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gout

Classification: - stages of gout - acute intermittent gout - intercritical gout (time between acute gout attacks) - chronic recurrent & tophaceous gout - persistent synovitis, formation of tophi Etiology: precipitating factors/associations 1) hyperuricemia 2) 5-10% of patients with have simultaneous attack of gout & pseudogout 2) gout may occur in Heberden's or Bouchard's nodes in older women taking thiazide diuretics 3) 25% of patients with cardiac transplantation have gout 4) may be precipitated by surgery, severe illness or trauma a) myocardial infarction b) infection 5) often occurs in the setting of renal failure [6] 6) may occur in association with cyclosporine use [6] 7) alcohol predisposes men to gout [10,85] a) spirits & beer confer greater risk than wine b) 'Moonshine' alcohol contains lead which impairs uric acid secretion 8) starting or stopping allopurinol [28] 9) glycogen storage disease [82] 10) myeloproliferative disease [82] 11) high levels of serum glycoprotein acetyls, markers of neutrophil activation predict recurrent gout attacks [86] 12) other risk factors: a) hypertension & antihypertensives 1] diuretics a] thiazide diuretics (HR=1.7); HCTZ is a common trigger of acute gout b] loop diuretics (HR=2.4) [27] 2] beta-blockers 3] ACE inhibitors 4] ARBs - exception: losartan (modest uricosuric effect) 5] not calcium channel blockers b) organ transplantation with use of calcineurin antagonists (cyclosporine) [2] c) dehydration [28] d) high-fructose corn syrup [16] e) binge eating or fasting [28] f) shellfish, red meat [82] g) processed foods (chips, refined carbohydrates) [82] h) diabetes mellitus type-2 [62] i) obesity [78] j) lead toxicity [2] k) sleep apnea [82] l) metabolic syndrome [84] Epidemiology: 1) 0.1-0.4% of population, higher in southeast Asians 2) family history in 6-18% 3) most common in middle-aged men 4) rare in premenopausal females 5) as common in older women as older men 6) 5% of men > 65 years of age [6] Pathology: 1) hyperuricemia: overproduction (10%), underexcretion (90%) 2) crystalization of monosodium urate in a synovial joint 3) coating of crystals with immunoglobulin & complement 4) phagocytosis of crystals by neutrophils 5) chemotaxis, activation of kallikrein system 6) release of lysosomal enzymes into synovial fluid 7) tendon involvement is common in patients with tophaceous gout [39] a) Achilles tendon (52%) b) peroneal tendon (29%) 8) extensor surfaces of extremities & finger pads are other sites of gouty tophi 9) ligament involvement is rare Genetics: - HPRT-related form Kelley-Seegmiller syndrome associated with defects in HPRT1 - hyperuricemia & gout may be associated with defects &/or polymorphisms in urate transporters URAT1 & GLUT9 [20] - asymptomatic sons of people with gout frequently have hyperuricemia & intra-articular monosodium urate crystal deposits [64] Clinical manifestations: 1) gout is generally monoarticular; 10% of initial attacks involve > 1 joint - asymmetric involvement of joints [82] 2) rapid joint swelling with extreme tenderness 3) attacks begin suddenly & generally reach maximum intensity within 8-12 hours [82] 4) the most common joints affected (in decreasing order) are: a) 1st metatarsophalangeal (MTP) joint (podagra) in 50% b) medial TMT, ankle, heel, knee, wrist, elbow, shoulder, finger c) common in distal & proximal interphalangeal joints in hands [6] 5) most patients do NOT have systemic manifestations, i.e. fever * images [82] Diagnostic criteria: presence of 6 of the following:* - multiple attacks of acute arthritis - inflammation maximizes in 1 day - attack of monoarthritis - joint erythema - pain or swelling of 1st metatarsophalangeal joint - unilateral 1st metatarsophalangeal joint attack - unilateral tarsal joint attack - tophus (suspected) - hyperuricemia - asymmetric swelling within a joint visible on physical exam or radiography - subcortical cysts without erosions visible on radiography - monosodium urate monohydrate microcrystals (negatively birefringent, needle-shaped) within synovial fluid neutrophils during attack - only intracellular crystals are diagnostic of acute attack [2] - joint fluid cultures negative for organisms during attack * identification of crystals in synovial fluid not essential