Gout Management Flashcards
How is Gout diagnosed?
Subjective - Clinical Presentation:
- Pain, swelling, warmth, redness
- Severe pain for several hours
- Wakes up from sleep at night due to pain
- Usually the big toe (MTP)
- Monoarticular joint pain
Objective:
- Hyperuricemia
- Joint aspirate (Synovial fluid MSU crystals)
- Tissue sections of tophaceous deposits
Define Gout
Deposition of monosodium urate (MSU) crystals in the joints (articular or periarticular) due to purine metabolism imbalances or renal excretion problems
Risk factors for gout
- Obese individuals
- Male > Female
- Male < 30 y.o. and premenopausal women with inherited enzyme defect of renal disease
- Lifestyle and diet
Explain the pathophysiology of gout attacks
- Impaired purine metabolism
- Salvage pathway impaired
- Degradation pathway for guanine and adenine is promoted - Renal excretion problems
(Urate transporter 1, GLUT9)
Goals of gout therapy
- Reduce pain and inflammation of acute attack SAFELY
- Prevention of future gout attacks
- Improve QOL
- Prevent joint destruction and tophi formation
- Address associated comorbidities
What are the four stages of gout?
- Asymptomatic Hyperuricemia
- Acute Gout Attack (1st MTP excruciating)
- Inter-critical phase between flares
- Chronic Gout (Recurrence, tophi)
Normal serum uric acid levels in the body
Male: 210 - 420 µmol/L
Female: 150 - 350 µmol/L
How is an acute flare managed? (Pharmacologically and non-pharmacologically)
Colchicine 1.5 mg/day within 24 hours:
- One-off Tx: 1 mg followed by 0.5 mg one hour later (Low-dose regimen)
- Alternate Tx: 0.5 mg BD to TDS until acute flare resolves
PO NSAIDs
- Diclofenac (Accumulate in synovial fluid)
- Celecoxib
PO Corticosteroids
Intra-articular Corticosteroids
Topical Ice
Side effects and Precautions of Colchicine and NSAIDs
Colchicine:
- Dose-related (Frequency) GI effects (N/V/D)
- DDIs: Macrolide, azoles, statins, NDHP CCBs
NSAIDs: CV, Renal, GI, Asthma, Allergy effects
- Add PPI to NSAIDs
When should you initiate urate lowering therapy?
History of kidney stones or CKD 3-5
Diuretic therapy
≥ 2 recurrent gout attacks in the past year
Tophi formation
Clinical or imaging findings of gouty arthropathy
What is the target goal for ULT?
Non-tophaceous gout: 360 µmol/L (6 mg/dL)
Tophaceous gout: 300 µmol/L (5 mg/dL)
ULT Treatment:
- Dosing
- Titration
- Maximum dose
- Caution
Allopurinol 100-300 mg/day (Safe for renal)
- Uptitrate 50-100mg/day every 2-8 weeks until target serum uric acid levels reached
- Maximum 800-900 mg/day
- Caution in SCAR risk patients (SJS, TEN) - Renal issues and elderly do HLA-B*5801 testing
Febuxostat (Initial ≤ 40 mg OD)
- Uptitration to 80 mg OD
- Caution in HF, CHD
Probenecid
- Initial 250 mg BD 1 wk; Uptitrate to 500 mg BD
- Titration in 500 mg every 4 weeks
- Usual maintenance ≤ 2 g/day
- CI in urolithiasis, CKD < 50 mL/min
When do most SCAR reactions occur after ULT?
First few weeks to months after initiation
RASHES acronym for allopurinol-induced SCAR
Renal impairment
Agent concomitantly used - Diuretics
Starting dose of allopurinol is high
HLA-B*5801 allele present
Escalation of allopurinol dose is rapid
Seniority in age
Why is routine genotyping not done for ULT?
- Absence of HLA-B*5801 allele can also result in SCAR (Non-genetic factors)
- Low positive predictive value
- Lack of alternative cost-effective ULT options
