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