Crystal Arthropathies Flashcards
What is gout
Common disorder of uric acid metabolism
Monosodium urate crystals get deposited in soft tissues
What does the variation of gout depend on
Variation reflects environmental, dietary and genetic influences
how much of the population does gout affect
1% of population
Who is gout common in
men and men earlier than women
What is the main crystals that are formed in gout
Monosodium urate crystals
What happens if gout is untreated
Joint destruction
Renal damage - most of the monosodium urate crystals are excreted via the kidney therefore higher risk of kidney stones and thus kidney damage
describe attacks of gout
- may have gout attacks and then may never get another one or you may a few months later
Why are men more at risk of developing gout
Men are more at risk of developing gout as serum uric acid levels are higher to begin with, urinci acid levels start to increase at the time of puberty in men whereas in women it doesn’t start to develop and raise until menopause
How long does uric acid have to increase before the onset of gout
Uric acid levels raised for 20 years before onset of gout
describe the pathophysiology of gout
Presence of urate crystals in the synovial fluid are not enough to cause an attack as they are inert as they are coated with serum proteins already present in the synovial fluid
Get a sudden increase in the number of crystals that are forming and the body is not able to respond by coating the crystals with the serum proteins and thus there are some uncoated cryrstals in the joint which trigger the attack
Crystals can be uptake by neutrophils, pierce the neutrophil and cause it to die, cell releases the proteins, proteins call in more white blood cells and cause inflammation and pain, proteins lower pH making it possible for more crystals to form
When are the crystals in gout not harmful
Presence Clumps (microtophi) of highly negatively charged monosodium urate crystals normally coated with serum proteins are inert and are not enough to cause an attack as they are inert as they are coated with serum proteins already present in the synovial fluid
when is gout unlikely to start before the age of
Gout unlikely before 30 years of age
what joint is gout more likely to affect
Podagra (inflammation of 1st MTP joint)
50% of cases
- less blood supply and colder so already has a lower pH
when does gout begin
Begins suddenly and reach maximum intensity with 8-12 hours
What joints does gout affect
Acute monoarticular
- 90% of cases
Small lower extremity joints
What patients characteristic for this with gout
- male
- high uric acid
- overweight
What is the joint must commonly affected by gout
1st metatarsal phalagenal joint
what is the largest joint affected by gout
knee
what over areas of the body are affected by gout
- renal damage
- tophi in cartilage
describe what the symptoms of gout
Joint
- Red
- Hot
- Exquisitely tender
- Pain starts acutely and usually at night
how long does gout take to resolve itself
Untreated 1st attacks resolve spontaneously in less than 2 weeks
gout has …
intermittent cycles
every time you have a gout flare…
- become more painful
- last longer
- until eventually the pain is there all the time due to the damage to the bone and joint
What happens if gout is 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
rat bite erosions - were the joint capsule is inserting, these are on the main shaft
what happens in an acute gout attack
- phagocytosis of crystals
- cell swelling and inflammationsome activation
- cytokine production and vasodilation
- neutrophil and monocytes influx
What happens in chronic tophaceous gout
- neutrophil death by NETosis
- packaging of MSU crystals
- inactivation of inflammatory cytokines
- resolution of inflammation
What is tophi
Urate crystals in soft tissues
how many patients with gout have tophi
Develop in 50% of patients with untreated gout
Develop after 10 years
usually patients who are untreated
describe the histology of tophi
Foreign body-type giant cell reaction to the deposited crystals
The crystalline nature of this material is not obvious in formalin-fixed specimen
tissue macrophages around the central core and lymphocytes further out
What are the causes of a gout attack
uric acid is an end stage by-product of purine metabolism
- and humans remove uric acid by renal excretion(70%) and faeces (30%)
- when there is insufficient excretion, which is the cause of 90% of the cases of gout, this can lead to urate levels building up
- When excretion insufficient to maintain serum urate levels below saturation (6.8mg/dL) hyperuricemia may develop
what is the cause of 90% of cases of gout attack
Overproduction 10% of cases
Under excretion 90% of cases
what the risk factors for gout
- male gender
- age
- obesity
- ethnicitiy
- polymorphism
- kidney disease
- overconsumption of foots high in purines - beef, pork, lamb, seafood, beer, alcoholic beverages
what can lead to under excretion of uric acid
- renal insufficiency
- dehydration
- thiazide diuretics
what are the 11 or more variables that are used by GPs to diagnose gout
- more than 1 attack of acute arthritis
2, maximum inflammation developed within 1 day - mono arthritis attack
- redness observed over joints
- first MTP joint painful or swollen
- unilateral first MTP joint attack
- unilateral tarsal joint attack
- Tophus
- hyperuricaemia
- asymmetrical swelling within a joint on X ray
- subcortical cysts without erosions on X ray
- have to have greater than or equal to 6 out of a 11 for probable gout
- Urate crystals during acute = definitive gout
- > 4 to <8 = uncertain synovial fluid analysis
-
what symptom is definitive gout
Urate crystals during acute = definitive gout
what if the 11 or more variables used for gout score is 4 or less what can the condition be
RA
pseudogout
psoriatic arthritis
septic arthritis
reactive arthritis
what are out factors that can highlight that it can be gout
