gout and pseudo Flashcards
what is a typical presentation of gout
acute swelling and erythema of the 1st metatarsal-phalangeal joint (podagra)
what age group and gender is gout usually seen in
middle aged males
what criteria can be used for a less typical presentation of gout
the Neijmegen criteria
what is required for a definitive diagnosis of gout
requires the identification of urate crystals in synovial fluid in joints or from trophi
what is a tophus
a deposit of uric acid crystals in the form of of monosodium urate
- appear as chalky white deposits and are markers of severe disease
- typically in digits or over the elbows
what causes gout
excess uric acid in the blood stream or hyperuricaemia leads to deposits that then leads to inflammation
what is a typical history of gout
- usually history of an attack in past year if 2nd time
- severe pain usually in a single joint (monoathritis)
- acute onset (<24hours often overnight) with episodes lasting 1-2 weeks
- 1st MTPJ, foot or ankle but can involve any joint
- axial skeleton and proximal joints rarely involved
- self limiting 5-14 days
- max severity 2-6 hours
- synovitis, swelling and erythema
- fever, malaise and confusion
- puruitus(itch) and desquammation skin shedding
how will joints feel on examination with gout
tender, hot red and swollen
what diagnosis needs to be excluded with gout
septic athritis
what are the 3 main diff diagnosis
- septic arthritis
- pseudo-gout secondary to chonodrocalcinosis
- psoriatic arthritis
what investigations are there for gout 4
- baseline renal and liver function
- convalescent serum urate (4-6 weeks after attack as low during attack)
- x-ray of symptomatic joint (erosions in established disease)
- screen patient for cardiovascular RF
- Synovial aspirate usually not performed in primary care
what are the 7 criteria for the nijmegen criteria and what number is needed to be certain of gout
-male 2
-previous reported arthritis attack 2
-onset within 1 day
-joint redness
-first metatarsophalangeal joint involvement 2.5
-hypertension or >1 cardiovascular disease
-serum uric acid >0.35 mmol/l
need greater than 8 point
why is serum urate lower during an attack
in 50% of patients will have normal levels due to a direct effect of inflammation on urate excretion
how long should you wait for serum urate measurement after an attack
4-6 weeks
what other condition though has elevated urate levels
severe psoriasis
what drug should be used when initiating or increasing the dose of a ULT and why
- colchicine 500mcg BD which if tolerated and required increase to max QID
- used as prophylaxis against acute attacks secondary to ULT therapy
when should colchicine be reduced and what is it contraindicated in
side effects of diarrhoea and colic occur
- renal or hepatic failed
- P-glycoprotein inhibitor eg verapamil, cyclosporin
- CYP3A4 inhibitor vir, mycin and azole
what is the prophylactic treatment dosage of colchicine and how long can it be used
2x daily
500mg
up to 6 months
when should urate lowering therapy be offered 4
- in patients with trophi
- recurrent attack >2 attacks/yr
- renal impairment
- diuretics
what level of serum urate should be aimed for, but what level for long term mainentance
<0.3 mmol/l but for long term mainentance below 0.36 are adequate
management of gout
- low dose NSAID
- local ice packs
- oral colchicine
- joint aspiration
- ult
- lifestyle
what is the first line urate lowering agent for gout and how should it be titrated and what does the patient need to be told
how does it work
allopurinol
xanthine oxidase inhibitor
-start at a low dose and titrate upwards every 4 weeks until uric acid is <0.3
- remind patients that allopurinol may increase the risk of acute attacks of gout just after initiating treatment and some weeks after
BUT THEY should not stop their allopurinol
-can be given with colchicine to reduce risk
what is the second line therapy to allopurinol for ULT, what needs to be checked, and how should it be given dosage
febuxostat
