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Gout

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(Redirected from Hyperuricemia)

Other Names

  • Gouty Arthritis
  • Monosodium Urate Cystal Arthropathy
  • Crystal Arthropathy
  • Tophus or tophi
  • Podagra
  • Hyperuricemia
  • Tophaceous Gout

Background

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Gout Review Pod

History

  • First documented in ancient Egypt[1]

Epidemiology

  • Prevalence
    • Men (3-6%), Women (1-3%)[2]
    • Roughly 8.3 million people in the US[3]
    • Hyperuricemia, or serum uric acid level greater than 6 mg/dL, seen in 21% of US population
  • Typical age between 40 and 69 years of age

Introduction

Schematic of uric acid crystal formation and swallowing[4]
Schematic of overproduction and under excretion of uric acid[4]
Overview of the development of gout[5]
Impact of uric acid on human finger[4]

General

  • Occurs due to monosodium urate crystal deposition in the synovial fluid of joints
  • Causes painful, swollen joints, most classically at the 1st MTPJ
  • Treatment involves acute anti-inflammatories and chronic urate lowering therapy

Role of Diet

  • Foods
    • Foods high in purine increase risk of developing gout or gout flare
    • Fish (e.g., anchovies, sardines, scallops, mussels)
    • Meats (e.g., bacon, beef, liver, turkey, veal, venison)
    • Paradoxically, purine rich vegetables do not increase uric acid or risk of developing gout[6]
  • Alcohol
    • Beer associated with highest risk, less so with liquor (moderate), wine (low)[7]

Affected Joints[8]

  • First metatarsophalangeal joint (56% to 78%)
  • Midfoot (25% to 50%)
  • Ankle (18% to 60%)
  • Upper limb (13% to 46%)
  • interphalangeal joints (6% to 25%)

Hyperuricemia

  • Defined as serum uric acid level greater than 6 mg/dL
  • Can be relatively benign, only only 22% of men with a serum uric acid greater than 9 mg/dL develop gout over a 5-year period[9]
  • MSU crystals formation, deposition occurs at uric acid levels > 6.8 mg/dL[10]

Tophi or tophaceous gout

  • Due to repetitive accumulation of MSU crystals
  • Increased risk of tophi: temperature, mechanical trauma, previous disease, underlying osteoarthritis

Stages of Gout

  • Asymptomatic hyperuricemia
    • Preliminary stage, many will never develop gout
  • Acute gout
    • Abrupt onset, joint is erythematous, warm, swollen, and tender
    • Suspect if acute onset of monoarticular joint pain, maximum intensity occurring within 12 hours
  • Intercritical or interval gout
    • Acute symptoms resolved, low-grade inflammation remains, causing unnoticed damage
    • Persistent hyperuricemia drives MSU crystal deposition, tophi development
    • Leads to erosive changes which can be seen radiographically
  • Chronic gout
    • Persistent arthralgia or repeated episodes of acute gout, usually complicated by tophi formation
    • About 30% of patients develop chronic gout within 5 years[11]
    • Acute gout difficult to recognize in patients with chronic gout, presentation can mimic osteoarthritis

Associated Conditions

  • Gout increases risk of
    • Myocardial Infarction[12]

Risk Factors

  • Non-modifiable risk factors
    • Male gender (2-6x)
    • Increased age (linearly until age 80)[13]
    • Family history
    • Ethnicity: Taiwanese, Pacific Islander, and New Zealand Maori
    • Living in high-income countries
  • Behavioral risk factors
    • Diet rich in red meat, seafood
    • Diet heavy in fructose-rich food and beverages
    • Alcohol consumption
    • Physical inactivity
  • Medications
    • Loop diuretic
    • Tacrolimus, cyclosporine
    • Niacin
    • Aspirin
  • Systemic Illness
  • Genetic[14][15]
    • SLC2A9 (Glut-9 transporter)
    • SLC22A11 (OAT1 transporter)
    • SLC22A12 (URAT1 transporter)
    • Hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme deficiency

Differential Diagnosis

Clinical Features

Gouty inflammation of the 1st MTPJ[4]

