The 100 top-cited articles in gout: A bibliometric analysis

Abstract

Background:

Numerous studies have investigated gout; however, a focused bibliometric evaluation of the most influential publications remains limited. This study identified and analyzed the top 100 most-cited articles on gout.

Methods:

The Web of Science Core Collection Science Citation Index Expanded database was searched using the term “gout.” Articles published from January 1, 2000 to April 30, 2026 were screened. The top 100 most-cited articles were selected, and data on citation rank, publication year, journal, impact factor, country, institution, author, study type, research topic, and keywords were extracted. Bibliometric analyses were performed to characterize publication patterns and research trends.

Results:

The most-cited article was published in 2006 and received 4359 citations. The top 100 articles were published in 34 journals, with Annals of the Rheumatic Diseases contributing the largest proportion. The United States was the leading contributing country. The University of Pennsylvania was the most productive institution, and Choi HK was the most prolific author. Observational studies were the most common study design. Keyword co-occurrence analysis identified 4 major research domains: epidemiology, pathophysiological mechanisms, pain management, and comorbidities. Frequently occurring keywords included hyperuricemia, gout, management, risk, arthritis, uric acid, prevalence, coronary heart disease, quality of life, and febuxostat.

Conclusion:

This bibliometric analysis summarizes the most influential publications in gout research from 2000 to 2026. Major research priorities have shifted from serum urate, diagnosis, and pharmacological treatment toward risk assessment, long-term outcomes, disease burden, and comprehensive management. Hyperuricemia and urate-lowering therapy remain central themes, while emerging topics such as gut microbiota suggest increasing interest in multidisciplinary and precision approaches to gout care.

1. Introduction

Gout is a metabolic arthritic disorder characterized by elevated serum urate levels and the deposition of monosodium urate (MSU) crystals in joints and surrounding tissues. The disease can lead to recurrent episodes of acute inflammatory arthritis, tophi formation, irreversible joint damage, and renal impairment, while also increasing the risk of cardiovascular diseases (CVDs), metabolic syndrome, and other comorbidities. As a consequence of dietary changes, increasing obesity rates, sedentary lifestyles, and other environmental factors, both the incidence and prevalence of gout have risen substantially worldwide over recent decades. Moreover, the age of disease onset has gradually decreased, making gout an increasingly important public health concern that imposes a considerable socioeconomic burden. Consequently, gout has become a major focus of research in the fields of rheumatology, immunology, and metabolic diseases.

With the continuous advancement of basic science and clinical investigations, the volume of gout-related publications has expanded rapidly, contributing to an increasingly sophisticated body of knowledge. Among these publications, highly cited articles represent the most influential and widely recognized scientific contributions within the field. Such studies often establish foundational theories, report landmark discoveries, and shape authoritative clinical guidelines and therapeutic strategies. Therefore, highly cited literature provides valuable insight into the intellectual foundations, historical development, and scientific evolution of a research discipline.

To date, most bibliometric studies on gout have focused on the overall publication landscape, emphasizing publication trends, collaborative networks, and keyword-based hotspot analyses. Although these investigations have provided a broad overview of research activity, they have paid relatively little attention to the most influential publications that have fundamentally shaped the field. As a result, a systematic evaluation of highly cited articles remains lacking, limiting our understanding of the seminal studies, major scientific breakthroughs, and knowledge structure underlying contemporary gout research.

By characterizing the most influential literature in gout research, this study provides a historical perspective on the evolution of scientific knowledge, highlights established and emerging research priorities, and offers evidence-based insights for researchers seeking to identify future directions and opportunities in the field.

2. Methods

2.1. Inclusion criteria and exclusion criteria

A comprehensive literature search was conducted in the Science Citation Index Expanded (SCI-Expanded) database of the Web of Science Core Collection to identify influential publications related to gout. Given that gout was the primary focus of this study, the search strategy was defined as TS = “gout.” The search was restricted to articles published between January 1, 2000, and April 30, 2026. The inclusion criteria were as follows: publications indexed in the SCI-Expanded database; document type classified as original research articles; articles published in English; and studies in which gout was a central research topic. Search results were ranked in descending order according to the total number of citations, and the 100 most-cited articles closely related to gout were manually selected for further analysis. The exclusion criteria included review articles, guidelines, recommendations, position statements, meta-analyses, commentaries, letters, editorials, conference papers, and publications unrelated to the main topic of gout. The detailed screening process is illustrated (Fig. 1). To ensure the accuracy and reliability of study selection, all eligible articles were independently screened and verified by 2 investigators (Z.B. Zhao and Y.Y. Wang). Any discrepancies regarding article eligibility were resolved through discussion and consultation with a third senior reviewer (C.J. Li) until consensus was reached. This study does not require ethical review because all the data are from publicly available databases and do not involve human participants or identifiable personal information.

Figure 1.

Flowchart for gout research data collection and analysis.

2.2. Article selection and classification criteria

This study selected the top 100 most-cited articles in the field of gout as the research sample, using citation count as the ranking criterion. The primary objective was to investigate the characteristics, hotspots, and evolution of highly cited publications in the field. Highly cited articles represent the most recognized and influential contributions within a discipline and thus possess exemplary research value. In addition, a detailed manual review and quantitative analysis of multiple dimensions (including content, research topics, authorship, and institutional affiliations) were conducted. Considering both the research timeline and the analytical workload, a sample size of 100 articles was deemed reasonable, balancing comprehensiveness and efficiency. This sample size is also commonly employed in bibliometric studies within the field. It should be noted that the selection was not random; instead, it was purposefully directed toward high-impact literature in alignment with the study objectives. This approach effectively minimizes selection bias while ensuring that the sample accurately reflects the core and seminal research in gout.

All citation data were retrieved from the SCI-Expanded database within the Web of Science Core Collection on May 6, 2026. To minimize potential bias caused by continuous citation accumulation, all citation data were extracted on a single predefined date (May 6, 2026). This approach ensured consistency in citation measurements across all included publications. To minimize potential bias caused by continuous citation accumulation, all citation data were extracted on a single predefined date (May 6, 2026). This approach ensured consistency in citation measurements across all included publications.

Articles were categorized based on study design and research focus.

Study type classification:

• Observational studies included cross-sectional studies, case–control studies, and retrospective or prospective cohort studies.

• Clinical studies were defined as investigations involving human patients, in which cases were collected and interventions (pharmacological or otherwise) were applied to alleviate gout symptoms or pain.

• Animal experimental studies were defined as investigations using experimental animals, in which interventions (e.g., drugs or other approaches) were employed to explore therapeutic effects or elucidate the pathophysiological mechanisms of gout.

Research content classification:

• Epidemiological research included studies analyzing the incidence, prevalence, diagnosis, or case collection of gout.

• Mechanistic research encompassed studies investigating the pathophysiological mechanisms of gout or the action mechanisms of targeted drugs.

• Gout pain management research included studies assessing interventions aimed at alleviating gout symptoms or pain.

• Gout-related disease research referred to studies exploring diseases secondary to gout or comorbid conditions associated with gout.

2.3. Citation analysis

This study was conducted in accordance with established methodologies commonly used in previous bibliometric analyses. In addition to citation counts, the following information was extracted from each included article: publication year, total citations, research topic, study type, 1st author, country of origin, affiliated institution, and journal information.

To improve data accuracy and reduce inconsistencies arising from variations in naming conventions, all retrieved terms underwent a standardization process prior to analysis. Specifically, different expressions referring to the same author, institution, country, or keyword were merged into a unified format.

