Crystal arthropathies Flashcards
What molecule is innvolved in gout
Uric acid
What % of the population have gout
1
In which sex is gout more common
Men
What crystals are deposited in gout, and where
Monosodium urate crystals
Soft tissues
What happens if gout is left untreated
Joint destruction
Renal damage
At what age does uric acid rise peak in men and women
men– puberty
women– menopause
What is the peak age of onset of gout in men and women
men– 4th to 6th decade
women– 6th to 8th decade
How many years are uric acid levels higher before gout onset
20
What triggers a gout attack
Uncoated crystals or a sudden change in concentration
What are uric acid crystals usually coated in
Serum proteins
Can urate crystals cause gout attack if they are found in the synovial membrane
No
Which joints does gout usually affect
Small, lower extremity joints
What is podagra
Inflammation of first MTP joint
Describe the onset of a gout attack
begins suddenly
maximum intensity within 8-12 hours
Name some joints commonly affected by gout
Knee, ankle, toes, elbow, sometimes shoulder
How does the joint appear/ feel in gout
Red, hot, tender, pain starts acuteley and usually at night
How long does first attack of gout take to resolve if untreated
< 2 weeks
In what % of gout does it initally present as polyarticular athritis
10
What drug is commonly associated with polyarticular athritis upon first presentation of gout
Thiazide diuertic (esp old ladies)
What can happen if gout is left untreated (5)
- Attacks become polyarticular
- More proximal and upper extremity joints involved
- Attacks more frequent and last longer
- Symmetrical, chronic polyarticular athritis
- Can affect other synovial structures
What are tophi
Urate crystals in soft tissue
In what % of untreatedd gout patients to tophi appear
50%
When do tophi develop
After 10 years
Uric acid is the end stage by product of the metabolism of which molecule
Purine
How do humans remove uric acid
Via renal excretion and faeces
What value is ‘saturation’ of serum urate
6.8mg/dL
What may be develop if excretion is insufficient to maintain serum urate levels below saturation
Hyperuricemia
Is over production of urate or under excretion more common in gout
Over excretion (90%)
Describe the ‘pathway’ of risk factors leading to gout
- Elevated purine sources/ general risk factor lead to increased purines
- This leads to xanthine
- This leads to hyperuricemia
- This leads to reduced renal clearance
What are some causes of elevated purine sources
- Catabolism of purines
- Tumour lysis syndrome
- Diet
What foods are high in purines
Beef, pork, lamb, seafood, beer, alcohol
Risk factors for gout
Male Age, Obesity Kidney disease Ethnicity Polymorphisms
What are the risks of hyperuricemia
Joint inflammation Kidney/ bladder stones Nephropathy CV disease Met. syndromes
What can cause decreased renal clearance
Drugs like aspirin
Fructose
What can cause under-excretion of uric acid
Renal insufficiency
Dehydration
Diuretics
What must serum levels of urate be higher than for a gout diagnosis
5.88mg/dL
What score out of 11 is required for a diagnosis of probable gout
6
What, combined with score, is required to turn diagnosis from probable to definite gout
Urate crystals during acute attack
What score is required for a diagnosis of ‘not gout’
<4
What are some differentials of gout
RA Pseudogout Psoriatic arthritis Septic arthritis Reactive arthritis
How is synovial fluid used for a gout diagnosis
- Inflammatory
- WBC >2000
- Predominance of polymorphonucleur neutrophils
How do urate crystals appear in synovial fluid under polarising light
Needle like
High negatively birefringent
Is the presence of hyperuricemia diagnostic
No
Serum uric acid levels above what value should be treated
Above 11mg/dL
What abnormalities would be seen in a person with gout on x-ray or ultrasound
- Soft tissue swelling
- Increased blood flow
- Maintenance of joint space
- Erosion outside joint capsule. These erosions have overhanging edges called rat bites
What does DECT stand for
dual energy computed tomography
What abnormalities can be detected on a DECT scant
- Uric acid crystal deposits in all late stage patients, and in 60% of early
What are the clinical uses of DECT
- Measure MSU volume
- Changes in actual MSU treatment
- Predict gout flare
What does MSU stand for
monosodium urate
How do tophaceous deposits lead to bone erosion
- MSU crystals surrounded by granulomatous tissue reaction
- Produces pro-inflammatory cytokines
- Stimulates osteoclasts via RANKL
What pro-inflammatory cytokines are involved in gout
IL1, TNF, IL6
4 ways to treat an acute attack of gout
- NSAID
- Colchicine
- Coticosteroids
- IL1 biologicals
When should NSAIDS be stopped
When symptoms absent for 2 days
Why is colchicine second line
Narrow theurapeutic window
Toxicity risk
Name 3 IL1 biologicals
Rilonacept
Canakinumab
Anakinra
When are IL1 biologicals used
For patients who have severe and frequent flares
Name 3 drugs used in the chronic management of gout
- Allopuinol
- Probenecid
- Rasburicase
How does allopurinol work
Blocks xanthine oxidase reducing generation of uric acid
How does probenecid work
Increases uric acid secretion, fewer significant adverse effects
How does rasburicase work
Catalyses conversion of uric acid to allantoin
What is the proper name for pseudogout
Calcium pyrophosphate deposition disease/ chondrocalcinosis
What is psudogout
The acute deposition of calcium pyrophosphate crystals in and around joints
What are the features of pseudo-osteoathritis
Osteophytes and soft tissue calcification seen on radiographs
What is the underlying pathophysiology of pseudogout (in brief)
- Release of CPPD crystals into joint space
- Phagocytosis of crystals by monocyte-macrophages or neutrophils
- Release of cytokines causing inflammation
What is the joint most commonly affected by pseudogout
Knee
What can trigger an acute attack of pseudogout
Trauma
Rapid reduction of serum calcium conc.
How does synovial fluid appear in pseudogout
- Mild to moderate inflammation
- Rhomboid shaped, weakly birefringent crystals
How is pseudogout treated
Intra-articular corticosteroids
NSAIDs
