Rheumatoid Arthritis (RA) is a type of inflammatory arthritis and an autoimmune disorder, caused when the body turns on itself for some reason.
An overactive immune system can be just as harmful as a weak one and happens when the body’s immune system defense improperly identifies the synovial membrane as “foreign” and begins attacking it. This antigen response results in inflammation and damaged cartilage and tissues in and around the joints.
Candidates for a precipitating antigen include three groups of infectious micro-organisms: bacteria, mycoplasmas, and viruses, especially the Epstein-Barr virus. With long-term or intensive exposure to the antigen, normal antibodies (Ig – immunoglobulins) become auto-antibodies, that is, antibodies that attack the host tissues. Because they are usually present in those with RA, these transformed antibodies are called rheumatoid factors (RFs), which aggregate, or group, into complexes and generate inflammation.
Causes of RA point to infections, genetic predispositions, and endocrine factors. It is believed that genetic susceptibility develops when an abnormal or altered IgG antibodies are exposed to an antigen and then passed on. Whichever offending organism is at fault, those who are genetically susceptible end up with the joint lining becoming inflamed, especially the part that meets the cartilage.
Over time, chronic inflammation makes the joint lining thick and overgrown, which then begins to invade the cartilage, other joint-supporting tissues, and even the bone, weakening the entire structure. Eventually, the weakened joint becomes more painful and less able to perform. Under pressure, it may even become dislocated and deformed.
RA is a particularly frustrating disease because of spontaneous remissions and unpredictable exacerbations. It hits suddenly, usually appearing in the same joint on both sides of the body.
In its mildest form, RA is characterized by joint discomfort, but in the more severe cases, it causes painfully deformed joints and harms body organ systems. It occurs worldwide, striking females three times more often than males with peak periods for women being between the ages of 30 and 60.
However, it can strike at any age, including older persons and children. About 10% will have a single episode followed by a spontaneous long-term remission. The other 90% will suffer from chronic joint inflammation with occasional flare-ups, but the disease becomes progressively worse over time.
Since RA is a chronic systemic disease affecting the body’s connective tissues, it is also classified as a collagen disease. The first joint tissue to be affected is the synovial membrane. This soon spreads to the articular cartilage, joint capsule, and surrounding ligaments and tendons, causing pain, deformity, and loss of function.
The joints most commonly affected are in the fingers, feet, wrists, elbows, ankles, and knees; but the shoulders, hips, and cervical spine may also become involved. Affected joints stiffen after an activity or rest, especially first thing in the morning.
Deformities are common if the disease actively progresses. The fingers may become fixed in a characteristic “swan’s neck” appearance or “boutonniere” deformity from marked edema and congestion in the joints. The hands appear foreshortened, the wrists boggy. Carpal tunnel syndrome may develop from synovial pressure on the median nerve, causing tingling in the fingers.
The most common finding, outside the joints, is the gradual appearance of rheumatoid nodules (subcutaneous, round or oval, nontender masses), usually on such pressure areas as the elbows.
Besides joint inflammation, RA can cause fever, malaise, rash, lymph node or spleen enlargement, and Reynaud phenomenon, which is a lack of circulation to the fingers and toes. Along with the swollen, tender, and inflamed joints, there may also be weight loss and a general feeling of sickness, soreness, stiffness, and aching. The eyes and mouth dry out if the tear and salivary glands become involved. Patients often appear undernourished and chronically ill. Most are anemic because of the effect of the disease on blood-forming organs.
Stages of RA
Joint change generally occurs in four general stages, but along with these is the atrophy of muscles, bones, and skin adjacent to the affected joint.
- Stage One: Synovitis develops from congestion and edema of the synovial membrane and joint capsule.
- Stage Two: Formation of pannus occurs, covering the cartilage and eventually destroying the joint capsule and bone.
- Stage Three: Fibrous ankylosis, which is a fibrous invasion of pannus and scar tissue that fills the joint space, occurs. Bone atrophy and mal-alignment cause visible deformities and disrupt the articulation of opposing bones. This, in turn, causes muscle atrophy and imbalance that may also include partial dislocations (subluxations).
- Stage Four: Fibrous tissue begins to calcify, resulting in bony ankylosis (total immobility).
Pathophysiology of RA
Rheumatoid factors (RFs) usually consist of two classes of immunoglobulin antibodies – antibodies for IgM and IgG (occasionally IgA). Their main targets are portions of the immunoglobulin molecule.
