Gout

1. Gout Dr. Pamela Leventis Consultant Rheumatologist Epsom & St. Helier NHS Trust

2. A disease of Kings

3. GOUT – Outline • Epidemiology • Diagnostic difficulties • Management (EULAR/BSR guidelines) • Gout – Top tips

4. Epidemiology • Commonest Inflammatory Arthritis in men • Mean UK prevalence – 1.4% • Prevalence increases with age • >7% of men >75 yrs, >4% of women >75 yrs (Mikuls et al., 2005)

5. Hyperuricaemiathe biggest risk factor for gout Underwood M BMJ 2006;332:1315-1319 • Laboratory reference ranges differ between populations – usually 2SDs above/below mean • Theoretical Saturation of serum urate – 360μmol/l

6. Pathogenesis Gout is due to extracellular deposition of uric acid crystals in joints Synovial fluid examination under polarised light – negatively birefringentcrytals

7. Gout Diagnosis

8. A first hand description The victim goes to bed and sleeps in good health. About 2 o'clock in the morning, he is awakened by a severe pain in the great toe; more rarely in the heel, ankle or instep. This pain is like that of a dislocation, and yet the parts feel as if cold water were poured over them. Then follows chills and shiver and a little fever. The pain which at first moderate becomes more intense. With its intensity the chills and shivers increase. After a time this comes to a full height, accommodating itself to the bones and ligaments of the tarsus and metatarsus. Now it is a violent stretching and tearing of the ligaments-- now it is a gnawing pain and now a pressure and tightening. So exquisite and lively meanwhile is the feeling of the part affected, that it cannot bear the weight of bedclothes nor the jar of a person walking in the room. Thomas Sydenham 1683

9. Podagra ‘seizing the foot’ >97% specificity for gout in context of supportive clinical presentation and hyperuricaemia (Rigby and Wood, 1994)

10. Why can gout be difficult to diagnose? • Atypical Joint/tendon/bursa involvement • Pre-existing joint pathology • Gout- a great mimic Roddy E, Doherty M. Gout. In: Warburton L (ed). Musculoskeletal disorders in primary care. London: RCGP. In press 2011. Roddy E. (2011) Arthritis Research UK

11. Gout or Septic Arthritis?

12. Gout or Cellulitis?

13. Gout or Rheumatoid arthritis?

14. Diagnostic ambiguity • Gout flare can be associated with • Normal Serum urate (~10%) • ?serum urate lowered during acute phase response (Urano et al., 2002) • Gout triggered by drop in serum urate • Mild Leucocytosis • Low grade fever • Normal X-ray • Synovial fluid examination • 63-78% sensitivity – degree of operator dependence/sample quality (Swan et al., 2002) • Crystals may co-exist with sepsis (case series 30 patients – Yu et al. (2003))

15. Gout Management

16. Goals of Therapy 1. Minimise morbidity of acute flare 2. Prevent future flares, and thereby prevent joint damage and disability • Patient Education and Lifestyle changes • Pharmacological Prophylaxis if indicated

17. ManagementAcute Gouty Flare BSR Guidelines (Jordan et al., 2007) • 1st line • Full dose NSAID continued for 1-2 weeks – unless contraindication • If risk of peptic ulcer disease – co-prescribe Proton pump inhibitor • Alternatively • Colchicine 500μg bd-qds (higher dosing associated with disproportionate toxicity) • Intra-articular corticosteroid injection for monoarticular flare • Oral prednisolone for severe/polyarticular flare • Urate lowering therapies should not be commenced or stopped during acute gout

18. ManagementLong term ProphylaxisNon – pharmacological • Diet (www.ukgoutsociety.org) • Alcohol < 21 U/wk ♂, <14 U/wk ♀ • Obesity – aim for ideal BMI • Exercise • Smoking • Strong association between gout and the metabolic syndrome (Choi et al., 2007) • Annual Screen- BP/Weight/fasting lipid profile/glucose