for diagnosis [2] Laboratory: 1) synovial fluid analysis a) confirm diagnosis of gout & rule out septic arthritis b) monosodium urate crystals in synovial fluid 1] negatively birefringent, needle-shaped within leukocytes 2] 50% of synovial fluids from 1st metatarsal joint in asymptomatic patients with gout will have urate crystals c) 2000-75,000 neutrophils/uL - synovial fluid leukocyte count > 50,000/uL suggests infectious arthritis d) obtain Gram stain & culture to rule out infectious arthritis e) if a predominance of neutrophils, unless intracellular uric acid crystals are seen (diagnostic of acute gout) then assume infectious arthritis even if gram stain is negative [2,26]* f) synovial fluid is clear or white in patients with gout [82] 2) 30% of patients with chronic gout have a low titer of rheumatoid factor 3) serum uric acid a) elevated serum uric acid is not diagnostic of gout [2] b) 1/3 of patients with acute gouty arthritis have levels < 8 mg/dL, thus a normal serum urate level does not exclude an acute gouty attack [18] - serum urate > 5.9 mg/dL is one of diagnostic criteria for gout [82] c) serum urate is a strong non-linear concentration-dependent predictor of incident gout [66] will develop gout within 5 years d) ~1/2 of those with serum urate concentrations >=10 mg/dL develop clinically evident gout over 15 years [66] e) 20% of individuals with sustained serum urate > 9 mg/dL f) goal of management is maintenance < 6.0 mg/dL g) saturation level of serum urate is 6.8 mg/dL 4) 24 hour urine for uric acid & creatinine a) uric acid/creatinine ratio is normally < 0.4 b) values > 0.4 indicate overproduction of uric acid c) a 40% decrease in urinary uric acid excretion occurs at all serum levels of uric acid in patients with gout [12] d) urine microscopy for urate crystals in urine ? 5) HLA-B*5801 allele-testing of Hans Chinese & Thai persons for risk for severe allopurinol sensitivity [31] 6) increased blood lead levels associated with increased risk for gout - apparently no threshold for the risk as risk increases even at low, non-toxic levels of blood lead [30] 7) see ARUP consult [29] * WBC count may be < 6000/uL (10% of 30 hospitalized cases) [46] * it seems the concept of antibiotic stewardship may be lost; there is no discussion of NNT vs NNH * image of monosodium urate crystals [82] * image of synovial fluid from patient with gout [82] Radiology: - X-ray of affect joint* - punched-out bony erosions with sclerotic border & overhanging osteophytes (chronic) - subcortical cysts & periarticular erosions may be seen [2] - periarticular soft tissue swelling without calcification in tophi - dual-energy CT may be useful for suspected but unproven crystal-induced arthritis [23] - ultrasound may be helpful in patients with probable gout despite negative or technically difficult arthrocentesis [59] * images [82] Differential diagnosis: 1) pseudogout (CPPD) less likely to present in hallux 2) infectious arthritis [2] - gout may coexist with infectious arthritis [2,6] - negative gram stain insufficient to rule out infection [2] - only intracellular crystals diagnostic of acute gout [2] 3) traumatic arthritis - trauma can also trigger gouty arthritis [2] 4) basic calcium phosphate deposition - unlikely to be seen in synovial fluid by light microscopy except as aggregates stained with alizarin red [2] 5) osteoarthritis 6) other forms of inflammatory arthritis - reactive arthritis, rheumatoid arthritis, psoriatic arthritis, acute rheumatic fever [2] 7) absence of swelling & failure of glucocorticoids to provide relief suggest diagnosis other than gout 8) see gout diagnostic rule Complications: - excess risk for cardiovascular events (RR=1.06 for men & 1.25 for women) [44] - largest excess risk for peripheral vascular disease - tophi - milk of urate bulla described in patient on cyclosporine [55] - gout flare may provoke venous thromboembolism [88] * gout may lower risk of Alzheimer's disease (see risk of Alzheimer's disease) Management: === acute attacks === 1) NSAIDs 1st line [2]; indomethacin - naproxen 750 mg initial dose; then 250 mg TID for 1 week [76] - avoid aspirin [28] 2) colchicine (Colcrys FDA-approved form) a) IV colchicine 2 mg (no longer recommended [57]) b) Colcrys 1.2 mg, followed in 1 hour by 0.6 mg [24,57] - may add adjunctive IV