Gout Treatment Megan Chan, PGY-2 UHCMC 2015

Gout Acute gouty arthritis = monosodium urate crystals in synovial fluid leukocytes – Serum urate ≥ 6.8 = insoluble in extracellular fluids Tophi = painless nodular deposits of monosodium urate crystals in tissues Chronic urate nephropathy – Crystals deposit in renal medullary interstitium Uric acid nephrolithiasis content/uploads/image/2012_2/12%20Tophus/2aj.jpg mages/corporate/X- ray-Toe-Joint-with- Tophus-with- Calcification-Gout.jpg

Risk Factors Obesity HTN HLD HF Insulin resistance Hyperglycemia Renal disease Older age Genetics High purine/fructose diet Alcohol Meds: loop & thiazide diuretics, acetylsalicylic acid, ASA

Usually Monoarticular In order of frequency: – 1 st metatarsophalangeal joint = Podagra – Ankle – Heel – Knee – Fingers – Elbows

Lifestyle Modifications Diet Weight loss Alcohol cessation Mead T, Arabindoo K, Smith B. Managing gout: there's more we can do. J Fam Pract. 2014;63(12):

Diagnosing gout How good is joint aspiration to look for negatively birefringent crystals? – 85% sensitive, 100% specific Is imaging necessary to diagnose gout? – No, but if you got it you may see subcortical bone cysts, tophi, erosions /AA00BB07-78FF-45BD-90119D22B17E6D32.jpg

Acute Gout How useful is a uric acid level during an acute flare? – Helpful if elevated but may be falsely normal/low (25-40% of pts) 2/2 cytokine effect So when is the most accurate time to check serum uric acid levels? – ≥ 2 weeks after complete resolution of a flare

Acute Attacks Initiating treatment within 24 hours has been associated with decrease pain and shorter duration of symptoms. For mild-moderate pain involving a few small joints or 1-2 large joints  Monotherapy: – NSAIDS Naproxen 500mg BID, Indomethacin 50mg TID – Colchicine (unless >36 hrs after symptom onset due to diminished benefit) – Corticosteroids Prednisone 30-50mg daily  taper over 7-10 days post flare to prevent rebound attacks

Acute Attacks For severe pain (>6 out of 10) and/or polyarticular (≥4 joints in more than 1 region of the body)  Combination therapy: – Colchicine + NSAID – Colchicine + corticosteroids For NPO pts, can give intraarticular/IV/IM steroids or SQ ACTH Continue acute treatment until attack resolves (~5-14 days)

Mead T, Arabindoo K, Smith B. Managing gout: there's more we can do. J Fam Pract. 2014;63(12):

Chronic Gout Tx Criteria for Urate Lowering Therapy (ULT): – Presence of tophi – ≥ 2 acute attacks per year (some tx after 1 flare) – CKD stage 2-5 – Hx of urolithiasis Start ULT + anti-inflammatory prophylaxis AFTER an acute gout attack resolves. If on ULT prior to a gout attack, continue regimen. If gout symptoms persist despite serum urate level < 6.0, increase ULT to obtain a target of <5.0. When do you start ULT therapy? What do you do with ULT therapy if pt is on it and has an acute attack? What do you do if your pt still has symptoms when their serum urate is <6.0?

Urate Lowering Therapy Allopurinol = first line – xanthine oxidase inhibitor – Consider Rheum involvement if GFR <50 Febuxostat—reports of hepatic failure but not commonly seen clinically – xanthine oxidase inhibitor – Use in renal insufficiency Probenecid = alterative to those with xanthine oxidase allergy or intolerance – Increases urinary uric acid secretion – Hardly used because it’s difficult to tolerate and increases risk of nephrolithiasis

Allopurinol Hypersensitivity 1 in every 1000 patients SJS/TEN, eosinophilia, leukocytosis, fever, hepatitis, renal failure High mortality (20-25%) and no cure! Screen for HLA-B*5801 allele in high risk groups: – Koreans with CKD stage 3 or worse – All Han Chinese & Thai patients

Mead T, Arabindoo K, Smith B. Managing gout: there's more we can do. J Fam Pract. 2014;63(12):

Anti-inflammatory Prophylaxis Should be started with ULT to prevent flares: – Low-dose Colchicine (0.6 daily or BID) – Low-dose NSAIDS (Indomethacin 25mg BID) – Oral steroids (<10mg/day) = second line Should continue for whichever is greater: – 3 months after target serum urate level is achieved in those with no tophi – 6 months after target serum urate level is achieved and tophi have resolved Sometimes can take 1-2 years to wean people off without flares occurring

How long should ULT be continued? Indefinitely! How often should you monitor serum uric acid levels? – Every 2-5 weeks until target is achieved – Then every 6 months

Refractory Gout If urate does not reach goal <6mg/dL (or <5mg/dL) at max doses of first-line xanthine oxidase inhibitors. Add uricosuric agent: – Probenecid, Fenofibrate, Losartan Last resort: Pegloticase = IV pegylated q2 wks recombinant form of urate oxidase enzyme that converts uric acid to allantoin (water soluble) – Can develop Ab over time that cause infusion reactions Investigational: Anakinra = IL-1 inhibitor Note: Low adherence rate to gout therapy (<50% will take tx as prescribed in their first year). Check for this first!

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Summary Practice Recommendations Prescribe an anti-inflammatory drug when initiating ULT (grade A). Increase the dose of ULT to achieve a lower target of <5mg/dL if gout symptoms persist despite a serum urate level <6mg/dL (grade B). Do not initiate ULT during an acute gout flare. However, if already on ULT regimen when a flare occurs, do no stop it (grade C). Asymptomatic hyperuricemia does not equal gout and should not be treated with ULT. – However some rheumatologist will treat urate levels >13 in young pt to prevent consequences of deposition.

References Mead T, Arabindoo K, Smith B. Managing gout: there's more we can do. J Fam Pract. 2014;63(12): UptoDate Special thanks to Dr. Pioro for the special Rheum insights!