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Rheumatology5043 papers

Acute polyarthritis

Last edited: 2 h ago

Overview

Acute polyarthritis, particularly in the context of gout, refers to sudden and severe inflammation affecting multiple joints. This condition is characterized by intense pain, swelling, redness, and warmth in affected joints, predominantly impacting the lower extremities such as the toes and ankles, though it can involve any joint. Gout disproportionately affects middle-aged to elderly individuals, with a higher prevalence in men compared to women, though postmenopausal women also face increased risk. The clinical significance lies in its potential to cause significant morbidity, including chronic joint damage and systemic complications if not managed effectively. Understanding and promptly addressing acute polyarthritis is crucial in day-to-day practice to prevent long-term disability and improve patient quality of life 1 3 4.

Pathophysiology

Gout arises from hyperuricemia, where serum uric acid levels exceed the saturation point, leading to the formation of monosodium urate (MSU) crystals within joints and surrounding tissues. These crystals act as potent danger signals, triggering innate immune responses primarily through the NLRP3 inflammasome pathway. Upon recognition by pattern recognition receptors on immune cells like macrophages and neutrophils, the NLRP3 inflammasome is activated, resulting in the production of pro-inflammatory cytokines such as IL-1β. This cytokine storm initiates a robust inflammatory cascade characterized by neutrophil infiltration, release of inflammatory mediators, and the formation of neutrophil extracellular traps (NETs), which further perpetuate inflammation and contribute to tissue damage and tophus development 1 8 12. Additionally, circadian rhythms influence gout flares, with peak activity often observed at night, highlighting the temporal regulation of inflammatory processes in this condition 12.

Epidemiology

Globally, the prevalence of gout ranges widely, from approximately 0.1% to 10%, with significant regional variations 3. The incidence of gout has been rising, particularly in developed regions, driven by factors such as obesity, metabolic syndrome, and dietary changes 3 4 5. Men are more commonly affected than women, with a peak incidence in middle age, though postmenopausal women also experience increased risk due to hormonal changes 3. Geographic disparities exist, with higher prevalence noted in economically developed areas compared to inland regions 5. Epidemiological studies indicate a concerning trend towards younger onset of gout, emphasizing the growing public health burden of this condition 3 4.

Clinical Presentation

Acute polyarthritis in gout typically presents with sudden onset of severe joint pain, often in the lower extremities, particularly the first metatarsophalangeal joint (podagra). Patients describe intense pain, erythema, swelling, and warmth around the affected joints. Atypical presentations can occur, including involvement of less common joints like wrists, ankles, or knees, and may mimic other inflammatory arthropathies. Red-flag features include persistent joint swelling, systemic symptoms like fever, and the presence of tophi, which are visible chalky deposits under the skin. Prompt recognition of these symptoms is crucial for timely intervention to prevent chronic joint damage 1 3.

Diagnosis

The diagnosis of acute polyarthritis in the context of gout involves a combination of clinical assessment and laboratory testing. Key steps include:

Clinical Evaluation: Detailed history focusing on joint symptoms, dietary habits, and comorbidities.

Laboratory Tests:

- Serum Uric Acid (SUA): Elevated levels (typically >6.8 mg/dL or >0.36 mmol/L) support the diagnosis. - Synovial Fluid Analysis: If available, aspiration and analysis showing needle-shaped MSU crystals under polarized light microscopy is diagnostic. - Imaging: Ultrasound or MRI may reveal urate crystal deposits or tophi.

Differential Diagnosis:

Septic Arthritis: Foul-smelling synovial fluid, elevated white blood cell count, and positive cultures differentiate it.

Rheumatoid Arthritis: Presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies helps distinguish.

Pseudogout: Calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluid analysis identify this condition.

Management

Initial Management

Acute Flares:

- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): High-dose therapy (e.g., indomethacin 75 mg three times daily) for short-term use. - Colchicine: 1-2 mg initially, followed by 0.5-1 mg after 1 hour if needed (maximum 4 mg/day). - Corticosteroids: Oral (e.g., prednisolone 40 mg daily for 3-5 days) or intra-articular injection for severe cases.

