DR Zareen Naz

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/under excretion/both
Hyperuricemia ≠ Gout
URIC ACID CRYSTALS
(NHS Fife, Gout Management Guidelines, 2010)
 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

 Leading to :
 gout, urolithiasis, nephropathy, metabolic
syndrome (HPT, DM/ obesity, CKD)
 Serum [urate] >540μmol/L (9mg/dL) were
greater incidence for gout

 Increased daily urinary urate excretion is 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

 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
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)
 Urate/gouty nephropathy

 Acute urate nephropathy

 Urate crystals  renal tubules  obstructive ARF
 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
 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. Presence of tophus
3. 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

 To detect complications
 Renal imaging
 Skeletal x-rays
 To detect medical conditions gout or hyperuricemia

 Serum creatinine/urea
 Serum blood glucose
 Fasting lipid profile

 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 under excretion of
urate
 Range : 2-4 mmol/24h or 0.34-0.67g/24h
 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
 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.
Management of Gout, CPG 2008, MOH Malaysia
 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
Treatment : Acute gouty arthritis

 1. NSAIDs
 Diclofenac, indomethacin, mefenemic acid etc

 Caution in h/o 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
2. 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
 SE (eg. N&V, abd. pain, profuse diarrhea) limit its
usefulness
 Dosage : 0.5mg – 0.6mg BD-QID
 3. Steroids

 Can be considered in elderly people and patients with

renal/liver impairment, IHD, 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)

 Urate lowering therapy
(hypouricaemic therapy)
 1. Allopurinol : (Zyloric)

 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
 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
 colchicine (0.5mg BD) can be used as
prophylaxis to reduce frequency of attacks.
 For patient who can’t tolerate colchicine, low
dose NSAIDs can be used
 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
2. PROBENECID

 Dosage : 0.5 – 1g in divided doses, may be

increased to 1.5 – 2g
 SE :
 GI disturbance
 Hypersensitive rash
- uric acid overproduction and over excretion (24
hrs urinary urate excretion more than
800mg/day)
- urate nephropath
- urate nephrolithiasis
Treatment of urate nephropathy
 Increase urine output
 3L of H2O/day with urine output >2.5L
 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
Treatment of urate nephrolithiasis
 Intrarenal stones <5mm can be observed unless
causing pain
 Intrarenal stone 5 – 15mm or complex staghorn
calculi  refer to urologist
 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
 Decrease urate excretion
 Dietary purine intake restriction
 Treat with allopurinol
 Surgical intervention
 Last resort for gouty arthritis
 Removal of tophi
 Joint replacement
 Ulceration of tophi : debridement, dressing
with sodium bicarbonate solution

 Indications for chronic tophaceous gout :

 Advanced tophi deposition resulting in major joint
destruction
 When to reduce ULT?????
 If serum urate <360μmol/L , and have been no
gouty attacks for 1 year  can reduce T.
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
Gout
 Characterized by deposition of Na urate crystals
in the joint  painful arthritis.
 Acute attacks treated with indomethecin,
naproxen, or other NSAIDs, but not with aspirin
(incr plasma urate levels at low doses by
inhibiting uric acid secretion in the renal
tubules).
 Colchicine – bonds tubulin in leukocytes 
prevents polymerization in microtubules 
inhibits the phagocytic activity and migration of
leukocytes to the area of uric acid deposition 
decr inflammatory repsonse.
Prophylactic treatment of Gout
 Allopurinol lowers plasma urate by inhibiting
xanthine oxidase (xanthine  uric acid).
 Uricosuric drugs (sulfinpyrazone, probenicid)
inhibit renal tubular reabsorption of uric acid 
incr excretion.
 Should drink plenty of H2O to prevent
crystallization of urate in the urine.
 These drugs less effective and more toxic than
allopurinol.
Treatment of Gout