Rheumatoid arthritis: Clinical

Rheumatoid arthritis is a chronic inflammatory disorder that gradually affects synovial joints, but can also cause extra-articular disease as well. Rheumatoid arthritis has been linked to HLA-DR1 and HLA-DR4. Each time there’s a flare, there’s an increase in synovial and immune cells, and over time, that results in a thick, swollen synovial membrane with granulation tissue - called a pannus. The pannus can damage cartilage and other soft tissues and also erode bone. Typically, rheumatoid arthritis affects at least three joints, generally ones in the hands and feet. The disease tends to be symmetric, progressive, and over time it causes joint deformities like crooked fingers.

So the typical articular manifestations in rheumatoid arthritis are pain, swelling, and loss of mobility in the affected joints, but doesn’t usually cause redness or warmth because the inflammatory process is so gradual. Usually, there’s morning stiffness that improves after 30 minutes of movement. The most frequent sites of involvement are the proximal interphalangeal joints and metacarpo-phalangeal joints of the hand, whereas the distal interphalangeal joints is rarely involved because there’s very little synovium in that joint. When these joints are affected, it typically causes reduced grip strength.

In the feet, usually the metatarsophalangeal joints are affected, and it causes a person to bear more weight on the heels and hyperextend the toes. Other joints that can be involved are the wrists, elbows, shoulders, knees, and ankles. Hip involvement usually only happens later in the disease, and that can cause pain in the groin, thigh, or low back. One very dangerous spot is the C1-C2 joint, which is only synovial joint in the spine. When it’s affected it can cause neck pain, and if it’s not managed properly it can lead to spinal cord compression and tetraplegia.

The system inflammation in rheumatoid arthritis results in cytokines that can cause extra-articular symptoms. For example, cytokines can trigger fever, fatigue, and a loss of appetite that can eventually lead to weight loss. Rheumatoid arthritis can lead to vasculitis and specifically the formation of atheromatous plaques, which can lead to myocardial infarction and stroke. In fact, cardiovascular disease is the primary cause of mortality associated with rheumatoid arthritis. In skeletal muscle, cytokines cause muscle breakdown, and in the skin they lead to the formation of rheumatoid nodules over bony prominences. Rheumatoid nodules are round collections of macrophages and lymphocytes that have a central area of necrosis. In the liver, lots of hepcidin is made and that causes decreased iron absorption in the intestines, and allows iron to get trapped in the macrophages - leading to lower serum iron levels. In the lung, fibroblasts get activated, causing pulmonary fibrosis, and the pleural lining gets inflamed, leading to pleural effusions.