Gouty Inflammation

  • Naomi SchlesingerEmail author
  • Johnson C. Kay


Inflammation and hyperuricemia drive the gout cascade. Understanding of the role of inflammation, including involvement of the innate immune system, helps to improve the diagnosis and therapeutic course of the disease. Treatment of acute and chronic gouty inflammation is of utmost importance in preventing long-term disability. In this chapter, we discuss the clinical presentation of gout and its diagnosis, immunopathogenesis, and treatment. The anti-inflammatory therapies used to combat gouty inflammation are highlighted.


Gout Inflammation Hyperuricemia Monosodium urate crystal NLRP3 (cryopyrin) inflammasome Interleukin-1 Anti-inflammatory drugs Prophylaxis 



American College of Physicians


American College of Rheumatology


Adrenocorticotropic hormone


Damage-associated molecular patterns


Dual-energy computed tomography


European League Against Rheumatism


Food and Drug Administration




Monosodium urate




NACHT, LRR and PYD domains-containing protein 3


Non-steroidal anti-inflammatory drugs


Serum urate


Triamcinolone acetonide


Toll-like receptor


Tumor necrosis factor


Urate lowering therapy




  1. 1.
    Zhu Y, Pandya B, Choi H. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136–314.CrossRefGoogle Scholar
  2. 2.
    Petersel D, Schlesinger N. Treatment of acute gout in hospitalized patients. J Rheumatol. 2007;34:1566–8.PubMedGoogle Scholar
  3. 3.
    Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67:1739–42.CrossRefGoogle Scholar
  4. 4.
    Roseff R, Wohlgethan JR, Sipe JD, Canoso JJ. The acute phase response in gout. J Rheumatol. 1987;14:974–7.PubMedGoogle Scholar
  5. 5.
    Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44:2737–45.CrossRefGoogle Scholar
  6. 6.
    Svenungsson E, Jensen-Urstad K, Heimburger M, et al. Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation. 2001;104:1887–93.CrossRefGoogle Scholar
  7. 7.
    Garcia-Martinez I, Shaker ME, Mehal WZ. Therapeutic opportunities in damage-associated molecular pattern-driven metabolic diseases. Antioxid Redox Signal. 2015;23(17):1305–15.CrossRefGoogle Scholar
  8. 8.
    Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425:516–21.CrossRefGoogle Scholar
  9. 9.
    Martin WJ, Walton M, Harper J. Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout. Arthritis Rheum. 2009;60:281–9.CrossRefGoogle Scholar
  10. 10.
    Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest. 2006;116:2262–71.CrossRefGoogle Scholar
  11. 11.
    Torres R, Macdonald L, Croll SD, et al. Hyperalgesia, synovitis, and multiple biomarkers of inflammation are suppressed by IL-1 inhibition in a novel animal model of gouty arthritis. Ann Rheum Dis. 2009;68:1602–8.CrossRefGoogle Scholar
  12. 12.
    Martinon F, Tschopp J. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell. 2004;117:561–74.CrossRefGoogle Scholar
  13. 13.
    Sanz JM, Di Virgilio F. Kinetics and mechanism of ATP-dependent IL-1 beta release from microglial cells. J Immunol. 2000;164:4893–8.CrossRefGoogle Scholar
  14. 14.
    Joosten LAB, Netea MG, Mylona E, et al. Fatty acids engagement with TLR2 drive IL-1β production via ASC-caspase-1 pathway by urate crystals in gouty arthritis. Arthritis Rheum. 2010;62(11):3237–48.CrossRefGoogle Scholar
  15. 15.
    Schlesinger N. Diagnosis of gout: a review to aid the clinician. Gout Hyperuricemia. 2015;2(4):118–20.Google Scholar
  16. 16.
    Schlesinger N, Baker DG, Beutler AM, Hoffman BI, Schumacher HR Jr. Acute gouty arthritis is seasonal. J Rheumatol. 1998;25(2):342–4.PubMedGoogle Scholar
  17. 17.
    Lally EV, Zimmerman B, Ho G, Kaplan SR. Urate-mediated inflammation in nodal arthritis: clinical and roentgenographic correlations. Arthritis Rheum. 1989;32:86–90.CrossRefGoogle Scholar
  18. 18.
    Reginato AJ, Schumacher HR. Crystal associated arthropathies. Clin Geriatr Med. 1988;4:295–322.CrossRefGoogle Scholar
  19. 19.
    Neogi T, Jansen TLTA, Dalbeth N, et al. 2015 gout classification criteria: an American College of Rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2015;74:1789–98.CrossRefGoogle Scholar
  20. 20.
    Schlesinger N, Watson DJ, Norquist JM. Serum urate during acute gout. J Rheumatol. 2009;36(6):1287–9.CrossRefGoogle Scholar