History

  • Key history: onset, timeline, location, previous joint trauma or injury, other arthralgias, dietary intake, alcohol consumption, and medications
  • In acute flares, patients complain of sudden onset joint swelling, pain and tenderness
  • First metatarsophalangeal joint (56% to 78% of patients) most commonly affected
  • Derm: draining of chalk-like substance from a subcutaneous nodule under transparent skin, suggesting tophus
  • Less commonly: ocular, spinal, and visceral manifestations mimicking a tumor or infection

Physical Exam

  • Evaluate affected joint(s) for erythema, swelling, rubor, presence of effusion
  • Tender to palpation with limited range of motion

Evaluation

(A) Anteroposterior radiography of feet of a patient with gout showing increased volume and density of soft tissues adjacent to the first metatarsophalangeal (MTP) joint (arrow). One can also observe bone erosion in distal metaphysis of the first metatarsal. (B) Detail of the previous image showing the head of the first left metatarsal, evidencing bone erosion marked with an asterisk (*) with raised edges, and Martel's sign (arrow). (C) Ultrasound image with longitudinal section of the foot at the level of the first MTP joint, showing the cortical bone of the head of first metatarsal (large arrow), the MTP joint space of the hallux, the cartilage of the head of the first metatarsal (*) and a thin hyperechoic layer overlying the coating cartilage (small arrow), characterizing the double contour sign. (D) Detail of the previous image showing the bone surface (arrow) of the head of the first metatarsal, articular cartilage (*) and the thin hyperechoic layer (small arrow), characterizing the double contour sign. P, proximal; D, distal; TS, subcutaneous tissue; ESP, phalangeal space of hallux; TE, extensor hallucis tendon.[16]
Ultrasound images of gout patients. A, A single tophi in the left first metatarsophalangeal (MTP) joint with longest diameter shown. B, Double contour sign in the left knee joint. C, Synovial hypertrophy in the right first MTP joint. D, Bone erosions in the right distal metatarsal bone.[17]
Advanced erosive gout on CT. Axial CT images of bilateral 1st MTP joints demonstrate severe erosive changes (arrow) related to chronic gout with intra-articular erosions and subchondral deposits (arrowhead). Note the preservation of bone density adjacent to erosions, a feature of gout.[18]
maging of gouty joint in an adolescent. (A) Synovitis on MRI with and without IV contrast of the right ankle with osteitis in the distal tibia and talar dome. Talar dome lesion was thought to represent an osteochondritis dissecans/osteonecrosis. (B) Radiographs performed 15 months later show marked joint space loss with persistent talar dome lesion which likely represents an intraosseous tophus.[19]

General

  • Diagnosis can be made clinically
    • Unless suspicious of septic arthritis, which must be excluded with arthrocentesis
    • See ACR/EULAR Criteria below

Arthrocentesis and Synovial Fluid Analysis

  • Arthrocentesis
    • Indicated if moderate or intermediate risk OR need to exclude septic arthritis
  • Monosodium urate crystals
    • Appear negatively birefringent on polarized light microscopy, pathognomonic
    • Note that septic arthritis can coexist with gout, presence of crystals does not exclude SA[20]
    • Optimal timing is during acute gout flare
    • Only seen 70% of the time during intercritical period of acute flare[21]
  • Synovial fluid labs which should routinely be ordered when evaluating for SA
    • Culture and gram stain
    • Culture
    • Cell count
    • Protein and glucose
    • Crystal analysis
    • Synovial lactate

Serology

  • Uric Acid
    • Typically elevated in individuals with gout (> 5.8 mg per dL)
    • Acute gout attack: 14% of patients with low/ normal uric acid[22]
    • Elevated uric acid does not equate to gout as many hyperuricemia patients never develop gout[23]
  • Other
    • Must consider blood cultures, ESR, CRP if septic arthritis a consideration

Radiography

  • Standard evaluation of affected joint
    • Often normal
  • Potential findings in gout
    • Nonspecific soft tissue swelling
    • Chronic: punched-out erosions, interosseous tophi[24]

