CHAPTER 16

OSTEOARTHRITIS, GOUT AND PSEUDOGOUT

Katherine G. Nickerson M.D.

Table of Contents

Osteoarthritis

Osteoarthritis (OA) represents a progressive process of softening, ulceration, and destruction of articular cartilage frequently associated with the formation of bony and cartilaginous excrescences at joint margins (osteophytes). Although the pathogenesis of primary (idiopathic) OA is not understood, it is probably caused by factors that disrupt the balance between cartilage synthesis and breakdown and thus represents a disturbance in cartilage physiology rather than simple mechanical wear and tear. Clinically, it is slowly progressive, occurs late in life, and principally affects the hands and large weight-bearing joints. OA can also represent the final common pathway of a variety of other insults to cartilage integrity, as listed in Table 1.[i]

Pain is the primary presenting complaint of patients with osteoarthritis, and is usually described as a deep, dull ache localized to the affected joint. The pain from osteoarthritis is not caused by articular cartilage, which is aneural. The mechanism of pain can be multifactorial.[ii] Subchondral bone can have microfractures or symptomatic medullary hypertension, osteophytes can cause stretching of nerve endings in the periosteum, ligaments may be stretched, the joint capsule can be inflamed or distended, the synovium may be inflamed and muscles may spasm. Disability associated with the pain of OA is common, and by some estimates, osteoarthritis of the knee is the leading cause of chronic disability in the United States.[iii]

Epidemiology and Risk Factors:

            Age is the single strongest risk factor for OA, and the prevalence of OA in the population over age 50 is high, although ascertainment varies with the technique (radiologic, autopsy, clinical symptoms). Over 50 percent of people age 60 and greater have some clinical signs of OA, and the prevalence increases with age.[iv] Men and women are equally affected by OA of the hips, but women more frequently have hand and knee involvement. Obesity is a risk factor for OA of weight-bearing joints, and heredity (especially in OA of the hands and generalized OA) is an additional risk factor. Trauma to a joint, particularly fracture or ligament injury, is clearly associated with subsequent OA. The role of repetitive use without overt injury (i.e. running, repetitive stereotypic movements) remains somewhat controversial. It appears, however, that in the absence of underlying anatomical abnormalities, weakness or soft tissue injuries, normal joints tolerate prolonged and vigorous exercise without accelerating the development of OA.

TABLE 1: Classification of Osteoarthritis

Diagnosis:

                As noted, patients with OA most often present with pain. They may also have limited range of motion and bony deformities. Unless the condition is accompanied by CPPD (see below), they do not usually have inflammatory signs. An exception is in OA of the hand where there may be an inflammatory phase in the evolution of Heberden’s and Bouchard’s nodes (bony deformities of the DIP and PIP joints, respectively). This usually resolves, however, leaving deformities that may be cosmetically distressing but are rarely the cause of significant disability. OA may be accompanied by morning stiffness, but it is usually brief (a few minutes) compared to patients with inflammatory arthritis (hours). The physical examination may demonstrate bony deformities, crepitus, and limited range of motion. Gait disturbances are common.

Laboratory tests are normal and joint fluid, if obtained, has normal viscosity and a non-inflammatory profile (< 2000 WBC). It is an error to assume that the presence of a positive ANA, an elevated ESR, or the presence of rheumatoid factor excludes the diagnosis of OA; age alone can cause all of these abnormalities. OA can also co-exist with other arthritides, such as RA and gout or pseudogout. Although there is active interest in using serologic and synovial fluid biomarkers for diagnosis and assessment of disease activity, these are still investigational. Standard x-rays are poor tools for the diagnosis of OA; they are neither sensitive nor specific. More than 90 percent of persons over the age of 40 will have some radiographic change consistent with OA on hip and knee films, for example, but only about 30 percent will have symptoms.[v] Neither joint-space narrowing nor the presence of osteophytes is correlated with intraarticular pathology in patients with early OA.

Treatment of osteoarthritis:

            There is no cure for OA. Patients must understand their role in managing pain, maintaining mobility and minimizing disability. Progression of disease, either symptomatically or radiographically is not inevitable. In fact, many patients with OA of the hip or knee remain stable over long periods of time. It is thus important to be encouraging and hopeful.

