What is the treatment approach for hyperuricemia in pediatric patients?

Treatment of Hyperuricemia in Pediatric Patients

The treatment approach for hyperuricemia in pediatric patients depends critically on the underlying cause and risk stratification: high-risk patients (particularly those with malignancy-related tumor lysis syndrome) require aggressive hydration plus rasburicase, intermediate-risk patients should receive hydration plus allopurinol (or single-dose rasburicase), and low-risk patients need only close monitoring, while asymptomatic hyperuricemia without gout or tumor lysis syndrome should not be treated. 1, 2

Risk Stratification and Context-Specific Management

High-Risk Pediatric Patients (Malignancy/Tumor Lysis Syndrome)

For high-risk pediatric patients, particularly those with leukemia, lymphoma, or solid tumors receiving chemotherapy, rasburicase combined with aggressive hydration is the recommended initial management. 1

• Rasburicase rapidly degrades existing uric acid to allantoin (5-10 times more soluble than uric acid), making it superior to allopurinol when pre-existing hyperuricemia ≥7.5 mg/dL is present 1, 3
• Hydration should target 2-3 L/m²/day with urine output goals of 80-100 mL/m²/h, using one-quarter normal saline with 5% dextrose 3
• Critical contraindication: Screen for G6PD deficiency before rasburicase administration, particularly in African American, Mediterranean, or Southeast Asian patients, as rasburicase can cause methemoglobinemia or hemolytic anemia in G6PD-deficient patients 1, 3
• These patients should be admitted to an intensive care unit or similarly monitored area with ready access to dialysis 1
• Rasburicase is FDA-approved for pediatric patients ages 1 month to 17 years for initial management of plasma uric acid levels in malignancy-related tumor lysis syndrome 4

Intermediate-Risk Pediatric Patients

For intermediate-risk pediatric patients, allopurinol combined with hydration is the appropriate first-line therapy, though a single dose of rasburicase may be considered. 1

• Allopurinol dosing: 10 mg/kg/day divided every 8 hours orally (maximum 800 mg/day) or 50-100 mg/m² every 8 hours (maximum 300 mg/m²/day) 3, 5
• For children 6-10 years with secondary hyperuricemia from malignancies: 300 mg daily; children under 6 years: 150 mg daily 5
• Allopurinol blocks xanthine oxidase, preventing new uric acid formation but does not reduce existing elevated levels 1
• Dose reduction by 50% or more is mandatory in renal impairment: with creatinine clearance 10-20 mL/min use 200 mg daily; with creatinine clearance <10 mL/min use maximum 100 mg daily 3, 5

Low-Risk Pediatric Patients

For pediatric patients unlikely to develop tumor lysis syndrome, a watch-and-wait approach with close monitoring is entirely appropriate without pharmacologic intervention. 1

Asymptomatic Hyperuricemia Without Malignancy

Asymptomatic hyperuricemia discovered incidentally on laboratory testing should NOT be treated in pediatric patients, as no data support metabolic health benefits from targeting asymptomatic hyperuricemia without symptoms such as gout or tophi. 2

• Treatment is indicated only for documented gout attacks, chronic gouty arthritis, visible tophi, or high-risk tumor lysis syndrome 2
• Gout is extremely rare in children; when present, it necessitates evaluation for underlying enzymatic defects in purine metabolism or chronic conditions (Down syndrome, metabolic disease, congenital heart disease) 6, 7
• Obesity is a major cause of hyperuricemia in otherwise healthy children and adolescents, associated with metabolic syndrome components 6

Critical Hydration Principles

• Withhold potassium, calcium, and phosphate from initial hydration fluids due to risks of hyperkalemia, hyperphosphatemia, and calcium phosphate precipitation 3
• Monitor urine-specific gravity and maintain at 1.010 3
• Urinary alkalinization is NOT recommended: no unequivocal evidence of efficacy exists, and alkalinization may increase calcium phosphate crystal precipitation risk 1
• Alkalinization is only indicated for patients with metabolic acidosis 1

Special Populations: Cardiac Surgery Patients

In pediatric cardiac surgery patients with hyperuricemia, fluid management must be adapted to cardiac function and volume status, with cardiac function taking precedence over standard aggressive hydration protocols. 3

• These patients often have compromised cardiac output and may not tolerate aggressive fluid loading 3
• Allopurinol remains first-line unless severe pre-existing hyperuricemia (≥7.5 mg/dL) is present, in which case rasburicase is preferred 3

Critical Safety Considerations

Allopurinol-Specific Warnings

• Skin rash is the most frequent adverse reaction; treatment must be discontinued immediately if rash develops due to potential for life-threatening hypersensitivity reactions 8, 5
• Allopurinol can cause Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome with 25% mortality rate 8
• Patients with HLA-B*5801 haplotype have 80-580 fold increased risk of allopurinol hypersensitivity (6-7% frequency in Asian populations, 1% in European populations) 8
• Drug interactions requiring dose adjustments: reduce 6-mercaptopurine or azathioprine doses by 65-75% when starting allopurinol; adjust for concurrent thiazide diuretics, cyclosporine, and dicumarol 3
• Allopurinol reduces clearance of high-dose methotrexate and is contraindicated with cyclophosphamide due to increased bone marrow suppression 1

Rasburicase-Specific Warnings

• Contraindicated in pregnancy (may cause fetal harm based on animal studies showing structural abnormalities and embryo-fetal mortality at 5-times human exposure) 4
• Breastfeeding not recommended during treatment and for 2 weeks after last dose 4
• Children <2 years had higher uric acid AUC and lower rates of achieving normal uric acid by 48 hours (83%) compared to ages 2-17 years (93%) 4

Monitoring Parameters

• Serum uric acid levels should be monitored regularly to guide therapy, with target <6.0 mg/dL in gout patients 2, 5
• Renal function (creatinine clearance) is crucial for determining allopurinol dosing 3, 5
• Electrolytes must be monitored for hyperkalemia and hyperphosphatemia 3
• Response to therapy in children with malignancy-associated hyperuricemia should be evaluated after approximately 48 hours 5

Common Pitfalls to Avoid

• Do not use allopurinol alone if uric acid is already ≥7.5 mg/dL, as it will not reduce pre-existing levels quickly enough 3
• Do not continue full-dose allopurinol in renal impairment without dose reduction 3, 5
• Do not add potassium to IV fluids initially due to hyperkalemia risk 3
• Do not use standard aggressive hydration protocols in cardiac patients without considering cardiac function 3
• Do not administer rasburicase without screening for G6PD deficiency 1, 3