RFs bind with their target self-antigens in the blood and synovial membrane, forming immune complexes (antigen-antibody). Synovial inflammation (synovitis) occurs when the immune complexes in blood and synovial tissue trigger the inflammatory response by activating the plasma protein complement. This stimulation activates kinin and prostaglandin release that increases the permeability of blood vessels in the synovial membranes. This attracts several types of leukocytes and lymphocytes to the synovial membrane out of the circulation.
The phagocytes of inflammation (neutrophils and macrophages) ingest the immune complexes which releases powerful enzymes that degrade synovial tissue and articular cartilage. The immune system’s B and T lymphocytes are also activated. The B lymphocytes are stimulated into producing more RFs, and the T lymphocytes produce enzymes that increase the inflammatory response.
A microorganism, which may originally be responsible, can be killed off and removed from the body. However, in an autoimmune response, the newly targeted self-antigens (immunoglobulins) are in constant supply and unable to stop. They keep on perpetuating the formation of immune complexes indefinitely.
Inflammatory and immune processes have several damaging effects on the synovial membrane. Inflammation causes hemorrhage, coagulation, and fibrin deposits on the synovial membrane, in the intracellular matrix, and in the synovial fluid. Over denuded areas of the synovial membrane, fibrin develops into granualtion tissue called pannus, which is the earliest tissue produced in the healing process.
Researchers disagree about whether pannus is a cause or an effect of articular cartilage involvement in RA. Some believe that, as the disease progresses, pannus extends from the synovial membrane into adjacent articular cartilage and destroys the cartilage. Others think that pannus forms on articular cartilage after the cartilage has been destroyed by inflammation. In any case, pannus formation does not lead to synovial or articular regeneration, but rather to formation of scar tissue that immobilizes the joint.
Along with the swelling caused by leukocyte infiltration, the synovial membrane undergoes hyperplastic thickening as its cells abnormally proliferate and enlarge. As synovial inflammation progresses to involve its blood vessels, small venules (a tiny vessel that collects blood from the capillaries and joins to form veins) become occluded by hypertrophied endothelial cells, fibrin, platelets, and inflammatory cells.
These vascular derangements decrease blood flow to the synovial tissue and compromised circulation. This, coupled with increased metabolic needs due to hypertrophy and hyperplasia, causes hypoxia (oxygen depletion) and metabolic acidosis. Acidosis stimulates the release of hydrolytic enzymes from synovial cells into the surrounding tissue, initiating erosion of the articular cartilage and inflammation spreads into the supporting ligaments and tendons.
Diagnosing RA:
- X-rays: In the early stages, X-rays will show bone demineralization and soft-tissue swelling. Later, they show loss of cartilage and the narrowing of joint spaces. Finally, they will show cartilage and bone destruction, erosion, subluxations, and deformities.
- RF test: The rheumatoid factor test will come back positive in about 80% of the patients, as indicated by a titer of 1:160 or higher.
- Synovial fluid analysis: This test will show increased volume and turbidity but a decrease in viscosity and complement (C3 and C4) levels. WBCs (white blood cells) will often be more than 10,000/mm.
- Serum protein electrophoresis: This test may show elevated serum globulins.
- Erythrocyte sedimentation rate: It is elevated in 85-90% of patients. It may be useful in monitoring response to therapy, since an elevation frequently parallels disease activity.
- CBC: A complete blood count will usually indicate moderate anemia and slight leukocytosis in the RA patient.
Complications of RA
One major complication is vasculitis (inflammation of a vessel), which can lead to skin lesions or cysts, leg ulcers, and multiple systemic complications. The formation of cysts in the articular cartilage or subchondral bone occasionally communicates with the skin surface (usually the sole of the foot) and can drain through passages called fistulas.
Thromboses of these vessels may lead to myocardial infarctions (heart attacks), cerebrovascular occlusions (strokes), kidney damage, and vascular insufficiency in the hands and fingers (Raynaud’s phenomenon), which may produce numbness or tingling in the feet or weakness and loss of sensation in the fingers. (The vascular changes are primarily noted in individuals receiving steroid therapy; thus, there is some concern that the therapy may play a role in initiating these lesions.)