Exercise and physical therapy

            Maintaining muscle strength and range of motion, and learning about body mechanics may be extremely helpful. It is possible to reverse the downward spiral of pain, inactivity and muscle weakness through exercise or a physical therapy program. The patient may be able to do this on his or her own. Multiple studies have demonstrated the efficacy of exercise. A randomized controlled trial of supervised walking in patients with moderate OA of the knee demonstrated that those who walked had decreased pain, decreased need for medications, and improved function.[vi] Motivated patients may also benefit from aerobic exercise such as swimming, walking or bicycling.[vii] Low impact activities are preferable when there is OA in weight-bearing joints. Some patients are helped by a formal course of physical therapy, where they can learn isometric exercises to maintain strength, as well as to improve range of motion. The goal should be to educate patients to do as much as possible on their own. Prescriptions for physical therapy can be simple, e.g. “Dx: OA of the knee; Rx: range of motion and strengthening exercises.” We strongly suggest that all patients with OA be counseled about the advantages of exercise and referred to physical therapy if interested.

TABLE 2: Goals of physical therapy in OA (adapted from Minor)[viii]

Pharmacologic therapy

            Every treatment guideline for the management of osteoarthritis concludes that acetaminophen should be the drug of first choice.  Although NSAIDs are heavily marketed and prescribed, their use for OA has been called into question.[ix] Despite expert recommendations that they not be used as first-line drugs for OA, NSAIDs often are; 50 percent of all NSAID prescriptions are for the treatment of OA.[x]  NSAIDs were first developed as anti-inflammatory agents to treat conditions such as rheumatoid arthritis. They have been widely used for other indications because of their excellent analgesic properties. Cyclooxygenase-2 (COX-2) inhibitors have also been heavily marketed for use in OA; these agents are effective analgesics but are extremely expensive and no long-term safety data are available. There are, also, no trials comparing analgesic efficacy of these agents to acetaminophen.  Specific COX-2 inhibitors, such as celecoxib (Celebrex), are associated with fewer “endoscopic ulcers” than traditional NSAIDs, which inhibit both COX-1 and COX-2 enzymes.[xi]^,[xii] The long-term implications of this observation are unclear, as is the significance of endoscopic ulcers. There has been at least one case report of gastropathy due to celecoxib.[xiii] 

There are at least four reasons why the long-term use of NSAIDs in OA has been questioned:

Ø      Lack of efficacy: While NSAIDs are clearly superior to placebo in providing pain relief, they have not been shown to be superior to acetaminophen in the treatment of OA. There are hundreds of trials comparing various agents to placebo, but very few that compare NSAIDs and acetaminophen directly; all of these trials show that the two classes are equivalent. For example, one study compared acetaminophen to low and high dose ibuprofen in patients with OA of the knees;[xiv] there was no difference in pain relief among the three groups. 

Ø      Toxicity: This is a non-trivial concern, particularly in the elderly. The dose-dependent, age-dependent risk of GI bleed, perforation and death is well known. Ten to twenty percent of people taking NSAIDs have dyspepsia, and an estimated 7.3 of every 1000 patients with OA who take NSAIDs for one year have a serious gastrointestinal complication.[xv] NSAIDs can also cause or exacerbate hypertension, hyperkalemia, congestive heart failure, and renal insufficiency.

Ø      Possible adverse effect on cartilage: There is circumstantial evidence that NSAIDs may accelerate articular breakdown in patients with OA. In vitro and animal studies demonstrate decreased proteoglycan synthesis and marked acceleration in cartilage destruction in the presence of NSAIDs. One trial of indomethacin in OA of the hip showed that patients on indomethacin came to hip replacement more quickly than a control population.[xvi] The surgeons in this study were not blinded, however, and the radiographic methods used in the study have been criticized. More definitive studies of this question are underway.

Ø      Cost: The average cost of a year’s supply of NSAIDs is more than five times that of high-dose generic acetaminophen.

Our recommendation is that chronic NSAID (or COX-2 inhibitor) use is to be avoided if possible. If a patient is taking an NSAID, it is appropriate to substitute high-dose acetaminophen for a month or two and see if the patient notices a difference. It is important to review proper dosing (standing as well as prn for breakthrough). A patient with normal hepatic function can be given up to four grams a day of acetaminophen (two extra-strength tylenol QID). If acetaminophen alone fails to relieve pain, and the patient is doing everything possible in terms of physical therapy, exercise and nonpharmacologic modalities for pain relief, and the joints in question are not candidates for joint replacement, other analgesics can be considered. These include tramadol (Ultram), codeine, codeine plus tylenol, propoxyphene (Darvon) and  propoxyphene plus tylenol (Darvocet).