dexamethasone 8 mg or oral prednisone 20-40 mg tapered over 8 days [8] - 0.5 mg TID for 4 days [76] c) may be less effective when administered later during an acute attack [2] d) caution in elderly & in patients with CKD or peptic ulcer disease e) contraindicated when eGFR < 10 mL/min 3) prednisone or prednisolone 20-50 mg QD for 5-7 days [17] - prednisolone 30 mg QD for 5 days as effective as indomethacin with fewer adverse effects [14,52] - ref [28] recommends prednisone over ibuprofen in patients with mild renal insufficiency & diabetes mellitus in good control 4) sulfinpyrazone (uricosuric) 5) intra-articular glucocorticoids a) good choice for post-myocardial infarction or potential adverse effect of oral agents (NSAIDs, colchicine) [2] b) involvement of 1-2 accessible joints (knee, wrist, elbow, ankle) c) not for small hand joints 6) do not use allopurinol or febuxostat to treat an acute attack 7) ice packs on target joint for 30 minutes QID [7] === maintenance === 1) more than one acute attack within a year 2) colchicine, NSAID or glucocorticoid for prophylaxis with allopurinol 3) agents to treat hyperuricemia (allopurinol 1st line) [77] a) indications - recurrent gout attacks or tophi [2] - >= 2 gout attacks within 1 year - 1 attack within 1 year in the setting of chronic renal failure stage 2 or higher [2] (not sure about this indication) - 1 attack within 1 year in the setting of urolithiasis [2] - radiographic evidence of joint damage attributable to gout b) target serum uric acid < 6 mg/dL; < 5 mg/dL if tophi [31] - target of < 6 mg/dL questioned [2,57] (ACP) - mean daily dose of allopurinol = 460 mg [70] c) colchicine 0.6 mg PO QD 1] for 2-4 weeks prior to uric acid lowering therapy & for 3-6 months when starting allopurinol [28,77] a] ONLY necessary when colchicine is in use for treatment of gout flare(s) [2] b] not for tophaceous gout without flare c] for 3 months after serum uric acid has normalized d] 6 months if tophaceous gout [28] e] colchicine prevents gout flares, but a rebound in flares may occur if colchicine is stopped [89] 2] naproxen 250 mg BID with PPI or prednisone <= 10 mg/day alternatives [28] 3] colchicine may also diminish cardiovascular risk [54] 4] caution for use in combination with CYP3A4 inibitors d) allopurinol, start with 100 mg PO BID when gout is quiescent 1] dosage adjustment with renal insufficiency - allopurinol +/- prednisone for tophaceous gout without flare 2] titrate to serum urate of < 6.0 mg/dL [2] - target of < 6 mg/dL questioned [2,57] 3] maximum dose 800 mg QD 4] discontinue immediately if rash develops [2] 5] use associated with lower risk of chronic renal failure [69] 6] initiation reduces mortality in patients with chronic renal failure [79] 7] check HLA-B*58:01 in Han Chinese, Taiwanese, Korean & Blacks prior to initiating allopurinol e) febuxostat (Uloric) inhibits xanthine oxidase - useful if allopurinol contraindicated (HLA-B*58:01) or CKD - maximum dose 120 mg QD - no dosage adjustment needed for creatinine clearance > 30 mL/min [28] - has not been demonstrated to improve clinical outcomes [28] - mortality higher with febuxostat than allopurinol [63] - all-cause mortality (RR=1.22); CV mortality (RR=1.34) f) avoid use in combination with theophylline, mercaptopurine or azathioprine with allopurinol or febuxostat as these drugs are metabolized by xanthine oxidase, thus may accumulate to toxic levels [2] g) combination of xanthine oxidase inhibitor (allopurinol or febuxostat) with lesinurad if xanthine oxidase inhibitor alone is insufficient - allopurinol/lesinurad (Duzallo) may lower serum uric acid more than allopurinol alone but does not improve clinical outcomes [67] h) probenecid (uricosuric), start with 500 mg PO BID - eGFR > 60 mL/min/1.73 m2 [2]; do not use if CKD3 or higher - can promote uric acid-stone formation in patients with high urinary uric acid [34] i) ascorbate 500 mg QD may lower serum urate [11] j) allopurinol or febuxostat (Uloric) recommended as 1st line [33] - allopurinol & febuxostat both achieve serum urate goals [80] - allopurinol is noninferior to febuxostat in controlling flares - similar outcomes in stage 3 chronic kidney disease [80] k) fenofibrate reduces serum urate & incidence of gout in patients with diabetes mellitus type-2 [62] l) urate-lowering therapy