1. DR CHIA KOK KING
Medical & Health Officer
PKD Langkawi, Kedah
2.
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
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
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
12.
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
14.
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
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
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
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