PHM142 Fall 2013 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson Rheumatoid Arthritis By: Angela Fok, Jinglin Tang, Christine Wong, Joanna Yee October 23rd, 2013
Overview • What is Rheumatoid Arthritis? • Mechanisms Behind Rheumatoid Arthritis • Symptoms • Complications • Diagnostic Tests • Risk Factors • Treatment • Summary • References
What is Rheumatoid Arthritis? • Autoimmune disease • Results in chronic inflammation in the joints and also other areas of the body • Characterized by joint inflammation, cartilage destruction, and bone erosion • Progressive illness • Flares and remission
MECHANISM BEHIND RHEUMATOID ARTHRITISHALLMARKS OF THE DISEASE Cartilage Destruction Joint Inflammation Bone Erosion
IMMUNESYSTEM ACTIVATION Normal RA
Causes unknown, but possible initiators are cigarette smoke, bacterial products, viral components, and other environmental stimuli • Activated macrophages, mast cells, NK cells in synovial membrane release pro-inflammatory cytokines • Most important pro-inflammatory cytokines are TNF-α, IL-6, IL-1 • These cytokines act to: 1. Recruit more immune cells (T-cells, B-cells, neutrophils) 2. Stimulate macrophages and synovial fibroblasts to secrete more cytokines to maintain the inflammatory response. 3. Stimulate proliferation of synoviocytes • Stimulate B-cells to produce autoantibodies: rheumatoid factor and anti-citrullinated protein antibody (ACPA)
Cartilage Destruction • Influx of activated cells and proliferation of synovioctyes results in a hyperplastic synovial lining with villi • Villi allows better access of secreted cytokines and enzymes to cartilage and bone
Cartilage Destruction • Activated synovial fibroblasts and macrophages in synovial lining release matrix metalloproteinases (MMPs), degrades the collagen type II network in cartilage matrix • TNF-α and IL-1 activate chondrocytes to secrete more cytokines and MMPs to enhance inflammatory response and aggravate cartilage destruction Articular Cartilage Hyperplastic synoviallining
Bone Erosion • Excessive TNF-α stimulates osteoclastogenesis, leads to greater bone resorption TNF-α Bone Osteoclast
Symptoms Early Symptoms • Fever and fatigue • Low-grade fever (under 100oF) • Extreme fatigue 4-6 hours after waking up • Symmetrical pattern of inflammation • Pain on one side of the body is usually replicated on the other side • Joint pain and swelling • Prolonged stiffness of the joints after waking up or after periods of inactivity • Malaise • General sense of not feeling well
Severe and Further Advanced Rheumatoid Arthritis • Rheumatoid nodules: hard, fleshed-colored lumps • Under the skin of the arms, hands, and elbows • Vary in size • Usually not painful
Dry mouth and eyes • Difficulty swallowing or talking • Pleurisy • Severe tightness or sharp pain in the chest when inhaling • Due to inflammation of membranes surroundings the lungs • Deformities • Wrists, elbows, ankles, and knees bent at unnatural angles • Impedes ability to move
Complications • Many complications are due to chronic inflammation • Osteoporosis • Higher risk of infections • Carpal tunnel syndrome (CTS) • Heart problems • Lung disease • Eg. Pulmonary hypertension Carpal Tunnel Syndrome (CTS)
Diagnostic Tests 1. Rheumatoid Factor • Measures the antibody, rheumatoid factor in blood that is present in joints
2. Erythrocyte Sedimentation Rate (SED rate) • Tests the rate at which red blood cells sediment in a period of one hour • A higher sedimentation rate indicates greater inflammation 3. C-Reactive Protein (CRP) • A protein found in blood • High levels of CRP indicate active inflammation
4. Tests for Anemia • Anemia is a common complication • Determines amount of RBC/hematocrit and iron
Risk Factors • Gender • 3X as prevalent in women • Age • Highest among those in their 60s • Genetics • HLA class II genotypes • Family History • Smoking • Alcohol • Oral Contraceptives
Treatment: Approach • No known cure • Treatment goals = decrease joint inflammation and pain, manage joint function, maintain joint structure • Combination of medications, rest, joint-strengthening exercises, protection of joints, and education • Customized for each patient
Treatment: Drugs 1. Relieve symptoms and reduce inflammation • NSAIDS (Aspirin, ibuprofen, etc...) • Corticosteroids (cortisone) 2. Promotes remission and prevent joint destruction • Disease-modifying antirheumatic drugs (DMARDS) • Methotrexate (Rheumatrex) • Hydroxychloroquine (Plaquenil)
Summary • Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation, cartilage destruction, and bone erosion • Joint inflammation is caused by the cytokines (TNF-α, IL-6, IL-1) secreted by overly active immune system cells • Activated chondrocytes, synovial fibroblasts, and macrophages secrete metalloproteinases (MMPs) that degrade the collagen type II network in cartilage matrix • Excessive TNF-α stimulates osteoclastogenesis which leads to greater bone resorption • Symptoms: fever, fatigue, symmetrical pattern of inflammation, rheumatoid nodules, and abnormal deformities • Complications: heart problems, lung disease, carpal tunnel syndrome, increased risk of osteoporosis, and infections • Diagnostic Tests: 1. Rheumatoid Factor (most common) 2. Erythrocyte Sedimentation Rate (SED rate) 3. C-Reactive Protein 4. Tests for Anemia • There is no known cure, but drugs (eg: NSAIDS and methotrexate) can be used to treat the symptoms and promote remission
References • Firestein GS, Budd RC, Harris ED, McInnes IB, Ruddy S, Sergent JS. Kelley’s Textbook of Rheumatology. 8th ed. Philadelphia, PA: Elsevier Saunders; 2009. p 1035-1086. • Harvey, S. (2013, March 13). Rheumatoid arthritis. Retrieved from http://umm.edu/health/medical/reports/articles/rheumatoid-arthritis • Health Life Editorial Team. (July 29, 2010). Rheumatoid Arthritis Symptoms. Retrieved from http://www.healthline.com/health/rheumatoid-arthritis-symptoms#1 • Mayo Clinic Staff. (July 27, 2013) . Rheumatoid Arthritis . Retrieved from http://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020/DSECTION=complications • McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011; 365:2205-2219. • Pfizer Inc. (2013). What is Rheumatoid Arthritis? Retrieved from http://www.arthritis.com/rheumatoid_arthritis_symptoms