is associated with lower all-cause mortality (RR=0.5 & cardiovascular mortality (RR=0.3) [51] 4) combination colchicine/hypouricemic agent if any evidence of active disease including tophi or flares [2] - how long to wait until increasing dose of hyperuricemic agent after a flare not addressed [28] === refractory gout === 1) pegloticase (Krystexxa) FDA-approved for refractory gout a) discontinue xanthine oxidase inhibitor b) 8 mg IV every 2 weeks c) pretreatment with glucocorticoid & antihistamine 2) rilonacept (IL1-beta inhibitor) for refractory gout [2] 3) canakinumab or anakinra (IL1 receptor antagonist) may be effective for severe or refractory gout [2,71] - canakinumab reduces risk of gout flares (RR < 0.5) without lowering serum uric acid [65,68] - canakinumab FDA-approved for treatment of gout flares in adults with contraindications to NSAIDs, colchicine, or repeated glucocorticoids [14] - anakinra usually effective for hospitalized patients with severe gout [74] === other considerations === 1) discontinue thiazide diuretics & low-dose aspirin a) associated with increased serum uric acid b) may exacerbate gout [2] c) losartan & calcium channel blockers may lower serum urate [2] 2) flozins may decrease risk of gout in patients with type 2 diabetes [75] 3) avoid foods rich in purines [9] a) beef, pork lamb b) seafood (fish & shellfish) c) purine-rich vegetables OK (peas, beans, lentils) d) total protein NOT associated with gout 4) avoid alcohol, especially beer, spirits [10,13] 5) avoid soda (high-fructose corn syrup), diet soda ok [15,22] 6) dietary factors that reduce risk of gout a) coffee [20] b) low-fat dairy products may be beneficial (relative risk 0.56) [2,9] c) vitamin C d) DASH diet may reduce risk of gout in men [60] & women [81] - the DASH diet limits purine intake & has uricosuric effects [60] 7) treat lead poisoning; avoid exposure to lead 8) treat obesity === prognosis === - attacks may resolve spontaneously in a couple of weeks [82] - if left untreated gout may involve more joints & larger joints & attacks may occur more frequently & last longer [82]

Interactions

disease interactions

Related

crystals in synovial fluid gout diagnostic rule gouty cellulitis hyperuricemia pseudogout [calcium pyrophosphate dihydrate crystal deposition] or CPPD disease

Specific

saturnine gout

General

chronic inflammation crystalline arthritis (crytalline arthropathy)

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 858-61
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  4. Meyers & Mounteagudo, Clin Exp Rheumatololgy 105-109, 1985
  5. Michet et al Mayo Clin Proc 70:1205, 1996
  6. Weiner S, In: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  7. Journal Watch 22(7):52, 2002 Schlesinger N et al Local ice therapy during bouts of acute gouty arthritis. J Rheumatol 29:331, 2002 PMID: 11838852
  8. Prescriber's Letter 10(10):58 2003
  9. Choi HK et al, Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 350:1093, 2004 PMID: 15014182 - Johnson RJ & Rideout BA Uric acid and diet--insights into the epidemic of cardiovascular disease. N Engl J Med 350:1071, 2004 PMID: 15014177
  10. Journal Watch 24(11):90, 2004 Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004 Apr 17;363(9417):1277-81. PMID: 15094272 - Zeng QY. Drinking alcohol and gout. Lancet. 2004 Apr 17;363(9417):1251-2. No abstract. PMID: 15094267
  11. Journal Watch 25(14):114-15, 2005 Huang HY, Appel LJ, Choi MJ, Gelber AC, Charleston J, Norkus EP, Miller ER 3rd. The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial. Arthritis Rheum. 2005 Jun;52(6):1843-7. PMID: 15934094
  12. Yu TF & Gutman AB, Ann Intern Med 1961; 55:179 Internal Medicine World Report 2006; 21(2) suppl
  13. Ferri's Clinical Advisor, Instant Diagnosis and Treatment, Ferri FF (ed), Mosby, Philadelphia, 2003
  14. Man CY, Cheung IT, Cameron PA, Rainer TH. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial. Ann Emerg Med. 2007 May;49(5):670-7. Epub 2007 Feb 5. PMID: 17276548
  15. NetScape, Jan 7, 2008 cites January 2008 issue of Arthritis Care & Research
  16. Choi HK and Curhan G, Soft drinks, fructose consumption, and the risk of gout in men: Prospective cohort study. BMJ 2008, 336:309 PMID: 18244959
  17. Prescriber's Letter 15(9): 2008 Corticosteroids for the Management of Gout Detail-Document#: 240905 (subscription needed) http://www.prescribersletter.com
