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Rheumatoid Arthritis. Goals General Approach to Arthritis Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity.

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Presentation on theme: "Rheumatoid Arthritis. Goals General Approach to Arthritis Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity."— Presentation transcript:

1 Rheumatoid Arthritis

2 Goals General Approach to Arthritis Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course

3 Approach to Arthritis

4 Joint Pain most common symptom Pain (arthralgia) vs. Inflammation (arthritis) Inflammation: heat, redness, pain, swelling, loss of function inflammatory arthritis (RA, SLE) vs. pain syndrome (fibromyalgia)

5 Number of Joints Affected Inflammatory vs. Non-Inflammatory

6 Number of Joints Affected Monoarticular Crystal-induced Infection Reactive Arthritis Hemarthrosis OA: joint effusions Autoimmune disease Psoriasis, IBD, AS, Behçet's Oligo/Polyarticular Monoarticular causes RA SLE Viral infection B19 Acute Serum Sickness Untreated Crystal-induced Vasculidities

7 Inflammatory vs. Non-Inflammatory Inflammatory: i.e. RA Generalized AM stiffness > 30 min Resolves with movement Classic signs of inflammation Non-Inflammatory: i.e. Osteoarthritis Localized AM stiffness < 30 min


9 Arthrocentesis Confirm diagnoses Differentiate between inflammatory & noninflammatory Therapeutic/Adjunct to Antibiotics Labs: cell count w/diff crystal analysis Gram stain & Culture WBC >2000/µL indicates inflammatory arthritis Arthroscopy Evaluate ligamentous & cartilaginous integrity Biopsy Infectioun: aspirate thick or loculated fluid

10 Rheumatoid Arthritis

11 RA Systemic inflammatory autoimmune disorder ~1% of population Onset: 52 years 40-70 years of age <60 - 3-5:1 female predominance

12 Genetics Increased incidence among Pima & Chippewa Native American tribes (5%) Genetic & Environmental HLA-DRB1*0401 & HLA-DRB1*0404 Increased risk Increased joint damage Increased joint surgery

13 Pathophysiology


15 Immunology Macrophages: Produce cytokines Cytokines (TNF-α) cause systemic features Release chemokines  recruit PMNs into synovial fluid/membrane TNF-α & IL-1: Proliferation of T cells Activation of B cells Initiates proinflammatory/joint- damaging processes TH-1 cells: Mediate disease processes Activate B cells B cells: Release cytokines Plasma cells that produce Ab Osteoclasts: Bone erosion Juxta-articular & Systemic osteoporosis

16 Pathophysiology Swelling of Synovial lining Angiogenesis Rapid division/growth of cells = Pannus Synovial thickening/hyperplasia Inflammatory vascularized tissue Generation of Metalloproteinases Cytokine release Infiltration of leukocytes Change in cell-surface adhesion molecules & cytokines Destruction of bone & cartilage

17 Bottom Line Proliferation Destruction of joints Disability

18 Disease Trigger Subclinical vs. Viral trigger Lab manifestations up to 10 yrs before clinical RF & anti-CCP (anti–cyclic citrullinated peptide) Ab Increased CRP subclinical inflammatory disease ADLs: > 50% of pts stop working w/i 5-10 years of disease onset ~ 80% disabled to some degree > 20 years Life expectancy: decreased by 3-18 years

19 Clinical Presentation Gradual onset Stiffness & Swelling Intermittent or Migratory involvement Extraarticular manifestations Myalgia, fatigue, low-grade fever, wt loss, depression

20 Stiffness & Swelling Pain with pressure to joint Pain with movement of joint Swelling due to hypertrophy Effusion Heat Redness

21 Physical Exam Decreased grip strength Boxing glove edema Carpal tunnel Ulnar deviation Boutonniere/Swan neck deformities Extensor tendon rupture

22 Extraarticular Involvement Anemia Rheumatoid nodules Pleuropericarditis Neuropathy Episcleritis, Scleritis Splenomegaly Sjogren’s Vasculitis

23 Differential Seronegative polyarthritis Psoriatic arthritis Crystal-induced Tophaceous gout Pseudogout Erosive inflammatory OA Reiter’s Enteropathic arthritis SLE Paraneoplastic syndrome

24 Diagnostic Criteria

25 Symmetric peripheral polyarthritis AM Stiffness >1 hour Rheumatoid nodules Laboratory features Radiographic bone erosions

26 Symmetric Peripheral Polyarthritis 3 or more Joints for >6 weeks Small Joints Hands & Feet Peripheral to Proximal MCP and PIP Joints SPARES DIP MTP & Plantar subluxation Leads to Deformity & Destruction of Joints Erosion of cartilage and bone

27 Stiffness AM or after Prolonged Inactivity Bilateral In/Around Joints > 1 hours Reflects severe joint inflammation Better with movement Present >6 weeks

28 Rheumatoid Nodules Extensor surfaces elbows Very Specific Only occur in ~30% Late in Disease

29 Laboratory Features RF 70-80% of pts Overlap with HCV/Cryoglobulinemia Anti-Cyclic Citrulline Peptide (anti-CCP) Rare overlap with HCV Acute Phase reactants ESR, CRP  monitoring disease activity

30 Rheumatoid Factor IgM against IgG IgM+ pts: more severe disease & poorer outcome Non-specific SLE, Sjögren's, Sarcoidosis, Chronic infections

31 Anti-CCP IgG against synovial membrane peptides damaged via inflammation Value in IgM-RF negative Sensitivity (65%) & Specificity (95%) Predictive of Erosive Disease Disease severity Radiologic progression Poor functional outcomes

