1. Rheumatoid Arthritis Rheumatoid Arthritis

2. Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24. RHEUMATOID ARTHRITIS Overview Chronic inflammatory disease of unknown etiology Chronic inflammatory disease of unknown etiology Complex, multifactorial pathogenesis Complex, multifactorial pathogenesis Fluctuating clinical course; unpredictable prognosis Fluctuating clinical course; unpredictable prognosis Characterized by Characterized by –Progressive destruction of synovial joints with loss of cartilage and bone –Damaged ligaments and tendons –Loss of physical function and quality of life –Premature death

3. Sangha O. Rheumatology. 2000;39(suppl 2):3–12. MacGregor AJ, Silman AJ. In: Klippel JH, Dieppe PA, eds. Rheumatology. Vol 1. 2nd ed. London: Mosby;1998:2.1–2.6. RHEUMATOID ARTHRITIS Epidemiology Affects approximately 1% of the global adult population Affects approximately 1% of the global adult population Estimated annual incidence Estimated annual incidence –Males: 0.1–0.2 per 1000 –Females: 0.2–0.4 per 1000 Occurs 2 to 3 times more often in women than in men Occurs 2 to 3 times more often in women than in men Incidence largely consistent racially and geographically Incidence largely consistent racially and geographically Peak age of onset between the ages of 45 and 65 years Peak age of onset between the ages of 45 and 65 years

4. RHEUMATOID ARTHRITIS Worldwide Incidence and Prevalence Maini RN. Acta Orthop Scand Suppl. 1998;281:6–13. Prevalence (per 100) W. Europeans/0.8– W. Europeans/0.8–1.1 North Americans (Whites) North Americans (Whites) Chinese–0.4 Chinese0.3–0.4 Amerindians (Chippewa, Pima)5–8 W. Europeans/ 0.24–3.340.1–1.50 North Americans (Whites) North Americans (Whites) WomenMen Incidence (per 1000/year)

5. Patients usually experience moderate disability within 2 years of diagnosis and are severely disabled by 10 years Patients usually experience moderate disability within 2 years of diagnosis and are severely disabled by 10 years Approximately 30% of patients are unable to work within 10 years of RA onset Approximately 30% of patients are unable to work within 10 years of RA onset Patients experience feelings of helplessness and other psychological distress due to their increasing dependence upon help from others Patients experience feelings of helplessness and other psychological distress due to their increasing dependence upon help from others Patients may be prevented from carrying out social roles Patients may be prevented from carrying out social roles Alarcón GS. Rheum Dis Clin North Am. 1995;21:589–604. Wolfe F, Hawley D. J Rheumatol. 1998;25:2108–2117. Pincus T. Drugs. 1995;50(suppl 1):1–14. RHEUMATOID ARTHRITIS Social and Psychological Burden

6. Estimated costs of RA were $8.74 billion in 1994, 0.3% of the gross domestic product (GDP) Estimated costs of RA were $8.74 billion in 1994, 0.3% of the gross domestic product (GDP) Direct medical costs are $5,919/case/year Direct medical costs are $5,919/case/year Indirect costs Indirect costs –3 to 4 times higher than direct costs –$11,750 per person-year in patients with early RA Lifetime costs of RA rival those of coronary artery disease or stroke Lifetime costs of RA rival those of coronary artery disease or stroke Yelin E. J Rheumatol Suppl. 1996;44:47–61. Yelin E, Wanke LA. Arthritis Rheum. 1999;42:1209–1218. Allaire SH et al. Pharmacoeconomics. 1994;6:513–522. Merkesdal S et al. Arthritis Rheum. 2001;44:528–534. RHEUMATOID ARTHRITIS Economic Burden (US)

7. RHEUMATOID ARTHRITIS Economic Burden (Europe) In West Germany, the costs of RA were >40 billion DM (US $17.6 billion) in 1994 for treatment alone In West Germany, the costs of RA were >40 billion DM (US $17.6 billion) in 1994 for treatment alone In the UK, average RA outpatient cost/case/year was £798 (US $1,126) and £1,253 (US $1,769) per inpatient in 1997 In the UK, average RA outpatient cost/case/year was £798 (US $1,126) and £1,253 (US $1,769) per inpatient in 1997 RA per capita costs average: RA per capita costs average: –49% of cost of cancer –68% of cost of stroke –82% of cost of coronary heart disease –5X cost of motor vehicle accidents Knorr U. Versicherungsmedizin. 1994. Rothfuss J. Akt Rheumatol. 1997. Lubeck DP et al. Arthritis Rheum. 1986;29:488–493. Lorig KR et al. Arthritis Rheum. 1993;36:439–446.

