The onset of the disease is most frequent in fourth and fifth decades of life (Luqmani et al., 2006).
The aetiology of the disease is not specifically known and has been suggested to be multifactorial. The class II major histocompatibility complex allele HLA-DR4 and related alleles are known to be major genetic risk factors for RA. It has been suggested that RA might be a manifestation of the response to an infectious agent in a genetically susceptible host. Activation of autoimmune mechanisms is the key aetiologic event in sustaining the chronic inflammatory process so characteristic of RA (Scott et al., 2000).
The main event in pathophysiology is inflammatory synovitis. Subsequently through a cascade of multiple immune events through mediation of a host of immune cells, the synovial fibroblasts are activated. Added to cartilage degradation, osteoclasts are activated that leads to erosion of bone. The chemokines and cytokines lead to synovitis, cartilage and bone damage, and systemic manifestations of RA (Luqmani et al., 2009). Altman (2008) notes that these immunologic abnormalities arise from various immune complexes, which originate from the inflamed synovial cells that serve as a target for such immune injuries. The plasma cells that are recruited produce antibodies known as rheumatoid factors. These actively contribute to these complexes which ultimately lead to joint destruction. With further inflammation chemotaxis ensues leading to recruitment of macrophage cells with associate vasculitis. Primarily CD4+ lymphocytes infiltrate the synovial cells. These together produce inflammatory cytokines and chemokines, namely tumor necrosis factors, granulocyte-macrophage colony stimulating factors, interleukins, and gamma-interferon. These are known inflammatory mediators leading to further joint inflammation and systemic manifestations of the disease. When the disease is chronic, the synovial membrane is very much thickened and is projected into the joint cavity. The synovium is the seat of inflammation, which produce collagenase and stromelysin leading to further degeneration of joint cartilage. Interluekin-1 and tumor necrosis factor-alpha contribute to this process and stimulate osteoclasts, thus leading to bone erosion. Prostaglandins are released. With the maintenance of inflammation, fibrous tissue is deposited within the joint. The synovial tissue appears very much proliferates and highly vascular, leading to pannus which further potentiates release of inflammatory chemokines leading to all round erosion of the joint structures such as cartilage, bone, articular capsule, and the periarticular ligaments. Most of the inflammatory cells are neutrophils. In some patients rheumatoid nodules develop (Altman 2008).
Clinically RA presents as chronic polyarthritis of symmetrical synovial joints of hands, wrists, knees, and feet with an insidious onset of fatigue, generalised weakness, and vague musculoskeletal symptoms for weeks or months. Pain, tenderness, and swelling in the affected joints get aggravated with movement. Generalised stiffness of joints noted in the mornings for about duration of greater than 1 hour is invariable. Swelling and tenderness in the joints lead to motion limitation and hence impairment of physical function. These lead to fibrous or bony ankylosis of the joint leading to fixed deformities (Scott et al., 2000).