Crystal Arthropathies Flashcards
What is gout?
- common disorder or uric acid metabolism
- sudden onset of acute flares
- often in 1st metatarsal pharyngeal joint
- more common in men as higher uric acid levels
- peak age is 40-60 for men, 60-80 for women post menopause
- uric acid levels elevated 20 years before onset
What happens if gout is untreated?
- joint destruction
- renal damage
- after first attack there is variable length of time before next attack if untreated
- second attack longer and more painful
- time between attacks will get shorter and become more severe = eventually chronic
What is the basic pathophysiology of gout?
- monosodium urate crystals get deposited in small joints
How is it a mostly inert disease?
- urinate crystals in synovial fluid not enough to causy flares
- crystals normally coated with serum proteins which make them inert (apolipoprotein E/B)
How is it an acute disease?
- when large increase in uric acid
- bone serum proteins don’t have enough time to coat crystals
What happens when there are uncoated crystals present?
- crystals embedded in synovium cause an immune response
- neutrophils enter joint and phagocytose crystals
- crystals sharp so neutrophils break
- release lysosomes, cytokines, IL1 and 8
- further inflammatory reaction = pain
- lowering pH by releasing contents so more crystals form
- repeats cycle
In what joints does it occur more in?
- distal as less blood supply
- colder and lower pH
- can often spread to larger joints but rare
What is podagra?
- inflammation of 1st MTP joint
What can it lead to?
- renal damage
- bursitis
What are the features of the joints?
- hot
- red
- exquisitely tender
- pain starts acutely, usually at night
- initially presents as polyarticular arthritis
What is the significance of intermittent cycles?
- some will have attack again
- untreated 1st attacks resolve spontaneously in less than 2 weeks
- lifestyle factor important
What are the features of untreated attacks?
- become polyarticular
- more proximal and upper extremity joints involved
- attacks more frequent and last longer
- chronic polyarticular arthritis almost symmetrical
- can affect other synovial structures
What are ratphytes?
can get erosions outside joint surface (where tendons insert)
What is tophi?
- urate crystals in soft tissues
- in 50% of untreated gout cases
- after 10 years develop
What is the histology of gout?
- giant cell reaction to deposited crystals
- tissue macrophage (histocytes) form outer barrier surrounded by lymphocytes
What is uric acid?
- end stage by product of purine metabolism from DNA and RNA from diet
- mainly in meat, high protein foods = beer/pork/lamb/seafood/beer
- removed by renal excretion and faeces
What is hyperuricemia?
- when excretion is insufficient to maintain serum urate levels below saturation
- 6.8ml/dL
- due to renal insufficiency, dehydration, diuretics
- rarely related to overproduction of uric acid
What are some risk factors?
- male
- age
- obesity
- ethnicity (pacific islanders)
- polymorphisms (genetics)
- kidney disease
What causes elevated purine source?
- catabolism of purines
- tumor lysis syndrome
- diet
What are some hyperuricemia related risks?
- joint inflammation
- kidney or bladder stones
- nephropathy
- CV disease
- metabolic syndrome
What are some causes of decreased renal clearance?
- drugs (aspirin)
- fructose
- genetic factors
- kidney disease
What is the gout criteria for diagnosis?
11 or more variables:
- more than 1 attack of acute arthritis
- max inflammation developed within 1 day
- monoarthritis attack
- redness observed over joints
- first MTP joint painful/swollen
- tophus
- hyperuricemia
> or equal to 6/11 = probably gout
4<8 = uncertain, synovial fluid analysis need
<4 = not gout
What are the differential diagnoses?
- RA
- pseudogout
- septic arthritis
- reactive arthritis
What is the synovial fluid like in gout?
- inflammatory
- WBC count greater than 2000/ul
- predominance of polymorphonuclear neutrophils
Why is elevated serum uric acid not diagnostic?
- people have it without gout
- only 5-20% of those with gout have it
What are the imaging methods?
- x-ray
- ultrasound
- DEXA
What would an x-ray show?
- maintenance of joint space
- erosion outside joint capsule
- erosion with overhanging edges
What would an US show?
- soft tissue swelling
- Doppler = increased blood flow to that joint
What would a DEXA show?
- detect uric acid crystal deposits in all late stage gout
- detect a lot with early stage too
- measure monosodium urate volume and changes following treatment
- predict gout flare
How would there be joint damage?
- tophaceous deposits= bone erosions
- MSU crystals surrounded by granulomatous tissue reaction
- produce pro-inflammatory cytokines (IL1,6 TNFa)
- stimulate osteoclasts
What are the acute treatment methods?
- NSAIDs
- colchicine
- corticosteroids
- IL1 biologicals
How should NSAIDs be used?
- start with highest dose for 2-3 days
- taper down over 2 weeks
- gout symptoms should be absent for 2 days before treatment stopped
Why are colchicine second line?
- narrow therapeutic window
- risk of toxicity
Who are corticosteroids used for?
- those who cannot use NSAID or colchicine
What biologicals should be used?
- riloncept
- canakinumab
- anakinra
- reduce length of attack and reoccurrences
- for patients who have severe/frequent flares
What are the long term treatment methods?
- allopurinol
- probenecid
- rasburicase
What is allopurinol?
- blocks xanthine oxidase
- reduces generation of uric acid
- alternative is febuxostat
What is probenecid?
- uricosuric
- increases uric acid excretion
- fewer significant adverse effects
What is rasburicase?
- catalyses conversion of acid allantoin
What is pseudogout?
- other crystal arthroplasty
- calcium pyrophosphate deposition disease (CPDD)
- metabolic arthropathy associated with OA
- chondrocalcinosis
- acute deposition of crystal in and around joints
- majority of patients asymptomatic
What are the features of pseudogout?
- half of those over 85 have evidence of chondrocalcinosis
- pseudo OA with osteophytes and soft tissue calcifications
- asymptomatic where only radiographic findings
- normally crystals do not interfere with joint
- acute = triggered by trauma/reduction of serum calcium = release of calcium in joint, stimulates osteoclasts
- knee commonly affected
How is pseudogout diagnosed?
- synovial fluid analysis
- US
What is synovial fluid like is pseudogout?
- mild to moderate inflammation
- rhomboid shaped weak birefringent crystals
What does an US show in pseudogout?
- calcification within soft tissue and articular cartilage
- chrondocalcinosis of articular disc/atypical OA of hands
- OA in same/neighbouring joints
