Based on Malaysia MOH CPG Guideline

1. DR CHIA KOK KING
Medical & Health Officer
PKD Langkawi, Kedah

3. Gout
 A metabolic disease characterized by
recurrent attack of acute inflammatory
arthritis caused by elevated levels of uric
acid in 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

4. (NHS Fife, Gout ManagementGuidelines, 2010)

5. Asymptomatic hyperuricemia
 Serum [urate] abnormally high without SSx
 Male >420μmol/L (7mg/dL)
 Female >360μmol/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] >540μmol/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)

6. 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. 1st metatarsophalangeal joint (podagra)
II. Forefoot/instep
III. Ankle joint
IV. Knee joint
V. Wrist joint
VI. Elbow joint
VII. 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

7. 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 μmol/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

9. 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

10. Diagnostic criteria
 Two of the following criteria are required for
clinical diagnosis :
1. Clear h/o at least 2 attacks of painful joint
swelling with complete resolution within 2
weeks
2. Clear history or observation of podagra
3. Presence of tophus
4. Rapid response to colchicine within 48 hours of
treatment initiation
 Definitive diagnosis : presence of
monosodium urate crystals seen in synovial
fluid/tissues

11. 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

13.  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

15.  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

16. 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.

17. 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
- > 770μmol/L (13mg/dL) in male
- > 600μmol/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

18. 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 neutrophils motility and activity, leading to a
net anti-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

19.  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 ManagementGuidelines, 2010)

20. Treatment : chronic gouty arthritis
Management of Gout, CPG 2008, MOH Malaysia

21. 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 well-
controlled
 Indications for ULT :
1. Frequent and disabling attacks of gouty arthritis (3 or
more attacks/year)
2. Clinical or radiographic signs of erosive gouty arthritis
3. The presence of tophaceous deposits
4. Urate nephropathy
5. Urate nephrolithiasis
6. Impending cytotoxic chemo-/radiotherapy for lymphoma
or leukemia

22.  D/W with patients regarding important points
at initiation of ULT
1. NSAIDs/colchicine do not lower serum urate
2. Hypouricemic drugs have no analgesic or anti-
inflammatory effect
3. ULT agent should not be stopped during an
attack after initiation
4. 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
5. Is a life-long treatment
6. Lifestyle modification is an important adjunct
therapy

23. Management of Gout, CPG 2008, MOH Malaysia

24. Xanthine oxidase inhibitor
ALLOPURINOL
 More superior than probenecid
 Primarily excreted by kidneys, thus need renal
adjustment
 Aim : reduce to <360μmol/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 can’t tolerate colchicine, low
dose NSAIDs can be used

25.  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 ManagementGuidelines, 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)

26. 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)
- urate nephropathy
- urate nephrolithiasis
 Losartan has modest uricosuric effect 
 Fenofibrate too 
Risk of crystal precipitation

27. (NHS Fife, Gout ManagementGuidelines, 2010)

28. 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

29. 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 lower ureter  may pass spontaneously
 If fail to pass after 2 weeks  refer for removal
 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

30. 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

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

32. 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 onT.
allopurinol 900mg OD
 Uncontrolled acute gout attacks when serum
urate <360μmol/L
 Renal impairment
 Adverse effects of ULT/Intolerance

33.  (NHS Fife, Gout ManagementGuidelines, 2010)

34. 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