Surgery

            Joint replacement surgery is reserved for patients with severe pain and/or  disability.[xvii] Total hip and total knee replacements are major surgical procedures, with all the concomitant risks. It is usual to lose two to four units of PRBCs. The rehabilitation period may take several months; adequate motivation to engage in physical therapy and adequate social support is essential. Because hip and knee prostheses have a limited life expectancy , joint replacement should usually be delayed until at least age 60. Other considerations may be obesity and limitations from other involved joints.

TABLE 3: Treatment of OA

Gout and Hyperuricemia

            Gout includes a range of clinical disorders, from the familiar, exquisitely painful, acute monoarticular arthritis to chronic, crippling polyarthritis. Gout is almost always associated with chronically elevated levels of serum uric acid, and acute attacks are often triggered by events that precipitously raise or lower the serum uric acid level. The dramatic inflammatory response that characterizes acute attacks of gout is probably triggered by uric acid crystals stimulating monocytes to release mediators such as IL-1 and tumor necrosis factor (TNF) that subsequently promote entry of neutrophils into the joint. The tendency of uric acid to crystallize in joints may partly be related to lower temperature (especially distal joints), and a decrease in solubility in synovial fluid compared to serum.

Epidemiology:

            The risk of developing gout is directly related to the level and duration of elevated uric acid. The overall prevalence is approximately 2-3 per thousand individuals, but for those with a serum uric acid greater than 9.0 mg, the five-year cumulative incidence is nearly 25 percent. In the general population, hyperuricemia rises with increasing age, weight, and serum creatinine: in 90 percent of patients, primary gout is related to underexcretion rather than overproduction of uric acid. The cause of this underexcretion is not known, but may be a renal tubular defect. In men, the uric acid level rises starting in puberty, while in women it rises after menopause, so that the onset is typically several decades earlier in men than women.

TABLE 4: Risk factors for hyperuricemia

            In many patients, the development of clinical gout is accelerated by secondary factors such as renal insufficiency, alcohol consumption, diuretic use, or low doses of aspirin, all of which inhibit renal excretion of uric acid. (Alcohol may also increase uric acid synthesis). Cyclosporine and nicotinic acid are also associated with hyperuricemia and gout. Myeloproliferative disorders, psoriasis, and hyperthyroidism may be associated with overproduction of uric acid and gout.

            Rare X-linked enzyme disorders such as those of hypoxanthine-guanine phosphorbosyl transferase (HPRT) deficiency (Lesch-Nyhan syndrome) and overactivity  of  phosphorbosyl pyrophosphate (PRPP) synthetase also lead to overproduction of uric acid and severe gout, as well as neurologic impairment. G6PD deficiency is also associated with gout.

            Gout is negatively associated with rheumatoid arthritis and other rheumatologic conditions, such as lupus and amyloidosis. This observation appears to be more than just an artifact of their incidence in separate populations (older men vs. younger women), and various explanations have been proffered, including low synovial complement levels, saturated Fc receptors, and the uricosuric effect of high-dose aspirin in RA patients.

Clinical Syndromes:

The clinical spectrum of gout includes four stages: asymptomatic hyperuricemia, acute attacks of gouty arthritis, intercritical gout, and chronic tophaceous gout.

Asymptomatic hyperuricemia

            Asymptomatic hyperuricemia  refers to the period of time in which the serum uric acid level is elevated without either attacks of acute gout or nephrolithiasis.  The risk of attacks of gout is related to the serum uric acid concentration, while the risk of nephrolithiasis increases in relation to the daily uric acid excretion. Asymptomatic hyperuricemia most often lasts throughout the individual’s lifetime. If gout occurs, it is usually after several decades of sustained hyperuricemia. Thus, among men, the peak incidence is in the fourth to sixth decade whereas in women it is several decades later. There is rarely an indication for treating asymptomatic hyperuricemia.

