T

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Gout
A metabolic disease characterized by recurrent attack
of acute inflammatory arthritis caused by elevated
levels ofuric acidin the blood (hyperuricemia).
Most common rheumatic disease of adulthood
The uric acid crystallizes and deposits in
joints,tendons, and surrounding tissues.
Hyperuricemia : overproduction/underexcretion/both

Hyperuricemia
Gout

(NHS Fife, Gout Management Guidelines,

2010)

Asymptomatic hyperuricemia
Serum [urate] abnormally high without SSx
Male >420mol/L (7mg/dL)
Female >360mol/L (6mg/dL)

Not life threatening and readily treatable

Routine prophylactic treatment is NOT required
A/W : gout, urolithiasis, nephropathy, metabolic
syndrome (HPT, DM/IFG/IGT, hyperTGemia, obesity, CKD)
Serum [urate] >540mol/L (9mg/dL) were a/w greater incidence
for gout
Increased daily urinary urate excretion is a/w higher risk of urate
and Ca oxalate stone formation (when >0.65mmol/L or 11mg/dL)
Renal involvement when serum urate level is more than 2x the
normal limit (0.77mmol/L or 13mg/dL in male; 0.60mmol/L or
10mg/dL) in female)

Gouty arthritis
1. Acute gout

Acute, self limiting, monoarticular

Painful, red, hot, swollen

Usually resolves within 2 weeks if untreated

May occur even if serum urate is normal

LL > UL

Commonly affected joints

I.
II.
III.
IV.
V.
VI.
VII.

1st metatarsophalangeal joint (podagra)

Forefoot/instep
Ankle joint
Knee joint
Wrist joint
Elbow joint
Finger joints

Extra-articular : olecranon bursa, Achilles tendon

O/E : erythematous, warm, swelling over involved joint
with extreme tenderness +/- fever skin desquamation
Duration : 2 3 weeks, with gradual complete resolution
of inflammatory signs

2. Intercritical gout

Asymptomatic period between attacks

3. Chronic gout

Polyarticular arthritis + tophi formation

Articular tophaceous gout may results in

destructive arthropathy and secondary OA

Tophaceous disease more like to occur in patients

with:

Polyarticular presentation
Serum urate level >540 mol/L (>9mg/dL)
Disease onset at younger age (40 years)

Sites of tophi

Digits of hands and feet (most common)

Pinna of ear (classic, less common)
Bursa around elbows and knees
Achilles tendon

Urate/gouty nephropathy
Acute urate nephropathy
Urate crystals renal tubules obstructive ARF
DeH2O, low urine pH are precipitating factors

Chronic urate nephropathy

Urate crystals interstitium and renal medulla
inflammation + surrounding fibrosis irreversible CRF
Renal impairment can occur in ~40% in chronic gout

Urate nephrolithiasis
Stones flank pain/ureteric colic/hematuria
Urate (radiolucent) / mixt. Calcium oxalate and/or calcium
phosphate (radio-opaque)
Contributing factors : hyperuricosuria, low urine output, acidic
urine
Urinary alkalinization (pot. Citrate or NaHCO3) dissolution of
existing stones and prevention of recurrence

Diagnostic criteria
Two of the following criteria are required for clinical
diagnosis :
1.
2.
3.
4.

Clear h/o at least 2 attacks of painful joint swelling with

complete resolution within 2 weeks
Clear history or observation of podagra
Presence of tophus
Rapid response to colchicine within 48 hours of
treatment initiation

Definitive diagnosis : presence of monosodium urate

crystals seen in synovial fluid/tissues

Investigations
Specific investigations for confirmation
Serum uric acid
Joint aspiration and crystal identification
Not widely available

To detect medical conditions a/w gout or hyperuricemia

FBC
Serum creatinine/urea
Serum blood glucose
Fasting lipid profile
UFEME
24h urinary urate excretion :
Useful if renal calculus proven to be urate stone
Indicated if on uricosuric agent
Assess risk of stone
Help to indicate whether overproduction or underexcretion of urate
Range : 2-4 mmol/24h or 0.34-0.67g/24h

To detect complications
Renal imaging
Skeletal x-rays

 Skeletal x-rays
Acute gouty arthritis : normal; soft tissue swelling
Chronic tophaceous gout : tophi, erosive bone lesions
(punched out lesions), joint space is preserved until late
stage, pathognomonic in foot and big toe