Particular attention was given to the relationships among authors, institutions, countries, and keywords within the database. Bibliometric analyses were performed to evaluate collaborative networks, knowledge structures, and research hotspots in the field of gout. Co-occurrence and collaboration patterns among these entities were further explored to identify influential contributors, major research themes, and emerging trends.

2.4. Statistical analysis and bibliometric network construction

Statistical analyses were conducted using Microsoft Excel. VOSviewer (version 6.4.R1, Centre for Science and Technology Studies, Leiden University, the Netherlands) was employed to construct co-occurrence networks for authors, countries, institutions, and keywords. CiteSpace (version 1.6.20, Drexel University, Philadelphia) was used to generate cluster maps, timeline visualizations, and keyword burst maps, facilitating the identification of research hotspots and temporal trends. In addition, Carrot2 software was applied to extract noun phrases from keywords and abstracts, thereby enhancing the visualization and interpretability of the keyword networks. These combined bibliometric and visualization approaches allowed for a comprehensive analysis of collaboration patterns, knowledge structures, and emerging trends in gout research.

3. Results

Based on total citation counts, the top 100 most-cited articles on gout were summarized in descending order (Table 1). These publications spanned the years 2000 to 2022, with the highest number of articles published in 2009 (n = 11). Regarding study design, observational studies predominated (n = 67), followed by clinical studies (n = 30) and animal experimental studies (n = 3). In terms of research focus, epidemiological studies accounted for the largest proportion (n = 41), followed by pain management studies (n = 38), mechanistic studies (n = 13), and studies on gout-related diseases (n = 8).

Table 1.

The top 100 cited articles in gout.

