Pathophysiology of Rheumatoid Arthritis
Despite intensive research, the cause of rheumatoid arthritis (RA) remains unknown. The pathogenesis of this disease is likely multifactorial, involving Autoimmunity and Genetic Factors in Rheumatoid Arthritis Etiology, which also are suspected of having a role. The clinical course of RA can vary considerably. While some patients experience only mild illness of short duration with minimal joint involvement, others experience relentless polyarthritis accompanied by marked joint deformities. The majority of patients follow an intermediate course. The main presenting symptoms of RA are pain, prolonged morning stiffness, swelling, Soft Tissue Swelling and Juxta-Articular Osteoporosis and tenderness of the joints (this is typically symmetrical), and impaired indices of physical function. Constitutional symptoms of RA include fever, weight loss, and fatigue and/or malaise. Manifestations or complications of RA include the following: joint deformities resulting from cartilage destruction and bone erosion, rheumatoid nodules, rheumatoid vasculitis, pleuropulmonary manifestations including pulmonary fibrosis, serositis, ocular inflammation, osteoporosis (possibly secondary to corticosteroid use), and the requirement for surgery to normalize functional capacity and/or range of motion.
Genetic Factors in Pathophysiology
Genetic Factors: Genetic factors appear to affect the pathophysiology of rheumatoid arthritis (RA), as they do the etiology of RA. Genetic Factors in Rheumatoid Arthritis Etiology Family studies reveal that RA has a genetic component. Siblings of patients with severe RA are at greater risk for developing RA than those of patients with mild disease. Certain human leukocyte antigen (HLA) serotypes confer an increased risk of developing RA. Multiple genetic factors have been identified that predispose an individual to develop RA, or increase the severity of RA. Deighton, et al., utilizing data from hospital- and population-based studies of monozygotic twin concordance rates and sibling recurrence risks of RA, estimated that the genetic component in RA is 37%. This same author published data 3 years later comparing affected individuals to their unaffected siblings among 231 siblings of the same gender (186 female, 45 male), and found that gender and HLA haplotype together accounted for about two-thirds of the inherited risk of RA.10848
Autoimmunity
Autoimmunity: Macrophage-derived cytokines appear to be involved in the induction and perpetuation of the chronic inflammatory processes of the joints seen in rheumatoid arthritis. High titers of serum rheumatoid factors, or autoantibodies to the Fc portion of the immunoglobulin G molecules, are associated with more severe joint disease and with extra-articular manifestations.10425
Cytokine Dysregulation
Cytokine Dysregulation: Although
the precise mechanism of bone and cartilage destruction in rheumatoid
arthritis (RA) is not completely understood, the cytokines interleukin
1 (IL-1), IL-6, and
Content on this page was last reviewed on March 31, 2008.
Content on this page was last changed on March 25, 2009.
References:| 10425. | Lundberg K, Nijenhuis S, Vossenaar ER, et al. Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res Ther. 2005;7(3):R458-R467. |
| 10848. | Deighton CM, Wentzel J, Cavanagh G, Roberts DF, Walker DJ. Contribution of inherited factors to rheumatoid arthritis. Ann Rheum Dis. 1992;51(2):182-185. |
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