Gout Flashcards
what is gout?
an inflammatory arthritis resulting from deposition of uric acid crystals in tissues and fluids
what is hyperuricemia
elevated serum urate concentration
what is acute arthritis
deposition of urate crystals in synovial fluid leukocyets, leading to an inflammatory response
what are tophi
deposits of monosodium urate crystals in tissues in and around joints
gout affects
1. more males than females
2. more females than males
3. the population in a bimodale age distribution
4. younger population 10% of the time
1
what is the peak age for gout diagnosis
40-50 in males
>60 in females
is there a genetic link to gout?
yes
in asymptomatic hyperuricemia, ____ go on to develop acute gout
25%
what are the 4 steps in the course of gout illness
asymptomatic hyperuricemia
acute gouty arthritis
intercritical gout
advanced gout
what enzyme is responsible for the production of uric acid
xanthine oxidase
what is present in animals to break down uric acid, but not in humans
uricase
causes of primary gout (overproduction)
idiopathic
genetic enzyme abnormalities
what causes primary gout with underexcretion of UA
idiopathic
what causes secondary overproduction of UA
excessive dietary intake
increased tissue breakdown (myeloproliferation or lymphoproliferative disorders, hemolytic diseases, psoriasis)
what causes secondary underexcretion of UA
decreased renal function
metabolic acidosis
dehydration
list some diet related factors that change SUA
meat, seafood intake
alcohol
high fructose content
drug related factors that change SUA
increases SUA: salicylates, diuretics, niacin, cyclosporin, tacrolimus, cytotoxic chemo
decreases SUA: allopurinol, febuxostat, probenecid, losartan
disease related factors that change SUA
CVD, CKD, nephrolithiasis, metabolic sx (obesity, insulin resistance, hyperlipidemia, HPTN)
what are 3 factors that lower the risk of gout
dairy
coffee (including decaf)
vit C
acute gouty arthritis is usually ____ and resolves ___________ within ______
usually monoarticular
resolves spontaneously in 7-10d
what is the clinical presentation of acute gout
rapid onset of pain with warmth, swelling, erythema that escalates over 8-12hrs
usually monoarticular, usually in big toe
presumptive diagnosis of gout if:
hyperuricemia present
acute monoarticular arthritis
gratifying clinical response to colchicine (complete resolution of sx within 48hrs, no recurrence for at least 1 wk)
what is intercritical gout
symptom free but urate crystal deposition continues + tophi increase in size
what is the typical patient of new onset gout
hyperuricemia, postmenopausal women, men >30yrs
what is the typical patient fo rlong standing fout
elderly men or women
how long do sx usually last for new onset gout
3-5 days, self limited
how long do sx last for long standing gout
5d to weeks
what are some associated findings for new onset gout
fever, elevated WBC count, elevated inflammatory markers
what are some associated findings for long standing gout
tophi
are patients pain free in intercritical gout
no- affected joints are uncomfortable, swollen
advanced gout is ______ (common/ uncommon) and occurs ____ after initial flare
uncommon
>10yrs
2 complications of gout
gouty nephropathy
CVD
what are 2 types of gouty nephropathy
uric acid nephrolithiasis
interstitial renal disease
uric acid nephrolithiasis depends on
SUA
acidity of urine (pH <6 decreases UA solubility)
urinary uric acid concentration
uric acid nephrolithiasis can lead to
acute renal failure secondary to ureter obstruction
what is interstitial renal disease/ urate nephropathy
long term deposition of urate crystals in renal parenchyma (micro tophi with giant cell inflammatory reaction)
what are some early signs of interstitial renal disease
proteinuria, inability to concentrate urine
why is hyperuricemia associated with increased risk of CVD
gout is a chronic systemic infalmmatory condition
lab findings in gout
hyperuricemia
leukocytosis
increased ESR and CRP
WBCs in synovial fluid + intracellular MSU crystals present
what is an 100% definitive dx for gout
intracellular MSU crystals found
what is seen on diagnostic imaging for gout?
none for early, maybe some soft tissue swelling
intermediate: microtophi on previously affected joints
late: bony erosions (punched out marginal erosions)
list 6 differential dx for gout
septic arthritis
erosive OA
pseudogout
trauma
cellulitis
early polyarticular disease
pseudogout sees a build up of
calcium pyrophosphate dihydrate crystals and calcium hydroxyapatite crystals
which diuretics are associated with gout
thiazide, loop
is ASA 81mg/d still a RF for gout?
yes- any salicylate even if <1g/d
what is the goal of gout tx
cure
goal of pain treatment in gout
> 20% in 24hrs
50% at 24hrs
nonpharm tx for gout
avoid contact with affected joints as much as possible
rest, ice, elevate
dietary: avoid purine and high fructose corn syrup intake
which of the following is true
1. in gout, exercising the joint will often relieve some stiffness and pain
2. gout pain is adequately controlled with NSAIDs + APAP in 80% of pts
3. NHPs may be of benefit in reducing UA
4. dietary restrictions in gout is more effective for chronic prophylaxis than acute
4
when to initiate tx in acute gout
within 24hrs (ideally 12hrs) of sx onset
T or F: monotx in acute gout is usually effective
T
when should you consider combination tx in gout flare
severe pain (>7/10)
affecting large joints
polyarticular
if no response to initial monotx (<20% in 24h, <50% > 24h)
what are some combo tx regimens for acute gout
colchicine + NSAID
colchicine + oral steroid
IA steroid + colchicine or NSAID + oral steroid
colchicine onset
within hrs
colchicine is effective in ___ of pts, most effective if begun within _____ of acute flare
in 2/3 of pts
within 12hrs
colchicine at lower doses than flare doses may be used for ____________.
