Gout Flashcards
What is gout?
Urate crystals that deposit in joints, soft tissues (cartilage, tendon, bursa), or in renal tissue
What conditions can result from gout?
- Gouty arthritis
- Tophi
- Nephropathy
- Uric acid nephrolithiasis (kidney stones)
What is the typical age of onset of attacks for males and females?
Male = after 30
Female= after 50
Unusual for gout attacks to occur before this age
What are the 4 stages of gouty arthritis?
- Asymptomatic hyperuricemia
- Gouty flare
- Intercritical gout (prophylaxis of gouty flare and management of hyperuricemia)
- Chronic gouty arthritis
What is asymptomatic hyperuricemia?
Elevated serum urate levels without clinical manifestations
What is considered elevated serum urate levels?
Female >360µmol/L
Male >420 µmol/L
When do serum urate levels typically increase in the life cycle of male and female?
Male= during puberty
Female= after menopause
When does the asymptomatic hyperuricemia phase end?
Following the patient’s first attack of gouty arthritis or urolithiasis
What drugs are associated with hyperuricemia and gout?
Alcohol
Cyclosporine
Cytotoxic chemotherapy Diuretics
Levodopa
Salicylates
Tacrolimus
Teriparatide
What conditions may increase risk of hyperuricemia and gout?
Atherosclerosis
CKD
Diabetes
Hyperlipidemia
Hypertension
What is a gouty flare?
Abrupt onset of excruciating pain and inflammation of joint
What time of the day does gouty flare typically occur?
During the night or early morning
How severe is the pain from gouty flare?
Patients cannot even tolerate light pressure such as a bedsheet on the affected joint
Are the joints of the upper or lower limb most often affected?
Mostly lower limb
Higher frequency of upper limb involvement with women
Are attacks usually monoarticular or polyarticular?
First attack are usually monoarticular.
Elderly patients often have polyarticular presentation
Which joint is often affected at first attack?
Podagra
What other joints can be involved?
In decreasing order:
insteps, ankles, heels, knees, wrists, interphalangeal joints and elbow
How long do attacks typically last? Do they resolve spontaneously?
Attacks often resolve spontaneously over 3-10 days
Can serum urate levels be used to rule out gout attacks?
Difficult to interpret.
Normal levels do not rule out acute gout attack
How are diagnosis of gout attacks typically made?
A triad:
- acute monoarthritis
- hyperuricemia
- dramatic response to colchicine
According to the 2015 ACR/EULAR gout classification criteria, patients need a score of ≥ __ /23 to fulfill gout classification
8
What are two other ways that patients can fulfill the classification criteria for gout?
Evidence of monosodium urate crystals in fluid from:
- a symptomatic joint or bursa
- tophus aspirate
What is an appropriate adjunctive non-pharm choice for gout flares?
Topical ice application
What are the first-line options for acute gout?
-NSAIDs
-colchicine
-oral corticosteroids
When should therapy for acute gout be started?
Within 24 hours of acute gout attack
What’s the current colchicine dose recommendation for treatment?
Colchicine 0.6mg
2 tabs STAT (1.2mg), then 1 tab (0.6mg) one hour later
What’s the current colchicine dose recommendation for prophylaxis?
1 tab (0.6mg) once or twice daily to be started 12 hours after last treatment dose
When can we no longer give colchicine?
More than 36 hours after onset of symptoms
How does colchicine work for gout attacks?
Disrupts the ability of the immune system to replicate which reduces inflammation, swelling and pain
How quickly does colchicine start working?
Within 30 min to 2 hours
May take a day or two for pain to start getting better
What are three administration counselling point for colchicine?
- Avoid grapefruit
- Take with food to lessen stomach upset
- No alcohol, as it can increase uric acid levels
What is the role of NSAIDs in gout flares?
-Reduce pain and swelling
How are NSAIDs typically dosed for flare attacks?
