Arthritis is a general term for approximately 100 diseases that produce either INFLAMMATION of connective tissues, particularly in joints, or noninflammatory degeneration of these tissues. The word means “joint inflammation,” but because other structures are also affected, the diseases are often called connective tissue diseases. The terms rheumatism and rheumatic diseases are also used. Besides conditions so named, the diseases include gout, lupus erythematosus, ankylosing spondylitis, degenerative joint disease, and many others, among them the more recently identified LYME DISEASE. Causes of these disorders include immune-system reactions and the wear and tear of aging, while research indicates that the nervous system may often be equally involved. About one out of seven Americans exhibit some form of arthritis. INFLAMMATORY CONNECTIVE TISSUE DISEASES This varied group of diseases produces inflammation in the connective tissues, particularly in the joints. The signs of inflammation–warmth, redness, swelling, and pain–may be apparent. Microscopic examination of the lesions reveals prominent blood vessels, abnormal accumulations of white blood cells, and varying degrees of wound healing with scarring. In some diseases, the inflammation is clearly an immune reaction, the body’s defense against invading microorganisms. In others, the cause is different or unknown. Infectious Arthritis This disease is most common in young adults. Infection in a joint is usually caused by bacteria or other microorganisms that invade the joint from its blood vessels. Within hours or a few days the joint, usually the knee or elbow, becomes inflamed. There is an abnormal accumulation of synovial, or joint, fluid, which may be cloudy and contain large numbers of white blood cells. Gonococcal arthritis, a complication of gonorrhea, is the most common form of infectious arthritis. Treatment with antibiotics and aspiration of synovial fluid is usually promptly effective, and only minor residual damage is done to the joint. Occasionally the infection is prolonged and produces joint destruction and requires surgery. Rheumatic Fever This is a form of infectious arthritis caused by hemolytic streptococcus, a bacterium. Unlike typical infectious arthritis, however, the disease is most common in children aged 5 to 15 years, begins weeks after the onset of the streptococcal infection, and streptococci cannot be isolated from the joint fluid. The inflammatory process may involve the heart and produce rheumatic heart disease. The symptoms of RHEUMATIC FEVER usually occur 2 to 3 weeks after the onset of a severe streptococcal sore throat. Acute pain and swelling “migrate” from joint to joint over a period of several days. The inflammation, which persists for less than three months, can usually be controlled by aspirin and rest, and it produces no residual deformity. Less than 1 percent of children with streptococcal sore throats develop rheumatic fever, and a small number of these will develop rheumatic heart disease. Rheumatic fever only rarely occurs if the streptococcal sore throat is treated early with an antibiotic such as penicillin. The inflammation of the joints and the heart in rheumatic fever apparently occurs because the body’s immune response to the streptococcus damages tissues. For this reason, rheumatic fever has been termed an autoimmune disease. Gout and Pseudogout The inflammatory process in these diseases is unrelated to infection. Rather, inflammation is incited by the deposition in the joint of uric acid present in the bloodstream. An attack of acute gouty arthritis is caused by the formation of needlelike crystals of the deposited uric acid. When these crystals are ingested by white blood cells, the cells release enzymes that evoke inflammations. Uric acid is a normal breakdown product of urine metabolism. Abnormally elevated blood levels of uric acid, which are associated with gouty arthritis, arise through either excessive production of uric acid or decreased excretion of uric acid by the kidneys. Some cases of hyperuricemia and gout are caused by known specific enzymatic defects. Many are associated with metabolic alterations that occur in obesity. When extreme, the gouty process results in large deposits of uric acid, or tophi, around joints. Acute attacks subside when the patient receives anti-inflammatory drugs. Further attacks may be prevented by colchicine, a drug that inhibits the ingestion of crystals by white blood cells. Serum uric acid levels decline and tophi resolve when the excess uric acid production is controlled by weight reduction and by drugs such as allopurinol, a purine analog that inhibits both formation of purines and their breakdown to uric acid. The disease usually affects men over age 40. The symptoms of pseudogout may mimic GOUT, but the inflammation is initiated by crystals of calcium pyrophosphate. They can be distinguished from uric acid crystals by polarization microscopy. The disease is treated with anti-inflammatory drugs. Rheumatoid Arthritis The symptoms of rheumatoid arthritis are attributable to inflammation of the connective tissues, but the cause is unknown. The major disability produced by rheumatoid arthritis has prompted a worldwide program of research devoted to finding its cause and cure. In rheumatoid arthritis, the synovial membranes, or inner linings of the joint capsules, are chronically inflamed. The synovial mass proliferates and thereby destroys cartilage, bone, and adjacent structures. The widespread inflammatory process also involves other tissue such as blood vessels, skin, nerves, muscles, heart, and lungs. The result is painful joints, loss of mobility, and generalized soreness and depression. Rheumatoid arthritis is predominantly a disease of women between the ages of 20 and 60. Probably many individuals have such a mild form of the disease that they never seek medical care. The typical patient with newly diagnosed rheumatoid arthritis is a 35-year-old woman who has been complaining for months of generalized aches and stiffness, particularly in her hands and fingers, for an hour after arising; swelling and pain in fingers, hands, wrists, and elbows; distressing fatigue in the early afternoon; and difficulty in sleeping. The affected joints are tender. The fingers have a