Long-term Management

Urate-Lowering Therapy (ULT):

- First-Line: - Allopurinol: Start at 100-300 mg daily, titrate up to achieve target SUA <0.36 mmol/L (<6 mg/dL). - Febuxostat: 40-80 mg daily, particularly in patients with renal impairment or those intolerant to allopurinol. - Second-Line: - Probenecid: For patients with adequate renal function, 500-1500 mg daily in divided doses. - Lesinurad: In combination with a xanthine oxidase inhibitor for refractory hyperuricemia. - Special Considerations: - Renal Impairment: Adjust dosing based on creatinine clearance; consider febuxostat over allopurinol. - Dialysis Patients: Monitor SUA levels closely; dosing adjustments may be necessary despite dialysis.

Monitoring: Regular SUA levels every 1-3 months until target achieved, then every 3-6 months.

Refractory Cases

Specialized Therapies:

- Pegadricase (Krystexy): For severe refractory gout, administered intravenously every 2-4 weeks. - Nanoencapsulated Sirolimus Plus Pegadricase (NASP): Novel approach for uncontrolled gout, administered every 4 weeks, establishing immunotolerance and mitigating anti-uricase antibodies.

Complications

Acute Complications:

- Joint Destruction: Persistent inflammation can lead to chronic joint damage and deformity. - Tophi: Deposits of urate crystals in soft tissues, leading to nodules and functional impairment.

Long-term Complications:

- Chronic Arthritis: Recurrent flares contribute to progressive joint destruction. - Renal Impairment: Uric acid nephropathy can develop, especially in poorly controlled cases. - Cardiovascular Risk: Hyperuricemia is associated with increased cardiovascular morbidity.

Referral Triggers: Persistent flares, inadequate response to therapy, renal involvement, or complex comorbidities warrant specialist referral.

Prognosis & Follow-up

The prognosis of gout is generally good with effective management, but chronic undertreatment can lead to significant joint damage and systemic complications. Key prognostic indicators include achieving and maintaining target SUA levels, absence of recurrent flares, and absence of tophi. Recommended follow-up intervals include:

Initial Follow-up: Within 1-2 weeks post-diagnosis to assess response to acute treatment.

SUA Monitoring: Every 1-3 months initially, then every 3-6 months once stable.

Clinical Assessment: Regular evaluations to monitor for signs of chronic joint damage or systemic complications.

Special Populations

Pregnancy: Allopurinol is generally avoided; febuxostat may be considered if necessary, with close monitoring.

Elderly: Increased risk of renal impairment; careful dosing adjustments are essential.

Renal Impairment: Adjust dosing of allopurinol and consider febuxostat; monitor SUA levels closely.

Ethnic Variations: Higher prevalence in certain populations (e.g., Korean, Thai, Chinese) may necessitate genetic screening for HLA-B5801 to guide allopurinol use.

Key Recommendations

Achieve Target Serum Uric Acid Levels: Aim for SUA <0.36 mmol/L (<6 mg/dL) using appropriate ULT (Evidence: Strong 1 3).

Initiate Prompt Acute Flare Treatment: Use NSAIDs, colchicine, or corticosteroids based on severity (Evidence: Strong 1).

Consider Genetic Factors in Allopurinol Use: Screen for HLA-B5801 in high-risk populations to avoid severe adverse reactions (Evidence: Moderate 7).

Monitor Renal Function in ULT Selection: Adjust dosing based on creatinine clearance, favoring febuxostat in renal impairment (Evidence: Moderate 2 5).

Regular Follow-up and SUA Monitoring: Ensure adherence and efficacy with frequent SUA checks (Evidence: Moderate 1 3).

Refer Complex Cases to Rheumatology: For refractory gout, renal involvement, or systemic complications (Evidence: Expert opinion 12).

Educate Patients on Lifestyle Modifications: Weight management, dietary changes, and alcohol reduction to prevent flares (Evidence: Moderate 3 4).

Consider Novel Therapies for Refractory Cases: Evaluate pegadricase or NASP in uncontrolled gout (Evidence: Moderate 13).

Screen for Metabolic Syndrome: Given the high comorbidity, manage associated risk factors (Evidence: Moderate 9).

Evaluate for Comorbidities: Regular assessment for cardiovascular risk and renal function in gout patients (Evidence: Moderate 5 10).

References

Showing 100 priority papers (full text preferred, most recent first) of 5043 indexed.