-Initiated at high doses and then quickly reduced once there is improvement
What are the agents of choice for NSAIDs in gout attacks?
- Celecoxib + PPI –> celecoxib alone
- Non-selective NSAID + PPI
How does high-dose celecoxib compare to non-selective NSAIDs?
High-dose celecoxib is as effective as non-selective NSAIDs in reducing pain.
Where does corticosteroids come into gout flare therapy?
Third-line
Available oral but also as intra-articular, IM, or IV which is good for patients who cannot tolerate oral therapy
What is the typical oral agent of choice for corticosteroids in gout flare therapy?
Short term course of prednisone (0.5mg/kg daily)
When would the intra-articular administration route be unsuitable for patients?
Polyarticular joint involvement
When is combination therapy recommended for gout flares?
Symptoms are severe
Attack is polyarticular
Large joints are involved
Monotherapy ineffective
What are typical combo therapy regimens for gout flares?
- Colchicine + NSAID
- Colchicine + oral corticosteroid
- Intra-articular corticosteroid + (NSAID, oral corticosteroid, or colchicine)
If patient has failed or cannot take colchicine, NSAIDs, or corticosteroid, what can they try?
Recombinant interluekin-1 beta receptor inhibitors like anakinra and canakinumab
Not currently approved in Canada
Why is it important to start therapy as early as possible for attacks?
Attack will resolve more quickly
Can you stop or alter the dose of urate-lowering drugs during an acute attack?
No, symptoms may be exacerbated or prolonged
What is intercritical gout?
Intercritical gout is the period between gout attacks when person has no symptoms
What is the goal of therapy in intercritical gout?
Prophylaxis of gouty flare and management of hyperuricemia
Do most patients end up experiencing a second attack?
Yes, most occur within 6-24 months of the first
What are some non-pharms for gout patients?
- Exercise (obesity BMI>30)
- Quit smoking
- Hydrate and healthy diet
- Limit purine intake (avoid liver and kidney, beef, lamb, pork, and sardines and shellfish)
- Limit high fructose corn syrup
- Limit alcohol
When should urate-lowering therapy (ULT) be recommended?
Any of the following:
* ≥ subcutaneous tophi
* evidence of radiographic damage
* ≥ 2 gout flares/year
* > 1 previous flare
* comorbid moderate-to-severe CKD (stage ≥3)
* serum urate concentration >535 µmol/L
* urolithiasis
When is ULT not recommended?
- Patient experiencing their first gout flare
- Asymptomatic hyperuricemia
What are two classes of ULT?
Xanthine oxidase inhibitors and uricosurics
What is the target serum urate level you want to treat-to-target?
What is special about this number?
<360 µmol/L
Saturation point of monosodium urate in the extracellular fluid
What serum urate target is recommended in patients with more severe gout (Ex: tophaceous gout)?
<300 µmol/L until dissolution of crystals, then can return to <360 µmol/L target
During intercritical gout period, which medications should be stopped?
Non-essential prescription medications that induce hyperuricemia (Ex: diuretics or salicylates)
Low-dose ASA can be continued for prevention of CV disease
Initiation or dose-adjustment of ULT during gout attack is not recommended, but what about during intercritical gout period?
Yes, important to adjust to optimal dose to prevent recurrent gout flares
What does ACR recommend for patient on HCTZ?
If for hypertension, ACR recommends switching to alternative regardless of disease activity
What are two medications that are part of the xanthine oxidase inhibitor class?
Allopurinol
Febuxostat
It’s typically not good to dose adjust or stop gout drugs during flare attacks, but is initiating drugs ok?
If so, can you start xanthine oxidase inhibitors?
Yes, it’s ok to initiate drugs like xanthine oxidase inhibitors during flare, as long as effective anti-inflammatory treatment has been started.
How does xanthine oxidase inhibitors work for gout?
Inhibit production of uric acid
What’s the dosing regimen for xanthine oxidase inhibitors?
