IC 17: Approach to the Management of Gout Flashcards
What are the diseases that are classified under gout syndrome?
- Recurrent acute gouty arthritis
- Tophi
- Interstitial renal disease
- Uric acid nephrolithiasis
What are factors that predispose one to gout?
- Alcohol consumption
- Sugary beverages
- Red meat
- Sedentary lifestyle
- Obesity
- Male > female
What is the pathway of purine metabolism?
- Glutamine produces nucleic acids in body tissues
- Nucleic acids break down into guanine and adenine
- Guanine and adenine forms hypoxanthine
- Hypoxanthine forms xanthine through xanthine oxidase
- Xanthine forms uric acid through xanthine oxidase
- Uric acid gets excreted in humans
What are the processes that involve purine in the body?
- Synthesis from glutamine and nucleic acid
- Salvage pathway (HGPRT + PRPP) salvages guanine and hypoxanthine to form nucleic acid
- Diet
What leads to gout in the body?
- Over-production of uric acid (primary due to inborn erorrs of metabolism) (secondary due to conditions that increase cell turnover and purine generation)
- Under-excretion of uric acid
- Uric acid leads to the deposition of urate crystals in periarticular fibrous tissue of synovial joints
What drugs or diet factors can lead to an increase in urate production?
- Excessive ethanol ingestion
- Excessive dietary purine ingestion
- Excessive fructose ingestion
- Cytotoxic drugs
What drugs or dietary factors decreases uric acid clearance?
- Diuretics (thiazides and loop diuretics)
- Cyclosporine and tacrolimus
- Low-dose salicylates
- Ethambutol
- Pyrazinamide
- Ethanol
- Levodopa
- Laxative abuse
- Salt restriction
- Nicotinic acid
What is the clinical presentation of an acute gouty attack?
- Usually monoarticular @ 1st MTP of great toe (coldest temperature)
- Wakes up from sleep by pain
- Severe pain for several hours (feels like joints are on fire)
- Joint is red, hot, swollen and tender
- Swelling and discomfort continues days to weeks thereafter
What is required for a diagnosis for gout?
- Presence of monosodium urate crystals in synovial fluid, tissue sections of tophaceous deposits
- Symptoms consistent of gout
What is the difference between acute gout and pseudogout?
- Acute gout: presence of uric acid crystals
- Pseudogout: presence of calcium crystals
What are the characteristics of joint aspirates for gout?
- Yellow in colour
- Cloudy
- Decreased viscosity
- WBC count of 2000-50000 cells/mm3
- Neutrophil count >50%
- Gram stain neg
- Crystals positive
What may be observed at the joints for patients with gout?
Tophi in the joints
What is the treatment goal for gout?
- Provide rapid, safe and effective pain relief
- Reduce future attacks (reduce SU conc)
- Address associated comorbidities
- Prevent joint destruction and tophi formation
- Increase quality of life
What are the various stages of gout?
- Asymptomatic hyperuricemia (high levels of uric acid on aspiration but no pain) (women > 6 (360); men > 7 (450))
- Acute gout (symptoms of gout, typically 1st MTP, excruciating pain)
- Inter-critical phase (asymptomatic hyperuricemia)
- Chronic gout (hyperuricemia, development of tophi, recurrent attack of acute gout)
Should a patient be treated when uric acid levels are high but they are asymptomatic ?
No
Should a patient be treated when uric acid levels are high but they are asymptomatic ?
No
Which drugs can be used for acute gouty attacks?
To be treated soonest possible (within 24 hours)
* Colchicine
* Oral NSAIDs/coxib
* Oral corticosteroids
* Intra-articular corticosteroids
* Can use combination but not NSAID + steroid
What is the dose of colchicine?
- One-off treatment with 1mg loading dose, followed by one dose of 0.5mg one hour later OR
- 0.5mg two to three times per day until acute flare resolves
What should be done about ULT during acute flares?