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Assessment of health-related quality of life of patients with gout and hyperuricemia in the Tianjin area according to the SF-6Dv2 scale. Frontiers in public health 2026. link 6 Tsai SF, Wu MJ, Chen CH. A real-world retrospective cohort study comparing brand-name febuxostat (feburic) and generic febuxostat (feuri). Science progress 2026. link 7 Xiao Y, Zhang T, Chen Q, Zhang Y, Chen B, Wang M et al.. Multi-omics analysis reveals the mechanism of verbenalin in treating gout via modulating purine metabolism, gut microbiota, and inflammatory pathways. Frontiers in immunology 2026. link 8 Zhang C, Liu C, Yang X, Lin X, Wang M, Yang Y. A bioinformatics and experimental study toward new therapeutic strategies: CXCL8 in gout progression. Medicine 2026. link 9 Li J, Zhang J, Li S, Yao X, Li R, Liu W. Multi-dimensional evidence establishing the causal association between metabolic syndrome and gout and the molecular mechanisms of comorbidity. Frontiers in immunology 2026. link 10 Wang YC, Huang AP, Huang CW, Islam MM, Kung WM. Association Between Gout and the Risk of Dementia: A Meta-Analysis of Observational Studies and Biological Mechanisms. International journal of rheumatic diseases 2026. link 11 Yang L, Sun Y, Li C, Sun H, Wei S, Zhu F et al.. Integrated multi-omics analysis of dampness-heat gout reveals diagnostic biomarkers and therapeutic targets. Frontiers in immunology 2026. link 12 Chen X, Zhang C, Zheng H, Shi Q, Chen B, Han J. Gout Inflammation Time Programming: Molecular Clock from Crystal Triggering to Tissue Remodeling. International journal of molecular sciences 2026. link 13 Baraf HSB, Schlesinger N, Strand V. Nanoencapsulated Sirolimus Plus Pegadricase (NASP) in Uncontrolled Gout: Current Status and Future Directions. Drugs 2026. link 14 Towiwat P, Bamrungsawad N, Buttham B, Nakham A, Upakdee N. 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Viral communities and identification of a parvovirus and two picornaviruses in geese with gout. The Journal of veterinary medical science 2026. link 24 Lin C, Shao S, Wu Q, Zhu Y, Lin S. Social Determinants of Health and Risk of Mortality in Adults with Gout or Hyperuricemia: Insights from the 1999-2018 NHANES. Balkan medical journal 2026. link 25 Zhang Q, Yu XH, Zhang WZ, Lyu XB, Lin HH, Zeng ST et al.. Machine learning based on systemic inflammation response index and risk of cardiovascular disease in gout: a retrospective study and clinical validation. Clinical rheumatology 2026. link 26 Wang Z, Tilley S, Peloquin C, Petrow E, Clancy M, Neogi T. Relation of Colchicine to Total Joint Arthroplasty Among People With Gout in a Population-Based Cohort Study. Arthritis & rheumatology (Hoboken, N.J.) 2026. link 27 Pan Y, Lin S, Pan N, Cheng S, Yao J, Liang P et al.. Tophus severity grading and surgical treatment: Chinese Medical Doctor Association Multidisciplinary Expert Consensus Statement and Recommendations, 2025. International journal of surgery (London, England) 2026. link 28 Troum OM, Botson JK, Fang F, Mohammad AS, Verma S, LaMoreaux B. Safety, Tolerability, and Efficacy of Shorter Infusion Durations of Pegloticase Administered to Patients With Uncontrolled Gout Receiving Methotrexate: AGILE Trial. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2026. link 29 Pryymachenko Y, Wilson R, Dalbeth N, Abbott JH, Stamp L. Cost-Effectiveness of Low-Dose Colchicine Prophylaxis When Starting Allopurinol Using the "Start-Low Go-Slow" Approach for Gout: Evidence From a Noninferiority Randomized Double-Blind Placebo-Controlled Trial. Arthritis care & research 2026. link 30 Barry A, England BR, Sayles H, Helget LN, Androsenko M, Wu H et al.. Improvements in Health-Related Quality of Life With Treat-to-Target Urate-Lowering Therapy in Gout: A Post Hoc Analysis of a Randomized Multicenter Trial. Arthritis care & research 2026. link 31 Helget LN, England BR, Roul P, Sayles H, Neogi T, O'Dell JR et al.. Long-Term Opioids in Gout: A Matched Cohort Study From the Veterans Health Administration. Arthritis care & research 2026. link 32 Zhu G, Luo Y, Zheng X, Mei Z, Ye Q, Peng J et al.. Multi-Omics Mechanism of Chronic Gout Arthritis and Discovery of the Thyroid Hormone-AMPK-Taurine Metabolic Axis. Cells 2025. link 33 Lee JW, Badrul Hisham MD, Low XY, Teh LK. Association between . Pharmacogenomics 2025. link 34 Wang Q, Liu Y, Zhu B. Accelerometer-derived physical activity patterns and risk of incident gout: a prospective cohort study of 97,387 UK Biobank participants. Arthritis research & therapy 2025. link 35 Nakayama A, Hayano K, Ueno M, Miyoshi Y, Nakashima H, Shimizu S et al.. Dysfunctional variants of ABCG2 create strong individual and population risks for progression of hyperuricemia: the potential for implementation of genome-personalized nursing. Human cell 2025. link 36 Bermejo-Álvarez I, Vázquez C, Irigaray-Moreno A, Quevedo-Romero I, Mediero A, Herrero-Beaumont G et al.. MSC administration resolves experimental acute gout increasing specialized pro-resolving mediators synthesis through a super-induction of prostaglandin E. Stem cell research & therapy 2025. link 37 Li