Rheumatoid arthritis is an inflammatory disease mainly characterized by inflammation of the synovial membrane of the joints. The disease may begin with general symptoms of malaise, such as fatigue, low-grade fever, and anemia, before affecting the joints. Unlike osteoarthritis, rheumatoid arthritis usually affects the small joints first, such as those in the fingers, hands, and feet. In the first stage of the disease there is swelling of the synovial lining, causing pain, warmth, stiffness, redness, and swelling around the joint. This is followed by the rapid division and growth of cells, or pannus, which causes the synovium to thicken. In the next stage of the disease, the inflamed cells release enzymes that may digest bone and cartilage, often causing the involved joint to lose its shape and alignment and leading to more pain and loss of movement. This condition is known as fibrous ankylosis (from the Greek ankulos, meaning “bent”). In the final stage of the disease the fibrous tissue may become calcified and form a solid fusion of bone, making the joint completely nonfunctional (bony ankylosis).