Ultrasound

  • General
    • Can be used to aid in diagnosis
    • Monitor disease progression/ management with urate lowering therapy
    • Aid in arthrocentesis
  • Double contour sign
    • Hyperechoic signal overlying an anechoic signal
    • Specificity: 96%, although the exact rate varies widely among joints[25]
  • Tophus
    • Heterogeneous, hyperechoic signal with poorly defined contours surrounded by an anechoic signal[26]
  • Snowstorm appearance
  • Diagnostic accuracy
    • Presence of 1/3 (double contour sign, tophus, snowstorm sign) LR+ 4.8, LR- 0.27[27]

CT

  • General
    • Can be used to aid in diagnosis
    • Can be used to evaluate degree of structure damage
  • Findings
    • Tophi
    • Bony erosions
  • Duel Energy CT
    • Can help identify MSU crystals (90% Se, 83% Sp)[28]

MRI

  • General
    • Often cost prohibitive
    • Not required for diagnosis or management
  • Findings
    • Visualize soft tissue, inflammatory changes
    • T2-weighted: tophi (medium-high signal changes), calcifications (low signal changes)

Classification

ACR/EULAR Gout Classification Criteria

  • General
    • From American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) 2015[29]
    • Notably does not require arthrocentesis
  • Points
    • Acute onset, with maximal symptoms on day 1: 0.5
    • Joint erythema: 1.0
    • Hypertension or cardiovascular disease: 1.5
    • Male sex: 2.0
    • Previous episode of arthritis or joint pain: 2.0
    • First metatarsophalangeal joint involvement: 2.5
    • Serum uric acid > 5.8 mg per dL (0.35 mmol per L): 3.5
  • Score
    • ≥ 8: high risk (diagnose gout)
    • 4.5 to 7.5: intermediate risk (needs arthrocentesis, crystal analysis)
    • ≤ 4: low risk (consider alternative diagnosis)

Management

Management of gout: An algorithm.[30]
Proposed treatment algorithm (courtesy of AAFP)

Lifestyle Modifications

  • Food avoidance
    • Low-fat
    • Low-purine
    • Fructose-containing soft drinks
  • Recommended foods[31]
    • Skim milk and low-fat yogurt, vegetables, soybeans, vegetable sources of protein, and cherries
  • Dietary Approaches to Stop Hypertension (DASH) Diet
    • 32% lower risk of developing gout (0.68; 95% CI, 0.57 to 0.80)[32]
  • Alcohol avoidance
  • Weight Loss
  • Increased Exercise

Acute Episode

  • NSAIDS
    • First line treatment unless contraindicated
    • Often used meds include naproxen, indomethacin, and sulindac
    • Comparable efficacy other medications at recommended doses[33]
  • Colchicine
    • Ideally started within first 24-36 hours
    • Low-dose (1.2 mg orally followed by 0.6 mg one hour later) as effective as high-dose colchicine (1.2 mg followed by 0.6 mg every hour for six hours)[34]
    • Low dose fewer adverse events (77% in high dose, 36% in low dose)
  • Oral Corticosteroids
    • Oral prednisolone (35 mg QD) is equal to naproxen (500 mg BID), no difference in pain relief or adverse effects[35]
  • Analgesia
    • Ice therapy helps in acute flares[36]
  • Other: Role unknown
    • Interleukin-1 inhibitors (anakinra [Kineret], canakinumab [Ilaris], or rilonacept [Arcalyst])

Chronic Management

  • General
    • ACP, AAFP recommend discuss benefits/ risks before initiating any urate lowering therapy (ULT)[37]
    • Review modifiable risk factors
    • Obtain baseline uric acid level
  • Indications for ULT
    • 3 or more episodes of gout
    • Failure to control uric acid with modification of risk factors
    • Persistent elevation over 6 mg/dL
    • Presence of tophi or uric acid nephrolithiasis
  • Titration
    • ACP does not recommend titrating ULT to 24 hour urine uric acid or serum uric acid
    • British Society for Rheumatology recommends titrating ULT to less than 0.3 mmol per L (5 mg/dL)
    • Reduction to < 5 mg/dL increased tophi reduction[38]
  • Allupurinol
    • First line therapy, dosage varies with severity
  • Febuxostat (Uloric)
    • Noninferior to allopurinol in preventing acute gout episodes[39]
    • However, febuxostat as higher cardiovascular risk and all cause mortality risk
  • Prophylaxis
    • ACR/EULAR recommend prophylaxis while initiating urate-lowering therapy
  • Pegloticase (Krystexxa)
    • Consider when allupurinol, febuxostat fail to control symptoms
    • Proven to lower serum uric acid levels
    • Benefits: quality of life, function, and pain; reduces tophi size in chronic gout[40]
  • Canakinumab [Ilaris]
    • Role not entirely clear
    • One study found it superior to IM steroids, NSAIDS and colchicine for acute gout during first 72 hours[41]

