Gout ﬂare in the critical care setting: diagnostic challenges and treatment options
1Rheumatology Division, Department of Internal Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 10300 Bangkok, Thailand
2Divison of Rheumatology, Department of Medicine, Faculty of Medicine, Thammasat University, 12120 Pathumthani, Thailand
DOI: 10.22514/sv.2021.217 Vol.18,Issue 3,May 2022 pp.9-17
Submitted: 07 July 2021 Accepted: 18 August 2021
Published: 08 May 2022
Gout is the most common form of crystal-induced arthritis. Gout flares are a frequent complication during hospital admissions, including the critical care settings. Inpatient gout flare is a multifactorial event influenced by a combination of gout-and hospitalization-related factors. Several factors can trigger gout flares through altered renal urate handling, serum urate fluctuation, and macrophage priming. Early detection of gout flares can aid in the reduction of unnecessary antibiotics use, laboratory investigations, and diagnostic procedures, leading to improved hospital outcomes. Identification of crystals in synovial fluid or tophi is the gold standard for gout diagnosis, but the procedure is sometimes contraindicated in the critical care setting. Hospitalized patients with gout usually have multiple comorbidities contributing to challenges in the management of gout flares, which are not present in outpatient or noncritical inpatient settings. In this review, we discuss the unique characteristics and impact of gout flares in the critical care setting, as well as the diagnostic challenges and options for the treatment of gout flares and hyperuricemia in this setting.
Gout; Hospitalization; Critical care; Uric acid; Urate-lowering therapy; Arthritis
Panchalee Satpanich,Kanon Jatuworapruk. Gout ﬂare in the critical care setting: diagnostic challenges and treatment options. Signa Vitae. 2022. 18(3);9-17.
 Singh JA, Gaffo A. Gout epidemiology and comorbidities. Seminars in Arthritis and Rheumatism. 2020; 50: S11–S16.
 Wright S, Chapman PT, Frampton C, O’Donnell JL, Raja R, Stamp LK. Management of Gout in a Hospital Setting: a Lost Opportunity. The Journal of Rheumatology. 2017; 44: 1493–1498.
 Zleik N, Elfishawi MM, Kvrgic Z, Michet CJ, Crowson CS, Matteson EL, et al. Hospitalization Increases the Risk of Acute Arthritic Flares in Gout: a Population-based Study over 2 Decades. The Journal of Rheumatology. 2018; 45: 1188–1191.
 Robinson PC, Kempe S, Tebbutt I, Roberts L. Epidemiology of inpatient gout in Australia and New Zealand: temporal trends, comorbidities and gout flare site. International Journal of Rheumatic Diseases. 2017; 20: 779–784.
 Russell MD, Yates M, Bechman K, Rutherford AI, Subesinghe S, Lanyon P, et al. Rising Incidence of Acute Hospital Admissions due to Gout. The Journal of Rheumatology. 2020; 47: 619–623.
 Fisher MC, Pillinger MH, Keenan RT. Inpatient gout: a review. Current Rheumatology Reports. 2014; 16: 458.
 Jeong H, Jeon CH. Clinical characteristics and risk factors for gout flare during the postsurgical period. Advances in Rheumatology. 2019; 59: 31.
 Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: a review. Frontiers in Pharmacology. 2015; 6: 262.
 Terkeltaub R. What makes gouty inflammation so variable? BMC Medicine. 2017; 15: 158.
 Kang EH, Lee EY, Lee YJ, Song YW, Lee EB. Clinical features and risk factors of postsurgical gout. Annals of the Rheumatic Diseases. 2008; 67: 1271–1275.
 Zhuo Y, Cai X, Hou Z, Zhu Z, Cai D. Postoperative Recurrent Gout Flares: A Cross-sectional Study From China. Journal of Clinical Rheumatology. 2020; 26: 197–203.
 Lin Y, Hsu H, Huang Y, Lee M, Huang W, Huang Y, et al. Gouty Arthritis in Acute Cerebrovascular Disease. Cerebrovascular Diseases. 2009; 28: 391–396.
 Jatuworapruk K, Grainger R, Dalbeth N, Taylor WJ. Development of a prediction model for inpatient gout flares in people with comorbid gout. Annals of the Rheumatic Diseases. 2019; 79: 418–423.
 Richette P, Bardin T. Purine-rich foods: an innocent bystander of gout attacks? Annals of the Rheumatic Diseases. 2012; 71: 1435–1436.
 Perez-Ruiz F, Castillo E, Chinchilla SP, Herrero-Beites AM. Clinical Manifestations and Diagnosis of Gout. Rheumatic Disease Clinics of North America. 2014; 40: 193–206.
 Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout. The Lancet. 2021; 397: 1843–1855.
 Neogi T, Jansen TLTA, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, et al. 2015 Gout classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases. 2015; 74: 1789–1798.
 Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castaneda J, et al. 2018 updated European League against Rheumatism evidence-based recommendations for the diagnosis of gout. Annals of the Rheumatic Diseases. 2020; 79: 31–38.
 Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. The Journal of Rheumatology. 2009; 36: 1287–1289.
 Dalbeth N, Choi HK, Joosten LAB, Khanna PP, Matsuo H, Perez-Ruiz F, et al. Gout. Nature Reviews Disease Primers. 2019; 5: 69.
 Pascart T, Liote F. Gout: state of the art after a decade of developments. Rheumatology. 2019; 58: 27–44.
 Ogdie A, Taylor WJ, Neogi T, Fransen J, Jansen TL, Schumacher HR, et al. Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison with Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard. Arthritis & Rheumatology. 2017; 69: 429–438.
 Chou H, Chin TY, Peh WCG. Dual-energy CT in gout - a review of current concepts and applications. Journal of Medical Radiation Sciences. 2017; 64: 41–51.