  18. Schlesinger N et al. Serum urate during acute gout. J Rheumatol 2009 Jun; 36:1287. PMID: 19369457
  19. FDA NEWS RELEASE - Sept. 14, 2010 FDA approves new drug for gout http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225810.htm - Sundy JS et al. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: Results of a phase II randomized study. Arthritis Rheum 2008 Sep; 58:2882. PMID: 18759308
  20. Doherty M New insights into the epidemiology of gout. Rheumatology 2009, 48:ii2-ii8 PMID: 19447779
  21. Prescriber's Letter 17(11): 2010 Management of Gout Detail-Document#: 261102 (subscription needed) http://www.prescribersletter.com
  22. Choi HK et al. Fructose-rich beverages and risk of gout in women. JAMA 2010 Nov 10 PMID: 21068145
  23. Glazebrook KN et al. Identification of intraarticular and periarticular uric acid crystals with dual-energy CT: Initial evaluation. Radiology 2011 Nov; 261:516. PMID: 21926378
  24. 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. PMID: 20131255
  25. Fox R Management of recurrent gout. BMJ. 2008 Feb 9;336(7639):329. Review. PMID: 18258969
  26. Janssens HJ et al Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet. 2008 May 31;371(9627):1854-60. PMID: 18514729 - Janssens HJ et al Systemic corticosteroids for acute gout. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005521. Review. PMID: 18425920
  27. McAdams DeMarco MA et al. Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study. Arthritis Rheum 2012 Jan; 64:121. PMID: 22031222
  28. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society - Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  29. ARUP Consult: Hyperuricemia - Gout The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hyperuricemia
  30. Krishnan E et al. Low-level lead exposure and the prevalence of gout: An observational study. Ann Intern Med 2012 Aug 21; 157:233. PMID: 22910934
  31. Khanna D et al 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia Arthritis Care & Research, 64(10):1431-1446, October 2012 PMID: 23024028 http://onlinelibrary.wiley.com/doi/10.1002/acr.21772/abstract (corresponding NGC guideline withdrawn Dec 2017) - Khanna D 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, 64(10):1447-61, October 2012 PMID: 23024029 http://onlinelibrary.wiley.com/doi/10.1002/acr.21773/abstract (corresponding NGC guideline withdrawn Dec 2017)
  32. Choi HK et al Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ. 2012 Jan 12;344:d8190 PMID: 22240117
  33. Prescriber's Letter 19(12): 2012 CHART: Comparison of Gout Therapies CHART: Colchicine Dosing and Drug Interactions GUIDELINES: 2012 American College of Rheumatology Guidelines for Management of Gout. Part 1: Systematic Nonpharmacologic and Pharmacologic Therapeutic Approaches to Hyperuricemia GUIDELINES: 2012 American College of Rheumatology Guidelines for Management of Gout. Part 2: Therapy and Antiinflammatory Prophylaxis of Acute Gouty Arthritis Detail-Document#: 281224 (subscription needed) http://www.prescribersletter.com
  34. Khanna D et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012 Oct; 64:1431 PMID: 23024028 - Pui K et al. Efficacy and tolerability of probenecid as urate-lowering therapy in gout; clinical experience in high-prevalence population. J Rheumatol 2013 Jun; 40:872. PMID: 23457380
  35. Yang LP. Oral colchicine (Colcrys): in the treatment and prophylaxis of gout. Drugs. 2010 Aug 20;70(12):1603-13 PMID: 20687623
  36. Neogi T. Clinical practice. Gout. N Engl J Med. 2011 Feb 3;364(5):443-52 PMID: 21288096 https://www.nejm.org/doi/pdf/10.1056/NEJMcp1001124
  37. Choi HK. A prescription for lifestyle change in patients with hyperuricemia and gout. Curr Opin Rheumatol. 2010 Mar;22(2):165-72. PMID: 20035225
  38. Pillinger MH, Keenan RT. Update on the management of hyperuricemia and gout. Bull NYU Hosp Jt Dis. 2008;66(3):231-9. PMID: 18937638
  39. Dalbeth N et al. Tendon involvement in the feet of patients with gout: A dual-energy CT study. Ann Rheum Dis 2013 Sep 1; 72:1545 PMID: 23334212 http://ard.bmj.com/content/72/9/1545
  40. Chao J, Terkeltaub R. A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout. Curr Rheumatol Rep. 2009 Apr;11(2):135-40. PMID: 19296886
