-18. 22 Lawrence RC., Arthritis Rheum 1998; 41:778-99.Lawrence RC., Arthritis Rheum 1998; 41:778-99. 33 Zink A., et al.,Zink A., et al., J RheumatolJ Rheumatol 2000; 27:613-22.2000; 27:613-22. 44 Boonen A.Boonen A. Clin Exp RheumatolClin Exp Rheumatol. 2002;20(suppl 28):S23-S26.. 2002;20(suppl 28):S23-S26. 55 Gran JT, et al.Gran JT, et al. Br J RheumatolBr J Rheumatol. 1997;36:766-771.. 1997;36:766-771. 66 Wolfe F., et al. Arthritis Rheum. 1994 Apr;37(4):481-94.Wolfe F., et al. Arthritis Rheum. 1994 Apr;37(4):481-94. 77 Myllykangas-Luosujarvi R, et al.Myllykangas-Luosujarvi R, et al. Br J Rheumatol.Br J Rheumatol. 1998;37:688-690.1998;37:688-690. 88 Khan MA, et al.Khan MA, et al. J Rheumatol.J Rheumatol. 1981;8:86-90.1981;8:86-90. 99 Braun J., Pincus T., Clin Exp Rheumatol. 2002; 20(6 Suppl 28):S16-22.Braun J., Pincus T., Clin Exp Rheumatol. 2002; 20(6 Suppl 28):S16-22.
  23. 23. AS: Signs and SymptomsAS: Signs and Symptoms Axial manifestations: • Chronic low back pain • With or without buttock pain • Inflammatory characteristics: – Occurs at night (second part) – Sleep disturbance – Morning stiffness • Limited lumbar motion Sengupta R & Stone MA. Nat Clin Pract Rheumatol 2007;3:496-503 Hultgren S et al. Scand J Rheumatol 2000;29:365-369 Linden VD et al. Chapter 10. In: Firestein, Budd, Harris, McInnes, Ruddy and Sergent, eds. Kelley’s Textbook of Rheumatology: Spondyloarthropathies. 8th ed. Saunders Elsevier;2009:p.1175 Inflammatory back pain (IBP) = Characteristic symptom MRI sacro-iliac joint
  24. 24. Peripheral manifestations Enthesitis Peripheral arthritis Dactylitis AS: Signs and SymptomsAS: Signs and Symptoms 50% patients with enthesitis1 1 Cruyssen BV et al. Ann Rheum Dis 2007;66:1072-1077 2 Sidiropoulos PI et al. Rheumatology 2008;47:355-361 Up to 58% patients ever had arthritis1 Much smaller number of patients2
  25. 25. Why are Dactylitis and Enthesitis Important? The first abnormality to appear in swollen joints associated with spondyloarthropathies is an enthesitis2 Likelihood of erosions is higher for digits with dactylitis than those without1 1 Brockbank. Ann Rheum Dis 2005;62:188-90; 2 McGonagle et al. The Lancet 1998;352.
  26. 26. AS: Extra-skeletal Signs and SymptomsAS: Extra-skeletal Signs and Symptoms Other common symptoms seen during the early stages of disease include: • Anorexia • Malaise • Low grade fever • Weight loss • Fatigue 1 Missaoui B. et al. Ann Readapt Med Phys 2006;49:305-8, 389-391 Linden VD et al. Chapter 10. In: Firestein, Budd, Harris, McInnes, Ruddy and Sergent, eds. Kelley’s Textbook of Rheumatology: Spondyloarthropathies. 8th ed. Saunders Elsevier;2009:p.1176 Fatigue is a frequent complaint of patients with AS1
  27. 27. AS:AS: Extra-articular Manifestations (EAM)Extra-articular Manifestations (EAM) EAM Prevalence in AS Patients (%) Anterior uveitis 30-50 IBD 5-10 Subclinical inflammation of the gut 25-49 Cardiac abnormalities Conduction disturbances Aortic insufficiency 1-33 1-10 Psoriasis 10-20 Renal abnormalities 10-35 Lung abnormalities Airways disease Interstitial abnormalities Emphysema 40-88 82 47-65 9-35 Bone abnormalities Osteoporosis Osteopenia 11-18 39-59 Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035 Terminal ileitis Anterior uveitis Cardiac abnormalities