X, Liu L, Tong S, Wang F, Zhu L, Cheng Q et al.. Alpha-1 Antitrypsin Mediates Spontaneous Resolution of Acute Gouty Inflammation Via Inhibiting Caspase 3/GSDME-dependent Macrophage Pyroptosis. Inflammation 2025. link 38 Chen C, Zheng X, Li Z, Wang H, Yao J. From genetic causality to druggable targets: A multiomics framework identifies ZSCAN16 in gout pathogenesis. Science progress 2025. link 39 Ren Y, Zhang S, Hu T, Xu Y, Tan Q. Global and regional burden of gout in middle-aged adults, 1990-2021, with projections to 2046: An observational study analysis for GBD 2021. Medicine 2025. link 40 Chen S, Li Z, Deng X, Gao L. Advances in Understanding the Mechanisms of Treatment for Gouty Arthritis: A Comprehensive Review. Physiological research 2025. link 41 Shi K, Guo Y, You T. Global burden of gout in age groups 10 to 54 years from 1990 to 2021: Trend of the global burden of disease study. Medicine 2025. link 42 Chen W, Chen W, Guo D, Wang Z, Shi Z, Zhong J. Kiesselbach's area nasal septal gouty tophus with an integrated "3 + 2" diagnostic algorithm: a case report. Journal of medical case reports 2025. link 43 Zhang H, Liu J, Lin R, Xie D, Lin W, Zhang Q et al.. Neutrophil-to-lymphocyte ratio predicts inpatient gout recurrence: a large-scale multicenter retrospective cohort with machine-learning validation. Frontiers in immunology 2025. link 44 Yu B, Qin Z, Wu Y, He C. Machine-learning and simulation identify food-derived xanthine oxidase inhibitors with in-vitro activity. Scientific reports 2025. link 45 Qian Y, Liu J, Xiao M, Chen W, Feng Y, Xie C et al.. Analysis of the efficacy of UBE in the treatment of tophus deposition within the lumbar spinal canal. Medicine 2025. link 46 Nie X, Liu Y, Yao X, Wu C, Gao X. Single coadministration of erythrocyte-uricase conjugate and immunosuppressant induces durable immune tolerance for gout therapy. Science advances 2025. link 47 Lou X, Guo R, Cao Y, Zhao W. Association of serum uric acid to high-density lipoprotein cholesterol ratio with all-cause mortality and cardiovascular disease mortality in patients with gout. BMC cardiovascular disorders 2025. link 48 Sun H, Yang L, Sun Y, Zhang X, Sun X, Zhao X et al.. Dysregulated bile acid metabolism as a novel player in gout progression: emerging therapeutic strategies. Frontiers in endocrinology 2025. link 49 Guo J, Lei T, Jiang Y, Wang P, Zhang Z, Yu X et al.. Circ_0058051 Targeted miR-129-5P Regulates Autophagy-Related Gene ATG7 to Promote the Inflammation of Gout. Mediators of inflammation 2025. link 50 Zhang X, Zhu M, Cui H, Fan J, Yang M, Jin Y et al.. A self-designed Chinese herbal formula alleviates GAstV infection-induced gout in goslings by inhibiting xanthine oxidase (XOD) and regulating intestinal microbiota. Poultry science 2025. link 51 Sun Y, Liu W, Li D, Cen Z, Shen Y, Zhao T et al.. Association between frailty and gout in middle-aged and older adults: A nationwide cross-sectional and Mendelian randomization study. Medicine 2025. link 52 Xu J, Lei M, Xu D. Trends in the global burden of gout attributable to kidney dysfunction, 1990-2021: a population-based analysis. Frontiers in endocrinology 2025. link 53 Li M, Zhang H, Chen S, Zhong F, Liu J, Wu J et al.. Development and validation of a multidimensional and interpretable artificial intelligence model to predict gout recurrence in hospitalised patients: a real-world, ambispective multicentre cohort study in China. BMC medicine 2025. link 54 Li Y, Yang X, Shi D, Mao L, Sun S. Machine learning models for predicting renal injury in patients with gout. Renal failure 2025. link 55 De Santo NG, De Santo LS, Bisaccia C. Gout in the "Anonymus Parisinus". Journal of nephrology 2025. link 56 Tian P, Zhao H, Wang B, Chen Y, Jia Z, Wang C et al.. Global burden of gout among young people from 1990 to 2021, with projections for 2050: A systematic analysis based on the Global Burden of Disease Study 2021. PloS one 2025. link 57 Nica V, Gaal O, Badii M, Cabău G, Mirea AM, Hotea I et al.. Gout Risk Allele Regulating . International journal of molecular sciences 2025. link 58 Fan B, Ye Y, Wang Z, Xu Y, Lu M, Cong W et al.. Establishment and evaluation of a model for clinical feature selection and prediction in gout patients with cardiovascular diseases: a retrospective cohort study. Frontiers in endocrinology 2025. link 59 Yoo H, Choi A, Kim M, Gye Y, Jo H, Kwok SK et al.. Auranofin Ameliorates Gouty Inflammation by Suppressing NLRP3 Activation and Neutrophil Migration via the IL-33/ST2-CXCL1 Axis. Cells 2025. link 60 Cheng Y, Feng Y, Huang M, Zhang L, Lin J, Zhao J et al.. Inverse and nonlinear relationships between Life's Essential 8 metrics and gout risk: A cross-sectional study. Medicine 2025. link 61 Zhang Z, Tian Z, Bian C, Tang F, Sun Y, Zhang M et al.. Development and mechanism of an XOD-targeting fermented traditional Chinese medicine formula for gout prevention in goslings. Poultry science 2025. link 62 Tao Y, Cai T, Pan Q, Yang L, Lin S, Haque M et al.. Genetic variants associated with gout identified through a genome-wide study in the UK biobank (N = 150 542). 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Original source