  41. Burns CM, Wortmann RL Gout therapeutics: new drugs for an old disease.. Lancet. 2011 Jan 8;377(9760):165-77. PMID: 20719377
  42. Fravel MA, Ernst ME. Management of gout in the older adult. Am J Geriatr Pharmacother. 2011 Oct;9(5):271-85. PMID: 21849262
  43. Richette P, Bardin T. Gout. Lancet. 2010 Jan 23;375(9711):318-28. PMID: 19692116
  44. Clarson LE et al. Increased risk of vascular disease associated with gout: A retrospective, matched cohort study in the UK Clinical Practice Research Datalink. Ann Rheum Dis 2015 Apr; 74:642 PMID: 25165032 http://ard.bmj.com/content/74/4/642
  45. Lu N et al. Gout and the risk of Alzheimer's disease: A population-based, BMI-matched cohort study. Ann Rheum Dis 2015 Mar 4 PMID: 25739830 http://ard.bmj.com/content/early/2015/02/11/annrheumdis-2014-206917
  46. Yu KH, Luo SF, Liou LB, Wu YJ, Tsai WP, Chen JY, Ho HH. Concomitant septic and gouty arthritis--an analysis of 30 cases. Rheumatology (Oxford). 2003 Sep;42(9):1062-6. Epub 2003 Apr 16. PMID: 12730521
  47. Crittenden DB, Pillinger MH. New therapies for gout. Annu Rev Med. 2013;64:325-37 PMID: 23327525
  48. Hamburger M, Baraf HS, Adamson TC 3rd et al 2011 Recommendations for the diagnosis and management of gout and hyperuricemia. Postgrad Med. 2011 Nov;123(6 Suppl 1):3-36. PMID: 22156509
  49. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006 Mar 9;440(7081):237-41. Epub 2006 Jan 11. PMID: 16407889
  50. 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 Oct;63(10):3136-41 PMID: 21800283
  51. Chen JH, Lan JL, Cheng CF et al. Effect of urate-lowering therapy on the risk of cardiovascular disease and all-cause mortality in patients with gout: A case-matched cohort study. J Rheumatol 2015 Sep; 42:1694. PMID: 26077411
  52. Rainer TH, Cheng CH, Janssens HJ et al Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial. Ann Intern Med. 2016 164:464. Apr 5; PMID: 26903390 http://annals.org/article.aspx?articleid=2494539
  53. Agency for Healthcare Research and Quality (AHRQ) Executive Summary - Feb. 24, 2016 Diagnosis of Gout https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2189
  54. Solomon DH, Liu CC, Kuo IH, Zak A, Kim SC. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: A cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis. 2016 Sep;75(9):1674-9 PMID: 26582823
  55. Robbins RC, Edison JD Milk of Urate Bulla. N Engl J Med 2016; 375:162. July 14, 2016 http://www.nejm.org/doi/full/10.1056/NEJMicm1512068
  56. Kienhorst LB, Janssens HJ, Fransen J et al Arthritis of the first metatarsophalangeal joint is not always gout: a prospective cohort study in primary care patients. Joint Bone Spine. 2014 Jul;81(4):342-6. PMID: 24468668
  57. Qaseem A, Harris RP, Forciea MA et al Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016. Nov 1 PMID: 27802508 http://annals.org/aim/article/2578528/management-acute-recurrent-gout-clinical-practice-guideline-from-american-college - Shekelle PG, Newberry SJ, FitzGerald JD et al Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2016. Nov 1 PMID: 27802478 http://annals.org/aim/article/2578526/management-gout-systematic-review-support-american-college-physicians-clinical-practice - Neogi T, Mikuls TR To Treat or Not to Treat (to Target) in Gout. Ann Intern Med. 2016. Nov 1 PMID: 27802507 http://annals.org/aim/article/2578453/treat-treat-target-gout - McLean RM The Long and Winding Road to Clinical Guidelines on the Diagnosis and Management of Gout. Ann Intern Med. 2016. Nov 1 PMID: 27802506 http://annals.org/aim/article/2578454/long-winding-road-clinical-guidelines-diagnosis-management-gout
  58. Qaseem A, McLean RM, Starkey M Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016. Nov 1 PMID: 27802479 http://annals.org/aim/article/2578527/diagnosis-acute-gout-clinical-practice-guideline-from-american-college-physicians - Newberry SJ, FitzGerald JD, Motala A Diagnosis of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2016. Nov 1 PMID: 27802505 http://annals.org/aim/article/2578824/diagnosis-gout-systematic-review-support-american-college-physicians-clinical-practice
  59. Brett AS Can Ultrasonography Help Diagnose Gout? Physician's First Watch, March 16, 2017 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - 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 Feb; 69:429 PMID: 27748084