Publication year	Citation	Average citation	Title	Research content	Study type	Country	Fist institute	Journal	IF	Cited reference count
2006	4359	217.95	Gout-associated uric acid crystals activate the NALP3 inflammasome	Mechanism of gout	Observational study	Switzerland	University of Lausanne	Nature	48.5	30
2011	1404	93.60	Prevalence of gout and hyperuricemia in the US general population The National Health and Nutrition Examination Survey 2007–2008	Epidemiology of gout	Observational study	USA	Boston University	Arthritis Rheum-US	#	41
2005	1027	48.90	Febuxostat compared with allopurinol in patients with hyperuricemia and gout	Pain management of gout	Clinical trials	USA	University of Chicago	New Engl J Med	78.5	37
2019	853	121.86	Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: The National Health and Nutrition Examination Survey, 2007–2016	Epidemiology of gout	Observational study	USA	Harvard University	Arthritis Rheumatol	10.9	43
2004	832	37.82	Purine-rich foods, dairy and protein intake, and the risk of gout in men	Epidemiology of gout	Observational study	USA	Harvard University	New Engl J Med	78.5	35
2018	706	88.25	Cardiovascular safety of febuxostat or allopurinol in patients with gout	Pain management of gout	Observational study	USA	University of Connecticut	New Engl J Med	78.5	22
2007	591	31.11	A pilot study of IL-1 inhibition by anakinra in acute gout	Mechanism of gout	Observational study	Switzerland	University of Lausanne	Arthritis Res Ther	4.6	17
2008	578	32.11	Association of 3 genetic loci with uric acid concentration and risk of gout: a genome-wide association study	Epidemiology of gout	Observational study	USA	National Institutes of Health (NIH)	LANCET	88.5	47
2012	556	39.71	Decreased extra-renal urate excretion is a common cause of hyperuricemia	Mechanism of gout	Observational study	Japan	Tokyo University of Pharmacy & Life Sciences	Nat Commun	15.7	41
2009	542	31.88	Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout	Epidemiology of gout	Observational study	USA	Johns Hopkins University	Proc Natl Acad Sci USA	9.1	30
2007	524	27.58	Independent impact of gout on mortality and risk for coronary heart disease	Gout-related diseases	Observational study	Canada	Arthritis Research Canada	Circulation	38.7	38
2012	510	36.43	Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007–2008	Gout-related diseases	Observational study	USA	Boston University	Am J Med	5.3	34
2015	508	46.18	Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study	Epidemiology of gout	Observational study	UK	University of Nottingham	Ann Rheum Dis	20.6	43
2008	492	27.33	Effects of febuxostat vs allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase iii, randomized, double-blind, parallel-group trial	Pain management of gout	Observational study	USA	University of Pennsylvania	Arthrit Rheum-Arthr	#	41
2011	485	32.33	Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment two randomized controlled trials	Pain management of gout	Clinical trials	USA	Duke University	JAMA-J Am Med Assoc	55	38
2010	410	25.63	The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial	Pain management of gout	Clinical trials	USA	Harvard University	Arch Intern Med	*	28
2008	388	21.56	Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study	Pain management of gout	Clinical trials	USA	University of Chicago	Arthritis Res Ther	4.6	49
2006	385	19.25	MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals	Mechanism of gout	Observational study	Canada	University of British Columbia	BMJ-Brit Med J	43	66
2010	385	24.06	High vs low dosing of oral colchicine for early acute gout flare twenty-four-hour outcome of the first multicentre, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study	Pain management of gout	Clinical trials	USA	University of Massachusetts System	J Clin Invest	13.6	62
2008	374	20.78	Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005	Pain management of gout	Clinical trials	USA	University of California System	Arthritis Rheum-US	*	27
2009	373	21.94	Common defects of ABCG2, a high-capacity urate exporter, cause gout: A function-based genetic analysis in a Japanese Population	Epidemiology of gout	Observational study	Belgium	Ghent University	Ann Rheum Dis	20.6	32
2003	371	16.13	Gout	Mechanism of gout	Observational study	USA	University of Miami	Am J Physiol-Cell Ph	4.8	59
2002	361	15.04	Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout	Pain management of gout	Clinical trials	USA	National Defense Medical College - Japan	Sci Transl Med	14.7	59
2007	347	18.26	Prevalence of the metabolic syndrome in patients with gout: The Third National Health and Nutrition Examination Survey	Epidemiology of gout	Observational study	Japan	US Department of Veterans Affairs	New Engl J Med	78.5	53
2004	356	16.18	A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: Evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy	Pain management of gout	Clinical trials	Spain	Hospital Universitario Cruces	Arthrit Rheum-Arthr	*	30
2006	339	16.95	Gout and the risk of acute myocardial infarction	Gout-related diseases	Observational study	Canada	University of British Columbia	Arthrit Rheum-Arthr	*	44
2011	336	22.40	Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout	Mechanism of gout	Observational study	Japan	Tokyo Women’s Medical University	Arthrit Rheum-Arthr	*	15
2004	331	15.05	Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population	Epidemiology of gout	Observational study	USA	Pennsylvania Commonwealth System of Higher Education (PCSHE)	Arthritis Rheum-US	*	36
2005	328	15.62	Gout epidemiology: results from the UK general practice research database, 1990–1999	Epidemiology of gout	Observational study	USA	Democritus University of Thrace	PLOS One	2.6	38
2017	321	35.67	β-Hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares	Mechanism of gout	Observational study	USA	Abbott Laboratories	J Rheumatol	3.4	14
2005	453	21.57	Obesity, weight change, hypertension, diuretic use, and risk of gout in men - The health professionals follow-up study	Epidemiology of gout	Observational study	USA	University of Alabama System	Ann Rheum Dis	20.6	30
2008	373	20.72	Probenecid, a gout remedy, inhibits pannexin 1 channels	Mechanism of gout	Observational study	USA	Yale University	Cell Rep	6.9	48
2016	309	30.90	Intestinal microbiota distinguish gout patients from healthy humans	Epidemiology of gout	Observational study	Singapore	National University of Singapore	Sci Rep-UK	3.9	42
2006	299	14.95	Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase	Pain management of gout	Observational study	USA	Duke University	Arthritis Res Ther	4.6	35
2002	283	11.79	Epidemiology of gout: Is the incidence rising?	Epidemiology of gout	Observational study	USA	Mayo Clinic	J Rheumatol	3.4	12
2020	275	45.83	Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomized, open-label, non-inferiority trial	Pain management of gout	Clinical trials	UK	University of Dundee	LANCET	88.5	22
2007	269	14.16	Diagnosis of gout by ultrasound	Epidemiology of gout	Observational study	USA	Rutgers University System	Rheumatology	4.4	30
2005	269	12.81	Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase	Pain management of gout	Observational study	Japan	Teijin Pharma Limited	Life Sci	5.1	45
2009	264	15.53	Dual-energy computed tomography in tophaceous gout	Epidemiology of gout	Observational study	Canada	University of British Columbia	Ann Rheum Dis	20.6	15
2004	254	11.55	Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis	Pain management of gout	Clinical trials	USA	United States Department of Defense	J Rheumatol	3.4	25
2012	254	18.14	Canakinumab for acute gouty arthritis in patients with limited treatment options: results from 2 randomized, multicentre, active-controlled, double-blind trials and their initial extensions	Pain management of gout	Clinical trials	USA	Rutgers University System	Ann Rheum Dis	20.6	46
2020	250	41.67	Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial	Pain management of gout	Clinical trials	Netherlands	Radboud University Nijmegen	LANCET Rheumatol	16.4	30
2014	240	20.00	Induced and preexisting anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients	Pain management of gout	Clinical trials	USA	Duke University	Arthritis Res Ther	4.6	21
2009	240	14.12	The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomized, single-blind pilot study	Pain management of gout	Clinical trials	USA	University of California System	Ann Rheum Dis	20.6	13
2006	239	11.95	Gout medication treatment patterns and adherence to standards of care from a managed care perspective	Pain management of gout	Clinical trials	USA	HealthCore, Inc	Mayo Clin Proc	6.7	15
2000	236	9.08	Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study	Pain management of gout	Clinical trials	South Africa	University of Witwatersrand	Ann Rheum Dis	20.6	29
2012	223	15.93	NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B4 in a murine model of gout	Mechanism of gout	Animal experiment	Brazil	Universidade Federal de Minas Gerais	Arthritis Rheum-US	*	50
2015	217	19.73	Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study	Epidemiology of gout	Observational study	USA	Mayo Clinic	Ann Rheum Dis	20.6	18
2000	217	8.35	The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study	Epidemiology of gout	Observational study	China	National Yang Ming Chiao Tung University	J Rheumatol	3.4	34
2015	217	19.73	A Role for Gut Microbiota and the Metabolite-Sensing Receptor GPR43 in a Murine Model of Gout	Mechanism of gout	Animal experiment	Brazil	Universidade Federal de Minas Gerais	Arthritis Rheumatol	10.9	44
2008	216	12.00	Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China	Epidemiology of gout	Observational study	China	Qingdao University	J Rheumatol	3.4	24
2008	216	12.00	Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomized equivalence trial	Pain management of gout	Clinical trials	Netherlands	Radboud University Nijmegen	LANCET	88.5	37
2013	213	16.38	Epidemiology of gout and hyperuricemia in Italy during the years 2005–2009: a nationwide population-based study	Epidemiology of gout	Observational study	Italy	University of Messina	Ann Rheum Dis	20.6	44
2002	211	8.79	Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output	Pain management of gout	Clinical trials	Spain	Hospital Universitario Cruces	Arthrit Rheum-Arthr	*	15
2005	210	10.00	Febuxostat, a Novel Non-purine Selective Inhibitor of Xanthine Oxidase	Pain management of gout	Clinical trials	USA	University of Chicago	Arthritis Rheum	*	42
2013	207	15.92	Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study	Pain management of gout	Clinical trials	UK	University of Nottingham	Ann Rheum Dis	20.6	26
2009	205	12.06	Clinical Efficacy and Safety of Successful Long-term Urate-Lowering with Febuxostat or Allopurinol in Subjects with Gout	Pain management of gout	Clinical trials	USA	University of Chicago	J Rheumatol	3.4	23
2011	201	13.40	Identification of Intraarticular and Periarticular Uric Acid Crystals with Dual-Energy CT: Initial Evaluation	Epidemiology of gout	Observational study	USA	Mayo Clinic	Radiology	15.2	31
2015	200	18.18	Urate crystal deposition in asymptomatic hyperuricemia and symptomatic gout: a dual-energy CT study	Epidemiology of gout	Observational study	New Zealand	University of Auckland	Ann Rheum Dis	20.6	20
2006	199	9.95	Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout	Epidemiology of gout	Observational study	New Zealand	University of Auckland	J Rheumatol	3.4	21
2008	196	10.89	Gout is associated with more comorbidities, poorer health-related quality of life and higher healthcare utilization in US veterans	Epidemiology of gout	Observational study	USA	US Department of Veterans Affairs	Ann Rheum Dis	20.6	47
2012	196	14.00	Antihypertensive drugs and risk of incident gout among patients with hypertension: population-based case-control study	Epidemiology of gout	Observational study	USA	Boston University	Brit Med J	*	43
2011	193	12.87	Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment	Pain management of gout	Clinical trials	New Zealand	University of Otago	Arthritis Rheum-US	*	32
2000	194	7.46	Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout	Pain management of gout	Observational study	China	Nanjing University	J Ethnopharmacol	5.4	20
2022	187	46.75	Association between gout flare and subsequent cardiovascular events among patients with gout	Gout-related diseases	Observational study	UK	University of Nottingham	JAMA-J Am Med Assoc	55	35
2016	187	18.70	Comorbidities in patients with gout prior to and following diagnosis: case-control study	Epidemiology of gout	Observational study	UK	University of Nottingham	Ann Rheum Dis	20.6	73
2017	186	20.67	The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: Prospective cohort study	Epidemiology of gout	Observational study	USA	Harvard University	BMJ-Brit Med J	43	55
2024	188	94.00	Global, regional, and national burden of gout, 1990–2020, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021	Epidemiology of gout	Observational study	Australia	University of Sydney	LANCET RHEUMATOL	16.4	37
2009	181	10.65	Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study	Pain management of gout	Clinical trials	USA	University of Pennsylvania	Rheumatology	4.4	36
2007	180	9.47	Concordance of the management of chronic gout in a UK primary-care population with the EULAR gout recommendations	Epidemiology of gout	Observational study	UK	University of Nottingham	Ann Rheum Dis	20.6	25
2007	179	9.42	Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout	Pain management of gout	Clinical trials	USA	Duke University	Arthritis Rheum-US	*	25
2017	179	19.89	Combined signature of the fecal microbiome and metabolome in patients with gout	Mechanism of gout	Observational study	China	Zhejiang Chinese Medical University	Front Microbiol	4.5	48
2012	176	12.57	Patient and provider barriers to effective management of gout in general practice: a qualitative study	Epidemiology of gout	Observational study	UK	University of Nottingham	Ann Rheum Dis	20.6	33
2021	176	35.20	Metagenomic analysis revealed the potential role of gut microbiome in gout	Mechanism of gout	Clinical trials	China	Guangzhou University of Chinese Medicine	NPJ Biofilms Microbi	9.2	52
2009	174	10.24	Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study	Pain management of gout	Clinical trials	USA	Rutgers University System	Ann Rheum Dis	20.6	34
2011	175	11.67	Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomized study	Pain management of gout	Clinical trials	Italy	Marche Polytechnic University	Osteoarthr Cartilage	9	32
2019	172	24.57	Gout and hyperuricemia in the USA: Prevalence and trends	Epidemiology of gout	Observational study	USA	Stanford University	Rheumatology	4.4	16
2012	172	12.29	Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout	Pain management of gout	Observational study	USA	New York University	J Rheumatol	3.4	59
2007	172	9.05	High-resolution ultrasonography of the first metatarsal phalangeal joint in gout: a controlled study	Epidemiology of gout	Observational study	UK	Queens University Belfast	Ann Rheum Dis	20.6	30
2012	169	12.07	Dual-energy CT in gout: a prospective validation study	Epidemiology of gout	Observational study	USA	Boston University	Ann Rheum Dis	20.6	18
2010	169	10.56	Gout: an independent risk factor for all-cause and cardiovascular mortality	Epidemiology of gout	Observational study	China	Chang Gung University	Rheumatology	4.4	22
2001	163	6.52	Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout?	Epidemiology of gout	Observational study	USA	University of Pennsylvania	J Rheumatol	3.4	10
2014	162	13.50	Tophaceous gout and high level of hyperuricemia are both associated with increased risk of mortality in patients with gout	Gout-related diseases	Observational study	Spain	Hospital Universitario Cruces	Ann Rheum Dis	20.6	36
2010	161	10.06	Epidemiology of gout in women fifty-two-year follow-up of a prospective cohort	Epidemiology of gout	Observational study	USA	Boston University	Arthritis Rheum-US	*	58
2009	161	9.47	Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography	Epidemiology of gout	Observational study	New Zealand	University of Auckland	Ann Rheum Dis	20.6	26
2006	160	8.00	Serum urate levels and gout flares – Analysis from managed care data	Epidemiology of gout	Observational study	USA	HealthCore, Inc	JCR-J Clin Rheumatol	1.8	9
2003	160	6.96	Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis	Mechanism of gout	Animal experiment	Canada	Adelaide University	Arthritis Rheum-US	*	59
2009	159	9.35	Quality of life and disability in patients with treatment-failure gout	Epidemiology of gout	Observational study	USA	University of Chicago	J Rheumatol	3.4	18
2001	152	6.08	Hyperuricemia and gout in Taiwan: Results from the Nutritional and Health Survey in Taiwan (1993–96)	Epidemiology of gout	Observational study	China	Academia Sinica - Taiwan	J Rheumatol	3.4	18
2017	151	16.78	Lesinurad combined with allopurinol: A randomized, double-blind, placebo-controlled study in gout patients with an inadequate response to standard-of-care allopurinol (a US-based study)	Pain management of gout	Clinical trials	USA	University of Alabama System	Arthritis Rheumatol	10.9	33
2001	149	5.96	Relation between adverse events associated with allopurinol and renal function in patients with gout	Epidemiology of gout	Clinical trials	Mexico	Hospital General de Mexico	Ann Rheum Dis	20.6	16
2008	148	8.22	Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile	Gout-related diseases	Observational study	Canada	University of British Columbia	Rheumatology	4.4	42
2012	146	10.43	Purine-rich foods intake and recurrent gout attacks	Pain management of gout	Observational study	USA	Boston University	Ann Rheum Dis	20.6	29
2010	145	9.06	Menopause, postmenopausal hormone use and risk of incident gout	Gout-related diseases	Observational study	USA	Boston University	Ann Rheum DiS	20.6	26
2016	143	14.30	Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes	Pain management of gout	Observational study	Japan	National Defense Medical College - Japan	Ann Rheum Dis	20.6	59
2003	143	6.22	Patient compliance, in rheumatoid arthritis, polymyalgia rheumatica, and gout	Pain management of gout	Observational study	Netherlands	Maastricht University	J Rheumatol	3.4	33
2009	142	8.35	A randomized controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300–600 mg/day vs benzbromarone 100–200 mg/day in patients with gout	Pain management of gout	Clinical trials	Netherlands	University of Groningen	Ann Rheum Dis	20.6	42
2004	142	6.45	Compliance with allopurinol therapy among managed care enrollees with gout: A retrospective analysis of administrative claims	Epidemiology of gout	Observational study	USA	UnitedHealth Group Incorporated	J Rheumatol	3.4	21
2009	141	8.29	Adherence with urate-lowering therapies for the treatment of gout	Pain management of gout	Observational study	USA	University of Massachusetts System	Arthritis Res Ther	4.6	21
2007	141	7.42	Gout and risk of Parkinson disease -: A prospective study	Gout-related diseases	Observational study	USA	University of Minnesota	Neurology	9.0	30

