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ARTHRITIS

Background

The prevalence of arthritis (chronic damage of the joints) increases with age because the most common form, osteoarthritis, is age related, and also because chronic arthritis, particularly rheumatoid arthritis, persists into old age even when starting in early adult life (Silman and Hoch-berg). Osteoarthritis and rheumatoid arthritis are common, and represent two distinct but related mechanisms of joint disease in old age: respectively, "wear and tear" and inflammation.

The clinical features of arthritis. Pain is the predominant symptom. Most pronounced on movement, it also occurs at rest, after exercise, and at night. The other main complaint is stiffness, occurring in the morning and after exercise, when it is termed "gelling." In inflammatory arthritis, morning stiffness exceeds thirty minutes. Joint swelling is common, due to synovitis (inflammation of the joint lining), synovial effusions (swelling due to fluid in the joint cavity), and bony swelling around joints. Crepitus, grating when joints are moved, characterizes osteoarthritis. Arthritis causes muscle weakness that may be profound. Finally, there may be loss of movement due to joint swelling, muscle weakness, and deformities when joints are damaged.

The effects of arthritis. Arthritis causes disability and impairs quality of life due to the direct effect of inflammation of the synovium (synovitis). The pain, inflammation, and joint destruction of synovitis are compounded by muscle weakness and decreased sense of joint (proprioception) (British League Against Rheumatism).

Osteoarthritis

Osteoarthritis is common and, at older ages, becomes virtually universal. It is an active process, not just wearing out of joints or "degenerative joint disease" (Joint Working Group of the British Society for Rheumalology and, Research Unit of the Royal College of Physicians).

Causes and disease mechanisms. There are progressive changes in osteoarthritic cartilage. Initially the collagen (the material that provides important lining of bones) framework is damaged by changes in structural complex sugars (proteoglycans), in the cartilage matrix, and in water content. Attempted repair increases the number and activity of cartilage cells (chondrocytes). This leads to the production of degradative enzymes. Subsequent fissuring, cartilage ulceration and matrix loss makes damage irreversible. There is variable accompanying inflammation of the synovium that lines the joints, as well as changes in adjacent bone. Predisposing factors for osteoarthritis include age, female sex, family history (indicating genetic predisposition), obesity, previous trauma, repetitive occupational stress, and previous inflammation, such as rheumatoid arthritis. Osteoarthritis increases with age. By sixty-five years most people have X-ray evidence of osteoarthritis, though under 30 percent have symptoms.

Clinical features. Pain is the dominant symptom. It is usually activity related, varies in severity, and has periods of remission. Associated symptoms include morning stiffness (usually under thirty minutes), postexercise gelling, bony swelling, limited movement, and muscle weakness. Examination shows bony swelling, tenderness, and crepitus. Effusions, usually in the knees, are common.

Osteoarthritis can involve one or many joints. Generalized osteoarthritis involves the small joints of the fingers, especially those at the knuckles closest to the ends, as well as the wrists, knees, and hips.

Investigations. Blood tests are usually normal, although some elevation of tests for inflammation can be seen. Tests for the protein known as rheumatoid factor are negative. X-rays show joint space loss, and increased bone underneath and at the edges of joints, called subchondral sclerosis and marginal bony outcroppings (osteophytes), respectively. In late disease, joints can be totally destroyed. Isotope bone scanning (scintigraphy) shows increased activity of the joints in early disease.

Rheumatoid arthritis

Rheumatoid arthritis, the most common type of inflammatory arthritis, is characterized by persisting inflammatory synovitis resulting in joint damage and systemic reactions, although it can vary in its severity and general effects (Scott et al.; Sewell).

Causes and disease mechanisms. The cause of rheumatoid arthritis is unknown, but is variously attributed to autoimmunity, bacterial infection, or viral infection. The synovium is infiltrated with white blood cells called lymphocytes, which are seen where inflammation is chronic. Synovial cells proliferate and blood vessels increase markedly. Synovial fluid contains many white blood cells known as polymorphonuclear leukocytes. There are accompanying destructive changes in joint cartilage and bone.

Rheumatoid arthritis is associated with rheumatoid factor production. Several different immunoglobulin classes can be involved, especially IgM and IgA. A minority of cases remain seronegative. Rheumatoid arthritis has a genetic component. It involves three times more women than men, its prevalence increases with age, and it involves 0.25–1 percent of adults and 3–5 percent of elderly women.

