As the disease becomes more chronic, fibroblasts infiltrate the inflamed joint capsule, which becomes thickened and boggy. The pannus progresses, causing more destruction and joint deformity. The progressive inflammation causes irreversible destructive changes in cartilage and bone. After months or years of periods of active disease and partial remissions, even if the inflammation subsides, fibrous tissue has often increased and further restricts motion, leading to fibrous ankylosis. The stiffened, deformed joint may become solidly fused by bony bridges across the joint space; this final stage is thus called bony ankylosis, clinically manifested as advanced secondary osteoarthritic change. Pain lessens as the inflammation subsides, but the joint damage persists, accounting for the stiffened and deformed joints, disability, and incapacitation.

The synovial proliferation along with the microvascular process called angiogenesis may behave like a benign tumor, which is partly caused by defects of some apoptotic genes and their molecules. Based on these molecules, researchers have studied intra-articular gene delivery of vectors carrying such apoptotic molecules as P53, FasL, and TRAIL to mimic surgical synovial ablation, termed molecular synovectomy.

CLINICAL MANIFESTATIONS

Early in the course of the illness, joint involvement is characterized by signs and symptoms of polyarthritis in the limbs, usually in a symmetric distribution. In pauciarticular (oligoarticular)-onset rheumatoid arthritis, only one or a few joints are involved. The affected joints become diffusely swollen, warm, and tender. Joint movement is painful, and the swelling of the joint capsules creates a feeling of stiffness. Generalized stiffness is also noted after long periods of inactivity, especially on arising in the morning. Depending on the severity of the illness, morning stiffness may last 1 to 2 or even longer hours, making routine daily activities difficult. Even early in the illness, the patient may be partially incapacitated.