IF = impact factors.

^*These journals do not have the latest IF.

The United States contributed the greatest number of publications, representing more than half of the top 100 articles (n = 52). Among institutions, Boston University (USA) was the most productive first institute (n = 7). Choi HK was the most prolific first author, with 9 publications. The 100 articles were published across 34 journals, with Annals of the Rheumatic Diseases publishing the largest number of articles (n = 25), followed by Journal of Rheumatology (n = 13). The article with the highest total citation count (4357 citations) was published in Nature in 2006 by the University of Lausanne, Switzerland.

Regarding journal impact factors (IF), The Lancet had the highest IF for 2024 to 2025 (IF = 88.5). Nearly half of the top 100 articles (48%) were published in journals with an IF >10, indicating that articles in high-impact journals generally received higher citation counts.

The article with both the highest total citation count and the highest annual citation rate was “Gout-associated uric acid crystals activate the NALP3 inflammasome” published by Martinon et al in Nature in 2006, which accumulated 4357 citations. This landmark mechanistic study demonstrated that MSU crystals and calcium pyrophosphate dihydrate crystals activate the NLRP3 (NALP3) inflammasome, leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) release. The resulting inflammatory cascade promotes neutrophil recruitment and triggers acute gout flares. These findings provided the first direct evidence linking crystal-induced inflammasome activation to the pathogenesis of gout and established the IL-1 signaling pathway as a key therapeutic target for gout-associated inflammation^[1].

3.1. Active authors and co-citation authors

Using VOSviewer, co-authorship and co-citation network maps of active authors and cited authors were constructed with a minimum occurrence threshold of 2 publications (Figs. 2 and 3). Among the top 100 most-cited articles, Choi HK was the most productive author, contributing to 10 publications. His research primarily focused on gout, hyperuricemia, CVD, prevalence, sugar-sweetened soft drinks and fructose consumption, and metabolic syndrome.

Figure 2.

The network of authors engaged in 100 top-cited gout.

Figure 3.

The network of co-citation authors engaged in 100 top-cited gout.

As the leading contributor in the field, Choi HK exhibited the largest total link strength, indicating a prominent and influential role in shaping gout research. Many of the landmark studies within this field were conducted or led by his research group. Furthermore, the collaboration network revealed strong intra-group connectivity and relatively limited external connections, suggesting long-term and stable collaborations among team members. Such collaborative relationships may have contributed to the production of high-quality studies with substantial academic impact, as reflected by their high citation counts.

As shown in Figure 2, the green cluster centered on Choi HK was the largest collaborative group within the network. This cluster demonstrated extensive links with multiple research groups, highlighting its strong cross-team and cross-institutionalcollaborative characteristics. The central position of this group suggests that it serves as a major hub connecting different research communities and facilitating knowledge exchange within the field of gout research.

The 2nd and 3rd most productive authors were Becker MA (n = 8) and Schumacher HR (n = 7), respectively. Their research primarily focused on urate-lowering therapies and clinical interventions for gout, with major topics including allopurinol, febuxostat, randomized controlled trials, pegloticase, and anti-pegloticase antibodies. Both authors played pivotal roles in advancing the clinical management of gout through a series of influential studies evaluating the efficacy and safety of emerging therapeutic agents.