Rheumatoid nodules may also invade the skin, cardiac valves, pericardium, pleura, lung parenchyma, and spleen. These nodules are identical to those encountered in some individuals with rheumatic fever and are characterized by central tissue necrosis surrounded by proliferating connective tissue. Also noted are large numbers of lymphocytes and occasional plasma cells. The skin nodules appear in about 20% of those affected with RA, mostly involving the arms and elbows. Less common sites are the scalp, back, hands, feet, buttocks, and knees.
Acute glaucoma may result with nodules forming on the sclera. Pulmonary involvement may result in diffuse pleuritis or multiple intraparenchymal nodules. Together, the occurrence of pulmonary nodules and pneumoconiosis (chronic inflammation of the lungs) creates a disorder called Caplan syndrome. Diffuse pulmonary fibrosis may occur because of immunologically mediated immune complex deposition. Rheumatoid nodules within the heart may cause deformities of the valves, particularly the aortic valve leaflets, and pericarditis. Lymphadenopathy of the nodes close to the affected joints may develop. Rheumatoid nodules within the spleen result in spenomegaly.
Another complication arises when these cysts rupture. This usually takes place when excessive pressure is placed on the joint through exercise or some other cause. Rupture releases inflammatory exudate into adjacent tissues, thereby spreading inflammation.
Other complications include the destruction of the tooth-like (odontoid) process of the second cervical vertebra. Sometimes cord compression can occur, particularly in patients with long-standing deforming RA. Such upper motor neuron signs as a positive Babinski reflex and muscle weakness, may also develop. RA can also cause temporomandibular joint disease which impairs chewing and causes earaches.
Treatment
In addition to the conventional or alternative forms of treatment (see separately), patients with RA are advised to have 10 to 12 hours of sleep out of each 24 hour period and are encouraged to maintain careful posture during this time. Pillows, or other devices, should be avoided that support the joints in a flexed position.
A firm mattress is also recommended with only one pillow under the head. During periods of severe attacks, the patient may require continuous bed rest in order to allow the body’s meager natural defenses against inflammation to work the best they can. However, it is necessary, even in acute phases, to balance rest with prescribed exercises.
The goal of physical therapy is to prevent and correct deformities, control pain, strengthen weakened muscles, and improve function. Applications of heat or cold may be used to improve circulation, promote relaxation, and relieve pain. When used in conjunction with exercise, heat can allow more freedom of joint movement.
Various forms of heat may be used including dry (heat lamp or hot water bottles), moist (paraffin baths, whirlpools etc), ultrasound, and diathermy. Diathermy is the use of high-frequency electrical currents to deliver moderate heat directly to the deeper tissues of the body.
Conventional treatment is designed to alleviate pain, reduce inflammation, stop or slow joint damage, and improve overall funtioning. This is accomplished with aspirin and NSAIDs, with limited doses of corticosteroids. Other treatments include injecting gold salts and methotrexate. Exercise and therapy are also used to keep the joints mobile. Surgery is the last resort in cases of severe joint damage.
(Taken from Life Extension, with permission)
Mayo Clinic Study Indicates Rheumatoid Arthritis Linked to Cardiovascular Disease Death
Findings from Mayo Clinic epidemiologists show that rheumatoid arthritis may be at fault for an increase in cardiovascular death of patients with the disease. The findings were published in Arthritis and Rheumatism in the March 2005 issue.
The study indicates that patients with rheumatoid arthritis have a greater risk of dying from cardiovascular disease than those without the disease, if they are suffering from inflammation of the blood vessels, joint swelling and rheumatoid lung disease.
The study followed 603 residents in Rochester, Minnesota with rheumatoid arthritis, from 1955 to death or until 2001. Hilal Maradit Kremers, MD, and colleagues collected and studied data on patients such as cardiac events, systemic inflammation indicators, cardiovascular risk factors and severity of rheumatoid arthritis.
The exact mechanism that causes heart disease when rheumatoid arthritis inflammation is present is still unknown. However, the researchers believe that if the rheumatoid arthritis inflammation is kept under control, it can lower cardiovascular disease deaths.
“Our previous research showed that rheumatoid arthritis patients have a higher risk of early death than others and that these deaths are mostly due to cardiovascular disease. We suspect that systemic inflammation promotes this risk. Our findings support this hypothesis,” said Sherine Gabriel, MD, senior author, rheumatologist and epidemiologist at the Mayo Clinic.
