Patient #1 Rheumatoid Arthritis Essentials For The Family Medicine Physician 45 y/o female Morning stiffness in her joints >1 hour Hands, Wrists, Knees, Ankles, Feet Polyarticular, symmetrical swelling of small joints of her hands (MCP, PIP) Hope Argenziano MD Autoimmune disease that causes progressive joint damage due to inflammation Unknown etiology Most common inflammatory arthritis Multisystem extra-articular manifestations Symmetrical arthritis that targets hands, wrists, feet, ankles MCPs, PIPs, spares the DIPs Chronic erosive arthritis that requires early aggressive treatment Joint swelling is hallmark and morning stiffness is usually greater than 1 hour 1
Pathogenesis Massive hyperplasia (type A synovial cells) Subintimal mononuclear cell infiltration Extensive infiltration by plasma cells, macrophages and lymphocytes Pannus formation Feldmann M, et al. Annu Rev of Immuno. 1996; 14:397-440. : Synovitis RA: Synovitis Normal Synovium Epidemiology 1% of world s population Females > males 2:1 Peak age 35-45 years, 1/3 after age of 60 years Gradual onset in 70%, Subacute 20%, Acute onset in 10% Without treatment, permanent joint damage occurs within 2 years after symptoms begin Diagnosis Classical Exam Findings Synovial joint swelling (synovitis) Chronic, Polyarticular, Symmetric Swann Neck deformity Boutonniere deformity Ulnar Deviation Nodules Tendon Rupture Most Common Joints Involved During the Course of RA MCP 90-95% PIP 80-90% Wrist 65-90% Knee 60-80% MTP 50-90% Shoulder 50-60% Ankle/subtalar 50-80% Cervical Spine (C1-2) 40-50% Hip 40-50% Elbow 40-50% Temporomandibular 20-30% 2
Ulnar Deviation and Nodules Boutonniere Deformity Swann Neck Deformity Tendon Rupture RA: Systemic Symptoms Fatigue Malaise Morning stiffness Diffuse musculoskeletal pain Low-grade fever Weight loss Anorexia Diagnosis Serologies Rheumatoid Factor Anti-CCP antibodies Elevated Acute Phase Reactants ESR (SED Rate) CRP Thrombocytosis Normochromic, normocytic anemia 25% have +ANA 3
Rheumatoid Factors B-cells - plasma cells- produce RF Antiglobulin antibodies that bind to the Fc portions of IgG 75-80% of RA patients Locally produced in synovial tissue Found in SLE and bacterial endocarditis Rheumatoid nodules Extraarticular manifestations Rheumatoid Factor in Rheumatic Diseases DISEASE INCIDENCE 80-90% Juvenile Chronic Arthritis 20% Ankylosing Spondylitis Reiter s Syndrome Psoriatic Arthritis Negative Negative Negative Systemic Lupus Erythematosus 40% Sjögren s Syndrome 90% Cryoglobulinemia >90% ACR Anti-Cyclic Citrullinated Peptide Antibodies Antibodies reactive with synthetic peptides containing the amino acid citrulline The post-translationally modified arginine residue are found in approximately 75% of RA sera with a high specificity IgG antibodies Radiographic Features of RA Abnormal alignment Periarticular osteoporosis Symmetric (uniform) joint space narrowing Deformities Marginal erosions Soft tissue swelling : Radiographic Changes 4
Compare the Radiographic Features of RA with those of OA RA OA Sclerosis ± + + + + Osteophytes ± + + + + Osteopenia + + + 0 Symmetry + + + + Erosions + + + 0 Cysts + + + + Narrowing + + + + + + Synovial Fluid 5,000 to 25,000 WBC s per cubic mm 85% are PMN Low glucose High protein PLEURAL DISEASE Pulmonary Manifestations 20% of patients First manifestation (occasionally) Pleural Effusions (Exudative) Low glucose (10-50 ml/dl) Protein > 4 gm/dl Low Ph Low CH50 Mononuclear cells 100-3,500/mm Thoracentesis Prednisone 40-60 g/day, 2-4 weeks NODULES Pulmonary Manifestations Solitary or multiple Cavitate and create fistula Caplan s Syndrome Coexistent Bronchogenic carcinoma 5
Interstitial Fibrosis Fibrosing alveolitis Smoker s are at high risk DLCO Fine diffuse dry rales BAL ( lymphocytes) ACR 2014 Classification Criteria for Patients must have four of seven criteria: - Morning stiffness lasting at least one hour* - Swelling in 3 or more joints* - Swelling in hand joints* - Symmetric joint swelling* - Erosions or decalcification on x-ray of hand - Rheumatoid Nodules - Abnormal Serum Rheumatoid Factor NSAID RA: Medical Treatment Corticosteroids Disease Modifying Anti-Rheumatic Drugs (DMARDS) Biologic agents ACR * Must be present at least 6 weeks. RA: Corticosteroids Usually prednisone Rapid onset of action Very effective anti-inflammatory activity Short term - high dose for acute flare Long term - low dose for maintenance Bridge therapy Intra-articular injection Disease-Modifying Antirheumatic Drugs Commonly Used in the United States DRUG DOSE EFFICACY TOXICITY- TREATMENT LIMITING Methotrexate 7.5-25 mg PO, SC, or IM + + + + + once weekly Sulfasalazine 500-3000 mg/d PO + + + + + + Gold sodium thiomalate Start with 10, 25, and then 50 + + + + + + + + mg/wk IM Hydroxychloroquine sulfate 400 mg/d PO + + + Azathioprine 100-150 mg/d, PO + + + + + Cyclosporine 2-5 mg/kg/d PO + + + + Leflunomide (Arava) Loading dose: 100 mg/d x 3 + + + + + d; Maintenance: 20 mg/d Etanercept (Enbrel) 25 mg SC twice a wk + + + + + Infliximab (Remicade) 3 mg/kg IV at wks 0, 2, 6 and + + + + + then q 8 wks Adalimumab (Humira) 40 mg SC q 2 wks +++ + Anakinra (Kineret) 100 mg SC d +++ + 6