  60. Rai SK, Fung TT, Lu N, Keller SF, Curhan GC, Choi HK. The dietary approaches to stop hypertension (DASH) diet, Western diet, and risk of gout in men: Prospective cohort study. BMJ 2017 May 9; 357:j1794. PMID: 28487277 Free PMC Article http://www.bmj.com/content/357/bmj.j1794 - Juraschek SP, Yokose C, McCormick N Effects of dietary patterns on serum urate: Results from a randomized trial of the effects of diet on hypertension. Arthritis Rheumatol 2021; 73(6): 1014-1020. PMID: 33615722 PMCID: PMC8169522 (available on 2022-06-01) https://www.medpagetoday.com/reading-room/acrr/generalrheumatology/94494
  61. Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. Am Fam Physician 2014 Dec 15; 90:831 PMID: 25591183 Free Article
  62. Waldman B, Ansquer JC, Sullivan DR et al Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. Lancet Diabetes & Endocrinology. Feb 26, 2018 PMID: 29496472 http://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(18)30029-9.pdf
  63. White WB, Saag KG, Becker MA et al Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. March 12, 2018 PMID: 29527974 http://www.nejm.org/doi/full/10.1056/NEJMoa1710895
  64. Cush J The 'Sons of Gout' Study. Are asymptomatic sons of people with gout at greater risk for the disease? MedPage Today. June 9, 2018 https://www.medpagetoday.com/rheumatology/generalrheumatology/73383 - Abhishek A, Courtney P, Jenkins W et al Monosodium urate crystal deposits are common in asymptomatic sons of people with gout -- The Sons of gout study. Arthritis Rheumatol. 2018 May 27. PMID: 29806203
  65. Walsh N IL-1 Blockade Appears Effective Against Gout. Canakinumab lowered the risk of attacks by more than half in post-MI patients. MedPage Today. June 14, 2018 https://www.medpagetoday.com/meetingcoverage/eular/73503 - Solomon D et al Serum urate, gout, and cardiovascular disease in a randomized controlled trial of canakinumab: a CANTOS secondary analysis. European Congress of Rheumatology (EULAR) 2018; abstract OP0014.
  66. Dalbeth N, Phipps-Green A, Frampton C et al. Relationship between serum urate concentration and clinically evident incident gout: An individual participant data analysis. Ann Rheum Dis 2018 Jul; 77:1048 PMID: 29463518 https://ard.bmj.com/content/77/7/1048
  67. Saag KG, Fitz-Patrick D, Kopicko J et al. 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). Arthritis Rheumatol 2017 Jan; 69:203. PMID: 27564409 Free Article https://onlinelibrary.wiley.com/doi/abs/10.1002/art.39840 - Bardin T, Keenan RT, Khanna PP et al. Lesinurad in combination with allopurinol: A randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis 2017 May; 76:811 PMID: 27821644 Free PMC Article https://ard.bmj.com/content/76/5/811
  68. Solomon DH, Glynn RJ, MacFadyen JG et al. Relationship of interleukin-1beta blockade with incident gout and serum uric acid levels: Exploratory analysis of a randomized controlled trial. Ann Intern Med 2018 Sep 18. 1-8 PMID: 30242335 http://annals.org/aim/article-abstract/2702477/relationship-interleukin-1-blockade-incident-gout-serum-uric-acid-levels
  69. Vargas-Santos AB, Peloquin CE, Zhang Y et al Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment. JAMA Intern Med. Published online October 8, 2018 PMID: 30304329 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2705694 - Zipursky J, Juurlink DN. Studying Drug Safety in the Real World. JAMA Intern Med. Published online October 8, 2018 PMID: 30304435 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2705690
  70. Doherty M, Jenkins W, Richardson H et al. Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: A randomised controlled trial. Lancet 2018 Oct 20; 392:1403. PMID: 30343856 Free PMC Article
  71. Thueringer JT, Doll NK, Gertner E. Anakinra for the treatment of acute severe gout in critically ill patients. Semin Arthritis Rheum. 2015 Aug;45(1):81-5. Epub 2015 Feb 20. PMID: 25795473
  72. Perez-Ruiz F, Castillo E, Chinchilla SP, Herrero-Beites AM. Clinical manifestations and diagnosis of gout. Rheum Dis Clin North Am. 2014 May;40(2):193-206. Review. PMID: 24703343
  73. Latourte A, Bardin T, Richette P. Prophylaxis for acute gout flares after initiation of urate- lowering therapy. Rheumatology (Oxford). 2014 Nov;53(11):1920-6. Review. PMID: 24758886