Male
Hypertension/other cardiovascular disease
Serum uric acid level more than 5.88mg/dL
what does the synovial fluid look like if you have gout
Inflammatory
WBC count greater than 2000/μL and possibly greater than 50,000/μL
Predominance of polymorphonuclear neutrophils (PMNs)
Polarizing light
- Urate crystals needle like and high negatively birefringent
How do you diagnose gout using serum uric acid
Presence of hyperuricemia is not diagnostic
- 5-8% of population have elevated serum uric acid levels (>7mg/dL)
- Only 5-20% of patients with hyperuricemia develop gout
- If higher than 11mg/dL should be treated
what level of serum uric acid should you be treated for gout
- If higher than 11mg/dL should be treated
How can you diagnose gout using imaging
Doppler ultrasound
- measure the blood flow/ soft tissue swelling
X rays can also be used
- maintenance of joint space
- erosion outside joint capsule
- erosions have overhanging edges - rat bite
what is a dual energy computed tomography able to detect
- Able to detect uric acid crystal deposits in all gout patients with late stage gout
- able to detect uric acid crystals in tophi
- Able to detect uric acid crystal deposits in 64% of patients with early stage gout
Not as sensitive as needle biopsy
What can a dual energy computed tomography be used for clinically
Can measure MSU volume
Changes in actual MSU following treatment
Predict gout flare
What is joint damage a feature of (rat bite)
Joint damage is a feature of all erosive/inflammatory arthropathies
- osteoclasts erode the bone- get more of these where you have the crystals
How are bony erosions/rat bites caused
MSU crystals surrounded by granulomatous tissue reaction
Produce pro-inflammatory cytokines (IL1, TNF, IL6)
Stimulate osteoclasts (RANKL) - these cause the reabsorption of bone, they accumulate underneath the crystals
tophaceous deposits can lead to…
bone erosion
what treatment is sued for gout
NSAIDs
- Start with highest dose for 2-3 days
- Taper down over 2 weeks
- Gout symptoms should be absent for 2 days before treatment stopped
Colchicine
- Now 2nd line because of narrow therapeutic window and risk of toxicity
- stops neutrophils and macrophages dividing
- mitotic inhibitor
Corticosteroids
- For those that can’t use NSAID or colchicine
What biologicals can be used for gout
IL1 biologicals
- Rilonacept, canakinumab, anakinra
- Reduces length of attack and reoccurrences
- Used for patients who have severe and frequent flares
- expensive therefore not first line
what lifestyle advice can you give someone with gout
diet advice
- low purine diet = reducing red meat, oily fish, yeast (beer), fish, fruits such as avocado
what food would you recommend for a low purine diet
- coffee
- cheese
- eggs
- bread
- butter
- vegetables
- milk
What is the treatment of chronic gout and how do they work
Allopurinol
- Blocks xanthine oxidase
- Reduces generation of uric acid
Probenecid
- Uricosuric
- Increases uric acid excretion
- Fewer significant adverse effects than allopurinol
Rasburicase
- Catalyses conversion of uric acid to allantoin which is more soluble
- these are all done once the attack as died down
what is the aim of the long term management of gout
Lowering of uric acid levels
what is pseudogout
- this is deposition of calcium pyrophosphate in and around joint
what is pseudogout sometimes known as
Calcium pyrophosphate deposition disease (CPDD
what joints do psuedogout affect
- need a joint with cartilage present in
- for example the knee
describe characteristics of pseudogout
Metabolic arthropathy
Chondrocalcinosis
What is chondrocalcinosis
Chondrocalcinosis is the deposition of CPPD crystals into fibrous or hyaline cartilage.
what disease is pseudogout associated with
Osteoarthritis
- they already have breakdown of cartilage and exposure of the bone
- therefore they have a higher prevalence of having calcium salts deposited in the joints themselves
how many people over the age of 85 have chondrocalcinosis
Around 50% of people over 85 years have evidence of chondrocalcinosis
what types are the two different types of findings with pseudogout
Pseudo-osteoarthritis (50% of cases) with osteophytes and soft tissue calcification on radiographs
Or
Asymptomatic where only radiographic findings and no other symptoms
describe the pathophysiology of pseudogout
Release of CPPD crystals into joint space followed by phagocytosis of crystals by monocyte-macrophages or neutrophils which then release cytokines and cause inflammation
what joint is commonly affected by pseudogout
Knee is most commonly affected joint but can affect any joint
What can trigger an attack of pseudogout
Trauma
Rapid reduction of serum calcium conc
What does the synovial fluid
- not as shiny as in gout
- Mild to moderate -inflammation 10,000-50,000 WBCs/μL 90% neutrophils (PMNs)
- Rhomboid shaped weakly birefringent crystals
- milder attack as they don’t cause as many neutrophils to burst
How do you diagnose psuedogout
Ultrasound may be helpful in diagnosing
what would the ultrasound show in pseudogout
Calcification within soft tissue
Calcification within the articular cartilage
- Parallel with condyle
what could does pseudogout show in radiographs
Chondrocalcinosis of articular disc and atypical OA of hands
Often OA in same or neighbouring joints
what is the treatment for pseudogout
Intra-articular corticosteroids
NSAIDs
where can you find cholesterol crystals
Cholesterol crystals
Rare finding in some cases of rheumatoid arthritis synovial fluid
describe the structure of cholesterol crystals
Cholesterol crystals have a plate like structure often notched
What is cholesterol crystals caused by
Defective drainage of synovial fluid back into venous system
Local destruction
Increased permeability of synovial membrane to LDL and HDL
Intraarticular bleeding
cholesterol crystals are..
difficult to clear
- perpetuation of the arthritis