prevention
if colchicine is used at lower doses for prevention, can it still be used for flares
no
colchicine effect
antiinflammatory
colchicine dosing in acute gout
1.2mg PO stat, then 0.6mg PO 1hr later (within 36hrs of flare onset)
how would you adjust colchicine dose for CrCl <30 or on dialysis
CrCL <30 = no dose adjustment, avoid if used in past 14d
dialysis: 0.6mg once daily, avoid if used in last 14d
what is the high dose colchicine regiment
1.2mg PO stat, then 0.6mg PO daily to BID until flare resolved for >24-48hrs (max 6mg/tx course)
what is the max colchicine for tx course
6mg
benefits of low dose over high dose colchicine
less overall AEs
less normal and severe diarrhea
colchicine SEs
N/V, cramping, diarrhea
myelosuppression, neuromuscular (rhabdo, peripheral neuropathy), liver failure
colchicine interacts with
CYp3A4 and P-gp inhibitors
dose of colchicine if on strong or med CYP3A4 or P-gpi
strong: 0.6mg stat, avoid for 3 d
med: 0.6-1.2mg stat, avoid for 3d
how to use NSAIDs for gout fare
high dose for 24-72hrs, then lower doses until sx resolved F1-2d
which NSAIDs are used in gout
indomethacin
naproxen
celecoxib
which NSAID is preferred for gout
all the same, indomethacin favored from historical perspective
which PO may be used in acute gout
prednisone
which IM CS may be used in acute gout
methylprednisone
efficacy of CS in acute gout
useful when CI to NSAIDs/ colchicine
comparable to NSAIDs
when should PO CS be used instead of IA ina cute gout
if >2 joints affected
dose if IA CS depends on
dize of joint
which CS are IA for gout
triamcinolone acetonide, methylprednisolone
when should IA CS be used in gout
if <1-2 large joints are affected
IA CS are usually used in combo with ________ (3) in gout
oral steroids, NSAIDs, or colchicine
anakinra and canakinumab are
IL1 inhibitors invovled in inflammatory response
use of anakinra and canakinumab
consider for tx of severe gout flares refractory or with Ci to other tx
what is the key to chronic gout tx
prevent recurrent attacks
when is gout prophylaxis recommended
=>2 flares/ yr, regardless of SUA
=>1 tophus on clinical exam or imaging
radiographic damage (any modality) attributable to gout
when is the ideal time to initiate chronic gout tx (urate lowering tx)
may be started during acute flare, as long as effective antiinflammatory management has been instituted
T or F: ongoing prophylactic gout tx may be paused during acute flare tx
F- do not pause
what is important to add when starting ULT
+ antiinflammatory to prevent acute flare during initiation
should we treat to target or treat to avoid sx in gout
either
what is the treat to target approach
target SUA <360 in all pts with gout
<300 if tophi or frequent flares until clinical remission is attained
what is the treat to avoid sx approach
do not monitor SUA
use a dose of urate lowering tx if necessary that prevents acute flares
nonpharm LT gout tx
pt education on role of uric acid excess, importance of adherence and self tx of future flares
weight loss for obese pts
screening for CVD and RF
stay well hydrated
T or F: gout pts should have a purine restricted diet
F- no RCTS and observational data shows low adherence
what is teh SUA target in pts with severe gout (tophi, freq flares)
<300
what are first line ULT
xanthine oxidase inhibitors - allopurinol and febuxostat
what are second line tx for gout/ if refractory to first line
uricosuric agents (increase renal excretion of uric acid)
probenecid, sulfinpyrazone, losartan, fenofibrate
how is adherence for xanthine oxidase inhibitors
low
does allopurinol need tirating
yes- to limit risk of acute flares and serious AEs
how to titrate allopurinol
start at 100mg/d or 50mg/d if CrCL <30
titrate in 50-100mg increments q2-5wks, 3-6mths to reach target dose
allopurinol doses should be divided if > ______ for _____ tolerability
if >300mg/d for GI tolerability
T or F: reduced renal function allopurinol dose adjustments are not evidence based
T
T or F: drug interactions resulting in allopurinol dose adjustments are evdience based
T
allopurinol mild AEs
skin rash, GI upset, diarrhea, HA, urticaria, leukopenia
allopurinol serious SEs
allopurinol hypersensitivity sx
sx of allopurinol hypersens sx
rash, hepatitis or interstitial nephritis, fever or eosinophilia or leukocytosis
risks for allopurinol hypersens sx
thiaxides, high initial dose, CKD
HLA-B*5801 allele
CrCL required for febuxostat use
> 30mL/min
describe febuxostat comp alopurinol in efficacy
not better than allopurinol in preventing gout + higher rate of gout flares
feboxustat should only be used isntead of allopurinol when
serious AE with allopurinol
febuxostat has the same _____ as allopurinol but different _____
same MOA
different structure
T or F: febuxostat may be better tolerated than allo ST, but evens out LT
T
T or F: asymptomatic hyperuricemia should have ULT to prevent flares
F- does not require tx
what are some options for a patient who requires prophylaxis for gout attacks but has previously had a minor rash on allopurinol
allopurinol desensitization for the minor reaction
try febuxostat