In the co-authorship network, Becker MA and Schumacher HR represented the core nodes of the green and red clusters, respectively. These clusters were characterized by dense internal collaborative relationships, reflecting long-standing and stable research partnerships. As leading authorities in gout clinical research and therapeutic development, their work has been extensively cited and has contributed substantially to the evidence base supporting contemporary gout treatment strategies. The prominent positions of these authors within the collaboration network further underscore their significant academic influence and their role in driving progress in both clinical and translational gout research.

3.2. Active countries and organizations

Using VOSviewer, country and institutional collaboration networks were constructed with a minimum threshold of 1 publication (Figs. 3 and 4). The results demonstrated extensive international collaboration among researchers in the field of gout. The United States was the leading contributor, accounting for 59 publications, followed by China (n = 11), the United Kingdom (n = 9), Canada (n = 9), and the Netherlands (n = 8) (Fig. 3). In terms of institutional productivity, 4 of the top 5 most productive institutions were located in the United States. The University of Pennsylvania ranked first with 12 publications, followed by the University of Chicago (n = 10), Harvard University (n = 8), Boston University (n = 8), and Duke University (n = 7) (Fig. 4). The collaboration network further revealed that the United States exhibited the highest total link strength, indicating the strongest level of international collaboration among all contributing countries. As the principal hub connecting nearly all major contributing countries, the United States has played a dominant role in generating highly influential gout research worldwide. China ranked second in node size and emerged as the leading contributor in Asia. Strong collaborative relationships were observed between China and several countries, including the United States, Singapore, and Switzerland, highlighting China’s increasingly important role in international gout research and global scientific cooperation.

Figure 4.

The network of countries engaged in 100 top-cited gout research.

In the institutional collaboration network (Fig. 5), U.S. institutions dominated the field. The University of Pennsylvania and the University of Chicago served as the largest hubs, maintaining extensive collaborations with numerous academic institutions and pharmaceutical companies. Other leading universities, including Harvard University, Johns Hopkins University, and Boston University, formed a tightly connected red cluster, reflecting long-term and stable academic collaborations. Pharmaceutical companies also played a significant role within the network. Nodes representing companies such as Novartis and Takeda highlighted the prevalence of industry–academia partnerships in highly cited gout research, particularly in the context of clinical trials for novel therapeutics. These patterns suggest that collaboration between pharmaceutical firms and research institutions has been a key driver of influential studies and the advancement of gout treatment.

Figure 5.

The network of organizations engaged in 100 top-cited gout research.

Overall, both the country-level and institution-level analyses demonstrated the dominant role of the United States in highly cited gout research. The United States occupied the central position within the global collaboration network and served as the primary driving force behind influential scientific output in the field. Collaborations among leading universities and research institutions were highly concentrated, resulting in the formation of several closely connected academic clusters. In contrast, the participation of peripheral countries and institutions was relatively limited, indicating an uneven distribution of research resources and academic influence. Furthermore, pharmaceutical companies occupied prominent positions within the institutional collaboration network, underscoring the critical role of industry–academia partnerships in producing highly cited gout research. Such collaborations were particularly evident in the development and evaluation of novel therapeutic agents, suggesting that translational research and drug development have become major drivers of scientific impact and innovation in the field of gout.

3.3. Analysis of journals and co-citation analysis of literature

Using a threshold of 5, co-citation, journal coupling, and bibliographic coupling networks were constructed to visualize the structural and disciplinary organization of gout research (Figs. 6–8). The analyses revealed a highly structured and interdisciplinary knowledge system within the field. The journal co-citation network indicated that Annals of the Rheumatic Diseases, Journal of Rheumatology, and Arthritis & Rheumatism formed the core platforms for knowledge dissemination. Among these, Annals of the Rheumatic Diseases occupied a central position in the network, acting as a bridge connecting basic research with clinical studies. The journal coupling network highlighted the distribution of current research frontiers, identifying 4 primary clusters: rheumatology, clinical epidemiology, immunology/basic science, and multidisciplinary medicine. This pattern reflects a shift in modern gout research from traditional clinical management toward mechanistic studies and interdisciplinary integration. The bibliographic co-citation network further demonstrated that seminal works, including Wallace SL (1977), Becker MA (2005), and Choi HK (2007), established the foundational knowledge for diagnostic criteria, pharmacological interventions, and epidemiological research in gout. Overall, the development of gout research follows an evolutionary trajectory: from establishing diagnostic standards, conducting epidemiological surveys, and optimizing pharmacological therapies, to investigating genetic susceptibility, urate transport mechanisms, and inflammatory signaling pathways. These findings illustrate the gradual transition of the field from classical clinical rheumatology toward a multidisciplinary research model integrating immunology, genetics, and precision medicine, thereby providing a robust academic foundation for future basic and translational studies.

Figure 6.

Journal co-citation network diagram engaged in 100 top-cited gout research.

Figure 8.

Reference literature network map for the study of 100 top-cited gout research.

Figure 7.

Journal literature coupling network diagram engaged in 100 top-cited gout research.

3.4. Analysis of keywords

To identify the research hotspots in gout, a dendrogram was generated based on keywords and abstracts (Fig. 9). In this visualization, each colored block represents a distinct research theme cluster. The size of each block corresponds to the number of articles associated with that theme, with larger blocks indicating higher research activity and interest. The analysis revealed that the high-frequency keywords were closely aligned with the core topics in gout research. The most frequently occurring terms included hyperuricemia (n = 34), management (n = 23), arthritis (n = 20), risk (n = 20), and gout (n = 18), reflecting the major thematic focus areas within the field. These clusters provide an overview of the dominant research directions and emerging priorities in gout studies.

Figure 9.

Visual investigation of keywords related to 100 top-cited gout research.

To comprehensively characterize the major research themes in gout, keyword analyses were performed using VOSviewer (version 6.4.R1) and CiteSpace (version 1.6.20) with a minimum occurrence threshold of 3. Keyword co-occurrence networks (Fig. 10), keyword density maps (Fig. 11), keyword clustering analyses (Fig. 12), timeline visualizations (Fig. 13), and keyword burst detection maps (Fig. 14) were generated to identify research hotspots and evolving trends within the field. Among all keywords, the 5 most frequently occurring terms were hyperuricemia (n = 34), gout (n = 28), management (n = 24), arthritis (n = 20), and uric acid (UA) (n = 19), highlighting the major areas of focus in gout research. The keyword density visualization reflected the citation intensity of related research topics, with warmer colors indicating higher citation frequencies. Two prominent centers, hyperuricemia and gout, were observed in the density map, demonstrating their central roles in the knowledge structure of the field (Fig. 11). Overall, the keyword analyses revealed that research on gout has been primarily centered on disease pathogenesis, urate metabolism, clinical management, and inflammatory arthritis, while also providing insights into the evolution of research priorities and emerging areas of interest over time.

Figure 10.

The network of keywords engaged in 100 top-cited gout research.

Figure 11.

The density network diagrams of keywords engaged in 100 top-cited gout research.

Figure 12.

The network of classification engaged in 100 top-cited gout research.

Figure 13.

The timeline graph of keyword clusters engaged in 100 top-cited gout research.

Figure 14.

Top 20 keywords with the strongest citation bursts.

In the keyword clustering network, nodes represent keywords, and links between nodes indicate co-occurrence relationships (Fig. 10). The modularity value (Q) of the network was 0.5916 (Q > 0.3), indicating a significant clustering structure, while the weighted average silhouette score (S) was 0.8467 (S > 0.7), suggesting high reliability of the clustering results.

