Pathophysiology

Inflammatory arthritis caused by the deposition of uric acid crystals in the joint. Hyperuricemia is defined as urate levels ≥ 6.8 mg/dL.

Purine Metabolism

Risk Factors

• Age
• Low kidney function
• Male
• High BP
• Obesity
• EtOH use

SSx

Severe pain and inflammation around tophi (urate deposits), most commonly in the big toe

Treatment

Acute Flairs

• NSAIDs at highest recommended dose until 24hr after SSx resolution
  • Indomethacin 50mg PO TID
  • Naproxen 750mg then 250mg PO q8hr
  • Sulindac (Clinoril) 200mg PO bid
• Colchicine
  • Load 1.2 mg PO then 0.6mg 1hr later
  • Continue 0.6mg QD or BID 12 hrs later until resolution of attack
  • CrCl < 30: Do not repeat treatment w/i 14d, and 0.3mg QD prophylactic dose
  • HD: 0.6mg PO x1 do not repeat w/i 14d, and 0.3mg twice weekly prophylactic dose
  • SEs
    • N / V / D
    • Bone marrow suppression, aplastic anemia, and thrombocytopenia
    • Myopathy
    • Rhabdo
  • Inhibits leukocyte migration and phagocytosis via interactions with microtubules
  • Comparable to NSAIDs in efficacy
  • Best to start w/i 24hr of SSx onset
• GCs
  • Most commonly used w/ multiple joint involvement or resistant cases
  • Prednisone, methylprednisolone, and triamcinolone all common
  • Prednisone 0.5 mg/kg QD x5-10d or 0.5 mg/kg x2-5d then 7-10d taper
  • Methylprednisolone 21d dose pack
  • Triamcinolone 60mg IM x1 dose then PO prednisone as above, or 2.5-40mg intra-articular x1 dose
• Combine Colchicine and NSAIDs, Colchicine and PO GCs, or Intra-articular GCs and any other treatment

Maintenance

• Indications
  • Two or more attacks per year
  • Presence of tophi
  • Presence of renal stones
  • CKD Stage 2 or worse

1. Xanthine Oxidase Inhibitors
   • Allopurinol 100mg PO QD NTE 800mg QD
     • Slowly titrate q2-4wks
     • 50mg PO QD w/ CKD 4
     • CrCl 10-20: NTE 200mg PO QD
     • CrCl 3-10: NTE 100mg PO QD
     • CrCl < 3: Consider QOD
     • SEs: Rash, pruritus, leukopenia, thrombocytopenia, N / V / D, SJS / TEN, eosinophilia, vasculitis
     • Screen fro HLA-B*5801 in Asian ethnicities to decrease risk of SJS / TEN
   • Febuxostat 40mg PO QD NTE 80mg QD
     • No renal adjustments
     • Do not initiate or stop during an attack
     • Data limited for CrCl < 30 and severe hepatic impairment
     • Expensive
     • SEs: Rash, N /D, LFT elevations, increased risk of thromboembolism
     • CI: Azathiprine, mercaptopurine, or theophylline use
     • Monitoring: LFTs at baseline, 2mo, and 4mo
2. Uricosurics (Added to above)
   • Inhibition of uric acid reabsorption in the PCT
   • Probenecid 250mg PO BID x7d then 500mg BID x14d NTE 2g qd
     • Titrate by 500mg q1-2wks as needed
     • SEs: Flushing, HA, GI Upset, Kidney Stones, Aplastic anemia / leukopenia
     • CIs: Salicylate use, blood dycrasias, uric acid kidney stones, CrCl < 50, acute attack
3. Uricase Therapy
   • Converts uric acid into allantoin
   • Pegloticase 8mg IV Infusion q2wks over 120min
   • Pretreat w/ antihistamines and GCs
   • SEs: Infusion related events, nephrolithiasis, anaphylaxis, arthralgia, CHF exacerbation, nausea
   • CIs: G6PD Deficiency
   • Avoid in CHF pts
4. Miscellaneous Therapies
   • Lesinurad (Zurampic) 200mg PO QD
     • Inhibits urate transporter increasing excretion
     • Can use with xanthine oxidase inhibitors
     • SEs: Acute renal failure (black-box), HA, GERD

Prophylaxis

• Colchicine 0.6mg PO QD or BID
• Naproxen 250mg PO BID
• < 10 mg prednisone equivalents QD

Monitoring

• Serum Urate x2-5 weeks during initiation, then q6mo once < 6 mg/dL