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Clinical characteristics of juvenile gout and treatment response to febuxostat
  1. Shaoling Zheng1,
  2. Pui Y Lee2,
  3. Yukai Huang1,
  4. Weiming Deng1,
  5. Zhixiang Huang1,
  6. Qidang Huang1,
  7. Shuyang Chen1,
  8. Tianwang Li1,3,4
  1. 1 Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China
  2. 2 Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA
  3. 3 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
  4. 4 Zhaoqing Central People‘s Hospital, Zhaoqing, Guangdong, China
  1. Correspondence to Dr Tianwang Li, Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China; litian-wang{at}

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Gout is a common form of inflammatory arthritis caused by hyperuricaemia and deposition of monosodium urate crystals.1 While risk factors and comorbidities associated with gout are well established in adults,2 3 few studies have examined gout in children.4 There is no treatment guideline for juvenile gout and little is known about the efficacy of urate-lowering therapy in children. Here, we describe the clinical characteristics of 111 patients with juvenile gout evaluated in our centre between 2016 and 2020. We also present data on the efficacy of febuxostat treatment in children.

Our cohort of patients with juvenile gout (age of onset ≤18 years) consisted of 107 males and 4 females. All patients met the 2015 ACR/EULAR Criteria for gout. The mean age of symptom onset was 15.2 years and the youngest patient was 9 years old (online supplemental table 1). Compared with adult gout cases (n=533) evaluated during the same period, body mass index was comparable between the groups (p=0.097). Hypertension and kidney stones were comorbidities of gout in adults but not children. Patients with juvenile gout were more likely to provide a family history of gout in first-degree or second-degree relatives (online supplemental table 1).

The most common site of gout attacks in children was finger joints while knee involvement was less prevalent compared with adults (figure 1A). The appearance of gout arthritis was difficult to distinguish from other forms of juvenile arthritis (figure 1B). Underscoring the importance of considering gout in the differential diagnosis of childhood arthritides, 51 patients (45.9%) would have fulfilled criteria for juvenile idiopathic arthritis (JIA) without confirmatory testing for gout (see online supplemental methods for further details on distinguishing juvenile gout and JIA). While the incidence of tophi was comparable between children and adults (28% vs 24%), tophi developed more rapidly in patients with juvenile gout (interval to tophi development: mean 1.5 years in children vs 7.5 years in adults; online supplemental table 1). Finger joints were the most common site for tophi development in children, compared with the metatarsophalangeal (MTP) joints in adults (online supplemental table 1). Birefringent crystals in the synovial fluid and tophi associated with juvenile gout are depicted in figure 1C and D.

Figure 1

Characteristics of gout in children and efficacy of febuxostat therapy. (A) Comparison of joint involvement in adults (n=533) and children (n=111) with gout. (B) Representative depiction of affected fingers and knee joint in juvenile gout. Red arrows indicate affected joints. (C) Polarised light microscopy image of synovial fluid birefringent crystals from patient with juvenile gout. (D) Tophi in third distal interphalangeal joint of a patient with juvenile gout. Red arrows indicated tophi on H&E section. (E) Comparison of the levels of serum uric acid and inflammatory markers in adults and children with gout. Box indicates median and IQR and whiskers denote 5th–95th percentile. (F) Serum uric acid levels in patients with juvenile gout at baseline (n=36), 1 month (n=37) and 3 months (n=24) after initiation of febuxostat therapy. *P<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Comparison of laboratory features revealed that patients with juvenile gout possessed higher serum uric acid levels than adults (mean 11.9 mg/dL vs 9.0 mg/dL; p=0.032) but less systemic inflammation, as reflected by lower erythrocyte sedimentation rate (mean 18 mm/hr vs 38 mm/hr; p<0.0001) and C-reactive protein levels (mean 9.5 mg/L vs 25.3 mg/L; p<0.0001).

Currently, there are no guidelines for the management of juvenile gout. Our patients with acute gout were treated with non-steroidal anti-inflammatory drugs and/or colchicine and counselled on dietary intervention. All patients with persistent hyperuricemia were offered urate-lowering treatment after acute gout attack was controlled. In our practice, the xanthine oxidase inhibitor febuxostat is the first-line treatment option for adults with gout due to the risk of allopurinol hypersensitivity.5 6 We employed a similar approach for juvenile gout and collected data from 37 patients treated with febuxostat (40 mg once a day).

A significant reduction in serum uric acid levels was observed after 1 month of febuxostat treatment (median reduction 3.6 mg/dL; figure 1F). The improvement in uric acid levels was sustained after 3 months. Importantly, the frequency of gout arthritis flare reduced markedly after treatment initiation (pretreatment: 176 events in 679 patient-months; post-treatment: 14 events in 493 patient-months; p<0.0001).

Adverse effects were recorded for four patients treated with febuxostat. Transient transaminase elevation was noted in 3 cases and resolved without treatment discontinuation. One patient developed rhabdomyolysis within 3 weeks of starting febuxostat and fully recovered 10 days after treatment discontinuation.

Juvenile gout is an aggressive joint disease that should be considered in the differential diagnosis for childhood arthritides. We showed that febuxostat is well tolerated in adolescents and effectively reduced uric acid levels and gout attacks. In our experience, the prognosis for patients with juvenile gout is generally favourable with effective control the uric acid levels. Larger controlled studies are needed to better understand the natural history of juvenile gout and the safety and efficacy of various urate-lowering agents in children.

Ethics statements

Patient consent for publication

Ethics approval

This study involves human participants and was approved by the Institutional Review Boards of Guangdong Second Provincial General Hospital (2019-NJJ-17-02). Participants gave informed consent to participate in the study before taking part.


We thank all patients and families for their participation.



  • Handling editor Josef S Smolen

  • SZ and PYL contributed equally.

  • Contributors SZ, PYL and TL conceived and designed the study. SZ, WD, ZH, QH and SC acquired data. SZ, PYL and YH analysed the data. SZ, PYL and TL drafted the manuscript and all authors edited the manuscript.

  • Competing interests None declared.

  • Patient and public involvement statement This research was done without direct patient involvement beyond sample collection. Patients did not participate in designing the study, analysing the data or drafting the manuscript.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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