Rheumatoid arthritis (ra) is defined as an autoimmune disease in which the synovial joint lining and, occasionally, other organ systems become inflamed as a result of an overactive immune system; the disorder affects diarthrodial joints. It is a chronic, systemic, and inflammatory disease process that leads to progressive articular joint destruction, most commonly in the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands. The exact etiology is unknown with multiple influences playing a role (see Table 80–1):
Table 80–1Possible Etiologies in Rheumatoid Arthritis |Favorite Table|Download (.pdf) Table 80–1 Possible Etiologies in Rheumatoid Arthritis
|Genetic ||Twin concordance studies show 15% of identical twins will both develop RA. There is also two fold higher incidence for people with the HLA-DR4 gene |
|Environmental ||Smoking is linked to an increased lifetime risk of developing RA |
Initially in RA, the synovium becomes hyperplastic and edematous. This further leads to new blood vessel proliferation and activation of synovial T cells. The activated T cells in turn initiate an inflammatory cascade (activation of B cells, autoantibody producing plasma cells, stimulation of macrophages and fibroblasts, and eventual secretion of proinflammatory mediators including interleukin 1 [IL-1], IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], and TNF-α). This cascade eventually leads to pannus formation, bony erosions, and localized osteoporosis. The formation of the rheumatoid pannus is capable of destroying cartilage, tendons, and bone (Fig. 80–1).
Pathophysiologic mechanisms of inflammation and joint destruction in Rheumatoid Arthritis (FGF, fibroblast growth factor; IFN, interferon; TGF, transforming growth factor).
Genetic predisposition along with environmental factors may trigger the development of rheumatoid arthritis (RA), with subsequent synovial T cell activation. CD4+ T cells become activated by antigen-presenting cells (APCs) through interactions between the T cell receptor and class II major histocompatibility complex (MHC)-peptide antigen (signal 1) with co-stimulation through the CD28-CD80/86 pathway, as well as other pathways (signal 2). In theory, ligands binding toll-like receptors (TLRs) may further stimulate activation of APCs inside the joint. Synovial CD4+ T cells differentiate into TH1 and TH17 cells, each with their distinctive cytokine profile. CD4+ TH cells in turn activate B cells, some of which are destined to differentiate into autoantibody-producing plasma cells. Immune complexes, possibly comprised of rheumatoid factors (RFs) and anti-cyclic citrullinated peptides (CCP) antibodies, may form inside the joint, activating the complement pathway and amplifying inflammation. T effector cells stimulate synovial macrophages (M) and fibroblasts (SF) to secrete proinflammatory mediators, among which is tumor necrosis factor α (TNF-α). TNF-α upregulates adhesion molecules on endothelial cells, promoting leukocyte influx into the joint. It also stimulates the production of other inflammatory mediators, such as interleukin 1 (IL-1), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). TNF-α has a critically important ...