 Renal imaging
Plain abd XR detects only 10% of all urate stones
IVU = investigation of choice for urate stones
US KUB : investigations of choise for nephrocalcinosis,
significant renal stones (>3mm) whether radio-opaque or
radiolucent, obstructive nephropathy
Plain CTU : most sensitive to detect any stone

Management
Lifestyle modification and dietary advice
Management of comorbidities
Nonessential prescriptions that induce
hyperuricaemia
Main aim :
- To achive ideal BW
- Prevent acute gouty attacks
- Reduce serum urate level
Strict purine-free diet reduced only 15 20% of
serum urate, thus is considered an adjunct
therapy to medication.

Treatment
Contributing factors eg. thiazide/loop diuretics; low
dose aspirin may be discontinued or substituted, if
appropriate
Pharmacotherapy of asymptomatic hyperuricemia
is NOT necessary, except :Persistent severe hyperuricemia
- > 770mol/L (13mg/dL) in male
- > 600mol/L (10mg/dL) in female
Persistent elevated urinary excretion of urate
- > 0.65mmol/L/day (11mg/day), a/w 50% increased risk of
urate calculi
Tumor lysis syndrome
- chemotherapy/radiotherapy extensive tumor cytolysis
=> require pre-hydration and allopurinol to prevent acute
urate nephropathy

Treatment : Acute gouty arthritis

Initiation within 24 hours of onset
If on Allopurinol, continue without interruption
NSAIDs
eg. Diclofenac, indomethacin, mefenemic acid etc
Caution in h/o PUD, HPT, renal impairment, IHD, liver impairment
COX-2 inhibitors (celecoxib, etoricoxib, parecoxib) = alternative for
above risk factors
Studies have shown that etoxicoxib (Arcoxia) has equal efficacy to
indomethacin

Colchicine
Inhibiting mitosis and neutrophilsmotility and activity, leading to a
netanti-inflammatory effect.
Alternative drug if CI to NSAIDs, but is poorly tolerated by elderly
Therapeutic index is narrow
Slower onset of action
Evidence base for prophylaxis is stronger than for NSAIDs (NHS Fife, Gout
Management Guidelines, 2010)

SE (eg. N&V, abd. pain, profuse diarrhea) limit its usefulness

Dosage : 0.5mg 0.6mg BD-QID

 Steroids
Can be considered in elderly people and
patients with renal/liver impairment, IHD,
PUD, hypersensitivity to NSAIDs
IM steroids eg. Triamcinolone (40-80mg.day)
or methylprednisolone (80mg/day) can be
given stat
Short course of oral prednisolone up to
0.5mg/kg/day can be given and tapered off
over 4 -10 days
SE of steroids are rare

(NHS Fife, Gout Management Guidelines,

2010)

Treatment : chronic gouty arthritis

Management of Gout, CPG 2008, MOH

Malaysia

Urate lowering therapy (hypouricaemic

therapy)
Allopurinol should not be started until acute attack has
resolved
May prolong attack or lead to rebound flares if started
during attack
Should be started 2 weeks after attack is wellcontrolled
Indications for ULT :
1.
2.
3.
4.
5.
6.

Frequent and disabling attacks of gouty arthritis (3 or

more attacks/year)
Clinical or radiographic signs of erosive gouty arthritis
The presence of tophaceous deposits
Urate nephropathy
Urate nephrolithiasis
Impending cytotoxic chemo-/radiotherapy for lymphoma
or leukemia

 D/W with patients regarding important points at

initiation of ULT
1.
2.
3.
4.

5.
6.

