Pathophysiology, symptoms, causes, risk factors, genetics, diagnosis and treatment.
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While the term “rheumatoid arthritis” means “inflammatory disease of the joints”, the condition of rheumatoid arthritis is in fact a systemic autoimmune disorder where the immune system mistakenly attacks the body's own tissues in various organs. In addition to synovial joints, the disease may affect the eyes, skin, mouth, lungs, heart and blood vessels.
Rheumatoid arthritis typically starts in small peripheral joints of the hands or feet. Usually, the same joints on both sides are affected. The disease then progresses to involve more proximal joints in the wrists, ankles, elbows, knees, shoulders and hips. In the affected joint, synovial tissue and cavity are infiltrated with immune cells and inflammatory factors that are destructive to joint structures. Left untreated, chronic joint inflammation will eventually lead to loss of cartilage and bone erosion, causing deformities and disability.
Symptoms usually appear gradually over weeks or months, although some people may develop them more rapidly. Patients typically experience joint pain and stiffness in the morning, or after a period of inactivity. The joints can be swollen. Other signs may include fatigue, weakness, and fever. For a small number of patients, symptoms may come and go, complicating the diagnosis.
Rheumatoid arthritis has a significant genetic factor. The susceptibility to the disease has been associated with a number of genes, in particular, those that encode class II major histocompatibility complex, MHC. MHC class II molecules play an important role in antigen recognition. They display pieces of pathogens and present them as antigens to T-helper cells - a crucial step in activation of T-cells. Several variations of MHC-II have been linked to increased risk for rheumatoid arthritis. These variations share a common sequence of 5 amino acids called the "shared epitope", which is thought to bind tightly to some self-antigens, causing erroneous activation of T-cells.
The most likely candidates for these self-antigens are citrullinated peptides. Citrullination is a post-translational modification that occurs on the amino acid arginine within a peptide. Citrullination is a normal process, required for normal function of several proteins, and is typically ignored by healthy immune systems. In rheumatoid arthritis, however, an autoimmune response is developed against citrullinated peptides. In fact, anti-citrullinated peptide antibodies can be detected in up to 80% of patients.
Other genetic susceptibilities include mutations in peptidyl arginine deiminase, PAD, the enzyme that catalyzes citrullination; and several other genes involved in T cell activation.
Notable environmental factors include smoking, which induces PAD expression in the airway; and some bacteria that produce a PAD-like enzyme, causing increased citrullination. Other risk factors include high-calorie low-fiber diets, and obesity.
Rheumatoid arthritis can occur at any age, but it most commonly starts in middle age. Women are somewhat more susceptible than men.
Diagnosis is based on physical exam and blood tests for autoantibodies and markers associated with inflammation. Signs of joint damage and deformities can be detected with imaging tests such as X-ray or MRI.
Early treatment with disease-modifying anti-rheumatic drugs can help prevent irreversible damage to the joints. There are 3 drug classes: conventional, biologic and targeted synthetic, each have their pluses and minuses. Different drugs have different mechanisms of action - they interfere with different steps in the complex inflammatory pathways.
Nonsteroidal anti-inflammatory drugs and corticosteroids are often prescribed to reduce pain and inflammation.
Physical therapy can help restore joint functions. Severely damaged joints may require surgeries to correct deformity or replace with an artificial joint.
24 авг 2024