SECONDARY GOUT

Hyperuricemia and gout may be a consequence of the overproduction of uric acid caused by an increased turnover of nucleic acids in myeloproliferative disorders, sickle cell anemia and other hemoglobinopathies, psoriasis, and other chronic diseases characterized by high rates of proliferation. Decreased excretion of uric acid can be a cause of secondary gout with prolonged use of diuretics and in nephritis due to lead poisoning (saturnine gout) or selective tubular dysfunction.

TREATMENT

Acute gouty arthritis can be effectively treated with high-dose NSAIDs, prednisone, intra-articular corticosteroids, an IL-1 antagonist, and, in some patients, with a low dose (1.2 mg followed by 0.6 mg 1 hour later) of colchicine. The choice of agent is usually dictated by comorbidities, patient preference, and cost. In the intercritical period between attacks, if the hyperuricemia is not excessive and the attacks are mild and infrequent, small daily doses of colchicine may suffice as prophylactic treatment. When the serum uric acid concentration is persistently high and attacks are frequent, and in all cases of chronic tophaceous gout, the serum uric acid level should be reduced to a level significantly below the saturation level of 6.7 mg/dL for the rest of the patient’s life. In most cases, this can be accomplished with administration of adequate daily dosages of the xanthine oxidase inhibitor allopurinol. Severe gout may require concurrent therapy with allopurinol and a uricosuric drug if the renal function is fairly normal. Frequent determinations of the serum uric acid concentration are required to monitor the effective dosage. This treatment program, which must be continued for the rest of the patient’s life, can virtually eliminate acute attacks of gouty arthritis, prevent the deposition of new urate crystals, and reduce existing tophaceous deposits over the course of several months. However, the initiation of hypouricemic therapy quite frequently causes acute attacks of gout. These attacks can be prevented or reduced with the use of low-dose daily colchicine (if renal function is good) for at least several months after initiating uric acid–lowering therapy. With proper treatment and patient compliance, gout can nearly always be controlled.

An uncommon, but severe complication of allopurinol is the risk of systemic hypersensitivity and desquamating skin reactions, which are more common in renally impaired individuals and those with the HLA-B5801 gene (which is particularly prevalent in some Asian populations). Febuxostat, an effective non–purine-selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol in these patients, although it is much more expensive in the United States.

Uric acid–lowering therapies may take years to resolve tophi. The speed of resolution is linked to how much the uric acid can be lowered. Pegloticase is a PEGylated mammalian recombinant uricase. In patients with severe chronic gout, pegloticase results in rapid and profound lowering of uric acid levels to well below 4 mg/dL (transiently to ~ 1 mg/dL right after infusion). Pegloticase is a treatment option (biweekly intravenous infusions) that may rapidly resolve tophi, but its use is complicated by anti-drug antibodies that cause significant infusion-related allergic reactions and loss of efficacy. The dramatic uric acid–lowering effect is predictably associated with dramatic and severe flares in gouty arthritis.