Clinical features. The onset of rheumatoid arthritis is usually insidious over several months, though some cases have an acute onset. Characteristic features are joint pain, swelling, and morning stiffness lasting several hours. Typically it involves small joints of the hands and wrists in a symmetrical distribution. Large joint involvement indicates severe disease. In early disease the findings are subtle, while in late disease there are obvious changes, such as the self-descriptive swan-neck and "boutonnière" deformities in the fingers. Large joint damage causes immobility and disability.

Features apart from joint inflammation (extra-articular features) are common. Rheumatoid nodules at sites like the elbow indicate severe, rheumatoid factor–positive disease. Other extra-articular features include dry eyes and dry mouth (Sjögren's syndrome), leg ulcers, nerve damage, lung disease, and inflammation of the pericardium, sclera, and blood vessels.

Investigations. Blood tests are usually abnormal. Rheumatoid factors are antibodies produced by the individual against constituent proteins (auto-antibodies). They bind to one end of normal immunoglobulin, the Fc portion. They occur in about two-thirds of cases, as well as in other disorders with persisting immune inflammation and in many healthy individuals. Other abnormalities reflect the systemic inflammatory response. The erythrocyte sedimentation rate is elevated. Specific measures of acute inflammation, such as C-reactive protein, are also elevated. By contrast hemoglobin levels can be low.

Juxta-articular erosions, a key diagnostic finding, are next to the joint on X-rays of the hands and feet. Other changes are osteoporosis around the joints and loss of joint space. In late disease there is destruction and ankylosis (fusion of the joint due to bone growth). Scintigraphy shows increased blood flow around involved joints in early disease, though such findings are not specific.

Seronegative arthropathies

Seronegative arthropathies usually involve only a few joints, are less severe than rheumatoid arthritis, and tests for rheumatoid factor are negative, (hence the term "seronegative"). Psoriatic athritis, the most important type in elderly people, is a specific type of arthritis seen in association with psoriasis. Other disorders include reactive arthritis, colitic arthritis in inflammatory bowel disease, and the peripheral arthritis of anklyosing spondylitis, a disorder characterized by involvement of the spine.

Classification and causes. Unifying themes are the presence of an infective trigger and the genetic risk associated with HLA-B27, one of the genes found in normal human white blood cells. This is found 95 percent of cases of ankylosing spondylitis and less often in the other disorders.

Ankylosing spondylitis, colitic arthritis, and reactive arthritis usually begin in early adult life; in the elderly the predominant clinical concern is their late consequences, mainly due to joint failure. Psoriatic arthritis may present de novo in the elderly.

Clinical features. There are a number of clinical patterns of psoriatic arthritis, including oligoarthritis (arthritis that involves only a few joints); a symmetrical polyarthritis, often indistinguishable from rheumatoid arthritis; distal arthritis of the distal interphalangeal joints; and arthritis mutilans, a rare cause of severe joint damage. Other forms of seronegative arthritis predominantly involve oligoarthritis.

Investigations. There are no specific laboratory tests. Acute-phase reactants like the ESR and C-reactive protein may be elevated. Rheumatoid factor is usually negative. X-rays may show marginal erosions. Isolated destruction of individual joints with pencil and cup deformities suggests psoriatic arthritis. Axial disease with sacroilitis and spinal fusion characterize ankylosing spondylitis.

Gout

Causes and disease mechanisms. Gout is a form of inflammatory arthritis that results from the deposition of urate crystals in the synovium (Van Doornum and Ryan). Uric acid, the end product of metabolism of some important proteins, results from endogenous purine metabolism with an important, though minor dietary contribution. In other words, while diet has some impact on gout, the idea of gout as chiefly the result of too much rich food and drink (the "patrician malady") is untrue. Hyperuricemia is seen prior to episodes of arthritis and progesses to gout when large increases in body stores of uric acid make it impossible for the body to adapt. Synovial urate crystals activate inflammatory pathways either directly or after coating by proteins such as immunoglobulins.

Hyperuricemia (high uric acid levels in the blood) is common, with a male predominance; it involves 5 percent of men. Risk factors include obesity, renal disease, high alcohol intake, and diuretic use. It is also seen as part of "syndrome X," which consists of abdominal obesity and high blood pressure, and is a potent risk for arthroscelerosis and heart disease. Gout is less common, involving 0.2–0.5 percent of men.

