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Difficult gout. Gout in the elderly and drug-induced gout

Difficult gout. Gout in the elderly and drug-induced gout. Increasing prevalence of gout and hyperuricaemia among elderly subjects. Wallace KL, et al. J Rheumatol 2004;31:1582-1587. Annual gout prevalence stratified by age. Wallace KL, et al. J Rheumatol 2004;31:1582-1587.

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Difficult gout. Gout in the elderly and drug-induced gout

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  1. Difficult gout. Gout in the elderly and drug-induced gout

  2. Increasing prevalence of gout and hyperuricaemia among elderly subjects Wallace KL, et al. J Rheumatol 2004;31:1582-1587.

  3. Annual gout prevalence stratified by age Wallace KL, et al. J Rheumatol 2004;31:1582-1587.

  4. UK prevalence of gout >75 years Men: 7.3% Women: 2.8% Overall 1.4% M F M F Mikuls, et al. Ann Rheum Dis 2005;64:267-272.

  5. Perception of disease and health-related quality of life in elderly patients with gout SF-36: Physical Component Summary (PCS) and Mental Component Summary (MCS) Lee SJ. Rheumatology 2009;48:582-586.

  6. Clinical features of gout in the elderly • Increased prevalence • Women more frequently affected • Small joints of the fingers more frequently involved • Polyarticular onset more common • Tophi occur earlier in the course of gout, often in atypical locations • Frequently associated with other joint diseases (OA, CPPD) • Comorbidities more common • Increased association with diuretic use By kind permission of L. Punzi, Rheumatology Unit, University of Padua Wise CM. Rheum Dis Clin N Am 2007;33:33-55. De Leonardis F, et al. Rheumatol Int 2007;28:1-7.

  7. Increased association with diuretic use • A high association with diuretic use and renal insufficiency has been noted in most elderly populations with gout • Diuretic use has been reported in more than 75% of patients who have elderly onset gout, with a frequency of 95% to 100% in women • Most small series of elderly patients who have atypical finger joint disease or tophaceous deposits report a consistent majority of patients taking diuretics • A retrospective cohort study documented an almost two-fold increase in the risk of initiation of anti-gout therapy in patients within 2 years of starting thiazide diuretics for hypertension compared to patients given non-thiazide therapy • Because of a lack of direct comparison to other elderly patients, it is unclear whether a decrease in renal function is peculiar to patients who have gout or merely reflects the trend seen in elderly populations in general Scott JT, Higgins CS. Ann Rheum Dis 1992;51:259-261. Fam AG, et al. J Rheumatol 1996;23:684-689. Gurwitz JH, et al. J Clin Epidemiol 1997;50:953-959. Janssens HJ, et al. Ann Rheum Dis 2006;65:1080-1083.

  8. Healthcare utilisation in older adults with gout Hanly JG, et al. J Rheumatol 2009;36:822-830.

  9. Total all-cause health care costs among gout patients Wu EQ, et al. J Manag Care Pharm 2008;14(2):164-175.

  10. Reasons why gouty patients present at an emergency department • Severity of the acute attack • Attack during the night • Elderly age • Comorbidity • Polypharmacy • Flares after the introduction of urate-lowering therapy By kind permission of L. Punzi, Rheumatology Unit, University of Padua Wise CM. Rheum Dis Clin N Am 2007;33:33-55. De Leonardis F, et al. Rheumatol Int 2007;28:1-7.

  11. Management of gout in the elderly: general aspects • Atypical presentation may make diagnosis difficult and hence may delay initiation of treatment • Colchicine is less effective • Use of NSAIDs or colchicine is limited by their side-effect profile • Use of uricosuric agents may be limited due to the presence of co-morbidities including renal disease • Restricting diet to eliminate purine-rich food is often challenging, and is of limited benefit • Drug interactions are more likely, as polypharmacy is common • Social, economic, and cognitive factors can affect compliance with medications and with laboratory monitoring • Trials on newer therapies often do not include elderly subjects Singh H, Torralba HB. Geriatrics 2008;63(7):13-8,20.

  12. Management of acute gout attacks in the elderly: the colchicine dilemma Morris I, et al. BMJ 2003;327:1275-1276.

  13. Colchicine in acute gout Morris I, et al. BMJ 2003;327:1275-1276.

  14. Incidence of adverse events according to colchicine dose Terkeltaub R, et al. Arthritis & Rheumatism 2010;62:1060-1068.

