1. Overview of Rheumatoid Arthritis Naureen Mirza, MD May 10, 2010

2. Epidemiology An annual incidence of approximately 0.2 per 1000 in males and 0.4 per 1000 in females A prevalence of 0.5-1% is reported in diverse populations worldwide Twin studies show the disease to have a heritability of 60% Hormonal and reproductive factors contribute to the female excess and parity Obesity, smoking, coffee consumption, and prior blood transfusion have also been identified as potential risk factors

3. Table 67-1. THE 1987 ARA CRITERIA (TRADITIONAL FORMAT)Table 67-1. THE 1987 ARA CRITERIA (TRADITIONAL FORMAT)Table 67-1. THE 1987 ARA CRITERIA (TRADITIONAL FORMAT)Table 67-1. THE 1987 ARA CRITERIA (TRADITIONAL FORMAT) 1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 h before maximal improvement 2. Arthritis in three or more joint areas Soft tissue swelling or fluid (not bony overgrowth) observed by a physician, present simultaneously for at least 6 weeks 3. Arthritis of hand joints Swelling of wrist, MCP or PIP joints for at least 6 weeks 4. Symmetric arthritis Simultaneous involvement of the same joint areas (defined in 2) on both sides of the body (bilateral involvement of PIP, MCP or MTP joints is acceptable without absolute symmetry) for at least 6 weeks 5. Rheumatoid nodules Subcutaneous nodules over bony prominences, extensor surfaces or in juxta-articular regions, observed by a physician 6. Rheumatoid factor Detected by a method positive in fewer than 5% of normal controls 7. Radiographic changes Typical of RA on posteroanterior hand and wrist radiographs; it must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (OA changes alone do not qualify)

4. New criteria for the diagnosis of RA Joint involvement 1 med-lg joint 0 2-10 Med-Lg joints 1 1-3 small joints 2 4-10 small joints 3 >10 small joints 5 Serology Neither RF or Anti ccp 0 At least one + with low titer 2 Atleast one with high titer 3 Duration of synovitis <6 weeks 0 >6 weeks 1 Acute phase reactants Neither CRP or ESR abnormal 0 Abnormal CRP or abnormal ESR 1 Score >=6 indicates “definite RA”

5. History In RA Chronological account of illness from the onset Onset: acute or gradual, with details Location of pain (local or referred): precise anatomy, presence/absence of swelling Pattern of joint involvement: axial, peripheral, symmetric Type of pain: quality and character Severity: pain threshold effects, interference with activities of daily living, range of joint movement Radiation of pain: local or deep referred type Clinical course: duration, frequency, periodicity, persistence Modifying factors: aggravating, relieving, medication effects Associated symptoms: fatigue, other systemic symptoms Duration of morning stiffness: non-restorative sleep pattern Present status: regional review of joints, extra-articular features, functional class, activities of daily living, psychologic state

6. CLINICAL EVALUATION OF RHEUMATOID ARTHRITIS - EXAMINATIONCLINICAL EVALUATION OF RHEUMATOID ARTHRITIS - EXAMINATIONCLINICAL EVALUATION OF RHEUMATOID ARTHRITIS - EXAMINATIONCLINICAL EVALUATION OF RHEUMATOID ARTHRITIS - EXAMINATION Extra-articular features Record presence of nodules, Raynaud's phenomenon, digital infarcts, episcleritis, peripheral neuropathy, palmar erythema, leg ulcers Note tendon sheath involvement, or tendon nodules, subluxation or rupture Check for anemia, splenomegaly, leukopenia, pleuritis or pericarditis, the sicca syndrome or renal involvement Articular: measures of inflammatory activity Check for tenderness, synovial effusion, grip strength Articular: measures of destruction and deformity Check for lax collaterals, subluxation, malalignment, metatarsal prolapse, hammer toes and bone-on-bone crepitus Examination

7. Articular manifestations Arthritis : Joint swelling, tenderness, warmth, limitation of motion, pain in range of motion, Morning stiffness Muscle atrophy Chronic deformities Ankylosis of the joint

11. Rheumatoid nodules 20% of RA patients with +tests for blood rheumatoid factors and rarely in RF – most commonly on pressure areas central fibrinoid necrosis with surrounding fibroblasts May occur in any organs as well May regress with treatment, but has been reported to increase with Methotrexate use believed to occur as a result of small vessel vasculitis with fibrinoid necrosis, which forms the center of the nodule, and surrounding fibroblastic proliferation

12. Histology of rheumatoid nodule Rheumatoid nodule with granulomatous transformation. There is prominent central fibrinoid necrosis, with surrounding palisading histiocytes and an outer layer of chronic fibrosing connective tissue with inflammatory cells including lymphocytes and fibroblasts.

