Crystal Arthropathies (Gout, Pseudogout) Flashcards
What is the epidemiology of gout?
M>F
Average age of onset 40-60yrs
What is the aetiology of gout?
Risk factors:
- Male
- Meat + seafood; purine-rich foods
- Alcohol
- Obesity + high triglycerides
Secondary to increased cell lysis/stress: (due to release of nucleic acids -> uric acid in blood)
- HTN
- Coronary artery disease
- DM
- CKD
- Heart failure
- Psoriasis
- Trauma, surgery
Secondary to drugs:
- Diuretics
- Chemotherapy
Primary:
- From an X-linked inherited gene; e.g. absence of HGPRT enzyme
- +ve FHx, presenting before 20yrs
What is the pathophysiology of gout?
An arthritis secondary to the deposition of monosodium urate (MSU) crystals within joints, causing acute inflammation and eventual tissue destruction
Duration + magnitude of hyperuricaemia is directly correlated with likelihood of developing gout (+ uric acid kidney stones)
- Although people without high levels don’t always develop gout and you can have gout with normal levels…
- Hyperuricaemia depends on effective renal excretion (90% are under excretors) and production of urate (10% are over producers)
Excretion failures are a more common cause of
gout
How does got present acutely?
Severe pain in a joint
- Highly tender to touch
- Swollen
- Erythematous
- Loss of function
- Increases and peaks over 6-24hrs
Joints affected:
- 50% of all and 70% of first attacks affect the first MTP joint - this is partially because of temperature changes - at cooler temperatures, uric acid crystallises; also called ‘Podagra’
- Other joints: knee, midtarsals, wrists, ankles, small hand joints, elbows
Systemic symptoms of fever and malaise
Attacks usually resolve spontaneously over 5-15 days, becoming asymptomatic by the end
What is chronic tophaceous gout?
Large crystal deposits produce irregular firm nodules mainly around extensor surfaces of the fingers, hands, forearms, elbows, Achilles tendons and ears
Typically, tophi are asymmetrical with a chalky appearance beneath the skin
Damage is usually found in the first MTP joints, midfoot, small finger joint and wrist, with restricted movement, crepitus and deformity
How do you investigate gout?
Polarised light microscopy:
- ‘Needle shaped, negatively birefringent MSU crystals’
- In synovial fluid aspirate or tophi
- Required to confirm a Dx of gout
- May also want to do an MC+S as infection is a differential or may co-exist
Uric acid:
- Serum uric acid - can be normal during an attack, and those with high MSU might never develop gout; most useful if significantly raised
- Renal uric acid - from 24hr urine sample - can be helpful if onset <25yrs as FHx +ve is more likely and these patients are likely overproducers of uric acid
Radiology:
- XR - chronic gout - punched-out lesions + areas of sclerosis + tophi; first changes are most commonly MTP
- USS, CT and MRI - can identify urate deposits, structural abnormalities and inflammation in gout
Fasting glucose + lipids:
- to rule out hyperglycaemia and hyperlipidaemia (as gout often co-occurs with metabolic syndrome)
How do you manage acute gout?
1) NSAIDs:
- Indometacin, diclofenac, naproxen = preferred
- Sooner stared, the more rapid the response
- Highest tolerable dose
- PPI co-prescription for those at risk
- Stocks should be kept at home
2) Colchicine:
- 500mcg 2-4x/day until symptoms relieved max 6mg/course
- Not to be repeated within 3 days
- Good if NSAIDs poorly tolerated, patients with HF or those on anticoag
3) Corticosteroids:
- PO, IM, IV or IA; IA can also be paired with aspiration = good for Dx and as a therapy itself
- Useful when 1 + 2 are contraindicated
- Short course of prednisolone
Other:
- Ice pack
- Rest
- Elevation + avoid trauma
- Other analgesia e.g. paracetamol +/- codeine
What do you do if people aren’t responsive to the traditional acute management?
If not improving within 2-3 days:
R/V Dx
Check medication compliance
Increase doses where possible
Give Canakinumab
- Monoclonal Ab inhibiting IL-1
Consider combining treatments or seek specialist advice
What non-pharmacological measures can you use to reduce your risk of attacks?
Lifestyle modification:
- Sensible alcohol intake (14units/wk + 3 alcohol free days); avoid beer/stout/port
- Keep hydrated
- Reduce purine rich food (esp herring, sardines, mussels; heart, liver, kidneys; yeast extracts, oatmeal, soya) - quantity of purine rich food is more important than absolute purine content in the food
- Avoid soft drinks with fructose - can increase levels of purines
- Weight loss if obese
- Regular exercise
- Smoking cessation
Risk factor management:
- Optimise drugs - thiazides/loops, low dose salicylates, chemotherapy etc.
- Optimise health conditions - HTN, CKD, hyperlipidaemia etc.
What drugs can you give for the prophylaxis of gout?
Xanthine-oxidase inhibitors:
- Allopurinol* (or febuxostat)
- 50-100mg and double every 2-4wks until plasma urate level <300micromoles/L
- Indications: 2+ attacks within 1yr; Tophi; renal insufficiency; comorbid renal stones ; continuing need for diuretics
- NEVER start during an acute attack as can exacerbate
- Wait 1-2wks after attack resolves
- For future attacks on allopurinol, continue taking but also take normal acute meds
- In the weeks after starting, an acute attack is likely
- Usage is often lifelong and will need monitoring
Other drug:
- Sulfinpyrazone = a uricosuric i.e. increases renal excretion of urate
What are some complications of gout?
Renal disease:
- Chronic urate nephropathy from widespread deposition of crystals in medulla and pyramids = inflammation + fibrosis
- Oxalate kidney stones
Severe degenerative arthritis
Secondary infections
What is the epidemiology of pseudogout?
Common in the elderly
- 1/2 of adults develop radiographic changes by age 80
What is the aetiology of pseduogoat?
Associated with:
- OA
- Hyperparathyroidism
- Haemochromatosis
- Wilsons disease
- Acromegaly
- Any cause of arthritis
- Dehydration
- Intercurrent illness
- Long term steroid use
- Dialysis
- Surgery/trauma
- Hypomagnesaemia
What is the pathophysiology of pseudogout?
Inflammation of joints caused by deposition of calcium pyrophosphate (CPP) crystals in articular and periarticular tissues
CPP disease encompasses:
- Asymptomatic CPPD = no over clinical consequences; isolated cartilage calcification or chondorcalcinosis; identified on imaging/histology
- OA with CPPD = both present together enough to cause symptoms
- Acute CPP crystal arthritis = pseudogout
- Chronic CPP crystal inflammatory arthritis
How do acute and chronic CPP crystal arthritis present?
ACUTE
Monoarticular or oligoarthritis:
- Mostly the knees; also wrists, shoulders, ankles, hands and feet (almost any joint can be affected)
- Presents similarly to gout but with less severe pain/swelling etc
- Usually resolving in <10days
CHRONIC
- Destructive changes like OA but worse, may become a destructive arthropathy and cause a neuropathic joint
- Mostly knees, wrists, shoulders and hips
