Gout Flashcards
(28 cards)
What is the pathophysiology behind gout?
When there is high uric acid in the body, uric acid crystals form in the joints
Inflammatory response to MSU occurs in a wide range of immune cells e.g. macrophages, dendritic cells
Signal 1 – normal production of inflammasome components, can be stimulated by a wide range of stimuli
Signal 2 – MSU crystals recognised by (unknown) receptor, which results in inflammasome activation
Inflammasome activation activates Caspase 1, which catalyses activation of IL-1β and Gasdermin-D
- Gasdermin-D cleavage results in the formation of pyroptotic pores
- IL-1β exits cell via pyroptotic pores, and other foreign materials can also enter the cell
- IL-1β binds to IL-1 receptors to result in inflammatory responses – eg translocation of p65 and p50 into the nucleus for DNA transcription of cytokine and chemokine genes
- Foreign materials may stimulate inflammatory responses in the cells that they enter as well
Inflammasome formation also results in potassium efflux via potassium channels
How does gout present?
- Usually monoarticular – e.g. 1st joint of big toe
- Pain wakes one up from sleep
- Severe pain for several hours, with the swelling & discomfort continuing for days to weeks thereafter
How is gout diagnosed?
Presence of MSU crystals in
- Synovial fluid – via joint aspirate
- Tissue sections of tophaceous deposits
Presence of Tophi – though they may only start appearing later on
Joint Aspirate Findings (not always helpful)
What are the goals of treatment for gout?
- Provide rapid, safe and effective pain relief
- Reduce future attacks
- Address associated comorbidities
- Prevent joint destruction and tophi formation
- Increase QoL
What are the stages of gout?
Asymptomatic hyperuricemia
Acute gout (1st attack)
Inter-critical phase (b/w flares)
Chronic gout
What therapy options can be used during acute gout attacks?
PO Colchicine, PO NSAIDs, PO/Intra-articular Corticosteroids
What is the MOA of colchicine?
- Binds to tubulin
- Prevents tubulin polymerization into microtubules
- Inhibits leukocyte migration and phagocytosis
- Inhibits leukotriene B4 (LTB4) and prostaglandin production
How should colchicine be dosed?
Load 1mg, then take another 0.5mg 1h later OR
0.5mg BD-TDS until the acute flare resolves
Note: greater likelihood of GI AE if dose >1.5mg/day
What are the side effects of colchicine?
N/V/D, abd pain, muscle weakness, unusual bleeding, pale lips, change in urine amt
When should urate-lowering therapy be started for patients with an acute flare?
Already on ULT – continue during the flare
Not on ULT yet – best to wait for flare to resolve for 2-4 weeks
* Rationale: ULT reduces plasma urate, which may cause uric acid from joints to leave and worsen the attack and/or cause periarticular involvement
* Can consider to not wait for flare to resolve – give them colchicine on standby
When should urate-lowering therapy be started for patients without an active acute flare?
Offer ULT to people with gout who have
→ Multiple or troublesome flares
→ CKD stages 3-5 (GFR categories G3-G5)
→ Diuretic therapy
→ Tophi
→ Chronic gouty arthritis
Discuss the option of ULT with patients who are not within these groups
What are the possible ULT options for gout?
Xanthine oxidase inhibitors - allopurinol, febuxostat
Uricosuric agents - probenecid
What is the MOA of the xanthine oxidase inhibitors?
Decrease uric acid production
What are the side effects of the xanthine oxidase inhibitors?
Rash, N/V/D, fever, sore throat, stomach ache, dark urine, jaundice
What is a precaution that needs to be taken before using xanthine oxidase inhibitors?
SCAR – test for HLA-B*5801 genotype (esp Chinese) + patient education
- Test if renally impaired, or older age (higher SCAR risk)
- Sx: Flu-like Sx, Mouth ulcers, sore throat, red/sore eyes, rash
- Rare, but can happen – esp 1st 3 months
What is the dosing for allopurinol?
Initiate at ≤100mg/day, titrate by ↑50-100mg Q2-8/52 based on Sx (monitor serum urate, toxicity)
Dose range: 100-800mg/day, usual maintenance >300mg/day
Start even lower if renally impaired
What is the dosing for febuxostat?
Initiate at 40mg OD
Increase to 80mg if not at target after 2-4/52
What are the contraindications for the xanthine oxidase inhibitors?
Pts w SCAR/hypersensitivity to allopurinol/febuxostat in the past
What is the MOA of probenecid?
Inhibit proximal tubule anion transport to inhibit uric acid reabsorption - ↑uric acid excr
What are the side effects of probenecid?
N/V, painful urination, lower back pain, allergic rxn, rash
What precautions need to be taken with probenecid?
Take plenty of fluid to minimize kidney stone formation (>2L)
Admin potassium citrate to keep urine pH >6.0
What is the dosing for probenecid?
Initiate 150mg BD 1/52, then 500mg BD
Continue increasing dose by 500mg Q4/52 as tolerated if Sx not controlled
Dose range is 500-3000mg/day, but usually ≤2g/day
Avoid in CrCl <50, contraindicated if CrCl <30
What are the contraindications for probenecid
G6PD deficiency
Avoid in CrCl <50, contraindicated if CrCl <30
What are the lab targets for gout?
Uric acid
→ Non-tophaceous gout <360 μmol/L
→ Tophaceous gout < 300 μmol/L