TABLE 5: Events that commonly trigger acute gouty arthritis

Acute gouty arthritis

            Attacks of acute gout usually last from two to ten days and are most often monoarticular at the outset. In about one half of all initial attacks, the first metatarsal joint (the great toe) is involved, and the term podagra is used. Next in order of frequency of involved sites are the insteps and ankles, heels, knees, and wrists. Any joint can be involved, but only rarely the shoulders, hips, spine or sacroiliac joints. More distal joints are frequently involved, in part because of their lower temperature. There are, in fact, rare reported cases of gout in persistently normouricemic people,[xviii] apparently related to the decreased temperature of their extremities. Any acute rise or fall in the serum uric acid level tends to bring about an attack. Thus, dehydration, an increase in diuretic therapy, alcohol ingestion, trauma, acute illness, surgery or the institution of allopurinol may all be associated with acute gout. The level of uric acid at the time of an acute attack, therefore, may not accurately reflect usual levels, and care should be taken in its interpretation. The typical gout attack begins at night, is intensely painful, and may be associated with fever and chills. A feeling for the experience comes from this classic description by Syndenham:

The victim goes to bed and sleeps in good health. About two o’clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle or instep. This pain is like that of a dislocation, and yet the parts feel as if cold water were poured over them. Then follow chills and shivers and a little fever. Now it is a violent stretching and tearing of the ligaments – now it is a gnawing pain and now a pressure and tightening…it cannot bear the weight of bedclothes, nor the jar of a person walking in the room. The night is passed in torture, sleeplessness, turning of the part affected, and perpetual change of posture; the tossing about of the body being as incessant as the pain of the tortured joint.[xix]

Intercritical Gout

Intervals between gout attacks are called intercritical periods and may vary in length from months to years. Most patients have a recurrence within the first year after their first attack, and the frequency of attacks usually increases with time in the absence of treatment. Later attacks may become polyarticular, more severe, longer, and accompanied by fever. Characteristic erosions with overhanging edges develop on x-ray as deposits of uric acid are laid down and erode bone. As this phase evolves, the patient may develop chronic polyarticular gout without pain-free intercritical periods. This persistent polyarthritis, which is erosive and deforming, may easily be mistaken for rheumatoid arthritis, and tophi can be mistaken for rheumatoid nodules. Joint aspiration or aspiration of a tophus is the key to making the correct diagnosis and instituting the appropriate therapy in a patient presenting with polyarthritis and an elevated serum uric acid level.

Chronic tophaceous gout

The length of time between the first attack of gout and the evolution of visible tophi is highly variable and may range from a few years to four decades. The degree of tophaceous deposition is largely a function of the degree and the duration of hyperuricemia. The classic location of tophi is the helix or antihelix of the ear, but they commonly occur on the knuckles, Achilles’ tendons, knees or feet. They are also commonly found along the extensor surface of the forearm or as saccular distentions of the olecranon bursa. As patients develop chronic tophaceous gout, acute attacks of arthritis may become less frequent and milder. Tophi can break down, ulcerate and extrude a white chalky or pasty material composed entirely of uric acid.

Hyperuricemia and the kidney

Uric acid kidney stones occur in 10 to 25 percent of patients with primary gout, and the risk rises by 50 percent in those with urinary uric acid excretion rates greater than 1000mg. Uric acid stones may be an indication for the institution of allopurinol and are a contradiction to uricosuric agents.

Although gout is frequently associated with renal insufficiency, hyperuricemia itself does not appear to be the cause of declining renal function. “Urate nephropathy” is no longer thought to be a real clinical entity, and the renal insufficiency commonly found in patients with gout is now considered to be caused by coexisting hypertension, nonsteroidal use or lead exposure (which can cause both “saturnine gout” and renal insufficiency). In contrast, the extremely high levels of uric acid seen in the tumor lysis syndromes and after chemotherapy can precipitate in the kidney and cause acute renal failure. For this reason, allopurinol is often used before chemotherapy.

Diagnosis of gout:

            The diagnosis of acute or chronic gouty arthritis is made by demonstrating intracellular monosodium urate crystals in joint fluid. Urate crystals are needle shaped and negatively birefringent as viewed under polarized light. Extracellular crystals can often be found in synovial fluid or tissues in the intercritical period, occasionally allowing a tentative diagnosis to be made even after an acute attack has subsided. During an acute attack, synovial fluid has a high WBC count (2,000 – 100,000) with a predominance of polymorphonuclear leukocytes. The glucose is usually normal. A culture should always be sent, as gout can coexist with infectious arthritis as well as calcium pyrophosphate crystal deposition disease (see below). In advanced tophaceous gout, x-rays may show characteristic erosions with overhanging edges representing erosive tophaceous deposits. In the absence of an active joint effusion to tap, a tentative diagnosis may be made on the basis of a classic history of acute, self-limited attacks of monoarthritis, followed by intercritical periods, accompanied by chronically elevated uric acid levels.