Ten major keyword clusters were identified, representing core research themes in gout:

• #0 following diagnosis: gout diagnosis and follow-up.

• #1 intestinal, microbiota, distinguish gout, patient: gut microbiota and disease associations.

• #2 high level: hyperuricemia.

• #3 causing gout: disease triggers and etiological factors.

• #4 nationwide, population-based, study: population-based epidemiological research.

• #5 role: mechanistic studies of gout pathophysiology.

• #6 calcium, pyrophosphate, deposition disease: differentiation of calcium pyrophosphate deposition disease.

• #7 non-purine, inhibitor: non-purine urate-lowering drugs.

• #8 fecal microbiome: fecal microbiome studies.

• #9 care enrollees: patient care and health management.

These clusters collectively capture the central research focus in the field of gout, encompassing diagnosis and follow-up, gut microbiota interactions, hyperuricemia, disease triggers, epidemiological studies, mechanistic investigations, differential diagnosis of calcium pyrophosphate deposition disease, developmentand evaluation of non-purine urate-lowering therapies, microbiome-related research, and patient health management.

To further explore the temporal evolution of research topics in gout, keyword timeline and burst analyses were conducted for publications from 2000 to 2026 (Figs. 13 and 14). These visualizations highlighted the emergence of 20 new keywords over this period (Fig. 14), reflecting the dynamic development of the field. The emerging keywords encompassed major aspects of gout research, including epidemiology, gut microbiology, diagnostic criteria, animal experimental studies, primary intervention strategies, and related comorbidities. Among the burst keywords, serum urate and therapy exhibited the highest burst strength, indicating that these topics have attracted increasing attention and represent focal points of recent research in gout.

The temporal analyses revealed distinct stage-specific characteristics in the evolution of gout research. The focus of the field has gradually shifted from fundamental epidemiological investigations and etiological studies to clinical diagnosis and pharmacological treatment, and more recently toward long-term prognosis, comorbidities, and disease burden. These findings suggest that gout research is undergoing a transition from the management of acute disease flares to a comprehensive, life-course approach emphasizing chronic disease management. Traditional themes, such as UA and therapy, remained prominent throughout the study period, highlighting their enduring importance as the fundamental pillars of gout research. In contrast, the emergence of topics such as the gut microbiota and cardiovascular outcomes reflects an expanding research scope that increasingly integrates metabolic, immunological, and translational perspectives. This trend indicates a growing interest in the complex interactions between gout and systemic health beyond the musculoskeletal system. Notably, the keywords with the strongest burst intensities were predominantly related to clinically relevant topics, including pharmacological interventions, treatment guidelines, and patient prognosis. This finding suggests that highly influential gout research has been largely driven by efforts to address practical clinical challenges and improve patient outcomes. Among all research themes, hyperuricemia remains the cornerstone of the field. As the fundamental pathogenic factor underlying gout, hyperuricemia serves as a critical link connecting multiple research domains, including gout, metabolic syndrome, CVD, and chronic kidney disease. Consequently, understanding the mechanisms, consequences, and management of hyperuricemia continues to represent one of the highest priorities in contemporary gout research.

4. Discussion

Gout is a metabolic rheumatic disease that poses a significant threat to human health. It is associated with a high prevalence and substantial disability burden worldwide, while its related cardiovascular and cerebrovascular complications contribute considerably to morbidity and mortality. As the global burden of gout continues to increase, understanding the historical development, influential contributions, and emerging trends in this field has become increasingly important. In the present study, we systematically analyzed the 100 most-cited articles in gout research. Through bibliometric and visualization analyses, we evaluated publication characteristics, leading authors, journals, countries, institutions, and research hotspots. By examining the most influential literature in the field, we identified the major contributors to gout research, mapped the intellectual structure of the discipline, and summarized the evolution of key research themes over time. These findings provide a comprehensive overview of the current state of gout research and offer valuable insights for future investigations and scientific development in this field.

Comparison with previous bibliometric studies further highlights the distinctive contributions of the present analysis. Lu et al^[2] focused on gouty arthritis and analyzed publications from the most recent decade, identifying the pathological mechanisms underlying gouty arthritis and the growing importance of urate-lowering therapy (ULT). Their study also suggested that the gut microbiota may become an important research direction in future gout investigations. Similarly, Wang et al^[3] conducted a bibliometric analysis of gout-related publications from the past decade and found that mechanistic research would remain a major focus of future studies, while also emphasizing the potential research value of the relationship between gout and heart failure. Wen et al^[4] examined gout research published over the previous 2 decades and provided a comprehensive overview of the developmental trends in the field. Their findings suggested that future research would increasingly focus on gout prevention as well as the development and evaluation of novel therapeutic agents. In contrast, Deng et al,^[5] whose analysis centered on gouty arthritis, identified a relative lack of research regarding the use of active compounds derived from traditional Chinese medicine for the treatment of gouty arthritis, indicating a potentially important area for future investigation. Consistent with these previous studies, our findings confirmed that hyperuricemia, ULT, disease mechanisms, and emerging topics such as the gut microbiota remain major research hotspots. However, by focusing specifically on the 100 most-cited articles, the present study provides a complementary perspective that emphasizes the intellectual foundations, landmark discoveries, and highly influential contributors that have shaped the evolution of gout research. This approach enables a deeper understanding of the historical development and knowledge structure of the field than analyses based solely on publication volume or recent research trends.

4.1. Analysis of bibliometric results

The bibliometric analysis of gout research revealed that hyperuricemia and gout are the central topics in the field, closely linked with keywords such as risk, management, therapy, serum urate, and arthritis, forming the core knowledge base of current research.

Collaboration networks at the country, institution, and author levels indicated that the United States, China, and the United Kingdom are the leading contributors, with the United States occupying a central position in the international collaboration network. Scholars such as Choi HK and Becker MA have formed stable collaborative teams, significantly advancing the understanding of gout epidemiology, risk factors, and therapeutic strategies.

Journal and literature analyses demonstrated a 3-tier knowledge structure comprising “classic articles (core journals) research frontiers.” Seminal studies by Wallace SL (1977), Becker MA (2005), and Choi HK (2007) established the foundational knowledge, which has been disseminated through core journals including Annals of the Rheumatic Diseases, Journal of Rheumatology, and Arthritis & Rheumatism. Over time, the field has extended toward emerging areas such as immunology, genetics, inflammatory mechanisms, and precision medicine, transitioning from traditional clinical research focused on diagnostic criteria, epidemiological surveys, and pharmacological interventions to a multidisciplinary, translational research paradigm integrating rheumatology, molecular biology, and clinical application.

Keyword co-occurrence, clustering, and hotspot analyses indicated a shift in research focus from urate levels, gout diagnosis, and pharmacological treatment toward disease risk assessment, long-term prognosis, and comprehensive management. High-frequency topics in recent years include hyperuricemia, risk, mortality, management, and metabolic syndrome. Emerging directions such as the intestinal microbiota and fecal microbiome have formed independent research hotspots, suggesting that gout research is evolving from classical metabolic dysfunction studies toward microecological regulation and multi-system disease associations.

Keyword burst analyses further confirmed that terms such as risk, mortality, burden, and management have remained highly active in recent years, indicating that research priorities have shifted from the disease itself to its broader impact, long-term outcomes, and precision management. Overall, the evolution of the field reflects a transition from mechanistic exploration toward risk prediction, clinical management, and interdisciplinary integration, providing a foundation for future basic, translational, and precision medicine research in gout.

