- Deposition of microcrystals in joints and periarticular tissues results in gout, pseudogout, and apatite disease.
- Primary gouty arthritis. Men are much more commonly affected than women; most premenopausal women with gout have a family history of the disease.
- The clinical phases of gout can be divided into (a) asymptomatic hyperuricemia, (b) acute gouty arthritis, and (c) chronic arthritis.
- Asymptomatic hyperuricemia (uric acid levels >8 mg/dL in men and >7 mg/dL in women)
- Primary gouty arthritis is characterized by hyperuricemia that is usually due to underexcretion of uric acid (90% of cases) rather than to overproduction. Urate crystals may be deposited in the joints, SC tissues (tophi), and kidneys.
- Secondary gout, like primary gout, can be caused by either defective renal excretion or overproduction of uric acid. Intrinsic renal disease, diuretic therapy, low-dose aspirin, nicotinic acid, cyclosporine, and ethanol all interfere with renal excretion of uric acid. Starvation, lactic acidosis, dehydration, pre-eclampsia, and diabetic ketoacidosis also can induce hyperuricemia.
- Pseudogout results when calcium pyrophosphate dihydrate crystals deposited in bone and cartilage are released into synovial fluid and induce acute inflammation. Risk factors include older age, advanced osteoarthritis (OA), neuropathic joint, gout, hyperparathyroidism, hemochromatosis, diabetes mellitus, hypothyroidism, and hypomagnesemia.
- Acute gouty arthritis presents as an excruciating attack of pain, usually in a single joint of the foot or ankle. Occasionally, a polyarticular onset can mimic RA.
- Chronic gouty arthritis. With time, acute gouty attacks occur more frequently, asymptomatic periods are shorter, and chronic joint deformity may appear. Overproduction of uric acid occurs in myeloproliferative and lymphoproliferative disorders, hemolytic anemia, polycythemia, and cyanotic congenital heart disease.
- Pseudogout may present as an acute monarthritis or oligoarthritis mimicking gout or as a chronic polyarthritis resembling RA or OA. Usually the knee or wrist is affected, although any synovial joint can be involved.
- Apatite disease may present with periarthritis or tendonitis, particularly in patients with chronic renal failure. An episodic ligoarthritis also may occur.
- A definitive diagnosis of gout or pseudogout is made by finding intracellular crystals in joint fluid examined with a compensated polarized light microscope.
- Urate crystals, which are diagnostic of gout, are needle shaped and strongly negatively birefringent. The calcium pyrophosphate dihydrate crystals seen in pseudogout are pleomorphic and weakly positively birefringent. Hydroxyapatite
- complexes, diagnostic of apatite disease, and basic calcium phosphate complexes can be identified only by electron microscopy and mass spectroscopy. In most cases, the arthritides associated with these compounds are suspected clinically but never confirmed.
- Acute gouty arthritis. The serum uric acid level is normal in 30% of patients with acute gout and, if elevated, should not be manipulated until an attack has resolved.
- Apatite disease should be suspected when no crystals are present in the synovial fluid.
- Asymptomatic hyperuricemia is not routinely treated because of expense, potential drug toxicity, and the low risk for adverse outcome from the hyperuricemia itself.
- Management of secondary gout includes treatment of the underlying disorder and allopurinol therapy.
- The treatment of apatite disease is similar to that for pseudogout.
- NSAIDs are the treatment of choice due to ease of administration and low toxicity. Clinical response may require12â??24 hours, and initial doses should be high, followed by rapid tapering over 2-8 days, One approach is to use indomethacin,
- 50 mg PO q6h for 2 days, followed by 50 mg PO q8h for 3 days and then 25 mg PO q8h for 2-3 days. The long-acting NSAIDs generally are not recommended for acute gout. Selective COX-2 inhibitors appear to have similar efficacy.
- Glucocorticoids are useful when NSAIDs are contraindicated. An intra-articular injection of glucocorticoids produces rapid dramatic relief.
- Alternatively, prednisone, 40-60 mg PO daily, can be given until a response is obtained and then should be tapered rapidly.
- Colchicine is most effective if given in the first 12-24 hours of an acute attack and usually brings relief in 6-2 hours. In view of the efficacy and tolerability of a short course of NSAIDs, colchicine is not commonly used to treat gout but is useful when NSAIDs or glucocorticoids are contraindicated or not tolerated.
- Oral administration is often associated with severe GI toxicity. The dosage during an acute attack is 0.5-0.6 mg (one tablet) q1-2h for three dosages started at the first sign of the attack. Alternatively, colchicine 0.6 mg bid in addition to an NSAID can be used. The previous dosage regimen of 0.5-0.6 mg (one tablet) q1-2h or 1.0-1.2 mg q2h until symptoms abate, GI toxicity develops, or the maximum dose of 6 mg in a 24-hour period is reached is not recommended as primary treatment for most cases due to toxicity.
