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Clinical presentation (men vs women, clinical story and progression)
- Men: 1st MTP joint involvement
- Women: knee presentation more common than foot presentation
- Can affect any joint in the feet, around the tendons, and less commonly in the knee
- Clinical story: acute onset of excruciating pain and swelling, often assc. with redness, affects a single joint at a time, lasting for a few days to a week before settling
- Progression: intermittent flares, untreated symptoms occur more frequently and don't get completely symptom free periods, but severity of flares decreases
- Initially self-limiting resolving problem
- Usually mon-articular presentation
- Hospital in-patients (esp those with CRF) may be poly-articular
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Prevalence, M:F ratio
- Prevalence: 1% of population
- M>F
- Affects 1st MTP joint first in 50% of cases
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Examination findings
- Neutrophil driven inflammatory process in the joint:
- low grade pyrexia
- tophi (in chronic untreated gout)
- Erythema
- swelling
- tenderness
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Differential Diagnosis
- septic arthritis
- Gout
- pseudogout
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Purine Metabolism
- Nucleic acid --> purine nucleotides --> hypoxanthine --> xanthine --> uric acid (excreted by kidney)
- First 2 conversions catalysed by HGPT
- HGPT: hypoxanthine-guanine thosphoylbosyltransferase
- Uricase: an unsyme that makes uric acid more soluble, but does not exist in humans
- Uric acid: must be excreted through kidneys in DCT
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Lesch-Nyham Syndrome
- Paediatric syndrome caused by mutation in HGPT
- Associated with hyperuricaemia
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Normal uric acid levels:
- ~214 µmol/L – 450 µmol/L
- already at the supersaturaed levels in the serum
- thus an increase above normal levels, uric acid will crystalise out, particularly in joints
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Risk Factors: Causes of Increased Uric Acid Syntehsis
- Purine rich foods: alchoholic drinks (esp beer), seafood (anchovies, sardines, herring), offal, legumes (dried beans), meat extracts (gravy), vegetables (mushrooms, spinach, asparagus, cauliflower)
- Genetic predisposition: Lesch-Nyhan Syndrome
- Increased cellular production: fructose (induces cellular production of purines), malignancy, psoriasis, lymphoproliferative disorders
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Risk Factors: Causes of Decreased Renal Uric Acid Extretion
- Renal disease
- Genetic predisposition: URAT1 genetic pleomorphism (in PCT) e.g. Maori population in NZ
- Insulin resistance/TIIDM - most important factor in current population - high levels of insulin inhibit ability of URAT1 to excrete uric acid (management is very similar, calorie restriction and weight reduction)
- Drugs: thiazed diueretics (bendrofluemethiazide), loop diuretics (furosemide), ciclosporin, low dose aspirin
- Lead toxicity
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Pathogenesis of acute attack and triggers
- Disease is asymptomatic until a trigger causes release of uric acid crystals into the synovial fluid.
- The innate immune system recognises the crystals and triggers an acute neutrophilic inflammatory response
- Leads to an acute attack (redness, swelling, excruciating pain
- Triggers: intercurrent infection, acute increase in serum uric acid (e.g. binge drinking, dehydration), acute decreased in serum uric acid (e.g. abstinence, treatment), local trauma
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Investigations and possible findings
- FBC: neutrophil leucocytosis (even more elevated if septic)
- Renal function: high creatinine (RF for developing gout)
- Uric acid: may be normal - levels can drop during an acute episode i.e. normal doesn't exclude gout
- CRP/ESR: both will be high
- Blood cultures: negative (important)
- Xray: usually
- Synovial fluid analysis: very important
- Polarised light microscopy: very important
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Polarised Light Microscopy
- Do not memorise which colour for which direction etc
- Remember: needle shaped crystals, blue to yellow discolouration depending on the direction of the filter
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Synovial fluid analysis: Normal, crystal synovitis, septic arthritis
- Normal: viscous, star, clear, o or low WCC
- Crystal: low viscosity, straw/opalescent, transucent, WCC + or ++
- Septic: runny, greenish, opaque, WCC +++
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Treatment (matchbox analogy)
- Matchbox analogy: gout is like having a box of matches inside the joint - if one of them goes up, then all of the matches go up. Thus need different strategies to treat it
- 1. Acute attacks: i.e. a fire extinguisher, NSAIDs, local steroid infections, oral steroids
- 2. Prophylaxis: i.e. water to make harder to light - Colchicine 2-3x per day - interferes with neutrophil microtubule formation (makes it more difficult to become activated)
- 3. Uric acid reduction: if you can decrease the levels, the crystals are progressively reaborbed
- Education: weight loss, lower calorie intake, lower intake of purine rich foods (esp alochol), treatment modifications (e.g. switch from thiazides to ACEi) NB: can risk a flare up by decreasing levels
- Allopurinol (1st line)/Febuxostat (2nd line): xanthine oxidase inhibitors
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