NSAIDs/colchicine do not lower serum urate

Hypouricemic drugs have no analgesic or antiinflammatory effect
ULT agent should not be stopped during an attack after
initiation
Possibility of more frequent attacks of acute gouty
arthritis at the initiation of therapy, especially in the first
3 months. Prophylactic NSAIDs/colchicine can be used to
reduce frequency of attack
Is a life-long treatment
Lifestyle modification is an important adjunct therapy

Management of Gout, CPG 2008, MOH

Malaysia

Xanthine oxidase inhibitor

ALLOPURINOL
More superior than probenecid
Primarily excreted by kidneys, thus need renal
adjustment
Aim : reduce to <360mol/L and maintain with
minimal dose of allopurinol
During initiation of allopurinol therapy, colchicine
(0.5mg BD) can be used as prophylaxis to reduce
frequency of attacks. Can be continued until patient is
attack free for 6 months or target serum urate level is
achieved for 1 month.
For patient who cant tolerate colchicine, low dose
NSAIDs can be used

 Normal renal function :

Start at 100 150mg OD, increasing by 100 150mg steps
every 2 - 5 weeks till 300mg OD, max 900mg/day (severe
disease)
With prophylactic colchicine 0.5mg BD for up to 12 months
(NHS Fife, Gout Management Guidelines, 2010)

Starting dose should be not >100mg/day and less in

moderate to severe CKD, with gradual upward titration (ACR,
Guidelines for Management of Gout, 2012)

Indications for starting allopurinol must be clear, as life

threatening complications can occur

Rash
Bone marrow suppression
Aplastic anemia
Agranulocytosis
Granulomatous hepatitis and jaundice
Hypersensitivity syndrome (fever, rashes, hepatitis,
eosinophilia, renal impairment)

Uricosuric agent
PROBENECID
An alternative to allopurinol in patients with NORMAL RENAL
FUNCTION
RP before commencement of probenecid
Dosage : 0.5 1g in divided doses, may be increased to 1.5
2g
SE :
GI disturbance
Hypersensitive rash

CI :
- uric acid overproduction and overexcretion (24 hrs urinary
urate excretion morethan 800mg/day)
Risk of crystal
- urate nephropathy
precipitation
- urate nephrolithiasis
Losartan has modest uricosuric effect
Fenofibrate too

(NHS Fife, Gout Management Guidelines,

2010)

Treatment of urate nephropathy

Increase urine output
3L of H2O/day with urine output >2.5L if not ESRF

Increase urine pH

Prevent urate stone formation and promote dissolution of stone

Target urine pH : 6.5 7
Potassium citrate 40 50mmol/day (max 100mmol/day)
Sodium salt : Ural sachet (with analgesic properties)
Dosage : 1 2 sachets QID

CI in renal impairment/hypernatraemia

Decrease urate excretion

Dietary purine intake restriction
Treat with allopurinol

Treatment of urate nephrolithiasis

Intrarenal stones <5mm can be observed unless causing
pain
Intrarenal stone 5 15mm or complex staghorn calculi
refer to urologist for ESWL or PCNL
Ureteric stones : conservative management
If uncomplicated (min obstruction/no sepsis), and size <5mm, at

spontaneously
If fail to pass after 2 weeks refer for removal
lower ureter may pass

Pure urate stones can be chemolysed by pot. Cit. or Ural

(oral/direct irrigation)
Long term chemoprophylaxis using pot. Cit. has shown to
be highly effective

Surgical intervention
Last resort for gouty arthritis
Removal of tophi
Joint fusion
Joint replacement

Ulceration of tophi : debridement, dressing with

sodium bicarbonate solution
Indications for chronic tophaceous gout :
Advanced tophi deposition resulting in major joint
destruction
Loss of involved joint movements a/w severe pain
Tophi collection causing pressure symptoms, eg carpal tunnel
syndrome of wrist
Tophaceous ulcer
Cosmetic eg ear lobe tophi

When to reduce ULT?????

If serum urate <360mol/L , and have been no gouty
attacks for 1 year can reduce T. allopurinol by
100mg.
Check serum urate 6 monthly, if still <360mol/L
can further reduce
Patients that have tophi are most likely to require
lifelong ULT

Referral to specialist

Unclear etiology
Refractory SSx (fails to respond within 14 days with
treatment)
Difficulty in achieving target serum urate
level/recurrent attacks despite on T. allopurinol 900mg
OD
Uncontrolled acute gout attacks when serum urate
<360mol/L
Renal impairment
Adverse effects of ULT/Intolerance

 (NHS Fife, Gout Management Guidelines, 2010)

References
Management of Gout, CPG 2008, MOH Malaysia
2012 American College of Rheumatology, Guidelines for
Management of Gout), part 1, part 2
NHS Fife, Gout Management Guidelines, 2010