Other

Rehab and Return to Play

Rehabilitation

  • No definitive guidelines

Return to Play

  • Consider after[44]
    • Complete resolution of acute symptoms
    • Restoration of joint function
    • Confirmation that the athlete poses no undue risk to themselves or others

Prognosis and Complications

Prognosis

  • Acute episode
    • Typically self limited, resolution in 1-2 weeks
  • Morbidity and mortality
    • No evidence ULT decreases the risk of cardiovascular events[45]

Complications

  • Degenerative Joint Disease
  • Secondary infections
  • Urate or uric acid nephropathy.
  • Nephrolithiasis
  • Nerve or spinal cord impingement.
  • Fractures in joints with tophaceous gout.

See Also

Internal

External

References

  1. ↑ Nuki G, Simkin PA. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther. 2006;8(suppl 1):S1.
  2. ↑ Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet. 2016;388(10055):2039–2052.
  3. ↑ Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136–3141.
  4. ↑ 4.0 4.1 4.2 4.3 Parthasarathy, Panchatcharam, and S. Vivekanandan. "Urate crystal deposition, prevention and various diagnosis techniques of GOUT arthritis disease: a comprehensive review." Health information science and systems 6 (2018): 1-13.
  5. ↑ Basnet, Rajesh, et al. "Xanthine oxidase and transforming growth factor beta-activated kinase 1: potential targets for gout intervention." Current rheumatology reviews 17.2 (2021): 153-161.
  6. ↑ Zaga L, Theodoratou E, Kyle J, et al. The association of dietary intake of purine-rich vegetables, sugar-sweetened beverages and dairy with plasma urate, in a cross-sectional study. PLoS One. 2012;7(6):e38123.
  7. ↑ Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 2011;23(2):192–202.
  8. ↑ Roddy E. Revisiting the pathogenesis of podagra: why does gout target the foot? J Foot Ankle Res. 2011;4(1):13.
  9. ↑ Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med. 1987;82(3):421–426.
  10. ↑ Schumacher HR Jr. The pathogenesis of gout. Cleve Clin J Med. 2008;75(suppl 5):S2–S4.
  11. ↑ Perez-Ruiz F, Calabozo M, Pijoan JI, et al. Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum. 2002;47(4):356–360.
  12. ↑ Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006;54(8):2688–2696.
  13. ↑ Kuo CF, Grainge MJ, Mallen C, et al. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2015;74(4):661–667.
  14. ↑ Reginato AM, Mount DB, Yang I, Choi HK. The genetics of hyperuricaemia and gout. Nat Rev Rheumatol. 2012;8(10):610–621.
  15. ↑ Yang Q, Köttgen A, Dehghan A, et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010;3(6):523–530.
  16. ↑ Fernandes, Eloy De Avila, et al. "Relevant aspects of imaging in the diagnosis and management of gout." Revista brasileira de reumatologia 57.1 (2017): 64-72.
  17. ↑ Han, Lin, et al. "Association of the quantity, duration, and type of alcohol consumption on the development of gouty Tophi." Arthritis Care & Research 75.5 (2023): 1079-1087.
  18. ↑ Girish, Gandikota, et al. "Imaging appearances in gout." Arthritis 2013.1 (2013): 673401.
  19. ↑ Morris, Hallie, et al. "Gout in a 15-year-old boy with juvenile idiopathic arthritis: a case study." Pediatric Rheumatology 12 (2014): 1-5.
  20. ↑ Yu KH, Luo SF, Liou LB, et al. Concomitant septic and gouty arthritis—an analysis of 30 cases. Rheumatology (Oxford). 2003;42(9):1062–1066.
  21. ↑ Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65(10):1301–1311.
  22. ↑ Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout [published correction appears in J Rheumatol. 2009;36(8):1851]. J Rheumatol. 2009;36(6):1287–1289.
  23. ↑ Tausche AK, Jansen TL, Schröder HE, et al. Gout—current diagnosis and treatment. Dtsch Arztebl Int. 2009;106(34-35):549–555.