Clinical features. Gout may be precipitated in patients with hyperuricemic gout by excess alcohol, metabolic disturbances due to surgery or trauma, or diuretic therapy. Classical gout involves the big toe (podagra), making it exquisitely painful, red, swollen, and tender. The onset may involve multiple joints, particularly those of the lower limbs. It is unusual for both lower limbs to be affected at the same time. Initial attacks often resolve after a few days and can be followed by recurrent episodes. These can progress to chronic arthritis. Some cases with established gout have subcutaenous urate crystals deposits (known as tophi) in the pinnae of the ears, fingers, and elbows.

Investigations. If joint fluid from an affected joint is aspired (which is often very difficult to do), detecting intracellular uric acid crystals under the microscope is diagnostic. Most patients have elevated serum uric acid levels, though only a minority of patients with hyperuricemia have gout. Acute attacks result in an elevated ESR and high white cell count. In established gout X-rays show punched-out erosions with sclerotic margins, often distant from the joint margins.

Calcium pyrophosphate deposition disease

Some patients have a disorder similar to gout without synovial fluid uric acid crystals (Fam). Instead they have intracellular calcium pyrophosphate dihydrate crystals, a condition known as pseudogout. Such crystals also occur in osteoarthritis and a range of arthropathies, so that they are an important cause of arthritis in older people.

Causes and disease mechanisms. Calcium pyrophosphate is widely distributed in the body, and it is unclear why it sometimes forms crystals that induce inflammation. These crystals are often associated with metabolic disturbances such as parathyroid disease and a blood disorder known as hemochromatosis. Pathologically the crystals trigger a cascade of inflammatory pathways that mirrors gout.

Pyrophosphate crystals account for up 50 percent of acute attacks of crystal arthritis. Similar crystals are seen in the cartilage of many elderly people, a condition termed chondrocalcinosis. Seen in a minority of seventy year olds but the majority of ninety year olds, its pathological significance is often uncertain.

Clinical features. As is suggested by the name, acute pseudogout is similar to classical gout and can be precipitated by metabolic disturbances such as trauma. The arthritis develops suddenly, with one or several inflamed, painful, swollen, and tender joints. It typically involves knees, shoulders, and wrists. Many patients have recurrent episodes. Some cases have chronic arthritis, often with some joint inflammation occurring over and above osteoarthritis.

Investigations. Intracellular pyrophosphate crystals are visible on polarizing light microscopy of aspirated synovial fluid. X-rays may show chondrocalcinosis, indicating crystal deposition in joint cartilage. Blood tests either are normal or show evidence of mild inflammation with a raised ESR.

Other arthropathies. Other forms of arthritis important in the elderly include septic arthritis and arthritis linked to polymyalgia rheumatica and malignancy. Septic arthritis often complicates pre-existing chronic arthritis, particularly rheumatoid arthritis, and results in an acute exacerbation of joint problems and systemic involvement. Unless there is a high threshold of diagnostic suspicion, it can be difficult to diagnose until the joint sepsis is advanced. Arthritis in polymyalgia rheumatica and malignancy is mild, polyarticular, nonerosive, and seronegative for rheumatoid factor.

Management

General principles. Management aims are controlling pain, minimizing disability, reducing progressive joint damage, and limiting functional and social handicaps. Most arthropathies can be managed by family physicians with a minority of cases needing specialist referral; the exception is rheumatoid arthritis, which invariably needs specialist input. General management principles for most forms of arthritis comprise patient education, lifestyle advice, treating pain with analgesics, and treating pain and inflammation with non-steroidal anti-inflammatory drugs (NSAIDs).

Nondrug treatments. Advice, education, and support that benefit patients or their care givers can be provided by medical and a variety of support staff (Puppione). Self-efficacy, maintaining general health and fitness, and avoiding obesity all need emphasis. Aids and appliances, such as walking sticks and footwear, have modest benefits, though not all elderly patients are willing or able to use them.

Exercise program that improve general fitness and muscle strength are effective. They involve lifestyle changes such as regular walking and specific muscle-strengthening program like quadriceps exercises. There is good evidence that they are effective in osteoarthritis, but evidence for rheumatoid arthritis and other arthropathies is less convincing.