Treatment of gout:

            There is rarely an indication for treating asymptomatic hyperuricemia. In the past, this condition was considered a possible risk factor for atherosclerosis and for chronic renal insufficiency, but both of these beliefs have been dispelled. The majority of patients with hyperuricemia have no symptoms and no adverse effects; therefore no treatment is warranted.

            During an acute attack of gout, changes in diuretics or other medications (including allopurinol) should be avoided. There is no indication for starting allopurinol during an acute attack of gout. The options for treatment include nonsteroidal anti-inflammatory drugs, colchicine, ACTH, oral or intraarticular corticosteroids, or, alternatively, pain medications alone.[xx]

            Nonsteroidals, unless contraindicated, should be the first line of treatment, keeping in mind the toxicities discussed above. Indomethacin is very effective in doses of 150-200 mg per day for two or three days and then tapered to 75-100mg daily over the next week. Naprosyn at doses of 500mg bid to tid or ibuprofen at a dose of 2400-3200 mg/day in divided doses. Other NSAIDS are probably also effective, but there is less experience with their use. COX-2 inhibitors have not been studied in the treatment of gout. In the face of renal insufficiency or severe hypertension, NSAIDS should be used in more sparing doses. Aspirin should be avoided, as low doses of aspirin inhibit renal clearance of uric acid, and very high doses increase renal clearance of uric acid – in either case potentially worsening or precipitating acute attacks.

            Colchicine is sometimes used as an alternative to nonsteroidals. It inhibits microtubules and the migration of polymorphonuclear neutrophils. Colchicine is most effective is administered in the first 24 hours after onset of symptoms: the earlier the better. It can be given orally, 0.6mg every hour, up to 6 to 8 tablets (4.8mg). However, diarrhea frequently ensues, and patients should be warned of this side effect. As the diarrhea often occurs before or coincidentally with relief of pain, the use of colchicine as a solitary agent is limited. Other adverse effects include bone marrow suppression, myopathy, neuropathy, oligospermia and amenorrhea. It should be used with caution in the face of renal insufficiency, hepatic insufficiency or marrow compromise. The use of intravenous colchicine is controversial because of its toxity; safer alternatives are almost always available.

            ACTH and intra-articular or systemic corticosteroids are alternatives whem nonsteroidals and colchicine are contraindicated because of the concurrence of gastrointestinal, cardiovascular or renal disease.[xxi]^,[xxii] ACTH, 40 IU given as a single IM injection may frequently be effective in treating acute gouty attacks. Its use is limited by the fact that it is rarely available outside of a hospital or emergency room. If symptoms persist, a second injection 12 hours later can be administered. Oral steroids, if appropriately tapered over a week, are usually very effective. One suggested regimen is prednisone 30 mg bid for two days, then 20 mg bid for two days, then 10mg bid for two days. Potential side effects of ACTH and short-course steroids are similar, and are usually limited to transient increases in blood sugar and blood pressure. The association of avascular necrosis with short courses of steroids remains controversial. Intraarticular steroids are useful when only one or two joints are involved and after infection has been excluded with a negative culture.

Prophylaxis of gout:

Patients whose lives are disrupted by frequent attacks of gout may be candidates for prophylactic therapy. Weight loss and restriction of alcohol should be recommended for all patients. Some patients describe attacks after eating particular foods with high purine content such as organ meats, herring, anchovies, sardines, bacon, or asparagus. Although may be useful to instruct these patients to avoid specific foods, general prudent dietary advice to maintain a normal weight and to avoid foods high in saturated fat will usually accomplish the same goal. If diuretics or other medications are a factor and alternative therapies are available, these changes should be made.

Colchicine, 0.6 mg once or twice daily, is usually effective prophylactic therapy. As the therapeutic window of this drug is extremely narrow, the dose may need to be adjusted in the setting of renal insufficiency, liver disease, or if the colchicine provokes diarrhea. Sometimes 0.6 mg every other day is effective in these patients. Colchicine should not be used at all in patients with bone marrow compromise. Myopathy, neuropathy and infertility can also result from chronic colchicine use. Patients should be carefully counseled about potential side effects.