- check liver function test prior to initiation
- start at a low dose and increase after 4 weeks if sua is still >0.3
what prior history may indicate potential hypersensitivity to febuxostat
- hypersensitivity to allopurinol
- renal disease
what is hyperuricaemia defined as
2 standard deviations above the mean population
what pathway catalyses to uric acid
xanthine oxidase catalyses the end of conversion of hypoxanthine to xanthine and then to uric acid
what is the main abnormality causing gout
90% of patients the main abnormality is reduced uric acid excretion by renal tubules due to impaired response to a purine load
how is uric acid excreted
1/3 by the gut and 2/3 by the kidneys
what gene regulates uric acid excretion in the kidneys
SLC2A9
inflammatory pathway in gout and septic arthritis
- Cellular debris, LPS and uric acid crystal all signal through NLRP3 inflammasome nod like receptor 3
- Cytoplasmic protein complex within monocyte/ macro lead to IL1 secrete
- Rapid recruit neutrophils
- Switches off after week or so
3 causes of gout
- reduced renal excretion
- increased production of uric acid
- increased intake
what causes reduced renal excretion of uric acid 6
- increased renal tubular absorb
2.renal failure - lead toxicity and immunosuppressants (tacrolimus and cyclosporin)
- lactic acidosis
5.alcohol (increase purine catabolism in liver so increase lactic acid blocks excretion)
6.drugs
thiazide diuretics
low dose asprin
cyclosporin
pyrazinamide
what 3 foods are high in uric acid
red meat
seafood
offal
what 5 things cause over production of uric acid
- myeloproliferative and lymphpro.. disease
- psoriasis
- high fructose intake
- glycogen storage disease
- inherited disorders
- Lesch-Nyhan syndrome (HPRT mutation)
- Phosphoribosyl pyrophosphate synthetase 1 mutation
risk factors for gout
- metabolic syndrome
- high alcohol intake (guanosine from beer)
- generalised OA
- diet high in fructose, red meat, low in vit d or coffee
- lead poisoning (saturnine gout)
how does OA increase the risk of gout
reduction in proteoglycan levels and other inhibitors of crystal formation
what is Lesch Nyhan syndrome
x linked recessive
assoc. to mental retardation, self-mutilation, choreoathetosis
main diff dx of gout
septic arthritis infective cellulitis reactive arthritis psoriatic arthritis pseudo-gout
will gout re-occur?
- usually presents as one joint and then can attack another joint a few days later= cluster attacks
- in most a second attach occurs in a year
- but can lead to chronic attack
- risk of renal failure
complications of gout
infection from trophi
renal failure
renal stone formation
investigations for gout
- aspiration of urate crystals
- increased turbidity and >90% neutrophils - biochemical screen due to metabolic syndrome risk
- renal function
- uric acid
- glucose
- lipid profile
- esr, crp, neutrophilia - x-ray erosions in trophaceous gout
normal uric acid levels
<0.3
dosage for allopurinol titration 2 categories
-start at 100mcg or 50mcg in elderly or renal impairment
-increase by 100mcg ever 4 weeks (50mcg in elderly/ renal)
until max dose 900mcg or SE occur
dosage of allopurinol when on azathioprine
1/4 of dosage as inhibits XO so prolongs the activation
side effects of febuxostat
- increased risk of gout flare up as more effective than allopurinol at reducing uric acid so higher risk
when is febuxostat CI
not in severe renal failure creatinine clearance <30ml/min
dosage of febuxostat
up to 120mcg
start 80mcg daily
what is pseudogout
calcium pyrophosphate dihydrate crystal deposition into joints
risk factor for chondrocalcinosis
age oa primary hyperparathyroid familial haemochromtotis hypophosphatasia
symptoms pseudogout
acute inflammatory arthritis warm tender erythematous joint fever commonly knee trigger factors include trauma, illness can get chronic arthropathic
investigation of pseudogout
joint aspiration: cppd crystals which are rhomboid
x-ray joint
raised pyrophosphate levels
management of pseudogout
joint aspiration
-steroids, colchicine or nsaids
