17 - Crystal Arthropathies Flashcards
Population with gout
1%
What age do people usually get gout
Men - 40-60
Women - 60-80
How long does uric acid levels rise before onset of gout
20 years
When do men uric acid levels start to rise
Puberty
When do women uric acid levels start to rise
During menopause
What is gout
Disorder of uric acid metabolism whereby negatively charged monosodium urate crystals are deposited in soft tissues causing an acute inflammatory process
What are 2 complications of gout
Joint destruction
Renal damage
Why does high levels of urate crystals in the synovial fluid not mean gout
The crystals are coated by serum proteins which are inert
What triggers a gout attack
Uncoated crystals
Sudden large change in concentration of crystals so there is not enough time to coat the proteins
In what conditions do monosodium urate crystals precipitate best
Colder conditions
Therefore flares usually early morning + in distal joints
What are the steps of a gout attack
1) Crystals embed in the synovium
2) This causes an immune response
3) Neutrophils phagocytose the crystals
4) Crystals are sharp and pop the neutrophil
5) Nutrophil releases it’s contents - lysosomes, free radicals, cytokine
6) Cytokines(mainly IL1) cause more white blood cells into the joint
7) Causes inflammation and pain
8) Proteins lower pH making it possible for more crystals to form quickly
THIS IS THE GOUT ATTACK!!!
What percent of cases are monoarticular in gout
90%
Which joints are more commonly affected by gout
Small, lower extremity joints e.g 1st MTP
Can spread to other joints e.g foot and ankle
What is podagra and what percent of cases does it appear in?
Inflammation of the 1st MTP joint
50% of cases
How does gout first present
Waking up with intense pain
How long before gout attack reaches maximum intensity
8-12 hours
What are the joint symptoms of gout
Red
Hot
Tender
What can untreated gout lead to over time
Attacks more frequent and last longer Polyarticular More proximal and upper extremity involvement Damage to the joint Rat bites
What are rat bites
Erosions to the shaft of the bone
What is a Tophi
Monosodium urate in soft tissue e.g cartilage or tendons in ear, kidney, bursae
How long before tophi develop
10 years
What do you see on a histology of tophi
Histocytes in the tissue which form an outer barrier - lymphocytes outside of them
This walls off the crystals from healthy tissue
Causes the lumps on the ski
What metabolism causes the end stage byproduct to be uric acid
Purine metabolism
Where does purine intake come from
Diet
Meat - high protein food
How is uric acid removed
Renal excretion
Faeces
What is hyperuricemia
Serum urate above 6.8ml/dL
What can cause hyperuricemia
Insufficient excretion of uric acid
Risk factors for gout
Male Obesity Age Ethnicity - pacific islanders Kidney disease
Diagnosis of gout
Mainly via history
What would you see in synovial fluid in gout
WBC - >2000uL
Polymorphonuclear neutrophils
Urate crystals
What conc does urate crystallise
6.8mg/dL
Why does elevated serum uric acid not equal gout diagnosis
presence of serum proteins to coat the crystals
Over what level should you treat someone for gout due to high serum uric acid
Higher than 11mg/dL
Features of X-ray in gout
Soft tissue swelling/increased blood flow
Erosion outside joint capsule
Rat bites
Maintenance of joint space
What is DECT
Dual Energy Computed Tomography
Able to detect uric acid crystal deposits
Clinical benefit of DECT
Able to predict gout flare
measure MSU volume
What causes joint damage in gout
Cytokines stimulate osteoclasts via RANKL
How do you treat an acute attack of gout
1) NSAIDs - high dose and taper down (symptoms should be absent for 2 days before u stop) 2) Colchicine 3) Corticosteroids 4) IL1 biologicals
What is MoA of colchicine
Microtubule inhibitor
IL1 biologicals
Rilonacept
Canakinumab
Anakinra
Lifestyle factors for gout
Low purine diet
Avoid meat, yeast, beer
Eat vegetables, coffee etc
Treatment for chronic gout
Aim to reduce uric acid levels
Allopurinol
Probenecid
Rasburicase
MoA for Allopurinol
Blocks xanthine oxidase (used in production of purines to urate)
Reduces generation of uric acid
MoA of Probenecid
Increases Uric Acid excretion
fewer adverse effects than allopurinol
MoA of Rasburicase
Catalyses conversion of uric acid to allantonin
Increases excretion of a less toxic substance
What is pseudogout
Deposition of calcium pyrophosphate in joints with soft tissue
Where is pseudogout most common
the knee
pathophysiology of pseudogout
Same as gout lol
What triggers an acute attack of psuedogout
Trauma
Rapid reduction of serum calcium concentration
What is in the synovial fluid of pseudogout
Mild to moderate inflammation 10,000 - 50,000
Rhomboid shaped weakly birefringement crystals
What would you see in pseudogout
Calcification in soft tissue
calcification in articular cartilage
Chondrocalcinosis of articular disk
Treatment of pseudogout
Intra articular corticosteroids
NSAID
