Gout

A rapid review

Jeremy Jones

The Hyperuricemia Cascade

Urate

Hyperuricemia

Overproduction Underexcretion

Associated

cardiovascular events

and mortality

Renal

manifestationsGout

Endogenous

purine synthesisDietary

purines

Tissue

nucleic acids

Silent

tissue

deposition

Main predisposing factors

1. Family history

2. Life style

• Inactive

• Obesity

• Wrong diet

• Alcohol

• etc

Hyperuricaemia

• Overproduction– Inherited tendency

– Severe enzyme deficencies

• Glucose 6 phosphatase

• Fructose 1 phosphatase aldolase

– Myeloproliferative

– Lymphoproliferative

– Polycythaemia

– Malignancy

– Psoriasis

– Drugs/dietary

• Alcohol, cytotoxic, DXT

• Undersecretors• Inherited

• Chronic renal failure

• Dehydration

• Starvation

• Drugs/dietary

• Alcohol,

• diuretics,

• aspirin,

• cyclosporin

Advanced

Gout

Long-term gouty

complications of

uncontrolled

hyperuricemia

Intercritical

Segments

The intervals

between

acute flares

Acute Flares

Acute inflammation

in the joint caused

by urate

crystallization

Asymptomatic

Hyperuricemia

Elevated serum urate

with no clinical

manifestations of gout

Uncontrolled Hyperuricemia

Evolution of Hyperuricemia and Gout

Asymptomatic

HyperuricemiaAcute Flares Advanced

Gout

Painless Intercritical

Segments

Painful

Intercritical

Segments

Pain

Time

Adapted from Klippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed.

Arthritis Foundation; 2001:313.

First attack of GOUT

• Almost always 1st MTP (podagra),

• Can be instep, heel, ankle.

• Comes in the night

• Precipitants of acute attacks

• Usually out of the blue

– Acute illness, trauma, surgery, alcohol and drugs

– will settle on its own

25% - 40% of patients during an acute

attack of gout will have normal levels of

urate

Evolution of Hyperuricemia and Gout

Asymptomatic

HyperuricemiaAcute Flares Advanced

Gout

Painless Intercritical

Segments

Painful

Intercritical

Segments

Pain

Time

Adapted from Klippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed.

Arthritis Foundation; 2001:313.

Common Sites of Acute Flares

Midfoot

Gout can occur

in bursae, tendons,

and joints

Olecranon Bursa

Elbow

Wrist

Knee

Ankle

Subtalar

1st MTP(eventually affected

in ~90% of

individuals with gout)

Fingers

Evolution of Hyperuricemia and Gout

Asymptomatic

HyperuricemiaAcute Flares Advanced

Gout

Painless Intercritical

Segments

Painful

Intercritical

Segments

Pain

Time

Adapted from Klippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed.

Arthritis Foundation; 2001:313.

Advanced GoutClinically Apparent Tophi

ACR Clinical Slide Collection on the Rheumatic Diseases, 1998.

Helix of the ear

Hands, fingers, and wrists

Gout kidney

Why treat gout?

• Prevent severe pain and disability of acute

attacks

• Present damage to joints from tophi

• Prevent tophi being deposited elsewhere

• Preserve kidney function

Treatment of gout

1. General

2. Acute gout

3. Lowering urate

Treatment of gout

General

• EDUCATION, EDUCATION, EDUCATION.

• LIFESTYLE MODIFICATION

• REVIEW DRUGS (Diuretics Especially)

• COMPLIANCE (it’s a man thing!)

Treatment of gout

Acute gout

NSAIDs

Colchicine

Steroids

NSAIDs

Colchicine

What is the dosing

regime of

colchicine?

Treatment of acute gout

Colchicine

• Therapeutic dose close to the toxic dose

So needs to be tailored to the patient

• Excreted by the kidney

So care in those with renal impairment

• Diarrhoea means too much drug, not that colchicine is contraindicated

• Therapeutic dose ranges from 0.5 mgs tds to 0.5 mg alternate days or even every third day

Treatment of acute gout

Steroids

• Useful in those unable to tolerate NSAIDs

and severe polyarticular gout

• Intra-articular will settle down a joint

• ACTH injection (Synacthen depot 1 mgs in

1 ml IMI) will settle polyarticular gout,

grumbling gout and the gouty grump.

• Intra-muscular steroids or tablets less

useful than ACTH

Treatment of gout

Lowering urate

• Do not start urate lowering drugs if there is

active gout

• It is likely to cause a flare and your patient will

lose faith in you and the drug

• If gout is a bit touchy, cover introduction of

urate lowering drug with Colchicine and/ or

NSAIDs.

• Treatment will be lifelong

Treatment of Gout

Lowering urate

ALLOPURINOL

• Competitively inhibits xanthine oxidases

• If there has been acute gout or poor renal function, start gingerly (100 mgs/day or alternate days)

• Cover with Colchicine/NSAID as necessary

• Dose must be tailored to individual; effective dose varies between 100-800mgs)

• Need to titrate to target urate level (<0.36 for gout; <0.30 for tophi resorption)

Treatment of gout

Lowering urate

Febuxostat– Nonpurine xanthine oxidase inhibitor– More selective than Allopurinol– Metabolised by the liver– Effective in moderate renal impairment– Very promising but ……– Used as second line to Allopurinol at the

moment

Treatment of gout

Lowering urate

Third LINE drugsPromote the clearance uric acid by inhibiting renal tubular

reabsorption

Probenecid

Sulphinpyrazone

Benzbromarone

New treatments

• Uricase

• Uricosuric

• Xanthine Oxidase

Inhibitors

• Biologic (IL6 inhibitor)

Pegloticase

Uricase PEG 20

Rasburicase

Lesinurad (Inhibits uric acid

resorption)

Oxpurinol

Anakinra

KEY MESSAGES

• Gout is very treatable disease and

should be treated seriously

• Must treat to target

• reduce SUA < 0.36mmol/l in all cases

• If tophi reduce SUA < 0.3 or under to

reabsorb them

• Treatment is lifelong

NZ atlas of health care variation• http://www.hqsc.govt.nz/our-programmes/health-quality-evaluation/projects/atlas-of-healthcare-variation/gout/