- If already on ULT, continue ULT during flare
- Initiate ULT (if indicated) after resolution of symptoms
- Consider ULT without waiting for the flare to resolve
What are the non-pharm treatment for acute flares of gout?
- Topical ice
- Limit alcohol intake
- Limit purine rich food
- Limit high-fructose corn syrup
- Weight management
What are the adverse effects of colchicine?
- Nausea, vomiting, diarrhoea
How should colchicine dose be adjusted in renal impairment?
Consider reducing dose or increasing dose interval
What should be done in a follow-up appointment after an acute gouty attack?
- Measure serum urate level
- Assess lifestyle and comorbidities
- Review medications and discuss risks and benefits of long-term ULT
What are some diet and lifestyle modifications that can be considered?
- Healthy, balanced diet
- Excess body weight or alcohol may exacerbate symptoms
What is the criteria for ULT?
- Frequent acute gout flares (two or more per year)
- Presence of tophus
- Clinical or imaging finding of gouty arthropathy
- History of urolithiasis (renal stones move into urinary tract)
What is the treatment target for ULT?
Non-tophaceous gout: < 360 (6)
Tophaceous gout: < 300 (5)
What is the MOA of ULT agents?
- Allopurinol, febuxostat (xanthine oxidase inhibitor) which decrease uric acid synthesis
- Probenecid (URAT1 and GLUT9 inhibitor) which increase uric acid excretion
What should be noted for the various ULT agents?
- Allopurinol: lower dose in renal impairment, risk of SCAR, contraindicated in patients with previous hypersensitivity to allopurinol
- Febuxostat: use with caution in HF and CHD, risk of SCAR, higher risk of death
- Probenecid: contraindicated in urolithiasis, not effective in CKD, not recommended in renal impairment (CrCl < 50), risk of haemolytic anemia in patients with G6PD deficiency
What dietary modifications need to be made when taking uricosuric agents?
Keep hydrated (>= 2L of water) to prevent kidney stones from forming
What are the presentations of SCAR?
- SJS and TEN: fever + mucocutaneous lesions leading to necrosis and sloughing of epidermis
- DRESS: rash + fever + multiorgan failure
What are some key factors that increase the risk of allopurinol-induced SCAR?
- Renal impairment
- Agent concomitant use of therapeutic agents like diuretics
- Starting dose high
- HLA B*5801
- Escalation that is rapid
- Seniority (old age)
Is routine testing for HLA-B*5801 done?
No because of low positive predictive value, testing is more useful in patients already at higher risk of allopurinol-induced SCAR
What are the drug interactions with allopurinol?
- Increase bone marrow suppression: 6-mercaptopurine, azathioprine, cyclophosphamide
- Increase hypersensitivity reaction/toxicity of allopurinol: ACEi, loop diuretics, thiazide/thiazide-like diuretics, ampicillin/amoxicillin
- Monitor for: carbamazepine, warfarin, theophylline
- Increase adverse effect of pegloticase
What can be used for prophylaxis against acute flares (ULT initiated with anti-inflammatory prophylaxis)?
- Colchicine 0.5mg OD
- Low dose oral NSAID/coxib
- Low dose oral corticosteroid
- For 3-6 months
What is the definition of clinical remission for gout?
No flares for >= 1 year and no tophi
What are some examples of high purine food?
- Asparagus
- Cauliflower
- Mushroom
- Red meat
- Anchovies
- Durian
- Peanuts
- Organ meat
What are some examples of high purine food?
- Asparagus
- Cauliflower
- Mushroom
- Red meat
- Anchovies
- Durian
- Peanuts
- Organ meat
What medication changes can be made for patients with gout?
- Switch hydrochlorothiazide to alternative antihypertensive
- Use losartan preferentially as antihypertensive
- Do not stop low-dose aspirin therapy if indicated
- Do not add/switch cholesterol-lowering agent to fenofibrate
