Gout – easy to misdiagnose
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Transcript Gout – easy to misdiagnose
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
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