Allopurinol therapy is indicated for patients with gout due to increased uric acid production, uric acid renal calculi, tophaceous or polyarticular gout, or as prophylaxis prior to cytolytic chemotherapy. Allopurinol inhibits xanthine oxidase and, thus, the formation of uric acid. Although generally well tolerated, it is associated with potential serious side effects, including rash, bone marrow suppression, hepatitis, and vasculitis. Renal insufficiency and concomitant diuretic use are risk factors for severe toxicity and the dose must be lowered in either setting. Some clinicians are inclined to institute allopurinol therapy earlier than others – arguing that even the first attack of gout reflects years of microcrystalline urate deposits in cartilage and other tissues and that prophylaxis with colchicine does not alter the progression of this process. Others argue that tophi or chronic gouty arthritis develop in only a minority of patients with gout and that allopurinol may reasonably be withheld until either a failure of colchicine prophylaxis or gross evidence of tophaceous deposits occurs. The level of uric acid may be a helpful tool in deciding which course to adopt; levels under 8 mg/dl are probably associated with only a small risk of the development of tophi, whereas at levels of 10 mg/dl or greater, the deposition of uric acid is likely to evolve much faster. When starting a patient on allopurinol, the patient’s gout must be quiescent and prophylactic colchicine should have been given for at least a week. Allopurinol should then be started at a dose of 100 mg a day and the dose titrated to the uric acid level, aiming for a level within the normal range. Colchicine should be continued during this titration to avoid attacks of gout induced by a falling uric acid level. The usual dose of allopurinol for a patient with normal renal function is 300mg/day. If the GFR is 40 ml/min, the recommended dose is 150 mg/day and when the GFR is less than 20, the recommended dose is 100 mg every second or third day.

Uricosuric agents such as probenecid and sulfinpyrazone may be useful in the appropriate setting. Although generally less effective than allopurinol, they may be helpful for patients under 60 years old without a history of uric acid stones, who have normal renal function and rates of urinary excretion less than 700 mg of uric acid per day.

Calcium Pyrophosphate Deposition Disease (CPPD): Pseudogout

Calcium pyrophosphate crystals were first identified in 1961 as a cause of acute arthritis simulating gout. The disease spectrum has since been expanded, as chronic, polyarticular forms of arthritis have been recognized. A great mimic, CPPD disease is also called pseudogout. It can simulate many of the other arthritides, presenting as acute, subacute or chronic disease.

The clincial prevalence of pseudogout compared to gout is approximately 1:2. If the presence of chondrocalcinosis on knee x-rays is used as a criterion, however, many minimally symptomatic, asymptomatic and undiagnosed patients are identified. The prevalence of chondrocalcinosis on x-ray is as high as 30 to 60 percent in people over 85 years. Although the majority of patients with CPDD have idiopathic disease, there are several metabolic disorders associated with the disease (Table 6). Pseudogout is clearly associated with hypercalcemic disorders such as hyperparathyroidism, as well as with hemochromatosis, where iron deposition in cartilage has been implicated. The precise disturbance in cartilage pathophysiology that leads to crystal formation is not known. Unless the disease is found in young patients or those with hypercalcemia or abnormal iron studies, there is no need for an extensive search for underlying metabolic causes.

TABLE 6: Classification of CPPD

            Diagnosis of CPPD is made by analysis of synovial fluid. The demonstration of intracellular birefringent calcium pyrophosphate dihydrate crystals is the most definitive way to make the diagnosis. However, these crystals may disintegrate after a few hours at room temperature – if there is a strong suspicion, repeat joint aspiration may be warranted. Linear calcifications along the fibrocartilage or hyaline cartilage of affected joints are called chondrocalcinosis and may provide adjunctive diagnostic information. Degenerative changes are often found in association.

            Treatment of CPPD is symptomatic. There is no agent that successfully reverses deposition or formation of calcium pyrophosphate in joints. Joint fluid aspiration, NSAIDS, and intraarticular corticosteroids are all useful for managing an acute attack. Colchicine 0.6 mg once or twice a day may be used as prophylaxis, as in gout.

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