Gout + Pseudogout Flashcards
What is the underlying pathophysiology of gout?
Inflammatory disease due to deposition of MSU crystals, which can form tophi in the joints and in site distal to joints
MSU crystals form due to hyperuricaemia (>6.0mg/dL serum uric acid)
What are the causes of hyperuricaemia?
Decreased fractional excretion via kidneys
Increased ingestion
-beer or fructose rich beverages
Increased degradation
-high cell turnover leads to rise in urea
Eg psoriasis/haematological malig
Advancing age
-F have rise in urate post meno
Genetic mutations
-can lead to increased synthesis of urea
What local factors influence the MSU crystal deposition?
What are gouty tophi and where are they commonly located?
Osteoarthritis
- damaged cartilage leads to exposed collagen fibres which can increase chance of crystal nucleation + growth
- colder temperatures i.e. ear helix + distal joints
Subcutaneous deposits of uric acid in hands (DIP joints especially) elbows and ears
What is the main differential for gout and why? How can you differentiate between them?
Septic arthritis= both affect single joint and cause it to become hot, swollen and painful
Aspirate the joint and fluid will show following for gout:
- no bacterial growth
- needle shaped crystals
- negative birefringent of polarised light
- monosodium urate crystals
What are the risk factors for gout?
How can these help with classifying whether the gout is primary or secondary?
Male Metabolic syndrome (up tp 70% of patients) -Obesity -hypertension -hyperlipidaemia -insulin resistance
- High meat + sea food consumption i.e. high purine diet
- Alcohol
- Diuretics + CVD or kidney disease i.e. compromised renal clearance
- FH
Primary gout:
-identified source which is causing an increase in uric acid
Secondary gout
-rise in uric acid levels due to compromised renal clearance
What are the clinical features of gout?
Rapid onset of symptoms i.e. usually overnight Symptoms at worse 6-12 hrs after onset Erythema Pain Swelling Fever
1st Metatarsophalangeal joint (base of big toe) -HALLMARK OF DISEASE Midfoot Ankle i.e. inflammation of Achilles tendon Knee Wrists Carpometacarpal joints (base of thumb) Elbow i.e. tophi
What investigations would be done if gout suspected?
How would gout present on an X-ray?
FBC= raised WCC ESR/CRP= raised U+E= assess renal function Blood cultures= to rule out infection Synovial fluid aspirate -polarised light microscopy for crystal identification
Maintained joint space
Lytic bone lesions (peri-articular)
Punched out erosions with sclerotic boarders and overhanging edges
What drugs can be used to manage flare ups of gout?
Which drug has significant side effects and what are they?
NSAIDs= 1st line unless px has renal disorder or CVD
-with PPI cover
Colchicine= 2nd line i.e. cause dose-dependent diarrhoea AND myelotoxicitis if used with lipid-lowering drugs
Steroids= 3rd line
Ice and rest
What is the management for chronic gout?
What is the aim of this treatment?
Life style advice= diet and alcohol
Prophylactic cover of Colchicine (started in initial treatment)
Allopurinol
-titrated against serum UA and renal function
Lower urate levels to below physiological threshold
What can trigger an acute gout attack?
Why are the attack self-limiting?
Shedding of MSU crystals into joint cavity
Activates monocytes and macrophages
Influx of neutrophils due to MSU crystals producing chemotaxic substances
Cytokines released to stimulate pro-inflammatory cascade
NLRP3-inflammasome activated i.e. multimolecular intracellular complex which converts pro IL-1 + pro IL-18 into active forms
MSU switches from producing pro inflammatory cytokines to anti-inflammatory
What is the difference between gout and pseudogout?
The difference is in the shape and composition of crystals
Gout crystals= needle-shaped + negatively birefringent
Pseudogout crystals= rhomboid shaped + positively birefingent
What is pseudogout and what is the underlying pathophysiology?
Calcium pyrophosphate (CPP) dihydrate crystals
CPP deposits occur in the mid-zone of articular cartilage
Magnesium can act as coenzyme to alkaline phosphatase and can increase CPP solubility
Hypercalcaemic can increase Ca + PPi products
What are the associated risk factors for pseudogout?
Age i.e. >55 Metabolic diseases -hypophosphatasia -primary hyperparathyroidism -haemochromatosis -hypomagnesaemia
Gout
Wilsons disease
How might someone with pseudogout present clinically?
Frq assymptomatic Affects knee/wrist/ankle and shoulder Sudden onset + self-limiting Haemarthrosis -bleeding into joint space is classic feature with CPP
What can trigger pseudo gout?
Trauma Intercurrent illness or surgery Bisphosphonate infusion Parathyroidectomy Joint lavage of affected joint -promotes crystal shedding GCSF in neutropenia