19. ManagementLong term Prophylaxis - Pharmacological When to initiate urate lowering therapies? • EULAR/BSR Guidelines • Uniform agreement for prompt treatment in: • Severe gout with X-ray changes • Tophaceous deposits • Chronic kidney disease • Nephrolithiasis • Urinary uric acid excretion exceeding 1100 mg/day (6.5 mmol) • Otherwise shared decision with patient re: risks/benefits of treatment/no treatment • BSR guidelines suggest initiation of treatment if ≥ 1 further attack within 12 months

20. ManagementLong term Prophylaxis - Pharmacological 1st line urate lowering therapy (BSR/EULAR guidelines) • Uricostatics – Xanthine oxidase inhibitor • Allopurinol – starting dose 100mg od • Consider Febuxostat first line in patients with chronic kidney disease Jordan et al., (2007)

21. ManagementLong term Prophylaxis - Pharmacological • Aim for plasma urate • <300μmol/l (BSR guidelines) • median [urate] for men in UK • <360 μmol/l (EULAR guidelines) • saturation point serum urate • Commence at least 2 weeks following resolution of acute attack • Consider low dose colchicine – 500μg od/bd for up to 6 months following initiation • 77% patients flare within 6 months of initiating allopurinol (Borstad et al. 2004)

22. Allopurinol dosing • Increase every 2-4 weeks by 100mg until target serum urate achieved. Maximum 900mg/day. • Start low – go slow approach recommended • To reduce likelihood of triggering attack • To minimise risk of toxicity (AHS) • Emphasis on target value

23. Allopurinol Hypersensitivity Syndrome • 1:300 patients • At risk groups: Elderly and Renal Impairment • Erythematous desquamating rash • Fever • Hepatitis • Eosinophilia • Worsening renal function • 20% mortality (Lee et al., 2008)

24. ManagementLong term Prophylaxis - Pharmacological 2nd line – failure to reach target serum urate • If normal renal function • uricosuric(Contraindicated if history of nephrolithiasis) • Sulphinpyrazone- 200-800mg/day • Probenecid – named patient basis • Benzbromarone if mild – moderate renal impairment (GFR 30-60ml/min) – named patient basis • Or combination therapy • Losartan and Fenofibrate – weak uricosurics

25. ManagementLong term Prophylaxis - Pharmacological • Febuxostat currently approved by NICE if: • adverse effects on allopurinol • OR further dose escalation contra-indicated with suboptimal serum urate • most common side effects • diarrhoea, nausea, headache, abnormal LFTs, rash

26. Renal Uric acid Excretion • Urinary uric acid:creatinine ratio to diagnose over excretors • Should be determined in : • Young patients diagnosed with gout <25 yrs • Patients with a family history of young onset gout • Patients with renal calculi

27. BSR gout treatment algorithm Jordan et al., 2007

28. Future Treatments • Uricases – convert urate to allantoin • ?debulkingurate load in tophaceous gout • IL-1 antagonists to treat severe acute flares • Anakinra, Canakinumab

29. Gout – Top Tips • Gout is very rare in pre-menopausal women, referral advised. • Hyperuricaemia + joint inflammation ≠ gout • Serum urate is often normal during a gouty flare. • X-rays are not useful in acute/early gout. • Avoid any changes to Allopurinol dosing during or within a fortnight of an acute flare of gout. • Commonest cause for Allopurinol failure is non compliance.

30. REFERENCES • Mikuls TR, Farrar JT, Bilker WB et al. Gout epidemiology: results from the UK general practice research database, 1990-1999. Ann Rheum Dis (2005), 64:267-272. • Underwood M. Diagnosis and management of gout. BMJ. 2006; 332: 1315-1319 • Lee H Y, Ariyasinghe J T N, Thirumoorthy T. Allopurinol hypersensitivity syndrome: a preventable severe cutaneous adverse reaction? Singapore Med J 2008; 49(5) : 384 • Borstad GC, Bryant LR, Abel MP et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol (2004), 31:2429-2432 • Zhang W, Doherty M, Pascual E et al. EULAR evidence based recommendations for gout. Parts I and II. Ann Rheum Dis (2006), 65:1301-1324 • Jordan KM, Cameron JS, Snaith M et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (2007), 46:1372-1374 • http://www.nice.org.uk/nicemedia/pdf/TA164Guidance.pdfFebuxostat for the management of hyperuricaemia in people with gout