1. To review the diagnosis of gout and its differential. 2. To understand the four stages of gout

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1 Objectives 1. To review the diagnosis of gout and its differential GOUT 2. To understand the four stages of gout 3. To develop an approach for the acute treatment of gout Anthony Lim 9/13/12 Cycle 3 4. To recognize when a pt should start ppx for gout and how to go about it Epidemiology ~ 3.9 million office visits per year Affects ~ 5% all men over age 65 Prevalence slowly increasing (obesity, aging population, diuretic-treated HTN) 90% pts men > 30 (peak age 40 60) More common in African-Americans Quality of rx suboptimal in up to ½ of pts Pathophysiology Risk Factors Any systemic factor that increases risk of hyperuricemia: High purine diet High levels meat and seafood, esp internal organs Dairy products: opposite effect EtOH use 12-year prospective study of ~ 50k males w/o gout > = 2 beers: 2.5x RR Beers > Spirits (1.6x) Wine not associated w/ increased risk Sugar-sweetened beverages/foods Obesity Diuretic Therapy Thiazides = Loop diuretics (RR 1.77) 1

2 Common Triggers for acute flares Infection IV contrast media Rapid fluctuations in [uric acid] Trauma Surgery Starvation Chemotherapy initiation Diuretic therapy (loop, thiazide) Diet/EtOH consumption Four Stages of Gout 1. Asymptomatic Hyperuricemia 2. Acute Gouty Arthritis 3. Interval Gout 4. Chronic Tophaceous Gout Stage 1: Asx Hyperuricemia Common and typically does not lead to gout Serum Uric Acid Level (mg/dl) % Greater than 9 4.5% Annual incidence of gout Stage 2: Acute Gouty Arthritis Initial attack often involves single LE joint First MTP (75%) > midtarsal, ankle, knee Polyarticular: < 20% Sudden onset exquisite pain Peaks w/in 24 48h Erythema, swelling, tenderness, warmth Occasionally accompanied by fever Typically lasts 5 7 days ACR: 6 of 12 criteria (e.g., monoarticular, pain, swelling, redness, < 24h, first MTP joint) Definitive Diagnosis Work-Up MSU crystals in synovial fluid Polarized microscopy, the crystals appear as bright negatively birefringent yellow crystals Se: 85%; Sp: 100% Joint Aspiration Serum Uric Acid X-ray should be measured two weeks or more after complete resolution of an acute gout flare both for accuracy and for establishing a baseline value. Often not necessary with initial attack 2

3 DDx Stage 3: Interval Gout Trauma Septic Arthritis (knee, + gram stain/cx, leukocytosis, fever. Defer steroid injection) Gonococcal arthritis (fever, rash, gonorrhea) Rheumatoid Arthritis (b/l, symmetric) Pseudogout (+ birefringence, rarer) Asx period after initial attack May last for years 60% have recurrence w/in 1y, 75% w/in 2y < 10% never have repeat bout Subsequent attacks Often polyarticular increased severity OA (Arthralgia/non-inflammatory, weight-bearing joints) Stage 4: Chronic Tophaceous Gout Occurs in pts w/ poorly controlled gout > 10-20y Tophi Seen only after several attacks Cause deformity & destruction of hard & soft tissue Common locations: extensor surface of forearms, elbows, knees, achilles tendons, pinna of external ear Renal Complications: Nephrolithiasis Chronic urate nephropathy Treatment Objectives 1. Symptom Control for acute attacks 2. Risk Factor modification 3. Prevention of recurrence 4. Preventing chronic sequelae (renal stones, tophi, destructive arthropathy) Non-Pharmacologic Rx Acute Treatment: Options Ice packs EtOH abstinence Dietary Modification Less red meat and seafood Avoid sweetbreads More dairy Weight loss 1. NSAIDs 2. Corticosteroids 3. Colchicine 4. Intra-articular Injections Substitution of diuretic therapy w/ other antihypertensives 3

4 Acute Treatment: NSAIDs Acute Treatment: Corticosteroids 1 st line No NSAID found to work better than others ASA avoided Regimens (~ 7 days): Indocin 50 mg po tid Naproxen 500 mg bid Ibuprofen 800 mg tid Consider dose reductions once sx s have improved Pts who cannot tolerate NSAIDs Improvement typically seen in 12-24h Dosing: Generally: mg/day x 3-5 days, then taper over 1 2 weeks Sample regimen: Ten days total 50 x 2, 40 x 2, 30 x 2, 20 x 2, 10 x 2 Acute Treatment: Injection Intra-articular injection w/ steroids Indication: Cannot tolerate NSAIDs Idealy only one affected joint Acute Treatment: Colchicine Second-line therapy Impairs neutrophil motility and activity Initial dose: 1.2 mg, 1 hr later 0.6 mg Subsequent Dosing: 0.6 mg bid Best if used w/in 1 st 24h of attack Common s/e: N/V/D Prophylaxis: Indications 1. > 2 attacks per year 2. Tophi 3. Joint damage by radiograph 4

5 Prophylaxis: Steps Allopurinol Mechanism 1. Start once acute phase of gout has completely resolved Fluctuations in [uric acid] worsens inflammation 2. Start w/ low dose Allopurinol (100 mg) Titrate up by 100 mg every 2 weeks until [uric acid] < 6 mg/dl (max dose: 800 mg) 2-5% minor rash Severe Hypersensitivity Syndrome (rare): fever, toxic epidermal necrolysis, hepatitis, eosinophilia 3. Administer concurrent ppx w/ low-dose colchicine (0.6 mg bid x 3-6m) reduces risk of flare-ups Prophylaxis: Probenecid Probenecid Mechanism Second-line therapy Sometimes combined w/ allopurinol for refractory hyperuricemia Uricosuric: Increase renal clearance of uric acid by inhibiting tubular absorption S/e: GI & kidney stones Prophylaxis: Other Agents Losartan & Fenofibrate (Tricor) Potentially useful adjunct rx for pts w/ gout, HTN, and HL Vitamin C Double-blinded placebo-controlled randomized trial 184 nonsmokers 500 mg/day Vitamin C vs placebo x 2 months Vit C group: significant mean decrease [uric acid] of 0.5 mg/dl 5

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7 Take-Home Points Synovial fluid MSU crystals provides definitive dx of gout Keep in mind the four stages of gout when evaluating a patient for gout For acute gout, NSAIDs = first line acute treatment. Steroids and Colchicine are second-line. PPx generally achieved via Allopurinol titration to serum uric acid < 6, along w/ colchicine initially to prevent acute flare THANKS!! References Becker MA. Clinical Manifestations and Diagnosis of Gout. UpToDate Becker MA. Treatment of Acute Gout. UpToDate Becker MA. Prevention of Recurrent Gout. UpToDate Pittman, JR, Bross, MH. Diagnosis and Management of Gout. American Family Physician 1999;59. Eggebeen AT. Gout: An Update. American Family Physician 2007; 76:801-8). 7