32 Other Lab Abnormalities AOCD Thrombocytosis Leukocytosis ANA 30-40% Inflammatory synovial fluid Hypoalbuminemia

33 Radiology Evaluate disease activity & joint damage Bony decalcification Baseline AP views Initiation of DMARDs

34 Radiological Studies Plain Films Bilateral hands & feet Only 25% of lesions Less expensive Through bone cortex around joint margins Color Doppler U/S & MRI Early signs of damage i.e. Erosions Bone Edema - even with normal findings on radiography



37 Disease Severity

38 Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated ESR & CRP No erosions/cartilage loss No extraarticular disease i.e. anemia Mild Disease

39 Moderate Disease 6-20 Inflamed joints Moderate functional limitation Elevated ESR/CRP Radiographic evidence of inflammation No extraarticular disease

40 Severe Disease >20 persistently inflamed joints Rapid decline in functional capacity Radiographic evidence of rapid progession of bony erosions & loss of cartilage Extraarticular disease: AOCD, Hypoalbuminemia

41 Prognostic Features RF & Anti-CCP antibodies Early development of multiple inflamed joints and joint erosions Severe functional limitation Female HLA epitope presence Lower socioeconomic status & Less education Persistent joint inflammation for >12 weeks

42 CV Disease Leading cause of death ~50% 2x more likely to develop MI chronic, inflammatory vascular burden  premature atherosclerosis MTX: elevated homocysteine levels Control inflammatory process = Decreased atherosclerosis/morbidity Lipid screening & treatment Control of obesity, Hyperhomocystinemia, DM, HTN ASA

43 Other diseases 70% more likely to have a stroke 70% higher risk for developing infection Likely 2/2 treatment 44x more likely to develop NHL

44 Staging Early <3 months Established/Persistent 6-12 months End-stage Significant joint destruction Functional disability

45 Management Early and aggressive disease control Rheumatologist Referral Early/Undiagnosed: NSAIDs, short course Corticosteroids Late/Uncontrolled: DMARD therapy depends on the presence or absence of joint damage, functional limitation, presence of predictive factors for poorer prognosis Goals achieve NED & inflammation no treatment to resolve erosions once they occur

46 Treatment Strategies

47 Therapy Non-Pharmacologic: Referral to PT/OT Evaluate ADLs Assistive devices/splints Weight loss Smoking cessation Pharmacologic: Anti-inflammatory Interrupt progression Development of erosions Joint space narrowing

48 Pharmacologic Therapy Analgesics NSAIDs Glucocorticoids SAARD/DMARD Anticytokine therapy

49 Analgesics Topical Capsaicin Diclofenac Oral Tylenol Opiods

50 NSAIDs Pros: Analgesic, Antipyretic, Anti- inflammatory Cons: Don’t alter disease progression Ineffective in Erosive disease GI/Ulcers Hepatotoxicity Nephrotoxicity AIN Bleeding – antiplatelet Rash Aseptic meningitis

51 Corticosteroids Decrease cytokines Slow Joint Inflammation Insomnia Emotional lability Fluid retention Weight gain HTN Hyperglycemia Osteoporosis Bisphosphonates: >5mg/d for >3months Cataracts Avascular necrosis Myopathy Psychosis

52 Disease modification SAARD – slow acting antirheumatic drugs DMARD – disease modifying antirheumatic drugs

53 Methotrexate Dihydrofolate reductase inhibitor Well tolerated, Mono/Combo Onset: 6-12 weeks Metabolism: Liver Clearance: Kidneys Monitoring: Baseline:CXR, PFTs, HIV, HBV/HCV CBC, LFTs Q4-8 weeks Caution with CRI Nausea Mucosal ulcerations Fatigue & Flu-like symptoms BM Toxicity Hepatotoxicity Treat with Folic acid, 1 mg/d

54 Leflunomide Inhibits dihydrooratate dehydrogenase Dec. activated T-cells Onset: rapid Efficacy: ≤6 weeks Monitoring: CBC, LFTs Derm - rash, alopecia Diarrhea BM toxicity Hepatotoxicity

55 Azathioprine Corticosteroid-sparing Monitoring: CBC Q1-2 months AST/ALT Infection BM Toxicity Hepatitis Malignancy

56 Cyclophosphamide Alkylating agent Monitoring: CBC, UA monthly Yearly UA +/- Cytology Alopecia Nausea Infection BM suppression  pancytopenia Infertility – pretreat women with Leuprolide Renal: hemorrhagic cystitis, bladder malignancy – treat with acrolein Oral more toxic than IV

57 Anticytokine therapy Anti-TNF alpha agents Etanercept Infliximab Adalimumab IL-1 receptor antagonist (Anakinra)

58 TNF-a Inhibitors Anti-inflammatory Block TNF-α (proinflammatory cytokine) Etanercept, Adalimumab (SQ), Infliximab (IV) Very expensive: > $15,000/patient Combo therapy with MTX Injection site reaction Infection Reactivated TB Infliximab infusion reaction Pancytopenia Autoantibody/SLE-like Exacerbate CHF Malignancy – lymphoma

59 More aggressive approach Combo therapy Adjunctive therapy: TNF-α antagonist

60 Disease Course Long Remission 10% Intermittent Disease 15-30% Progressive Disease

61 Summary Approach to Arthritis Number of Joints Affected Inflammatory vs. Non-Inflammatory Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course

62 Questions?

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