  15. 9 Management of chronic gout in the elderly: focus on allopurinol EULAR recommendations 2006 for the management of gout Allopurinol is an appropriate long-term urate lowering therapy. It should be started at low doses (e.g. 100 mg daily) and increased by 100 mg every 2-4 weeks if required. The dose should be adjusted in those with renal impairment. If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, a uricosuric agent or allopurinol desensitisation (the latter only in cases of mild rash). Zhang W, et al. Ann Rheum Dis 2006;65:1312-1324.

  16. Management of chronic gout in the elderly: allopurinol toxicity • Minor self-limiting drug reactions are relatively common, being estimated to occur in up to 10% of patients, and include itching, rash and gastrointestinal problems • The more serious, indeed potentially fatal, allopurinol hypersensitivity syndrome (ASH) is far less common, being estimated to occur in 0.4% of patients • ASH includes features such as eosinophilia, liver and renal dysfunction, vasculitis, bone marrow suppression and rash • Known risk factors for developing AHS include renal impairment, older age, comorbidities, use of thiazide diuretics and a genetic predisposition Kumar A, et al. Br Med J 1996;312:173-4. Fam AG, et al. Arthritis Rheum 2001;44:231-8. Rider TG, Jordan KM. Rheumatology 2010;49:5-14.

  17. Clinical use of febuxostat • No dose adjustment needed in: • Elderly • Mild to moderate renal function impairment • Mild to moderate (caution) liver function impairment • No dose adjustment needed while on: • Colchicine, indomethacin, naproxen • Warfarin • Hydrochlorothiazide • CYP 2D6 substrates SmPC febuxostat.

  18. Special precautions • Febuxostat is not recommended in: • patients with ischaemic heart disease or congestive heart failure • patients being treated with mercaptopurine or azathioprine • patients with severe renal function impairment (no experience) • patients with moderate or severe liver impairment • Caution is required when febuxostat is used in: • patients being treated with theophylline • patients with thyroid disorders SmPC febuxostat.

  19. Summary of the management of gout in the elderly Zhang W, et al. Ann Rheum Dis 2006;65:1301-1311. Richette P, et al. Lancet 2010;375:318-328. Terkeltaub R. Nature Rev Rheumatol 2010:6:30-38.

  20. Drug-induced gout

  21. Drugs potentially inducing hyperuricaemia by a reduction of renal excretion Cyclosporine Alcohol Nicotinic acid Thiazides Lasix (furosemide) or other loop diuretics Ethambutol Aspirin (low dose) Pyrazinamide Andrew JK, et al. Am J Manag Care 2005;11:S435-S442. Underwood M. BMJ 2006;332:1315-9.

  22. Frequent causes of decreased renal excretion of urate in the elderly • Drugs • Thiazides • Loop diuretics • Aspirin (low-dose) • Ethanol • Levodopa • Renal • Hypertension • Chronic renal failure (any aetiology) • Metabolic/endocrine • Obesity • Hypothyroidism • Hyperparathyroidism • Dehydration Wise CM. Rheum Dis Clin N Am 2007;33:33-55. Perez-Ruiz F. Rheumatology 2009;48:ii9-ii14.

  23. Cyclosporine and tacrolimus • Calcineurin inhibitors • Both drugs can impair renal uric acid excretion • High sUA/decreased UA excretion (reduced fractional excretion) • Mg leakage via tubular dysfunction (high fractional excretion) • Gout in organ transplant recipients • Heart and kidney tranplantation: higher sUA/MSU deposits along with ageing, chronic kidney disease, diuretics • Liver transplantation: 10-50% hyperuricaemia; low gout prevalence (2.6-6%) Perez-Ruiz F, et al. Transplantation 2001;71:696-698. Shibolet O, et al. Transplantation 2004;77:1576-1580. Fernández-Molina G, et al. Transplantation 2008;86:1543-1547.

  24. Anti-tuberculous drugs and hyperuricaemia • Pyrazinamide • Hyperuricaemic effect due to modulation of urate transport via the proximal tubules • Quickly reversible after the drug is stopped • Ethambutol • Effect not dependent on the dose • Reversible within 15 days after the drug is stopped • Rifampicin • Seen less frequently Merriman TR, et al. Joint Bone Spine 2011;78:35-40.

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