8. Symmetric joint pain Symmetric joint pain Swelling of small peripheral joints Swelling of small peripheral joints Morning joint stiffness of variable duration Morning joint stiffness of variable duration Other diffuse aching Other diffuse aching Fatigue, malaise, and depression may precede other symptoms by weeks or months Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24. RHEUMATOID ARTHRITIS Presenting Signs and Symptoms

9. Rosenberg A. In: Cotran RS, Kumar V, Collins T, eds. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia, PA: WB Saunders; 1999:1215–1268. RHEUMATOID ARTHRITIS Pathology and Clinical Manifestations Pathologic alterations Pathologic alterations –Synovial hyperplasia –Inflammatory infiltrate –Increased vascularity –Pannus formation

14. RHEUMATOID ARTHRITIS Clinical Manifestations

15. Early stage Early stage –Soft tissue swelling Intermediate stage Intermediate stage –Mild juxtaarticular osteoporosis –Narrowing of joint space and bone erosions Late stage Late stage –Large erosions, anatomic deformities, ankylosis Bower AC. In: Klippel JH, Dieppe PA, eds. Rheumatology. Vol 1. 2nd ed. Philadelphia, PA: WB Saunders; 1998;5:5.1–5.8. Resnick D et al. In: Kelley WN et al, eds. Textbook of Rheumatology. 5th ed. Philadelphia, PA: WB Saunders; 1997:626–685. RHEUMATOID ARTHRITIS Radiologic Features

17. Harris ED Jr. In: Kelley WN et al, eds. Textbook of Rheumatology. 5th ed. Philadelphia, PA: WB Saunders; 1997:898–932. Pincus T. In: Klippel JH, Dieppe PA, eds. Rheumatology. Vol 1. 2nd ed. London: Mosby; 1998;2:10.1–10.8. RHEUMATOID ARTHRITIS Laboratory Findings Rheumatoid factor positive in up to 80% of patients Rheumatoid factor positive in up to 80% of patients Antinuclear antibody positive in 80% of patients Antinuclear antibody positive in 80% of patients Acute phase reactants (ESR, CRP)  in almost all patients at some point Acute phase reactants (ESR, CRP)  in almost all patients at some point Chemistries normal, except slight  in albumin,  total protein, and  iron Chemistries normal, except slight  in albumin,  total protein, and  iron Hematologic findings Hematologic findings –Mild anemia in 25% to 35% of patients –Normal or slight  in white cell count –Thrombocytosis ESR = erythrocyte sedimentation rate; CRP = C-reactive protein.

18. RHEUMATOID ARTHRITIS Complications Rheumatoid nodules Rheumatoid nodules Cardiovascular: vasculitis, pericarditis Cardiovascular: vasculitis, pericarditis Pulmonary: pulmonary nodules, interstitial fibrosis, pleuritis Pulmonary: pulmonary nodules, interstitial fibrosis, pleuritis Ocular: scleritis, conjunctivitis Ocular: scleritis, conjunctivitis Neurologic: compression neuropathy, vasculitis Neurologic: compression neuropathy, vasculitis Skin: distal leg ulcers, palmar erythema Skin: distal leg ulcers, palmar erythema Hematologic: granulocytopenia (Felty’s syndrome), hyperviscosity Hematologic: granulocytopenia (Felty’s syndrome), hyperviscosity Renal/hepatic: amyloidosis,  liver enzymes Renal/hepatic: amyloidosis,  liver enzymes Harris ED Jr. In: Kelley WN et al, eds. Textbook of Rheumatology. 5th ed. Philadelphia, PA: WB Saunders; 1997:898–932. Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24.

19. Diagnosis of Rheumatoid Arthritis American College of Rheumatology Criteria Arnett FC et al. Arthritis Rheum. 1988;31:315–324. At least 4 of the following criteria Morning stiffness >1 hour Morning stiffness >1 hour Arthritis of  3 joint areas Arthritis of  3 joint areas Arthritis of hand joints Arthritis of hand joints Symmetric arthritis Symmetric arthritis Rheumatoid nodules Rheumatoid nodules Serum rheumatoid factor Serum rheumatoid factor Radiographic changes Radiographic changes Must be present for at least 6 weeks

20. RHEUMATOID ARTHRITIS Clinical Course Clinical course unpredictable but mostly progressive Clinical course unpredictable but mostly progressive Unfavorable prognostic markers Unfavorable prognostic markers – Male sex– Eosinophilia – Low socioeconomic status – Elevated ESR or CRP – Subcutaneous nodules – High RF factor titer – Systemic signs– Antinuclear antibodies – Persistent synovitis– Cryoglobulins – Thrombocytosis– Shared epitope (?) Disease activity reduced faster and radiographic evidence of joint damage lessened with early diagnosis and treatment Disease activity reduced faster and radiographic evidence of joint damage lessened with early diagnosis and treatment Albers JMC et al. Ann Rheum Dis. 2001;60:453–458. Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24.

21. TREATMENT OF RHEUMATOID ARTHRITIS Goals of Therapy Relieve symptoms, including fatigue, pain, swelling, and stiffness Relieve symptoms, including fatigue, pain, swelling, and stiffness Prevent joint destruction, loss of joint function, deformity, disability, and early death Prevent joint destruction, loss of joint function, deformity, disability, and early death Preserve quality of life Preserve quality of life Achieve clinical remission Achieve clinical remission Albers JMC et al. Ann Rheum Dis. 2001;60:453–458. Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24.

22. TREATMENT OF RHEUMATOID ARTHRITIS Conventional Pharmacotherapy Disease Modifying Antirheumatic Drugs (DMARDs) Azathioprine Azathioprine D-penicillamine D-penicillamine Hydroxychloroquine Hydroxychloroquine Injectable gold salts (oral gold) Injectable gold salts (oral gold) Leflunomide Leflunomide Methotrexate (MTX) Methotrexate (MTX) Sulfasalazine Sulfasalazine