Crystal Arthropathies

Question 1

What is gout?

Answer 1

• 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

Question 2

What happens if gout is untreated?

Answer 2

• 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

Question 3

What is the basic pathophysiology of gout?

Answer 3

• monosodium urate crystals get deposited in small joints

Question 4

How is it a mostly inert disease?

Answer 4

• urinate crystals in synovial fluid not enough to causy flares
• crystals normally coated with serum proteins which make them inert (apolipoprotein E/B)

Question 5

How is it an acute disease?

Answer 5

• when large increase in uric acid

- bone serum proteins don’t have enough time to coat crystals

Question 6

What happens when there are uncoated crystals present?

Answer 6

• 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

Question 7

In what joints does it occur more in?

Answer 7

• distal as less blood supply
• colder and lower pH
• can often spread to larger joints but rare

Question 8

What is podagra?

Answer 8

• inflammation of 1st MTP joint

Question 9

What can it lead to?

Answer 9

• renal damage

- bursitis

Question 10

What are the features of the joints?

Answer 10

• hot
• red
• exquisitely tender
• pain starts acutely, usually at night
• initially presents as polyarticular arthritis

Question 11

What is the significance of intermittent cycles?

Answer 11

• some will have attack again
• untreated 1st attacks resolve spontaneously in less than 2 weeks
• lifestyle factor important

Question 12

What are the features of untreated attacks?

Answer 12

• 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

Question 13

What are ratphytes?

Answer 13

can get erosions outside joint surface (where tendons insert)

Question 14

What is tophi?

Answer 14

• urate crystals in soft tissues
• in 50% of untreated gout cases
• after 10 years develop

Question 15

What is the histology of gout?

Answer 15

• giant cell reaction to deposited crystals

- tissue macrophage (histocytes) form outer barrier surrounded by lymphocytes

Question 16

What is uric acid?

Answer 16

• 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

Question 17

What is hyperuricemia?

Answer 17

• 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

Question 18

What are some risk factors?

Answer 18

• male
• age
• obesity
• ethnicity (pacific islanders)
• polymorphisms (genetics)
• kidney disease

Question 19

What causes elevated purine source?

Answer 19

• catabolism of purines
• tumor lysis syndrome
• diet

Question 20

What are some hyperuricemia related risks?

Answer 20

• joint inflammation
• kidney or bladder stones
• nephropathy
• CV disease
• metabolic syndrome

Question 21

What are some causes of decreased renal clearance?

Answer 21

• drugs (aspirin)
• fructose
• genetic factors
• kidney disease

Question 22

What is the gout criteria for diagnosis?

Answer 22

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

Question 23

What are the differential diagnoses?

Answer 23

• RA
• pseudogout
• septic arthritis
• reactive arthritis

Question 24

What is the synovial fluid like in gout?

Answer 24

• inflammatory
• WBC count greater than 2000/ul
• predominance of polymorphonuclear neutrophils

Question 25

Why is elevated serum uric acid not diagnostic?

Answer 25

- people have it without gout | - only 5-20% of those with gout have it

Question 26

What are the imaging methods?

Answer 26

- x-ray - ultrasound - DEXA

Question 27

What would an x-ray show?

Answer 27

- maintenance of joint space - erosion outside joint capsule - erosion with overhanging edges

Question 28

What would an US show?

Answer 28

- soft tissue swelling | - Doppler = increased blood flow to that joint

Question 29

What would a DEXA show?

Answer 29

- 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

Question 30

How would there be joint damage?

Answer 30

- tophaceous deposits= bone erosions - MSU crystals surrounded by granulomatous tissue reaction - produce pro-inflammatory cytokines (IL1,6 TNFa) - stimulate osteoclasts

Question 31

What are the acute treatment methods?

Answer 31

- NSAIDs - colchicine - corticosteroids - IL1 biologicals

Question 32

How should NSAIDs be used?

Answer 32

- start with highest dose for 2-3 days - taper down over 2 weeks - gout symptoms should be absent for 2 days before treatment stopped

Question 33

Why are colchicine second line?

Answer 33

- narrow therapeutic window | - risk of toxicity

Question 34

Who are corticosteroids used for?

Answer 34

- those who cannot use NSAID or colchicine

Question 35

What biologicals should be used?

Answer 35

- riloncept - canakinumab - anakinra - reduce length of attack and reoccurrences - for patients who have severe/frequent flares

Question 36

What are the long term treatment methods?

Answer 36

- allopurinol - probenecid - rasburicase

Question 37

What is allopurinol?

Answer 37

- blocks xanthine oxidase - reduces generation of uric acid - alternative is febuxostat

Question 38

What is probenecid?

Answer 38

- uricosuric - increases uric acid excretion - fewer significant adverse effects

Question 39

What is rasburicase?

Answer 39

- catalyses conversion of acid allantoin

Question 40

What is pseudogout?

Answer 40

- 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

Question 41

What are the features of pseudogout?

Answer 41

- 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

Question 42

How is pseudogout diagnosed?

Answer 42

- synovial fluid analysis | - US

Question 43

What is synovial fluid like is pseudogout?

Answer 43

- mild to moderate inflammation | - rhomboid shaped weak birefringent crystals

Question 44

What does an US show in pseudogout?

Answer 44

- calcification within soft tissue and articular cartilage - chrondocalcinosis of articular disc/atypical OA of hands - OA in same/neighbouring joints