Prevalence of gout and asymptomatic hyperuricemia in the pediatric population: a cross-sectional study of a Japanese health insurance database

Background Although gout is rare in children, chronic sustained hyperuricemia can lead to monosodium urate deposits progressing to gout, just as in adults. This study assessed prevalence and characteristics of gout and asymptomatic hyperuricemia, and incidence of gouty arthritis in the pediatric population, using data from Japanese health insurance claims. The diagnosis and treatment of pediatric gout and hyperuricemia were analyzed, and specific characteristics of those patients were assessed. Since Japanese guidelines recommend treatment with uric acid lowering drugs for asymptomatic hyperuricemia as well as for gout, these data were also used to investigate the real-world use of uric acid lowering drugs in a pediatric population. Methods This cross-sectional study was based on a 2016–2017 Japanese health insurance claims database, one of the largest epidemiology claims databases available in Japan, which included 356,790 males and 339,487 females 0–18 years of age. Outcomes were measured for prevalence, patient characteristics, treatment with uric acid lowering drugs for gout and asymptomatic hyperuricemia, and prevalence and incidence of gouty arthritis. Because uric acid can be elevated by some forms of chemotherapy, data from patients under treatment for malignancies were excluded from consideration. Results Total prevalence of gout and asymptomatic hyperuricemia in 0–18 year-olds was 0.040% (276/696,277 patients), with gout prevalence at 0.007% (48/696,277) and asymptomatic hyperuricemia at 0.033% (228/696,277). Prevalence of gout and asymptomatic hyperuricemia was highest in adolescent males, at 0.135% (176/130,823). The most common comorbidities for gout and asymptomatic hyperuricemia were metabolic syndrome at 42.8% (118/276) and kidney disease at 34.8% (96/276). Of the patients diagnosed with gout or asymptomatic hyperuricemia, 35.1% (97/276) were treated with uric acid lowering drugs. Gouty arthritis developed in 43.8% (21/48) of gout patients during the study, at an incidence of 0.65 flares/person-year. Conclusions Even the pediatric population could be affected by asymptomatic hyperuricemia, gout, and gouty arthritis, and uric acid lowering drugs are being used in this population even though those drugs have not been approved for pediatric indications. Such off-label use may indicate a potential need for therapeutic agents in this population. Trial registration UMIN000036029.

a cross-sectional study of a Japanese health insurance database Contents: in patients diagnosed with gout and asymptomatic hyperuricemia (n = 276) 7 Table S1 List of definitions

Gout
Patients for whom any of the following applied for the period from April 2016 to March 2017.
-Code M10 (Gout) under the ICD10 coding system twice or more in separate months -Code M10 (Gout) under the ICD10 coding system once or more, and one or more prescriptions for M04 (Antigout preparations) by ATC code and gout diagnosis shown on the same insurance claim form.
-Code M10 (Gout) under the ICD10 coding system once or more, and one or more prescriptions for M01A1 (Anti-rheumatics, non-steroidal plain) or H02A2 (Oral corticosteroids, plain) by ATC code and gout diagnosis shown on the same insurance claim form.
Satisfying the above criteria and with no instances of Code M352 (Behçet's disease) under the ICD10 coding system or Code 8831283 (familial Mediterranean fever) under Standard disease code.

Asymptomatic hyperuricemia
Patients for whom the definition of gout did not apply and any of the following applied for the period from April 2016 to March 2017.
-Code E790 (Hyperuricaemia without signs of inflammatory arthritis and tophaceous disease) under the ICD10 coding system twice or more in separate months.
-Code E790 (Hyperuricaemia without signs of inflammatory arthritis and tophaceous disease) under the ICD10 coding system once or more, and one or more prescriptions for M04 (Antigout preparations) by ATC code and diagnosis for hyperuricaemia without signs of inflammatory arthritis and tophaceous disease shown on the same insurance claim form.

Drug treatment with uric acid lowering drug for gout patients
Patients for whom the following applied for the period from April 2016 to March 2017.
coding system once or more, and one or more prescriptions for M04 (Antigout preparations excluding colchicine) by ATC code and gout diagnosis shown on the same insurance claim form.

Drug treatment with uric acid lowering drug for asymptomatic hyperuricemia patients
Patients for whom the definition of drug treatment with uric acid lowering drugs for gout did not apply and any of the following applied for the period from April 2016 to March 2017.
-Satisfying the definition of asymptomatic hyperuricemia, with code E790 (Hyperuricaemia without signs of inflammatory arthritis and tophaceous disease) under the ICD10 coding system once or more, and one or more prescriptions for M04 (Antigout preparations excluding colchicine) by ATC code and diagnosis for hyperuricaemia without signs of inflammatory arthritis and tophaceous disease shown on the same insurance claim form.

Malignant tumor
Patients for whom the following condition applied for the period from April 2016 to   note that colchicine is excluded * Use is defined as follows: Code M10 (Gout) under the ICD10 coding system once or more, and one or more prescriptions for each ATC code and diagnosis shown on the same insurance claim form during the survey period. † Use is defined as follows: Code M10 (Gout) or E790 (Hyperuricaemia without signs of inflammatory arthritis and tophaceous disease) under the ICD10 coding system once or more, and one or more prescriptions for each ATC code and diagnosis shown on the same insurance claim form is given during the survey period.

Gouty arthritis
Code M10 (Gout) by ICD10 coding system once or more, and diagnosis for gout and prescriptions for ATC codes M01A1 (Anti-rheumatics, non-steroidal plain) or H02A2 (Oral corticosteroids, plain), or colchicine (generic name) shown on the same insurance claim form.
Confirming of intervals between prescriptions for the above-mentioned drugs; if the same drug is prescribed a second time after a no-prescription interval of 14 days or more, that will be counted as a new attack of gouty arthritis.
ICD10 International statistical classification of diseases and related health problems 10th revision, ATC anatomical therapeutic chemical classification system, ACE angiotensin-converting enzyme, ARB angiotensin II receptor blocker, NSAID nonsteroidal antiinflammatory drug