13. Hematologic abnormalities AnemiaThrombocytosis Thrombocytopenia ( rare ) Eosinophilia(esp related to gold) Lymphadenopathy ( concomitant Sjogren’s syndrome may increase the risk of Lymphoma) Splenomegaly ( clinically in 5-10 % with active RA and upto 58% by radionuclide scanning)

14. Felty’s syndrome RA in combination with splenomegaly and leukopenia long-standing, seropositive, nodular, deforming RA 33% do not have active synovitis Lower extremity ulcers, hyperpigmentation, bacterial infections, ANAs, Also may have thrombocytopenia, hypocomplementemia, an increased risk for the development of lymphomas

15. NeutropeniaAnemiaThrombocytopeniaSplenomegaly large granular lymphocytes in these patients represent in vivo activated cytotoxic T cells and clonality is present. Large granular lymphocytes

16. Pulmonary manifestations Pulmonary nodules Pleural effusions (50%) Caplan’s syndrome Diffuse interstitial pulmonary fibrosis (28%) Bronchiolitis obliterans organizing pneumonia (BOOP) Obliterative bronchiolitis Drug induced Isolated pul. Arteritis (rare) Pulmonary hypertension (rare) Airway obstruction (38%)

17. Caplan’s syndrome

18. Cardiac disease in RA Pericarditis (50%) Premature cardiovascular disease ( TNF-α is produced by cardiac myocytes and resident macrophages during cardiac stress and may help trigger and perpetuate atherosclerosis) Myocardial and endocardial disease (clinically insignificant) Coronary arteritis Valvular abnormalities Rheumatoid nodule in the aortic valve cusp Rheumatoid nodule in the aortic valve cusp

19. Ocular Involvement Most common : Keratoconjuctivitis sicca (10-35%) Episcleritis : nodular or diffuse, appears acutely and causes eye redness and pain Scleritis is less common than episcleritis, but is more obviously correlated with vasculitis, long-standing arthritis and active joint inflammation. Untreated scleritis may progress to scleromalacia

20. Scleromalacia

21. Other uncommon manifestation of RA in the eye Uveitis Episcleral nodulosis Corneal filamentary keratitis Peripheral ulcerative keratitis Retinal detachments Macular edema Glucocorticoids, Gold and Chloroquine Brown's syndrome, which is defined as diplopia upon upward and inward gaze and is believed to be the result of inflammation and thickening of the superior tendons, and optic neuritis

22. Neurological manifestations Nerve compressions (Carpal tunnel, tarsal tunnel, atlantoaxial subluxation, subaxial c-spine involvement, extradural nodules) (Carpal tunnel, tarsal tunnel, atlantoaxial subluxation, subaxial c-spine involvement, extradural nodules) Stroke, seizure, hemorrhage, encephalopathy and meningitis as a result of cerebral vasculitis, amyloidosis or rheumatoid nodules, or both, in the dura and choroid plexus of the brain Most patients have long-standing RA with other extra- articular disease

23. Renal Involvement The kidneys are usually spared in RA, although a low-grade membranous nephropathy, glomerulitis, vasculitis and secondary reactive amyloidosis have all been described Renal abnormalities frequently result from the agents used in treating RA, notably gold, D-penicillamine, cyclosporin and NSAIDs, and usually manifest as membranous nephropathy and acute interstitial nephritis, often the result of a drug hypersensitivity reaction

24. Amyloidosis 0.7-5.8% of patients with RA Virtually every organ system may be involved in the secondary amyloidosis that complicates RA, including the heart, kidney, liver, spleen, intestines and skin. Renal manifestations of amyloidosis are the most common ones Poor prognosis : 4-year survival rates of about 58% are reported

25. Rheumatoid vasculitis Systemic vasculitis uncommon, usually with longstanding, poorly controlled disease pANCA More in patient’s with felty’s Skin: Nail fold infarcts. Leg ulcers, gangrene

26. Baker's popliteal cyst

31. Diagnosis CBCRF Anti ccp ESR X rays of affected joints Musculoskeletal ultrasound MRI

32. Additional testing PPD Chest X ray Hep B and C serologies ANA Joint aspiration Synovial biopsy Lyme serology

33. Treatment options NSAIDsHydroxychloroquine Steroids, systemic and intra articular MethotrexateSulfasalazineLeflunomide

34. More aggressive disease TNF inhibitors Abatacept (CTLA 4 IgG) Rituximab (Anti CD 20)