  28. 28. Spondyloarthritis and Classification Criteria Spondyloarthropathies Axial and Peripheral AMOR criteria (1990) ESSG criteria (1991) Axial Spondyloarthritis ASAS classification 2009 Ankylosing spondylitis Prototype of axial spondylitidis Modified New York criteria 1984 Peripheral Spondyloarthritis ASAS classification 2010 Psoriatic arthritis From Moll & Wright 1973 to CASPAR criteria 2006 Sieper et al. Ann Rheum Dis 2009;68:ii1-ii44 Taylor et al. Arthritis & Rheum 2006;54:2665-73 Van der Heijde et al. Ann Rheum Dis 2011;70:905-8 ESSG: European Spondyloarthropathy Study Group ASAS: Assessment of Spondyloarthritis International Society CASPAR: Classification criteria for psoriatic arthritis Infliximab (IFX) and Golimumab (GLM) indications
  29. 29. ASAS Classification Criteria for Axial SpAASAS Classification Criteria for Axial SpA In patients with back pain ≥3 months and age at onset <45 years Sacroiliitis* on imaging plus ≥1SpA feature** HLA-B27 plus ≥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 *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 Rudwaleit M et al. Ann Rheum Dis 2009;68(6):770-6 OR
  30. 30. 30 Psoriatic Arthritis
  31. 31. Psoriatic Arthritis ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994. Data on file, Centocor, Inc.
  32. 32. Pso patients6-8 • Psychosocial burden • Reactive depression • Higher suicidal ideation • Alcoholism  Metabolic Syndrome3-5 • Hyperlipidemia • Hypertension • Insulin resistent • Diabetes • Obesity ⇒ Higher risk of Cardiovascular disease (CVD) Ocular inflammation1 (Iritis/Uveitis/ Episcleritis) IBD2 Comorbidities in PsA Patients 1 Qieiro et al. Semin Arth Rheum 2002;31:264; 2 Scarpa et al. J Rheum 2000;27:1241; 3 Mallbris et al. Curr Rheum Rep 2006;8:355; 4 Neimann et al. J Am Acad Derm 2006;55:829; 5 Tam et al. 2008;47:718; 6 Kimball et al. Am J Clin Dermatol 2005;6:383-392; 7 Naldi et al. Br J Dermatol 1992;127:212-217; 8 Mrowietz U et al. Arch Dermatol Res 2006;298(7):309-319
  33. 33. Classical Description of PsA Using the Diagnostic Criteria of Moll and Wright  Including 5 clinical patterns: x Asymmetric mono-/oligoarthritis (~30% [range 12-70%])1-4 x Symmetric polyarthritis (~45% [range 15-65%])1-4 x Distal interphalangeal (DIP) joint involvement (~5%)1 x Axial (spondylitis and Sacroiliitis) (HLA-B27) (~5%)1,3 x Arthritis Mutilans (<5%)1,3 References see notes • However patterns may change over time and are therefore not useful for classification 5 HLA: Human leucocytes antigen
  34. 34. Paradigm shift in the treatment of inflammatory arthritis  Rationale for Treatment x Large body of evidence which shows joint damage is an early phenomenon of rheumatoid arthritis x Joint erosions occur in up to 93% of patients with less than 2 years of disease activity x The rate of radiographic progression is greatest in the first two years x Disability occurs early – 50% of patients with RA will be work disabled at 10 years x Severe disease is associated with increased mortality!
  35. 35. It’s like an Iceberg
  36. 36. It’s what you don’t see!
  37. 37. Approach to Inflammatory Arthritis  “Window of Opportunity” x Early and aggressive treatment may have long-term benefits  Principles of Treatment x Treat Early x Treat Appropriately
  38. 38. A Fire in the Joints If there’s a fire in the kitchen do you wait until it spreads to the living room or do you try and put it out?
  39. 39. 39 Principles of Treatment  Early diagnosis  Early initiation of treatment  Regular assessment (Disease Activity Scores)  “Treat to Target”  Annual review
  40. 40. 40 Reduction of Joint Damage Disease-modifying Anti- Rheumatic Drugs Methotrexate Sulfasalazine Leflunomide Hydroxychloroquine Azathioprine Ciclosporin Gold Penicillamine Biologic drugs  Anti-TNF therapy:  Infliximab  Etanercept  Adalimumab  Certolizumab  Golimumab  Rituximab  Abatacept  Tocilizumab
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