Rheumatoid Arthritis Year 4 Internal Medicine Notes

Rheumatoid Arthritis Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.3 / NGUGI -- Slide 1 Rheumatoid Arthritis John Kibanga\nLoise Njeri Slide 2 Introduction Rheumatoid arthritis (RA) is an idiopathic chronic inflammatory autoimmune disorder. It principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis. It is characterized by a clinical course of exacerbations and remissions It can also affect other body parts such as the eyes, lungs, blood vessels, heart and skin. Slide 3 Epidemiology The prevalence of rheumatoid arthritis is approximately: 0.24% worldwide \n0.8-1.0% in Europe and South Asia\n0.4% in South East Asia \n5% in Pima Indians (highest prevalence) The female to male ratio is 3:1 Peak incidence is 65 years Slide 4 Etiology It is an inflammatory autoimmune disorder of unknown etiology. Mostly it is triggered by an interaction between genetics factors and\nenvironmental factors The risk factors include:Genetic predisposition associated with HLA-DR4 and HLA-DR1 (Human Leukocyte Antigen class II histocompatibility D related beta chain- expressed on T cells) Environmental factors such as smoking, diet and infection.\nHormonal factors as premenopausal women are at the highest risk Obesity Family history of Rheumatoid Arthritis Slide 6 Pathogenesis The autoimmune response in RA is initiated by CD4+ helper T cells. Genetic predisposition and environmental factors contribute to the development, progression, and persistence of disease. Slide 7 Environmental factors cause modification of our own antigens e.g., type II collagen( major component of articular cartilage).\nThey are modified by a process called citrullination. A process in which arginine found in the type II collagen is converted into citrulline.\nDue to the susceptibility genes, HLA-DR1 and HLA DR4, immune cells are then unable to recognize these genes as self antigens.\nThese antigens are picked up by APCs and carried to the lymph nodes leading to activation of CD4+ T cells. Slide 8 1. CD4+ T HELPER CELLS These CD4+ T helper cells stimulate B cell proliferation and differentiation into plasma cells.\nThe plasma cells produce specific auto antibodies against the self antigens.\nThe T helper cells and autoantibodies enter the circulation and reach the joints. Slide 9 The activated CD4+ T cells cytokines.\nThe most important cytokine mediators include:IFN-γ from Th1 cells, which recruits macrophages and activates resident synovial cells.\nIL-17 from Th17 cells that recruits neutrophils and monocytes.\n TNF alpha and IL-1,IL-6 from macrophages stimulate resident synovial cells to proliferate. Slide 10 This results in formation of a pannus. Slide 11 A pannus is a thick swollen synovial membrane made up of granulation tissue fibroblasts, myofibroblasts and inflammatory cells. This pannus results in damage of cartilage and erosion of bone.\nThe activated synovial cells secrete proteases which break down the proteins in the articular cartilage, resulting in exposure of underlying bone, thus can rub against each other. Slide 12 TNF alpha and IL-1,IL-6 from macrophages also stimulate the production of enzymes like matrix metalloproteinases (MMPs) that break down cartilage and promote bone resorption. The cytokines produced also increase expression of RANKL on the surface of T cells. This allows T cells to bind RANK( a protein on the surface of osteoclasts). This further results in bone resorption. Slide 13 2. AUTO ANTIBODIES The autoantibodies, particularly rheumatoid factor (RF) (an IgM that targets Fc portion of altered IgG)and anti-citrullinated protein antibodies (ACPAs) enter the joint space where they bind to their targets resulting in formation of immune complexes.\nThe immune complexes lead to activation of the complement system. This results in secretion of complement proteins which result in synovial inflammation and thickening (hallmark of Rheumatoid arthritis). The chronic inflammation results in angiogenesis which allows for more inflammatory cells to reach the joint. Slide 14 As the disease progresses multiple joints get inflamed and destroyed.\nThe inflammatory cytokines also leave the tight joint space through the bloodstream and reach multiple organs to cause extraarticular manifestations. Slide 15 CLINICAL FEATURES Articular manifestations Polyarthralgia – symmetrical pain and swelling of affected joints (Also at rest). Joints that are frequently affected include:\nminor joints- metacarpophalangeal joints, proximal interphalangeal joints, wrist, and metatarsophalangeal joints major joints- shoulders, elbows, knees and ankles.\nRarely affected joints – distal interphalangeal, first carpometacarpal joint and axial skeleton (except the cervical spine) Morning stiffness that often lasts 30 minutes and improves with activity (immune system is more active at night and in the morning, resulting in secretion of more cytokines that settle within the joint space resulting in infl