Gout A rapid review Jeremy Jones
The Hyperuricemia Cascade Dietary purines Tissue nucleic acids Urate Endogenous purine synthesis Overproduction Hyperuricemia Underexcretion Silent tissue deposition Gout Renal manifestations Associated cardiovascular events and mortality
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
Asymptomatic Hyperuricemia Elevated serum urate with no clinical manifestations of gout Acute Flares Acute inflammation in the joint caused by urate crystallization Intercritical Segments The intervals between acute flares Advanced Gout Long-term gouty complications of uncontrolled hyperuricemia Uncontrolled Hyperuricemia
Pain Evolution of Hyperuricemia and Gout Painless Intercritical Segments Painful Intercritical Segments Asymptomatic Hyperuricemia Acute Flares Time Advanced Gout Adapted from Klippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed. Arthritis Foundation; 2001:313.
First attack of GOUT Almost always 1 st 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
Pain Evolution of Hyperuricemia and Gout Painless Intercritical Segments Painful Intercritical Segments Asymptomatic Hyperuricemia Acute Flares Time Advanced Gout Adapted from Klippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed. Arthritis Foundation; 2001:313.
Common Sites of Acute Flares Olecranon Bursa Gout can occur in bursae, tendons, and joints Elbow Wrist Fingers 1st MTP (eventually affected in ~90% of individuals with gout) Ankle Knee Subtalar Midfoot
Pain Evolution of Hyperuricemia and Gout Painless Intercritical Segments Painful Intercritical Segments Asymptomatic Hyperuricemia Acute Flares Time Advanced Gout Adapted from Klippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed. Arthritis Foundation; 2001:313.
Advanced Gout Clinically Apparent Tophi Helix of the ear Hands, fingers, and wrists ACR Clinical Slide Collection on the Rheumatic Diseases, 1998.
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
1. General 2. Acute gout 3. Lowering urate Treatment of gout
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 drugs Promote 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/