- IV colchicine is not recommended for general use and its administration in almost all circumstances is questionable.
Chronic gouty arthritis
- Colchicine (0.5-0.6 mg PO daily or bid) can be used prophylactically for acute attacks. The dosage needs to be adjusted in patients with renal insufficiency. Colchicine 0.6 mg every other day or every 3 days should be considered in patients with a creatinine clearance between 10 and 34 mL/min. Aspirin (uricoretentive), diuretics, large alcohol intake, and foods high in purines (sweetbreads, anchovies, sardines, liver, and kidney) should be avoided. The serum uric acid level should be lowered if arthritic attacks are frequent, renal damage is present, or serum or urine uric acid levels are elevated consistently. Maintenance colchicine, 0.5â??0.6 mg PO bid, should be given a few days before manipulation of the uric acid level to prevent precipitation of an acute attack. If no attacks occur after the uric acid has been maintained in the normal range for 6-8 weeks, colchicine can be discontinued.
- Allopurinol, a xanthine oxidase inhibitor, is effective therapy for hyperuricemia in most patients. Dosage and administration. The initial dosage is usually 300 mg PO daily. Daily doses can be increased by 100 mg every 2-4 weeks to achieve the minimum maintenance dosage that will keep the uric acid level within the normal range. In patients with impaired renal function, the daily dose should be reduced by 50 mg for each 20-mL/min decrease in the creatinine clearance. For patients with a creatinine clearance below 20 mL/min, the starting dosage is 100 mg every other or every third day. The daily dose should be decreased also in patients with hepatic impairment. The concomitant use of a uricosuric agent may hasten the mobilization of tophi. If an acute attack occurs during treatment with allopurinol, it should be continued at the same dosage while other agents are used to treat the attack. Side effects. Hypersensitivity reactions from a minor skin rash to a diffuse exfoliative dermatitis associated with fever, eosinophilia, and a combination of renal and hepatic injury occur in up to 5% of patients. Patients who have mild renal insufficiency and are receiving diuretics are at greatest risk. Severe cases are potentially fatal and usually require glucocorticoid therapy. Allopurinol may potentiate the effect of oral anticoagulants and blocks metabolism of azathioprine and 6-mercaptopurine, necessitating a 60%-75% reduction in dosage of these cytotoxic drugs.
- Febuxostat, a new class of uric acidâ??lowering drug, is a nonpurine selective inhibitor of the xanthine oxidase that is expected to be available Uricase catabolizes uric acid to the more soluble compound, allantoin. It is available in the United States for the treatment of tumor lysis syndrome.
- Uricosuric drugs lower serum uric acid levels by blocking renal tubular reabsorption of uric acid. A 24-hour measurement of creatinine clearance and urine uric acid should be obtained before therapy is started, as these drugs are ineffective with glomerular filtration rates of <50 mL/min. They are also not recommended for patients who already have high levels of urine uric acid (800 mg/24 hours) because of the risk of urate stone formation. This risk can be minimized by maintaining a high fluid intake and by alkalinizing the urine. If these drugs are being used when an acute gouty attack begins, they should be continued while other drugs are used to treat the acute attack. Probenecid Initial dosage is 500 mg PO daily, which can be raised in 500-mg increments every week until serum uric acid levels normalize or urine uric acid levels exceed 800 mg/24 hours. The maximum dose is 3,000 mg/d. Most patients require a total of 1.0-1.5 g/d in two to three divided doses.
- Salicylates and probenecid are antagonistic and should not be used together. Probenecid decreases renal excretion of penicillin, indomethacin, and sulfo- nylureas. Side effects are minimal.
- Sulfinpyrazone has uricosuric efficacy similar to that of probenecid; however, it also inhibits platelet function. The initial dosage of 50 mg PO bid can be increased in 100-mg increments weekly until serum uric acid levels normalize, to a maximum dose of 800 mg/d. Most patients require 300-400 mg/d in three to four divided doses.
- As in gout, the therapy of choice for most patients is a brief high-dose course of an NSAID (see Therapeutic Approaches to Rheumatic Disease).
- Oral corticosteroids can be used and colchicine also may relieve symptoms promptly, but toxicity limits its use. Dosage and administration are similar to the ones used in the treatment of gout.
- Maintenance daily PO colchicine may diminish the number of recurrent attacks. Allopurinol or uricosuric agents have no role in treating pseudogout.
- Aspiration of the inflammatory joint fluid often results in prompt improvement and intra-articular injection of glucocorticoids may hasten the response.