- Pick one of the xanthine oxidase inhibitors
- Titrate every 2-5 weeks until target serum urate level
- Once at target, check every 6 months
How do you decide between allopurinol and febuxostat?
Allopurinol preferred unless patient has failed or unable to tolerate
Allopurinol preferred even if moderate to severe CKD (stage ≥3)
Febuxostat has black box warning for greater frequency of adverse CV events
What is the dosing regiment for allopurinol?
Starting dose: ≤100mg daily
Average dose: >300 mg daily
What’s the dosing of allopurinol for patients with stage 4 CKD (GFR ≤29mL/min/1.73m^2)?
Start with 50mg daily
What’s a severe side effect we have to watch for with allopurinol?
Allopurinol hypersensitivity syndrome (AHS)
What increases the risk of getting AHS (rare, but severe)?
- High allopurinol starting dose
- Renal impairment
- Use of thiazide diuretics
- HLA-B*5801 genotype (more common in Han Chinese, Korean, Thai, and African- American descent)
While AHS is rare and severe, what’s a more common side effect of ULT agents?
Rash
Mild reactions can be desensitized and is an option for those who cannot be treated with other ULT agents.
Febuxostat is a second-line xanthine oxidase inhibitor. What is typical dosing?
Febuxostat 40mg daily and titrated up to 120mg daily
Febuxostat 80mg is the only strength available in Canada which is the typical max dose in Canada
When is febuxostat recommended to be avoided?
When is febuxostat contraindicated?
Should be avoided if patient has history of CVD or a new CVD related event
Contraindicated if patient is taking azathioprine or mercaptopurine
What are the most common side effects with febuxostat?
LFT abnormalities, nausea, diarrhea, arthralgias, and rash
Do you need to dose adjust febuxostat for mild-moderate and severe CKD?
Those with CKD stage 3 or 4 were less likely to have >10% decline in eGFR compared with placebo
If the selected xanthine oxidase inhibitor does not lead to target levels, what are our two options?
- Switch to another xanthine oxidase inhibitor
- Add-on therapy with uricosuric agent
What are three common uricosuric agents?
- Probenecid (only available through Health Canada’s Special Access Program)
- Fenofibrate
- Losartan
If patient has gout and hypertension, is losartan recommended to be the antihypertensive agent?
Yes
If patient has gout and high cholesterol, is fenofibrate recommended to be the cholesterol lowering agent?
No, side effects of fenofibrate outweigh the benefits
Why is sulfinpyrazone (uricosuric) rarely used?
Requires monitoring for blood dyscrasias and has increased risk of bleeding and skin rashes.
If all other uricosuric agents fail, what’s an agent that patients can try?
Benzbromarone (only available through Health Canada Special Access Program)
When are uricosurics contraindicated?
When urine uric acid levels are elevated (this indicated gross overproduction of uric acid)
OR
If CrCl less than 50mL/min or if patient has urolithiasis
What are uricases and how do they work?
Uricases metabolize uric acid to its end product. This enzyme is lacking in humans.
Not currently available in Canada, but is treatment for refractory hyperuricemia.
Rasburicase is available in Canada but is indicated for treatment and prevention of tumour lysis syndrome in cancer chemotherapy.
Is there any evidence for supplements for treatment of chronic gout?
No
Is ULT therapy long-term?
Yes, indefinitely.
Reduces the risk of gout flare after 1 year of use.
In general, starting an ULT may increase incidence of gout flare. What can we do to minimize this?
Starting ULT with a low-dose of NSAID or colchicine (protective effect)
When is it recommended to start ULT therapy?
During gout flare rather than after it has resolved
Following the initiation of the ULT therapy, how long should we continue concomitant anti-inflammatory prophylaxis for?
3-6 months
When does chronic tophaceous gout usually occur?
12 years from gout onset and only 2% develop severe crippling disease
What is the strongest risk factor for developing tophi?
High serum urate level