  21. 21.
    Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford). 2007;46(7):1116–21.CrossRefGoogle Scholar
  22. 22.
    Bongartz T, Glazebrook KN, Kavros SJ, et al. Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. Ann Rheum Dis. 2015;74(6):1072–7.CrossRefGoogle Scholar
  23. 23.
    Khanna D, Khanna PP, Fitzgerald JD, et al. American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res. 2012;64:1447–61.CrossRefGoogle Scholar
  24. 24.
    Richette P, Doherty M, Pascual E, et al. Updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29–42.Google Scholar
  25. 25.
    Qaseem A, Harris RP, Forciea MA. For the Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(1):58–68.CrossRefGoogle Scholar
  26. 26.
    Hollander JL. Collagenase, cartilage and cortisol. Editorial. N Engl J Med. 1974;290:50–1.CrossRefGoogle Scholar
  27. 27.
    Dorwart BB, Hansell JR, Schumacher HR Jr. Effects of cold and heat on urate crystal-induced synovitis in the dog. Arthritis Rheum. 1974;17:563–71.CrossRefGoogle Scholar
  28. 28.
    Schlesinger N, Detry MA, Holland BK, et al. Local ice therapy during bouts of acute gouty arthritis. J Rheumatol. 2002;29:331–4.PubMedGoogle Scholar
  29. 29.
    Blau LW. Cherry diet control for gout and arthritis. Tex Rep Biol Med. 1950;8:309–11.PubMedGoogle Scholar
  30. 30.
    Schlesinger N, Rabinowitz R, Schlesinger M. Pilot studies of cherry juice concentrate for gout flare prophylaxis. J Arthritis. 2012;1:1.Google Scholar
  31. 31.
  32. 32.
    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, randomised, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62:1060–8.CrossRefGoogle Scholar
  33. 33.
    Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol therapy: results of a double-blind, randomised study. Ann Rheum Dis. 2011;70(7):1264–71.CrossRefGoogle Scholar
  34. 34.
    Schlesinger N, De Meulemeester M, Pikhlak A, et al. Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat gouty arthritis by suppressing inflammation: results of a randomized, dose-ranging study. Arthritis Res Ther. 2011;13:R53.CrossRefGoogle Scholar
  35. 35.
    Misawa T, Takahama M, Kozaki T, et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 2013;14:454–60.CrossRefGoogle Scholar
  36. 36.
    Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest. 1995;96(2):994–1002.CrossRefGoogle Scholar
  37. 37.
    van Durme CMPG, Wechalekar MD, Buchbinder R, Schlesinger N, van der Heijde D, Landewé RBM. Nonsteroidal anti-inflammatory drugs for acute gout. Cochrane Database Syst Rev. 2014;(9):CD010120.Google Scholar
  38. 38.
  39. 39.
    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. Lancet. 2008;371(9627):1854–60.CrossRefGoogle Scholar
  40. 40.
    Man CY, Cheung IT, Cameron PA, Rainer TH. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute gout like arthritis: a double blind, randomized, controlled trial. Ann Emerg Med. 2007;49(5):670–7.CrossRefGoogle Scholar
  41. 41.
    Khanna D, Khanna PP, Fitzgerald JD, et al. American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res. 2012;64:1447–61.CrossRefGoogle Scholar
  42. 42.
    Getting SJ. Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther. 2006;111(1):1–15.CrossRefGoogle Scholar
  43. 43.
    Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum. 2002;46:2765–75.CrossRefGoogle Scholar
  44. 44.
    Daoussis D, Andonopoulos AP. Adrenocorticotropic hormone: a powerful but underappreciated therapeutic tool for acute crystal induced arthritis? World J Rheumatol. 2013;3(2):6–8.CrossRefGoogle Scholar
  45. 45.
    So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007;9(2):R28.CrossRefGoogle Scholar
  46. 46.
  47. 47.
    Ottaviani S, Moltò A, Ea H-K, et al. Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases. Arthritis Res Ther. 2013;15:R123.CrossRefGoogle Scholar
  48. 48.
    So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for treatment of acute flares in refractory gouty arthritis. Arthritis Rheum. 2010;62(10):3064–74.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of MedicineRutgers Robert Wood Johnson Gout Center, Rutgers Biomedical and Health Sciences BrunswickNew BrunswickUSA
  2. 2.Department of MedicineRutgers—Robert Wood Johnson Medical SchoolNew BrunswickUSA

Personalised recommendations