sausage-like appearance because of swelling at the proximal interphalangeal joints. The wrists, too, are swollen by overgrowth of synovium, and there are rheumatoid nodules at the elbows. Laboratory studies of the blood may reveal the presence of rheumatoid factors, proteins produced by the immune system in response to the rheumatic process. Although rheumatoid arthritis may prove to be infectious, it is not a conventional contagious disease. The minor tendency for familial occurrence is probably attributable to genetic factors. Immunology, including autoimmunity, is clearly important. Rheumatoid factors (anti-antibodies) form immune complexes that incite inflammation, and lymphocyte accumulations in the body cause swelling of tissues, including synovia. Systemic LUPUS ERYTHEMATOSUS is about one-tenth as common as rheumatoid arthritis. It has an even stronger predilection for women, especially those in the child-bearing ages. It is characterized by inflammation of blood vessels and potential involvement of several tissues and organs, particularly the skin, joints, kidneys, lungs, heart, nervous system, and blood cells. Some patients are acutely affected with a febrile disease that is life threatening because of renal disease, nervous system disease, or accompanying infections. Most have a more indolent disease that produces moderate disability from nondeforming arthritis, skin eruptions, and fatigue. As in rheumatoid arthritis, the body seems to react against itself rather than against an invading microorganism. Anti-self antibodies react with intact blood cells, nuclear components, and blood-vessel walls. The complexes that form in the patient’s blood precipitate in basement membranes of skin, kidneys, and nervous system and thus cause inflammation. Juvenile rheumatoid arthritis usually begins by age 5 or in the early teens. In most cases, tests for rheumatoid factors are negative and the disease becomes inactive by age 15. Ankylosing SPONDYLITIS occurs more commonly in men than women; it affects the spine and sacroiliac joints in particular, with resultant fusion of vertebrae and immobility. Tests for rheumatoid factors are negative, and tests for the tissue antigen HLA B27 are usually positive. NONINFLAMMATORY CONNECTIVE TISSUE DISEASES The joints and other connective tissues can be involved by trauma, endocrine disorders, metabolic abnormalities, congenital deformities, and other disease processes. The most important one is degenerative joint disease (OSTEOARTHRITIS). Degenerative Joint Disease. This is the most common form of arthritis and affects virtually all older adults to one degree or another. Most have few, if any associated symptoms, and the disease is diagnosed only because X rays of the vertebrae show characteristic spurs or because the fingers are knobbed by bony proliferations (Heberden’s nodes) at the distal interphalangeal joints. In some the spurs encroach on nerves as they emerge from the spinal canal and produce nerve-root syndromes. In others, the malpositioned joints are a source of ligamentous strain and abnormal muscular tension. The result is pain that becomes worse as the day goes on. Occasionally a severe form of the disease affects the hips. The destructive process results in restricted mobility of the hip joints and disabling pain, and major surgery may be required. The destroyed tissue is removed and replaced by a new joint made of plastic, an operation that is usually dramatically effective. Degenerative processes affect the ligaments and intervertebral disks of the spine. If a disk slips out, the syndrome of herniated disk may ensue. This is common in middle-aged men and usually affects the lumbar vertebrae, producing nerve-root irritation and ligamentous strain with resultant low-back pain and neurological deficits. Unless the symptoms remit with rest and analgesics, the disk may need to be surgically removed. These degenerative processes are in part caused by wear and tear. They affect primarily weight-bearing joints and joints subject to trauma or to malpositioned anatomy. Joints damaged by other forms of arthritis are prone to later degenerative joint disease. Heberden’s nodes are more prominent in the right hand of right-handed individuals and in the fingers of typists. Traumas produce microfractures in the cartilage that lines the articulating surfaces exposing raw underlying bone. The bone cells then release enzymes that destroy the protein and polysaccharide components of bone. Frayed pieces of cartilage may be taken up by white blood cells and thus add an element of inflammation. TREATMENT OF ARTHRITIS Accurate diagnosis and proper treatment usually follow naturally from the history, physical exam, and laboratory tests and from consideration of the pathophysiologic mechanisms. Infectious arthritis usually responds dramatically to appropriate antibiotics. The noninfectious inflammatory diseases are treated with drugs that suppress inflammation. Many of these drugs, for example, aspirin, indomethacin, and ibuprofen, appear to work by inhibiting synthesis of prostaglandins that mediate inflammation. Although certain adrenal cortical steroids are powerful inhibitors of inflammation, toxic side effects limit their usefulness. Similarly, drugs that inhibit proliferation of cells in the inflammatory masses have potentially severe side effects. Drugs that inhibit undesirable inflammation may also inhibit desired inflammatory responses. A result is a high frequency of secondary infections. More specific therapy, for example, allopurinol and colchicine in gout, is dependent on knowledge of the precise biochemical mechanisms of disease pathogenesis. Researchers are also studying the use of drugs that act on the nervous system. Despite the wear-and-tear origin of degenerative joint disease, it, too, may respond well to so-called anti-inflammatory drugs. Perhaps they are primarily acting as analgesics (pain-killers), or they may act by decreasing the secondary inflammation that follows joint trauma. Franklin Mullinax Bibliography: Arthritis Foundation, Understanding Arthritis (1986); Kelley, William N., et al., eds., Textbook of Rheumatology, 2d ed., (1985); McCarty, Daniel F., ed., Arthritis and Allied Conditions, 11th ed. (1988); Moll, J. M. H., Rheumatology in Clinical Practice (1987).