  24. ↑ Perez-Ruiz F, Dalbeth N, Urresola A, et al. Imaging of gout: findings and utility. Arthritis Res Ther. 2009;11(3):232.
  25. ↑ Mathieu S, Pereira B, Couderc M, Soubrier M. Usefulness of ultrasonography in the diagnosis of gout: a meta-analysis. Ann Rheum Dis. 2013;72(10):e23.
  26. ↑ de Ávila Fernandes E, Kubota ES, Sandim GB, et al.Ultrasound features of tophi in chronic tophaceous gout. Skeletal Radiol. 2011;40(3):309–315.
  27. ↑ Ogdie A, Taylor WJ, Neogi T, 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 Rheumatol. 2017;69(2):429–438.
  28. ↑ 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):1072–1077.
  29. ↑ Neogi T, Jansen TLTA, Dalbeth N, et al. 2015 gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative [published correction appears in Arthritis Rheumatol. 2016;68(2):515]. Arthritis Rheumatol. 2015;67(10):2557–2568.
  30. ↑ Pillinger, Michael H., and Brian F. Mandell. "Therapeutic approaches in the treatment of gout." Seminars in Arthritis and Rheumatism. Vol. 50. No. 3. WB Saunders, 2020.
  31. ↑ Hui M, Carr A, Cameron S, et al.; British Society for Rheumatology Standards, Audit and Guidelines Working Group.. The British Society for Rheumatology guideline for the management of gout [published correction appears in Rheumatology (Oxford). 2017;56(7):1246]. Rheumatology (Oxford). 2017;56(7):e1–e20.
  32. ↑ Rai SK, Fung TT, Lu N, et al. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study. BMJ. 2017;357:j1794.
  33. ↑ Khanna D, Khanna PP, Fitzgerald JD. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012;64(10):1447–1461.
  34. ↑ Terkeltaub RA, Furst DE, Bennett K, et al. 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 Rheum. 2010;62(4):1060–1068.
  35. ↑ Janssens HJEM, Janssen M, van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet. 2008;371(9627):1854–1860.
  36. ↑ Schlesinger N, Detry MA, Holland BK, et al. Local ice therapy during bouts of acute gouty arthritis. J Rheumatol. 2002;29(2):331–334.
  37. ↑ American Academy of Family Physicians. Management of acute and recurrent gout; April 2017. Accessed January 29, 2020. https://www.aafp.org/patient-care/clinical-recommendations/all/gout-cpg.html
  38. ↑ Perez-Ruiz F, Calabozo M, Pijoan JI, et al. Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum. 2002;47(4):356–360.
  39. ↑ White WB, Saag KG, Becker MA, et al.; CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018;378(13):1200–1210.
  40. ↑ Strand V, Khanna D, Singh JA, et al. Improved health-related quality of life and physical function in patients with refractory chronic gout following treatment with pegloticase: evidence from phase III randomized controlled trials. J Rheumatol. 2012;39(7):1450–1457.
  41. ↑ Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis. 2012;71(11):1839–1848.
  42. ↑ Stamp LK, O'Donnell JL, Frampton C, et al. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. Arthritis Rheum. 2013;65(6):1636–1642.
  43. ↑ Lee WB, Woo SH, Min BI, et al. Acupuncture for gouty arthritis: a concise report of a systematic and meta-analysis approach. Rheumatology (Oxford). 2013;52(7):1225–1232.
  44. ↑ Herring, Stanley A. "The team physician and return-to-play issues: a consensus statement." Medicine & Science in Sports & Exercise 34.7 (2002): 1212-1214.
  45. ↑ Zhang T, Pope JE. Cardiovascular effects of urate-lowering therapies in patients with chronic gout: a systematic review and meta-analysis. Rheumatology (Oxford). 2017;56(7):1144–1153.
Created by:
John Kiel on 7 July 2019 05:33:01
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Last edited:
20 October 2025 18:01:21
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Knee | Rheumatology | Foot
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