4.2. Analysis of the top-cited 100 articles

This study differs from typical bibliometric analyses of gout by specifically selecting the top 100 most-cited original research articles for in-depth evaluation. Highly cited publications generally have substantial academic influence, enabling a clear delineation of the evolution of the field while highlighting research hotspots and frontiers, thereby enhancing readability and interpretability. Keywords serve as key indicators of focus areas and emerging trends within a disease research domain. By analyzing keyword frequency, centrality, and burst patterns, this study systematically identified the major research hotspots in gout. The 100 highly cited articles were further categorized into 4 primary thematic areas: epidemiology of gout, pathophysiological mechanisms of gout, pain management in gout, and gout-related comorbidities. This structured approach provides a comprehensive overview of the core knowledge, research priorities, and development trends within the field.

4.2.1. Epidemiology of gout

Gout is the most common form of inflammatory arthritis worldwide, and its disease burden is expected to increase further with ongoing population aging. The incidence and prevalence of gout exhibit a pronounced sex disparity, with men being affected approximately 4 times more frequently than women. However, this difference becomes substantially less pronounced among individuals aged 65 years and older.^[6] Beyond recurrent episodes of acute arthritis, gout can lead to functional impairment, physical disability, and a marked reduction in health-related quality of life. Moreover, accumulating evidence indicates that gout is associated with increased risks of both morbidity and mortality, highlighting its substantial impact on individual health and healthcare systems worldwide.^[7]

Epidemiological studies have shown that the global prevalence of gout and hyperuricemia has been fluctuating and increasing overall, with relatively stable levels only in the 1990s and the 2010s.^[8,9] With the continuous optimization of diagnostic techniques and the cumulative exposure to unknown risk factors, the incidence of primary gout in coastal areas worldwide has been increasing year by year. Acute gouty arthritis can be initially screened and diagnosed through primary medical care.^[10,11] Imbalanced dietary structure, economic development level, genetic traits, and environmental exposure are the main causes of regional differences in incidence.^[12–14] The high-risk population often has multiple cardiovascular and metabolic complications such as obesity, diabetes, hypertension, and myocardial infarction (MI), which are important factors contributing to the deterioration of patients’ quality of life.^[15–17] In clinical management, the compliance of gout patients with ULT is generally low, and the recurrence rate after standardized treatment is still high. This problem is particularly prominent in the Italian population.^[18,19]

CVD is the leading cause of death among patients with gout, with coronary heart disease representing the most common cardiovascular complication.^[20–22] Accumulating evidence has demonstrated that gout is associated with significantly increased risks of both all-cause mortality and cardiovascular mortality. Furthermore, the presence of tophi has been shown to further worsen clinical outcomes and contribute to adverse prognoses. Among middle-aged men, gout has been identified as an independent risk factor for cardiovascular mortality, and gouty arthritis has been significantly associated with an increased risk of acute MI.^[23,24]

Health-related quality of life is closely associated with disease severity in patients with gout. Increased frequency of acute gout flares and greater tophus burden have been shown to substantially impair health-related quality of life, whereas comprehensive and standardized disease management can effectively improve clinical outcomes and overall quality of life.^[25] Patients with severe gout often experience significant functional limitations and disability, with frequent disease flares, polyarticular involvement, and severe pain serving as highly sensitive indicators of functional impairment and reduced quality of life.^[26]

Imaging examinations play a pivotal role in the precise diagnosis and disease assessment of gout. Dual-energy computed tomography has emerged as a noninvasive imaging modality with high sensitivity, specificity, and reproducibility, enabling the accurate detection of MSU crystal deposition in joints and surrounding soft tissues and providing objective evidence for clinical decision-making.^[27–29] In addition, dual-energy computed tomography can visually identify tophaceous lesions through color-coded imaging and, when combined with automated analysis software, allows quantitative measurement of tophus volume.^[30]

Beyond imaging-based diagnosis, the gut microbiota has recently attracted attention as a potential auxiliary biomarker for gout. Patients with gout, particularly those with concomitant abnormalities in glucose metabolism, exhibit characteristic alterations in gut microbial composition, including a reduced abundance of Faecalibacterium species and impaired butyrate-producing capacity.^[31] These findings suggest that microbiome-based approaches may offer novel opportunities for the diagnosis, risk stratification, and personalized management of gout.

Ultrasonography is an important noninvasive tool for the screening and evaluation of gout. It can effectively detect MSU crystal deposition on the cartilage surface, joint erosions, and tophaceous lesions, making it highly valuable in the differential diagnosis of crystal-induced arthropathies.^[32,33] Furthermore, ultrasonography enables dynamic monitoring of tophus burden over time. Previous studies have demonstrated an inverse relationship between tophus burden and serum urate levels; however, the clinical reliability of this assessment system requires further validation through randomized controlled trials.^[34]

High-resolution ultrasonography can identify subclinical joint damage and asymptomatic urate crystal deposition at an early stage, thereby facilitating early diagnosis and risk stratification in patients with gout.^[35] Comparative studies have further shown that patients with gout exhibit significantly greater urate deposition in joints and tendons than individuals with asymptomatic hyperuricemia, providing important imaging evidence for the diagnosis, staging, and severity assessment of gout.^[36]

4.2.2. Mechanisms of gout formation

The development of gout is a multifactorial process, with hyperuricemia serving as the central underlying factor.^[37] Elevated serum urate levels facilitate the formation of MSU crystals through the binding of urate to sodium ions. These crystals can deposit in joints, tendons, and surrounding soft tissues, thereby triggering localized inflammatory responses. Insufficient renal excretion of UA represents a major mechanism underlying hyperuricemia.^[38–40] Additionally, dysfunction of urate transporters, such as ABCG2, can impair UA excretion via both the kidney and intestine, further increasing the risk of gout development.^[41,42] Other independent factors contributing to hyperuricemia may operate irrespective of baseline serum urate levels or demographic characteristics.^[43]

MSU crystal deposition is a critical event in the initiation of acute gout flares.^[44,45] MSU crystals are recognized by innate immune cells and trigger activation of the NLRP3 inflammasome, resulting in the production and release of IL-1β.^[46,47] This process subsequently promotes neutrophil recruitment, neutrophil extracellular trap formation, and the development of local joint inflammation.^[48,49] The IL-1β/MyD88 signaling pathway plays a pivotal role in MSU-induced inflammatory responses and constitutes an important molecular mechanism underlying acute gouty inflammation and pain.^[50–54]

As the disease progresses, persistent MSU crystal deposition may lead to the formation of tophi.^[55,56] Tophi are chronic inflammatory structures composed of MSU crystals, immune cells, and pro-inflammatory mediators. Their presence can result in bone erosion, joint destruction, and progressive structural damage, thereby contributing substantially to the progression of chronic gout and the development of functional impairment and disability.^[57–59]

In addition, the development of gout is influenced by multiple metabolic and lifestyle factors. Obesity, weight gain, hypertension, the use of diuretics, alcohol consumption, high intake of meat and seafood, as well as the consumption of sugar-sweetenedbeverages and fructose, have all been associated with an increased risk of gout. Conversely, weight reduction and dairy product intake may confer a protective effect.^[60–63] Recent studies have also suggested that gut microbiota dysbiosis may contribute to gout pathogenesis by affecting UA metabolism, purine metabolism, short-chain fatty acid production, and inflammatory responses. These findings indicate that the “gut microbiota–metabolite–inflammation” axis represents a novel mechanistic pathway in the development of gout.^[64,65]

The pathogenesis of gout primarily involves hyperuricemia, MSU crystal deposition, inflammasome activation, IL-1β-mediated inflammatory responses, tophus formation, and the combined influence of metabolic and lifestyle factors. A mechanistic schematic of gout research is presented in Figure 15. Future studies should further investigate the roles of urate transporters, inflammatory signaling pathways, and the gut microbiota in the initiation and progression of gout.