  74. Liew JW, Gardner GC. Use of anakinra in hospitalized patients with crystal-associated arthritis. J Rheumatol 2019 Oct; 46:1345 PMID: 30647192 http://www.jrheum.org/content/46/10/1345
  75. Fralick M, Chen SK, Patorno E, Kim SC. Assessing the Risk for Gout With Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Population-Based Cohort Study. Ann Intern Med. 2020. Jan 14. PMID: 31931526 https://annals.org/aim/article-abstract/2758844/assessing-risk-gout-sodium-glucose-cotransporter-2-inhibitors-patients-type - McCormick N, Yokose C, Wei J et al Comparative Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and Hospitalizations. A General Population Cohort Study. Ann Intern Med. 2023 Jul 25 PMID: 37487215 https://www.acpjournals.org/doi/full/10.7326/M23-0724 - Wei J, Choi HK, Dalbeth M et al Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes. JAMA Netw Open. 2023;6(8):e2330885 PMID: 37624597 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808753
  76. Roddy E, Clarkson K, Blagojevic-Bucknall M et al. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care. Ann Rheum Dis 2020 Feb; 79:276-284 PMID: 31666237 Free Article https://ard.bmj.com/content/79/2/276
  77. FitzGerald JD, Dalbeth N, Mikuls T et al 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Rheumatology. May 10, 2020 PMID: 32390306 https://onlinelibrary.wiley.com/doi/full/10.1002/art.41247
  78. Walsh N Persistent or New Obesity Linked With Gout - Normal weight maintained throughout adulthood substantially lowered risk of gout. MedPage Today March 3, 2021 https://www.medpagetoday.com/rheumatology/generalrheumatology/91460 - Bai L, Zhou JB, Newson RB, Cardoso MA. Incident gout and weight change patterns: a retrospective cohort study of US adults. Arthritis Res Ther 2021 PMID: 33653403 Free article https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-021-02461-7
  79. Wei J et al. Allopurinol initiation and all-cause mortality among patients with gout and concurrent chronic kidney disease: A population-based cohort study. Ann Intern Med 2022 Jan 25; [e-pub]. PMID: 35073156 https://www.acpjournals.org/doi/10.7326/M21-2347
  80. O'Dell JR, Brophy MT, Pillinger MH et al. Comparative effectiveness of allopurinol and febuxostat in gout management. NEJM Evidence 2022 Feb 3; [e-pub]. PMID: 35434725 PMCID: PMC9012032 Free PMC article. https://evidence.nejm.org/doi/10.1056/EVIDoa2100028
  81. Yokose C, McCormick N, Lu N et al. Adherence to 2020 to 2025 dietary guidelines for Americans and the risk of new-onset female gout. JAMA Intern Med 2022. Jan 31;e217419 PMID: 35099520 PMCID: PMC8804972 (available on 2023-01-31) https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2788658
  82. Grimm LJ 'Tis the Season for Gout. Medscape. Nov 10, 2022 https://reference.medscape.com/slideshow/gout-knowledge-6005952
  83. Mikuls TR Gout. N Engl J Med 2022; 387:1877-1887. Nov 17 PMID: 36383714 https://www.nejm.org/doi/full/10.1056/NEJMcp2203385
  84. Eun Y et al. Altered risk of incident gout according to changes in metabolic syndrome status: A nationwide, population-based cohort study of 1.29 million young men. Arthritis Rheumatol 2023 May; 75:806. PMID: 36415898 https://onlinelibrary.wiley.com/doi/10.1002/art.42381
  85. Han L et al. Association of the quantity, duration, and type of alcohol consumption on the development of gouty tophi. Arthritis Care Res (Hoboken) 2023 May; 75:1079. PMID: 35695775 https://onlinelibrary.wiley.com/doi/10.1002/acr.24968
  86. Joshi AD et al. Prediagnostic glycoprotein acetyl levels and incident and recurrent flare risk accounting for serum urate levels: A population-based, prospective study and Mendelian randomization analysis. Arthritis Rheumatol 2023 Apr 12; [e-pub] PMID: 37043280 https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42523
  87. Hicks L FDA Approves Canakinumab for Gout Flares. Medscape. August 30, 2023 https://www.medscape.com/viewarticle/995993
  88. Cipolletta E et al. Risk of venous thromboembolism with gout flares. Arthritis Rheumatol 2023 Sep; 75:1638. PMID: 36808284 https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42480
  89. Stamp L et al. Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial. Ann Rheum Dis 2023 Dec; 82:1626. PMID: 37652661 https://ard.bmj.com/content/82/12/1626
  90. National Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS) Gout https://www.niams.nih.gov/health-topics/gout