Understanding Rheumatoid Arthritis

Rheumatoid arthritis (RA) strikes various tissues and organs, but it most frequently affects the joints of the wrists, fingers, hips, knees, feet and ankles. Unlike osteoarthritis, rheumatoid arthritis usually affects joints on both sides of the body equally, especially the smaller joints of the fingers or ankles. Rheumatoid arthritis is a progressive autoimmune disease. For reasons that remain unclear, the body’s immune system mistakenly attacks synovial cells, which line these types of joints. This triggers ongoing inflammation, which eventually damages joint tissue and nearby bone, causing swelling, stiffness, pain, fatigue, and even deformity. Pain and stiffness are typically worse in the morning. Surrounding tissues, or organs, may also be affected. Moving the slider from left to right, view the progression of RA from various small to larger joints throughout the body. Studies suggest that patients with more damage to hands and feet are more likely to develop damage in the large joints, such as the hips.    

Cartilage lined with synovial cells caps the ends of bones where bones meet to form joints, such as those in the fingers. After incorrectly targeting the body’s own synovial cells for attack, white blood cells called monocytes enter the joints and attack the cells. Proteins known as cytokines drive inflammation. One notable cytokine is tumor necrosis factor alpha. Eventually, the synovial lining thickens, and excess fluid is produced, causing joint swelling. Fibrous tissue, called pannus, forms between the joints. Inflammatory molecules called chemokines perpetuate the cycle of inflammation and tissue destruction. This ongoing cycle of white blood cell infiltration, remodeling of synovial tissue, and formation of autoantibodies, encourages the recruitment of yet another immune cell type, which specializes in the destruction of bone cells. Thus, a process that begins with damage to the joint lining often progresses to include the loss of adjacent bone.   

Here we clearly see the potential longterm damage caused by untreated RA in the hand. As inflammation progresses joints swell, the muscles of the hand atrophy, bone degenerates, and the bones of the fingers become misaligned. This kind of progressive damage yields the deformed, claw-like appearance of hands affected by severe RA. Patients with RA this severe may experience serious pain, stiffness and loss of function. RA may also affect organs such as the heart and lungs. For example, inflammation of the lining of the lungs (pleurisy) and accumulation of fluid around the lungs (pleural effusion) may cause painful breathing. Systemic inflammation caused by RA is believed to dramatically increase the chance that a patient will develop atherosclerosis, or hardening of the arteries. This significantly increases a patient’s risk of heart attack. 

Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, help relieve pain and inflammation by blocking a key enzyme involved in the inflammatory cascade. NSAIDs work by inhibiting an enzyme known as COX-2. Although COX-2 inhibition provides some symptomatic relief, and may slow the progression of RA inflammation, NSAIDs do not really address the underlying problem of an immune system in overdrive. Other drawbacks to longterm NSAID use include an increased risk of gastrointestinal side effects, such as stomach upset or gastric bleeding. 

Disease-modifying antirheumatic drugs (DMARDs) include powerful immune system suppressing agents, such as methotrexate and cyclosporin. These drugs can slow the progression of the disease by reducing the rate of damage to joint cartilage and bone. Older drugs, such as methotrexate and cyclosporin, are also used to treat cancer, or to prevent organ rejection after transplant. Newer “biologics” are DMARDs that have been created through genetic engineering. Many of these drugs specifically inhibit inflammatory cytokines, such as tumor necrosis factor alpha, which helps drive inflammation in RA. They are often used in combination with older medications, such as methotrexate. 

Patients disabled by rheumatoid arthritis may need surgery to remove damaged cartilage and repair or replace deformed joints. Surgical options include joint replacement, total hip replacement and synovectomy. Joint replacement involves the removal of damaged cartilage, followed by the attachment of prosthetic joint surfaces made of metal, ceramic or plastic. Artificial joints may last up to 20 years. Total hip replacement is an example of joint replacement surgery. An artificial ball and socket joint is implanted to replace damaged cartilage and bone. Doctors may recommend less invasive procedures before total joint replacement. These include minimally invasive arthroscopy to remove damaged bits of cartilage and bone, or synovectomy, to remove only damaged synovial tissue, or osteotomy, to remove damaged bone. Synovectomy involves the removal of the damaged synovial lining of an affected joint. The procedure may be performed by open incision (arthroplasty) or by minimally invasive techniques (arthroscopy). Synovectomy is often recommended for patients in the early stages of the disease, after more conservative therapies have failed.