Figure 15.

Mechanisms of gout formation.

4.2.3. Pain management of gout

Effective pain management in gout requires both prompt control of acute flares and sustained ULT for long-term disease management.^[66,67] The current therapeutic goal is to maintain serum urate levels below 6 mg/dL over the long term, thereby promoting the dissolution of MSU crystals, reducing the frequency of gout flares, and preventing tophus formation. Therefore, gout management should extend beyond acute pain relief and emphasize continuous, guideline-directed, and treat-to-target therapeutic strategies aimed at achieving and maintaining optimal serum urate levels.^[68]

Febuxostat and allopurinol are commonly used xanthine oxidase inhibitors that effectively reduce serum urate levels.^[69,70] Febuxostat, a non-purine selective xanthine oxidase inhibitor, has demonstrated robust efficacy in lowering urate levels and reducing tophus burden, and it can be used in certain patients with impaired renal function.^[71] However, its cardiovascular safety profile requires ongoing attention.^[72–74] Allopurinol remains the most widely used first-line urate-lowering agent; dose titration allows patients to achieve target urate levels, and long-term therapy is generally well tolerated without increasing the risk of adverse events.^[75–77] Nonetheless, caution is required regarding allopurinol hypersensitivity reactions, particularly in patients with renal impairment, necessitating careful initiation and dose adjustment.^[78–82]

Colchicine is primarily used for anti-inflammatory and analgesic treatment during acute gout flares and for prophylaxis at the initiation of ULT. Its therapeutic effects are related to the inhibition of neutrophil activity and modulation of inflammatory responses.^[83] However, colchicine is associated with dose-dependent gastrointestinal adverse effects and potential hepatic and renal toxicity, necessitating careful dose management and monitoring for adverse reactions in clinical practice.^[84]

For patients with refractory gout who are unresponsive to conventional therapy, intolerant to allopurinol, or with tophaceous deposits, pegloticase can significantly reduce serum urate levels and deplete tissue urate stores.^[85] Its efficacy may be affected by anti-drug antibodies, requiring attention to dosing frequency, treatment response, and immune-related adverse events.^[86–89]

In addition, uricosuric agents such as probenecid promote UA excretion by inhibiting renal tubular reabsorption.^[90] Non-pharmacological interventions are equally important and include patient education, lifestyle modification, dietary management, weight control, and strategies to improve treatment adherence.^[91] Nurse-led comprehensive management programs have demonstrated advantages in achieving target serum urate levels, improving patient acceptance, and enhancing cost-effectiveness.^[92,93]

Overall, pain management in gout should evolve from simply alleviating acute pain to a long-term, integrated management approach characterized by the goals of “urate-lowering to target (reducing flare recurrence) preventing tophi formation and joint damage.” Future research should further investigate the safety profiles of different pharmacologic agents, individualized treatment strategies, and the role of multidisciplinary management models in the long-term control of gout.

4.2.4. Gout-related diseases

Gout is closely associated with a wide range of systemic diseases. In addition to hyperuricemia, common comorbidities include hypertension, chronic kidney disease, obesity, diabetes mellitus, nephrolithiasis, MI, heart failure, and stroke.^[94] These associations highlight the strong metabolic, cardiovascular, and renal characteristics of gout as a systemic disease.

Gouty arthritis is the hallmark clinical manifestation of gout and is closely related to MSU crystal deposition and the subsequent inflammatory response.^[95–97] Effective control of inflammation is essential for preventing acute flares and reducing disease recurrence.^[98–100] Beyond conventional anti-inflammatory therapies, IL-1-targeted treatments, including canakinumab, anakinra, and rilonacept,^[101,102] have demonstrated efficacy in alleviating pain, suppressing inflammation, and reducing the risk of recurrent attacks.^[103] In addition, prophylactic colchicine administered during the initiation of ULT has been shown to reduce both the frequency and severity of acute gout flares.^[104] Furthermore, gout has been independently associated with nephrolithiasis, and these 2 conditions may share common pathophysiological mechanisms related to abnormalities in urate metabolism.

Metabolic syndrome is another major comorbidity frequently observed in patients with gout. Individuals with gout are at increased risk of developing metabolic, endocrine, and musculoskeletal complications, underscoring the importance of metabolic screening and comprehensive health assessment during long-term disease management.^[105] Hypertension is also a common and clinically significant comorbidity of gout.^[106] Certain antihypertensive agents, such as calcium channel blockers and losartan, may reduce the risk of gout by lowering serum urate levels. With regard to dietary interventions, the Dietary Approaches to Stop Hypertension diet has been associated with lower serum urate concentrations and a reduced risk of gout, whereas a Western dietary pattern has been linked to an increased risk of gout development.^[107]

Collectively, these findings indicate that gout should be regarded not merely as an inflammatory arthritis but as a complex systemic disorder closely intertwined with metabolic, cardiovascular, and renal diseases. Future research and clinical practice should emphasize integrated management strategies that address both gout and its associated comorbidities to improve long-term patient outcomes.

Management of gout-related comorbidities should evolve from a disease-specific approach focused solely on arthritis treatment to a comprehensive, systemic management strategy. In addition to controlling serum urate levels and suppressing inflammatory responses, clinicians should place greater emphasis on the screening, prevention, and management of cardiovascular, renal, and metabolic comorbidities. Such an integrated approach is essential for reducing disease burden, preventing complications, and improving long-term clinical outcomes and overall survival in patients with gout.

5. Conclusions

This study systematically analyzed the top 100 most-cited articles in gout research published between 2000 and 2026 through bibliometric, visualization, and literature review approaches. The characteristics of influential authors, journals, countries, institutions, and keywords were comprehensively evaluated, providing an overview of the intellectual structure and developmental trajectory of the field.

The findings indicate that gout and hyperuricemia research has established a well-defined knowledge framework centered on hyperuricemia, gout, risk, management, and therapy. The United States, China, and the United Kingdom were identified as the leading contributors, with the United States occupying a dominant position in both scientific productivity and international collaboration. According to the bibliometric analyses, the United States was the most productive country, the University of Pennsylvania was the leading institution, Choi HK was the most prolific author, and Annals of the Rheumatic Diseases was the journal publishing the largest number of highly cited articles.

Research hotspots have gradually shifted from traditional topics such as serum urate levels, disease diagnosis, and pharmacological treatment toward risk assessment, long-term outcomes, disease burden, and comprehensive disease management. Emerging areas, particularly gut microbiota-related research, have gained increasing attention, reflecting a transition toward multidisciplinary, translational, and precision medicine approaches in gout research.

Overall, future investigations should further strengthen international collaboration and place greater emphasis on the long-term outcomes of gout and hyperuricemia, risk prediction models, individualized treatment strategies, and novel pathogenic mechanisms. Advances in these areas are likely to shape future clinical trials and evidence-based practice, facilitate the development of personalized intervention strategies, and ultimately improve the long-term management and health outcomes of patients with gout and hyperuricemia.

Acknowledgments

We thank Yuan Wei for providing language suggestions. This person has agreed.

Author contributions

Conceptualization: Zibing Zhao.

Data curation: Huixin Yan.

Formal analysis: Jiaxun Zhang.

Methodology: Jiapeng Chai.

Supervision: Cuijuan Li.

Validation: Yayun Wang.

Visualization: Jinying Zhao.

Writing – original draft: Zibing Zhao, Yayun Wang.

Writing – review & editing: Cuijuan Li, Fuchun Wang.