Post on 02-Jun-2015
Principles• An attack usually subsides spontaneously
– May take long time
• Treatment reduces severity & shortens duration
• The early the treatment is started more prompt is the resolution
Options• NSAIDs• Steroid– Intra-articular– Oral or intramuscular
• Colchicine• Interleukin 1 beta inhibition (investigational)
NSAIDs• Aspirin avoided
• Drugs:– Indomethacin: 50 mg tid
– Naproxen 500 mg bd
• Dose halved after substantial improvement– Usually 3 d
• Continue until complete resolution: 7 to 10 d
• longer courses in attacks of several-day duration
Colchicine• Dose:– US FDA: 1.2 mg stat, 0.6 mg after 1 hr
– EULAR: 0.5 mg tid
• Patients on colchicine prophylaxis:– Return to prophylactic dose on the day after flare
treatment
• No or minimal response:– Alternative agents, including IA steroid
Drugs Increasing Risk of Toxicity
• Macrolide antibiotic
• Azole antifungals
• Calcium channel blockers
• Amiodarone
• Cyclosporin
• Statins
Steroids• Intolerance to colchicine or NSAIDs– Or have RFs for their toxicity: drugs, CKD, etc.
• Intra-articular: mono-articular– Triamc acetonide 40 mg in knee or equivalent methylpred
• Smaller doses in smaller joints
• Oral prednisolone– Polyarticular attack
– 30 to 50 mg daily in divided doses 1 to 2 days• Tapered over 7 to 10 days
Treatment of Acute Attacks
Major Subheadings
• Patient Education
• General measures
• Urate lowering therapy
• Prevention of gouty attacks during early
months
Patient Education• Pathophysiology• Natural course: variability• Therapy:– No cure– Role of lifestyle measures– Drugs• Tr of attacks: only drug tr in some• Prophylaxis: selective
– Prevention with urate lowering medicines
– Need for continuous intake & follow-up
Diet and Drugs• Avoidance of sugar sweetened beverages/foods or
beverages containing fructose
• Tempering a very high purine diet:– Sea food, red meat, offal
• Limiting intake of beer and spirits
• Withdrawal of thiazide*
• Losartan, fenofibrate and atorvastatin for tr of Ht, high cholesterol or TG*
* Less important if anti-hyperuricemic tr considered
Caloric Restriction in Overweight
• Increased proportion of protein
– low-fat dairy products, not red meat or fish
• Replacement of refined with complex carbohydrates
• Decreased saturated fat
Estimation of 24-hr UrinaryUric Acid
• Indications: Gout in
–men less than 25 years
–premenopausal women
Urate Lowering Therapy: Indications…
• >3 attacks per year
– 2/yr if disabling, prolonged, interferes with ADL
• Clinical or radiographic signs of chronic gouty joint disease
• Gout with renal insufficiency
• Urinary uric acid excretion >1100 mg/day (6.5 mmol)
Urate Lowering Therapy: Indications
• Serum uric acid persistently >10.1
• Tophi in soft tissues or subchondral bone
• Recurrent urate urolithiasis
• ? Strong family history of gout
Goals of Therapy
• Serum urate <6 mg/dL (<357 µmol/L)
– <5 mg/dL (<297 µmol/L) in patients with tophi
• A fall of <0.6 mg/mo ensures recurrence free achievement of target
General Principles• Should not be initiated during an attack– Conventional interval: 4 wk– Exceptions: • Inter-critical interval <4 wk• Chronic tophaceous gout
• Titrated against serum urate at 3 to 4 wks• Treatment should be– Continuous– Duration: indefinite
Choice of Drugs
• Xanthine oxidase inhibitors: – allopurinol, febuxostat
• Uricosuric drugs: – probenecid, sulfinpyrazone, benzbromarone
• Uricase: – pegloticase (porcine), rasburicase (recombinant)
Allopurinol• Urate-lowering drug of general choice– Particularly suitable for overproducers
• Started with 100 mg/day single dose– after meals with plenty of fluid
– Doses >300 mg divided
• Increased at 2 to 3 wks by 100 mg till target reached– Maximum: 900 mg/day
• Monitoring parameters– CBC, serum uric acid, ALT, S Cr, at start of therapy
Allopurinol: Adverse Effects• Diarrhea, and drug fever
• Rashes, rarely TEN and Steven Johnsons– Association: HLA- B*5801
• Leukopenia or thrombocytopenia
• Interstitial nephritis, vasculitis
• Allopurinol hypersensitivity syndrome (AHS):– erythematous rash, fever, eosinophilia, hepatitis, and
acute renal failure
– Rare but life-threatening, mortality 25%
Starting Dose and Titration of Allopurinol on eGFR
eGFR Starting dose Titration
≥60 ml/min 100 mg/day 100 mg every 2-3 wk
30-59 ml/min 100 mg/day 50 mg every 2-3 wk
10-29 ml/min 50 mg/day 50 mg every 2-3 wk
Febuxostat…
• Indications:– Intolerance/allergy to allopurinol
– Mild to moderate CKD
• 40 mg produces a reduction equivalent to 300 mg allopurinol
• Started at 40 mg/day– Increased to 80 mg if target not reached after 2 wks
– Maximum recommended dose 120 mg
Febuxostat• AEs:
– liver function abnormalities
–Nausea
– arthralgia
– rash
• Monitoring: transaminases
Uricosuric Drugs• Indication: Intolerance to allopurinol
• Requisite: 24-hr urinary uric acid <800 mg
• Contra-indications:
– Nephrolithiasis or uric acid nephropathy
– Uric acid overproduction
– Renal insufficiency
– Extensive tophi
Methods
• Low-slow approach with ULT
• Colchicine
• NSAIDs
• Anakinra or rilonacept
Colchicine
• Dose: 0.6 mg twice daily for patients with normal renal and hepatic function
• Duration:
– Tophi absent: 6 mo after normalization of urate
– Tophi present: until resolution of the tophi
• or it is clear that tophi will not resolve despite persistent normouricemia
Conclusions• Restrictive diets are no longer recommended
• ULT is selective, not for all pts with gout
• Avoid ULT during attack
• Patient education:
– importance of uninterrupted continuation of ULT for indefinite period
• Key to success: appropriate doctor-patient relation