Gout Flashcards
Describe the pathophysiology of Gout.
1) Overproduction
- inborn errors of metabolism; Or
- increased cell turnover & purine generation.
2) Underexcretion
- 90% of gout cases
Results in increased [uric acid], and deposition of urate crystals in periarticular fibrous tissue of synovial joints.
Describe the presentation of gout.
Attack usually occurs at 1st MTP of great toe.
Pt wakes from sleep by severe pain.
Feels like joint is on fire.
Swelling and discomfort for days to weeks.
How is Gout diagnosed?
Presence of Monosodium Urate crystals in either:
- Synovial fluid, or
- Tissue sections of tophaceous deposits.
Differentiate gout and pseudogout.
Gout - uric acid crystals in joint aspirate. Fluid is yellow and cloudy.
Pseudogout - calcium pyrophosphate deposition in joint aspirate.
What are the Goals of treatment for Gout?
- To reduce future attacks. (by reducing [SU])
- Pain relief - rapid, safe, effective.
- Address associated comorbidities.
- Prevent Escalation: joint destruction and tophi formation.
- Increase QoL.
Describe the management of Acute Gout flares.
1) Colchicine - 1g LD, and 0.5mg 1 hr later; OR 0.5mg BD/TID until flare resolves.
2) Oral NSAIDs / coxibs
3) Oral corticosteroids.
Describe the use of ULTs in acute gout flares and as prophylaxis.
Acute gout flares
- continue if alr taking, but do not start if not taking.
- May start during flare if flares are very frequent.
Prophylaxis
- started 2 to 4 weeks after flare when symptoms are resolved, for 3-6 mo.
- ULTs are only started if one of these is fulfilled:
1. Frequent acute gout flares (>= 2 / year)
2. Presence of tophus
3. Findings (clinical / imaging) of Gouty Arthropathy
4. Hx of urolithiasis
What are the serum Urate targets?
[Non-tophaceous gout] < 6mg/dL
[Tophaceous gout] < 5mg/dL
What are the considerations for ULTs?
Allopurinol - not to use if have HLA-B*58:01 allele.
Febuxostat - caution in HF and CHD.
Probenecid - contraindicated in urolithiasis. Not effective in CKD, avoid in CrCl < 50ml/min.
What is the MoA of Probenecid?
URAT1 and GLUT9 inhibitor -> reduced reabsorption of uric acid.
Important counselling points for Probenecid are:
- > = 2L of water daily, to prevent kidney stones from forming.
What are risk factors for Severe Cutaneous Adverse Reactions (SCAR) for Allopurinol?
Renal impairment;
Agents - concomitant diuretics, ACEi, ampicillin/amoxicillin;
Starting dose - of allopurinol is high;
HLA-B*58:01 - presence of allele;
Escalation - rapid escalation of allopurinol dose;
Seniority - older age.
The administration of allopurinol may lead to the raised concentrations of:
Carbamazepine
Warfarin
Theophylline
and leads to increased Bone marrow suppression for:
6-mercaptopurine
Azathioprine
Cyclophosphamide
The administration of allopurinol may lead to the increased toxic effects of:
Pegloticase (recombinant PEGylated uricase)
Allopurinol has an increased risk of hypersensitivity rxn occurring when administered with:
ACEi
Loop diuretics
Thiazide / thiazide-like diuretics
Ampicillin / amoxicillin
