Gout
Dr. Pamela Leventis
Consultant Rheumatologist
Epsom & St. Helier NHS Trust
A disease of Kings
GOUT – Outline
 Epidemiology
 Diagnostic difficulties
 Management (EULAR/BSR guidelines)
 Gout – Top tips
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)
Hyperuricaemia
the 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
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 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
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 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))
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
Management
Acute 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
Management
Long term Prophylaxis
Non – 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
Management
Long 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
Management
Long term Prophylaxis - Pharmacological
1st line urate lowering therapy (BSR/EULAR guidelines)
 Uricostatics – Xanthine oxidase inhibitor
 Allopurinol – starting dose 100mg od
Jordan et al., (2007)
 Consider Febuxostat first line in patients with chronic
kidney disease
Management
Long 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)
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
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)
Management
Long 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 3060ml/min) – named patient basis
 Or combination therapy
 Losartan and Fenofibrate – weak uricosurics
Management
Long 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
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
BSR gout treatment algorithm
Jordan et al., 2007
Future Treatments
 Uricases – convert urate to allantoin
 ?debulking urate load in tophaceous gout
 IL-1 antagonists to treat severe acute flares
 Anakinra, Canakinumab
Gout – Top Tips
1. Gout is very rare in pre-menopausal women,
2.
3.
4.
5.
6.
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.
REFERENCES
 Mikuls TR, Farrar JT, Bilker WB et al. Gout epidemiology: results from the UK

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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), 31:24292432
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