Gout Flashcards
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