 Bongartz T, Glazebrook KN, Kavros SJ, Murthy NS, Merry SP, Franz WB, et al. Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. Annals of the Rheumatic Diseases. 2015; 74: 1072–1077.
 Fam AG, Reis MD, Szalai JP. Acute gouty synovitis associated with “urate milk”. Journal of Rheumatology. 1997; 24: 2389–2393.
 Shah K, Spear J, Nathanson LA, McCauley J, Edlow JA. Does the presence of crystal arthritis rule out septic arthritis? The Journal of Emergency Medicine. 2007; 32: 23–26.
 Muangchan C, Bhurihirun T. An investigation of the independent risk factors that differentiate gout from pseudogout in patients with crystal-induced acute arthritis: a cross-sectional study. Rheumatology International. 2018; 38: 89–95.
 Neogi T. Clinical practice. Gout. The New England Journal of Medicine. 2011; 364: 443–452.
 FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care & Research. 2020; 72: 744–760.
 Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Annals of the Rheumatic Diseases. 2017; 76: 29–42.
 Hui M, Carr A, Cameron S, Davenport G, Doherty M, Forrester H, et al. The British Society for Rheumatology Guideline for the Management of Gout. Rheumatology. 2017; 56: 1056–1059.
 Billy CA, Lim RT, Ruospo M, Palmer SC, Strippoli GFM. Corticosteroid or Nonsteroidal Antiinflammatory Drugs for the Treatment of Acute Gout: a Systematic Review of Randomized Controlled Trials. The Journal of Rheumatology. 2018; 45: 128–136.
 Roddy E, Clarkson K, Blagojevic-Bucknall M, Mehta R, Oppong R, Avery A, et al. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care. Annals of the Rheumatic Diseases. 2020; 79: 276–284.
 Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care & Research. 2012; 64: 1447–1461.
 Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. The Lancet. 2008; 371: 1854–1860.
 Rubin BR, Burton R, Navarra S, Antigua J, Londoño J, Pryhuber KG, et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Arthritis and Rheumatism. 2004; 50: 598–606.
 Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis and Rheumatism. 2010; 62: 1060–1068.
 Drug and Therapeutics Bulletin. Latest guidance on the management of gout. British Medical Journal. 2018; 362: k2893.
 Estiverne C, Mount DB. The Management of Gout in Renal Disease. Seminars in Nephrology. 2020; 40: 600–613.
 Ritter J, Kerr LD, Valeriano-Marcet J, Spiera H. ACTH revisited: effective treatment for acute crystal induced synovitis in patients with multiple medical problems. The Journal of Rheumatology. 1994; 21: 696–699.
 Daoussis D, Antonopoulos I, Yiannopoulos G, Andonopoulos AP. ACTH as first line treatment for acute gout in 181 hospitalized patients. Joint Bone Spine. 2013; 80: 291–294.
 So A, Dumusc A, Nasi S. The role of IL-1 in gout: from bench to bedside. Rheumatology. 2018; 57: i12–i19.
 Liew JW, Gardner GC. Use of Anakinra in Hospitalized Patients with Crystal-associated Arthritis. The Journal of Rheumatology. 2019; 46: 1345–1349.
 Schlesinger N, Detry MA, Holland BK, Baker DG, Beutler AM, Rull M, et al. Local ice therapy during bouts of acute gouty arthritis. The Journal of Rheumatology. 2002; 29: 331–334.
 Jatuworapruk K, Grainger R, Dalbeth N, Lertnawapan R, Hanvivad-hanakul P, Towiwat P, et al. The GOUT-36 prediction rule for inpatient gout flare in people with comorbid gout: derivation and external validation. Rheumatology. 2021. (in press)
 Li Q, Li X, Wang J, Liu H, Kwong JS, Chen H, et al. Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. BMJ Open. 2019; 9: e026677.
 Hill EM, Sky K, Sit M, Collamer A, Higgs J. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. Journal of Clinical Rheumatology. 2015; 21: 120–125.
 Taylor TH, Mecchella JN, Larson RJ, Kerin KD, Mackenzie TA. Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. The American Journal of Medicine. 2012; 125: 1126–1134.e7.
 Sun R, Lu J, Li H, Cheng X, Xin Y, Li C. Evaluation of febuxostat initiation during an acute gout attack: a prospective, randomized clinical trial. Joint Bone Spine. 2020; 87: 461–466.
 Stamp LK, Taylor WJ, Jones PB, Dockerty JL, Drake J, Frampton C, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis and Rheumatism. 2012; 64: 2529–2536.
 Hanvivadhanakul P, Wongdet R. Outcome of Treatment in Gouty Arthritis Patients: a Retrospective Study. Journal of the Medical Association of Thailand. 2015; 98: S46–S50.
 Stamp LK, Barclay ML. How to prevent allopurinol hypersensitivity reactions? Rheumatology. 2017; 57: i35–i41.
 Lertnawapan R, Jatuworapruk K. Efficacy of febuxostat versus allopuri-nol and the predictors of achieving target serum urate in a cohort of Thai people with gout. Clinical Rheumatology. 2021; 40: 255–262.
 White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. The New England Journal of Medicine. 2018; 378: 1200–1210.
 Juge P, Truchetet M, Pillebout E, Ottaviani S, Vigneau C, Loustau C, et al. Efficacy and safety of febuxostat in 73 gouty patients with stage 4/5 chronic kidney disease: a retrospective study of 10 centers. Joint Bone Spine. 2017; 84: 595–598.
 Dalbeth N, Merriman TR, Stamp LK. Gout. The Lancet. 2016; 388: 2039–2052.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 0.5(2021) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.