[1]
Spatiotemporal immune gradients in gout: immune response-driven activation of the NLRP3-IL-1β axis and its transition to trained immunity. — Wang K, Li J, Li J, Zeng F, Li S, Chen P et al. Frontiers in immunology (2026)
[2]
Reduced Serum Urate Concentrations Despite Unchanged Allopurinol Dosing in Gout Patients Commenced on Dialysis: A Retrospective Chart Review. — Kamel N, Castelino R, Wright D, Sud K, Tarafdar S, Hughes S et al. Nephrology (Carlton, Vic.) (2026)
[3]
Prevalence of gout in the Sincan district of Ankara, Türkiye: a primary care-based cross-sectional study. — Kardaş RC, Ünsal Y, Yildirim D, Tüzün H, Ilhan MN, Küçük H et al. Turkish journal of medical sciences (2026)
[4]
Integrated multi-omics mapping of the causal landscape of gout across the circulating-tissue axis. — Huang L, Liu J, Zheng X, Zhang K, Chen Y, Chen X et al. Frontiers in immunology (2026)
[5]
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Estimation of the current healthcare costs of gout in Liaoning Province from 2015 to 2022 based on the SHA2011 accounting system. — Shi X, Zheng F, Wan Q, Chai P, Wang G, Pang Z et al. Frontiers in public health (2025)
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