Flashcards in Crystal Arthropathies Deck (30)
What is the epidemiology of gout?
Affects 1% of the population and is more common in men (there uric acid levels rise after puberty)
What is 'gout'?
Where monosodium rate crystals precipitate in the soft tissues and lead to joint destruction and renal damage if not treated
What are the main risk factors for the development of gout?
Elevated dietary intake of purines and under excretion of uric acid (renal insufficiency, dehydration and diuretics)
How long does it take for elevated uric acid levels to cause an attack of gout?
Approximately 20 years.
What is the main cause of gout?
Under excretion of uric acid by the kidneys
What is the clinical presentation of gout?
Acute and mono-articular affecting small joints of the lower extremity and usually affects the 1st metatarsal joint, inflammation at this joint is known as podagral. Joint will be red, hot, very tender and pain will start acutely and usually at night.
What is podagral?
Inflammation at the 1st metatarsal joint
How may gout be diagnosed from synovial fluid?
It will have inflammatory markers (CRP etc) with a WBC greater than 2000/µL with presence of many polymorphonuclear neutrophils.You may also be able to see needle-like urate crystals with polarising light
How may gout be diagnosed by imaging (x-ray/ultrasound)?
♣ Soft tissue swelling and increased blood flow
♣ Maintenance of joint space
♣ Erosion OUTSIDE of joint capsule
♣ Erosions have overhanging edges which appear like a rat bite
Outline the prognosis of untreated gout
if untreated the attacks will become polyarticular with more proximal and upper extremity joints involved. The attacks will become more frequent and last longer
What are tophi?
Urate crystals in soft tissues that develop in half of all patients with untreated gout after 10 years
What are the consequences of tophi?
They can lead to bone erosions; the crystals cause a reaction in the granulomatous tissue leading to the production of pro-inflammatory cytokines (IL-1, TNF and IL-6) which leads to the stimulation of osteoclasts due to RANKL expression
What is the pathophysiology of gout?
A gout attack is triggered by uncoated monosodium urate crystals or a large sudden change in the concentration of uric acid. Crystals activate IL-1 receptors directly and neutrophils present are phagocytic and will ingest the crystals leading to an inflammatory response
How do tophi appear histologically?
Appears as a foreign body-type giant cell reaction to the deposited crystals
How may acute gout be treated?
NSAIDs, colchicine (anti-mitotic), corticosteroids, IL-1 biologicals (rilonacept, canakinumab and anakinra), reduced purine intake
Name some examples of IL-1 antagonists.
Rilonacept, canakinumab and anakinra
How may allopurinol be used in the treatment of gout?
Blocks the action of xanthine oxidase which reduces the genreation of uric acid
How may probenecid be used in the treatment of gout?
Increases uric acid excretion
How may rasburicase be used in the treatment of gout?
Catalyses the conversion of uric acid to allantoin
How can dietary changes be used to treat gout?
Reduce purine intake by eating less yeast, meat extracts, mussels, nuts, mackerel/sardines, avacodos
Briefly outline the process of purine metabolism (relevant to gout)
Purines --> converted to xanthine --> xanthine oxidase catalyses conversion to --> urate --> urate oxidase can convert this to allantoin
What is pseudogout?
A form of chonedrocalcinosis where there acute deposition of calcium pyrophosphate crystals in and around the joints
Outline the pathophysiology of pseudgout
There is release of the calcium pyrophosphate crystals into the joint space, this is followed by phagocytosis of the crystals by monocyte-macrophages or neutrophils – which then release cytokines and cause inflammation. Acute attacks can be triggered by trauma or a rapid reduction of serum calcium concentration.
Outline the epidemiology of pseudogout
Around 50% of people aged 85+ have evidence of chrondrocalcinosis
Outline how pseudogout may be diagnosed
The crystals are rhomboid shaped and are found in the synovial fluid. These are taken up by neutrophils which try and digest the crystals. Ultrasounds may show calcification within the soft tissue and articular cartilage.
How may psuedogout be treated?
Intra-articular corticosteroids and NSAIDs
How can you distinguish between gout and pseudogout?
Psuedogout: usually affects the elderly, serum urate levels are normal, involvement of MTP is rare and crystals are rhomboid shaped
Gout: usually affects men and post-menopausal women, serum rate is elevated with rate-bite erosions on x-ray, needle-shaped crystals and involvement of 1st MTP is common
What foods are rich in purines?
Beef, pork, lamb, seafood, beer and alcohol
Which joint is almost always affected in gout?
1st metatarsal joint