Dr. Pamela Leventis

Consultant Rheumatologist

Epsom & St. Helier NHS Trust

Gout

A disease of Kings

GOUT – Outline

EpidemiologyDiagnostic difficultiesManagement (EULAR/BSR guidelines)Gout – Top tips

EpidemiologyCommonest 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)

Hyperuricaemiathe biggest risk factor for gout

Underwood M BMJ 2006;332:1315-1319

Laboratory reference ranges differ between populations – usually 2SDs above/below meanTheoretical Saturation of serum urate – 360μmol/l

Pathogenesis

Gout is due to extracellular deposition of uric acid crystals in joints

Synovial fluid examination under polarised light – negatively birefringent crytals

Gout Diagnosis

A first hand descriptionThe 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

Podagra

‘seizing the foot’ >97% specificity for gout in context of supportive clinical presentation and hyperuricaemia

(Rigby and Wood, 1994)

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

Gout or Septic Arthritis?

Gout or Cellulitis?

Gout or Rheumatoid arthritis?

Diagnostic ambiguity

Gout flare can be associated withNormal Serum urate (~10%)

?serum urate lowered during acute phase response (Urano et al., 2002)Gout triggered by drop in serum urate

Mild LeucocytosisLow grade feverNormal 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))

Gout Management

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

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 inhibitorAlternatively

Colchicine 500μg bd-qds (higher dosing associated with disproportionate toxicity)

Intra-articular corticosteroid injection for monoarticular flareOral prednisolone for severe/polyarticular flare

Urate lowering therapies should not be commenced or stopped during acute gout

ManagementLong term ProphylaxisNon – pharmacological

Diet (www.ukgoutsociety.org)Alcohol < 21 U/wk ♂, <14 U/wk ♀Obesity – aim for ideal BMIExerciseSmokingStrong association between gout and the metabolic syndrome

(Choi et al., 2007)Annual Screen- BP/Weight/fasting lipid profile/glucose

ManagementLong term Prophylaxis - Pharmacological

When to initiate urate lowering therapies?EULAR/BSR Guidelines

Uniform agreement for prompt treatment in:Severe gout with X-ray changesTophaceous depositsChronic kidney diseaseNephrolithiasisUrinary 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

ManagementLong term Prophylaxis - Pharmacological

1st line urate lowering therapy (BSR/EULAR guidelines)Uricostatics – Xanthine oxidase inhibitorAllopurinol – starting dose 100mg od

Consider Febuxostat first line in patients with chronic kidney disease

Jordan et al., (2007)

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 initiation77% patients flare within 6 months of initiating allopurinol

(Borstad et al. 2004)

Allopurinol dosingIncrease 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 attackTo minimise risk of toxicity (AHS)Emphasis on target value

Allopurinol Hypersensitivity Syndrome1:300 patientsAt risk groups: Elderly and Renal Impairment

Erythematous desquamating rashFeverHepatitisEosinophiliaWorsening renal function

20% mortality (Lee et al., 2008)

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/dayProbenecid – named patient basisBenzbromarone if mild – moderate renal impairment (GFR 30-

60ml/min) – named patient basis

Or combination therapyLosartan and Fenofibrate – weak uricosurics

ManagementLong term Prophylaxis - Pharmacological

Febuxostat currently approved by NICE if:adverse effects on allopurinol OR further dose escalation contra-indicated with suboptimal

serum uratemost common side effects

diarrhoea, nausea, headache, abnormal LFTs, rash

Renal Uric acid Excretion

Urinary uric acid:creatinine ratio to diagnose over excretors

Should be determined in :Young patients diagnosed with gout <25 yrsPatients with a family history of young onset goutPatients with renal calculi

BSR gout treatment algorithmJordan et al., 2007

Future Treatments

Uricases – convert urate to allantoin?debulking urate load in tophaceous gout

IL-1 antagonists to treat severe acute flaresAnakinra, Canakinumab

Gout – Top Tips1. Gout is very rare in pre-menopausal women,

referral advised.

2. Hyperuricaemia + joint inflammation ≠ gout

3. Serum urate is often normal during a gouty flare.

4. X-rays are not useful in acute/early gout.

5. Avoid any changes to Allopurinol dosing during or within a fortnight of an acute flare of gout.

6. Commonest cause for Allopurinol failure is non compliance.

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.pdf Febuxostat for the management of hyperuricaemia in people with gout