Analgesics and NSAIDs. Simple analgesics like acetaminophen are effective and safe in all forms of arthritis in the elderly (American College of Rheumatology). One disadvantage is that patients are reluctant to take enough acetaminophen (e.g., 1 gram four times daily). Other analgesics,such as tramadol and dihydrocodeine, are effective in relieving arthritic pain, though constipation with dihydrocodeine and disorientation with both drugs limit their use. Compound analgesics, especially coproxamol (dextropropoxyphene and acetaminophen) are widely used, though there is limited evidence that they are better than acetaminophen.

Nonsteroid anti-inflammatory drugs (NSAIDs) are widely used to treat pain and inflammation. Short courses of NSAIDs reduce pain and joint swelling over several days or weeks, and maintain these benefits for several months. There is limited evidence for longer-term benefits. The drawback with NSAIDs is their frequent adverse reactions. The most important are gastrointestinal reactions, which range from mild indigestion to severe gastrointestinal ulcers, hemorrhages, and perforations. Other reactions include rashes and renal and liver impairment. There are variations in the prevalence of severe gastrointestinal reactions with different NSAIDs. Older drugs like indomethacin cause more problems than newer drugs like nabumetone. Recently introduced coxibs like rofecoxib and celecoxib, which selectively inhibit COX-2 enzymes, have greater gastrointestinal safety (Jackson and Hawkey). Gastrointestinal risks are also reduced by coprescribing prostaglandin analogues like misoprostol, proton-pump inhibitors like omeprazole, or H-2 antagonists like randitine.

Disease modifying antirheumatic drugs (DMARDs). These chemically diverse drugs control synovitis in rheumatoid arthritis and seronegative arthritis by modulating the immune response (Simon and Yocm). They reduce synovitis, decrease erosive damage, and improve long-term function. They are given in addition to analgesics and NSAIDs. DMARDs include methotrexate, sulfasalazine, leflunomide, azathioprine, cyclosporin, gold injections, and antimalarials (chloroquine and hydroxychloroquine). All except the antimalarials require regular monitoring for blood and liver toxicity.

DMARDs should be started soon after the diagnosis of rheumatoid arthritis has been established. Combinations of two or more DMARDs are often used, for example, triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine. A recent development has been the introduction of antitumor necrosis factor (TNF) alpha immunotherapy, usually combined with methotrexate, to supplement DMARD therapy in severe disease.

Steroids. Local steroid injections benefit active inflammatory arthritis involving a single joint, irrespective of the cause, provided there is no sepsis. They can be repeated several times but should not be used excessively.

Systemic steroids, given intramuscularly or orally, are effective in acute active inflammatory arthritis, whatever the cause. They have a rapid onset of action, but their benefits may not be sustained. Their long-term use is limited by osteoporosis, thinning of the skin, increased sepsis, and other adverse reactions. It is imperative to prevent osteoporosis by giving calcium and vitamin D, with additional preventive therapy such as biphosphonates, in elderly patients on long-term systemic steroids therapy.

Other local treatments. Intra-articular artificial synovial fluid injections benefit osteoarthritis and reduce pain for up to six months. Local NSAIDs applied topically as creams or gels offer small benefits for osteoarthritis with limited adverse effects. There are similar benefits with local capsaicin, also applied topically as a cream.

Other medical treatments. Gout is treated by allopurinol, which inhibits uric acid formation. It has no value in acute gout and, because it may precipitate acute attacks, requires initial NSAID coprescription. Colchicine is an alternative approach in gout, but its efficacy is limited by diarrhea. Septic arthritis requires antibiotics; the choice depends upon the organisms involved.

Surgical treatment. The most important surgical treatment for osteoarthritis and joint failure is replacement. Many different joints can be replaced, but knees and hips are most important. Replacment reduces pain and improves function with few perioperative and postoperative complications. Most prostheses last many years. Indications for surgery include persistent pain, poor function, and anatomical evidence of joint destruction. Contra-indications include obesity, poor general health, and relative youth (as prostheses do not last indefinitely). Outcomes are better with single joint replacements, but many patients do well with multiple joint replacements. Other surgical interventions, including attempts to salvage existing joints by surface replacement, have fewer beneficial effects.

DAVID SCOTT

See also PAIN MANAGEMENT.

BIBLIOGRAPHY

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