Rheumatoid Arthritis

What is rheumatoid arthritis?

Arthritis of the metacarpophalangeal joints (1st, 2nd, and 3rd of the right hand) and deformity of the 5th finger of the right hand (so called “swan neck”) in patient affected by rheumatoid arthritisRheumatoid arthritis is a chronic disease that causes painful swelling and joint stiffness, limiting range of movement and function of the involved joints. Although joints are the most involved, inflammation can also develop in internal organs, like lungs, kidneys, heart, nervous system, blood vessels, eyes. When the disease is in the active phase stiffness is more intense at wake up and can last from one to more hours or, in severe cases even throughout the day. The length of time stiffness persists is very important because it differentiates rheumatoid arthritis from other arthropathies, like osteoarthrosis, where morning stiffness lasts about 10-20 minutes.

Smaller joints of the fingers, wrists, feet, knees and ankles are most commonly involved; more rarely it is seen in the hips, shoulders, elbows and spine. It is usually symmetric involving both sides: if the right wrist is involved often the left wrist will also be involved. Patients may complain of “extra-articular” symptoms which may indicate systemic involvement; amongst these: fatigue, weakness, weight loss, muscle pain (myalgies), fever, dryness of eyes  and mouth (known as “secondary Sjogren’s syndrome”), anemia, tendon inflammation, small painful nodules known as “rheumatoid nodules” commonly appear on the elbows and forearms.

Are the causes known?

Rheumatoid arthritis is an autoimmune disease caused by an alteration of the immune system cells that attack the joints in healthy people. The immune system, in healthy people protects the body against infective agents (virus, bacteria, etc.) by the action of specialized cells and molecules. In autoimmune diseases, these mechanisms are directed against tissues of the body itself.

Although what causes the disease is still unknown, recent research data have brought to light some important factors in the activation and upkeeping of inflammation. The principal target organ to be inflamed is the synovial membrane, made of cells that cover the joint: this membrane produces synovial liquid which lubricates and nourishes the joint cartilage. The pro-inflammatory substances released by immune cells determine swelling and damage the joint cartilage and bone.

When and how does it present?

Rheumatoid arthritis is the most common type of inflammatory arthritis and affects about 0.5 percent of the adult population. It is more often seen in females between the fourth and sixth decades of life, but onset can occur at any age.
Symptoms are often gradual, and can take weeks or months; morning stiffness occurs in hand movements, or in movements of the involved joints, that usually disappear during the day. They can occur periodically, and become persistent with painful tenderness of the joints. Most patients with rheumatoid arthritis present flares of disease activity alternated to periods of remission; disability is caused by joint damage that develops with time and is secondary to inflammation.

How is it diagnosed?

Rheumatoid arthritis may be difficult to diagnose seen that its onset may be gradual with slight symptoms and that various other diseases have a similar behaviour. For these reasons patients with a suspicion of rheumatoid arthritis should be referred to a rheumatologist for diagnosis and for correct therapy. Diagnosis is made by listening to the symptoms referred by patients and the signs observed during physical examination, for example, heat, joint pain and tenderness. Laboratory tests may be useful in confirming diagnosis (anemia, rheumatoid factor – an antibody found in 80% of patients with rheumatoid arthritis, or anti-citrulline – anti-CCP antibodies that have a specificity of 98% for this disease; increased erythrocyte sedimentation rate  - ESR, and/or elevated C-reactive protein). Radiographs may be valuable in diagnosis but show no anomalies in the initial phases of the disease (3-6 months). Joint ultrasound has gained a wider use as it is more sensitive in detecting hypertrophy of the synovial membrane and the intensity of joint and peri-articular inflammation than traditional radiographs (especially in the initial phase) and much less expensive than MRI. It is important to keep mind that for the majority of patients (usually those with symptoms from less than 6 months) there is no specific test to confirm diagnosis of rheumatoid arthritis, and diagnosis is made by an expert evaluation of symptoms and clinical signs.

What are the available treatment options?

Treatment of rheumatoid arthritis has greatly improved in the past 25 years offering patients a satisfactory control of symptoms and the possibility of maintaining their life-style.

Since no definitive cure is available, the aim of treatment is to reduce symptoms and improve disability with tailored medical treatment started as early as possible, to prevent permanent joint damage from inflammation. There is no single medication for all patients and often treatment is modified in the course of the disease.

Arthrocentesis of the knee with synovial aspiration of inflammatory fluid in patient affected by rheumatoid arthritisIdeal treatment is based on an early diagnosis, when the disease is still in the initial phase (< 6 weeks or 6 months), and on an aggressive medication. To quickly reduce joint inflammation and intensity of symptoms, first line therapy must include non-steroidal anti-inflammatory drugs (NSAID), like ibuprofen, naproxen, diclofenac, ketoprofen and the more recent COX2-inhibitors. Corticosteroids like prednisone can be given by mouth or intra-articular. However patients with severe joint swelling do not respond to therapy with NSAID and corticosteroids alone, thus they usually treated with disease modifying antirheumatic drugs (DMARDs). For the majority of patients with rheumatoid arthritis these medications greatly improve symptoms, joint function and quality of life. DMARDs used are: methotrexate, leflunomide, antimalarial drugs, ciclosporin, sulfasalazine, and gold salts.

In the last years treatment of inflammatory arthropathies has started to use biologic response modifier drugs or “biologic agents”, that act on specific molecules produced by cells of the immune system which cause inflammation and damage to joints and other organs that might be involved. These drugs also act as DMARDs because they slow down disease progression and are given when traditional therapies are ineffective. Treatments approved by the principal Drug Agencies are: adalimumab, anakinra, etanercept, infliximab, abatacept, rituximab. In some cases these drugs are given on their own, that is not combined to other immunesuppressive drugs, but in the majority of cases, for a better efficacy, they are given combined with methotrexate.

Ideal treatment however requires a multidisciplinary approach with the collaboration of rheumatologists, general practitioners, orthopaedic surgeons, physiatrists (for both physical and occupational therapy), psychologists.

Edited by: Riccardo Meliconi, MD and Luana Bancarella, MD
Rheumatology Unit - Istituto Ortopedico Rizzoli, Bologna

Content updated 22/11/2010 - 15:21
Content edited by: Prof. Riccardo Meliconi, MD; Luana Mancarella, MD (luana.mancarella@ior.it)
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