Crystal arthopathies and polymalgia rheumatic Flashcards
What are common crystal deposition diseases?
> Monosodium urate - gout
> Calcium pyrophosphate dihydrate (CPPD) - Pseudogout
> Basic calcium phosphate hydroxy-apatite (BCP) – calcific periarthritis/tendonitis
Which crystals are found in gout?
Monosodium urate
Monosodium urate crystals?
Gout
Which crystals are found in pseudogout?
Calcium pyrophosphate dihydrate (CPPD)
Which crystals are found in calcific periarthritis/tendonitits?
Basic calcium phosphate hydroxy-apatite (BCP)
Calcium pyrophosphate dihydrate (CPPD) crystals?
Pseudogout
Basic calcium phosphate hydroxy-apatite (BCP)?
Calcific periarthritis/tendonitis
What are typhus-tophi?
Massive accumulations of uric acid
What is the main contributor to the bodies rate pool?
> 2/3rds come from the production of uric acid when purines are degraded
> The rest comes from diet
How is uric acid excreted?
> 70% is excreted via the kidneys
> The rest is eliminated into the biliary tract
What is uric acid in the colon converted to?
Converted by colonic bacterial uricase to allantoin
What is the main cause of hyperuricaemia in gout usually?
Decreased efficiency of renal urate clearance
Where do purines come from?
> Diet
DNA/RNA
Recycled HGPRT (Hypoxanthine)
Why can alcohol increase the risk of gout?
> The metabolism of ethanol to acetylene CoA leads to adenine nucleotide degradation, resulting in increased formation of adenosine monophosphate, a precursor of uric acid.
> Alcohol also increases the lactic acid level in blood, which inhibits uric acid excretion
What can lead to hyperuricaemia - Overproduction?
Overproduction:
> Malignancy e.g lymphoproliferative, tumour lysis syndrome
> Severe exfoliative psoriasis
> Drugs e.g. ethanol, cytotoxic drugs
> Inborn errors of metabolism
> HGPRT deficiency
What can lead to hyperuricaemia - under excretion?
Under excretion:
> Renal impairment
> Hypertension
> Hypothyroidism
> Drugs e.g. alcohol, low dose aspirin, diuretics, cyclosporin
> Exercise, starvation, dehydration
> Lead poisoning
What is Lesch syndrome caused by?
Deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT)
What is the role of hypoxanthine-guanine phosphoribosyl transferase (HPRT)?
HPRT normally plays a key role in the recycling of the purine bases, hypoxanthine and guanine, into the purine nucleotide pools
In the absence of HPRT, these purine bases cannot be salvaged; instead, they are degraded and excreted as uric acid
The synthetic rate for purines is accelerated, presumably to compensate for purines lost by the failure of the salvage process.
How is Lesch Nyan syndrome inherited?
X-linked recessive
How does someone present with Lesch Nyan syndrome?
> Intellectual disability
> Aggressive and impulsive behaviour
> Self mutilation
> Gout
> Renal disease
Which population group is at highest risk of gout?
Older men
Why are men at higher risk for gout than women?
Men have higher urate levels than women and an increased prevalence of gout at all ages, though less pronounced in older age.
Oestrogen has a uricosuric effect, making gout very rare in younger women. However, after the menopause, urate levels rise and gout becomes increasingly prevalent.
When are woman at a higher risk of having gout and why?
Post menopause as Oestrogen has a uricosuric effect, this allows rate levels to rise and gout becomes increasingly prevalent
Why is increased age related with increased gout prevalence?
> An increase in sUA levels (mainly due to reduced renal function);
> Increased use of diuretics and other drugs that raise sUA;
> Age-related changes in connective tissues, which may encourage crystal formation;
> An increased prevalence of OA.
What is diagnosis of gout based on?
> History
Examination
Differential Diagnosis
Investigations
How do you manage acute flare of gout?
> NSAIDs
Colchicine
Steroids I/M, oral
When is hyperuricaemia treated (If asymptomatic it is not treated)?
If the context of gout: > 1st attack not treated unless: - Single attack of polyarticular gout - Tophaceous gout - Urate calculi - Renal insufficiency
> Treat if 2nd attack within 1 yr
Or Prophylactically prior to treating certain malignancies
Which drugs are used to lower uric acid?
> Xanthine oxidase inhibitor e.g. Allopurinol
> Febuxostat
> Uricosuric agents e.g. sulphinpyrazone, probenecid, benzbromarone (Used rarely)
> Canakinumab - IL-1 antagonist (Almost never used)
What are the rules in lowering uric acid levels?
> Wait until the acute attack has settled before attempting to reduce the urate level
> Use prophylactic NSAIDs or low dose colchicine/steroids until urate level normal
> Adjust allopurinol dose according to renal function
Other than drugs what is important in gout management?
> Lifestyle (Diet)
Hydration
Cardiovascular disease
Which part of the body is most commonly affected by gout?
The MTP joint of the big toe
Which part of the body is most commonly affected by pseudogout?
The knee
Who is most likely to be affected by pseudogout?
Elderly females
What is the aetiology of pseudogout?
> Idiopathic
Familial
Metabolic
What triggers are there in pseudogout?
> Trauma
> Intercurrent illness
What is the pattern for flares in pseudogout?
Erratic flares
How is Pseudogout managed?
> NSAIDs
I/A steroids
There are no prophylactic therapies
What is polymyaligia rheumatica?
An inflammatory condition in the elderly (>50yrs)
What is chondrocalcinosis?
Cartilage calcification seen on X-ray (Can occur in pseudogout, calcium pyrophosphate deposition)
What does calcium pyrophosphate deposition lead to?
> Acute inflammation = Pseudogout
> Chronic degeneration = Pseudo-osteoarthritis
What condition is associated with polymyalgia rheumatica?
Giant cell (Temporal) arteritis: - 20% patients with PMR have evidence of GCA
- 50% patients with GCA have evidence PMR
What findings are there in polymalgia rheumatica?
> Rise in ESR (>45 often 100) and CRP
Anaemia
Normal CK
How do you treat polymyalgia rheumatica?
Rapid response to low-dose corticosteroids
How does someone present with Polymyalgia rheumatica?
> SUDDEN onset of shoulder +/- pelvic girdle STIFFNESS
> Anaemia
> Malaise ; Weight loss ; fever; depression
> Arthralgia / synovitis occasionally
Who is most commonly affected by polymyalgia rheumatica?
> 50yrs, usually > 70yrs
F:M = 2:1
How is Polymyalgia rheumatica diagnosed?
- History
- Age > 50yrs
- ESR > 50
- Dramatic response to steroids
Differential diagnosis in polymyalgia rheumatica?
> Myalgic onset Inflammatory joint disease
> Underlying malignancy
e.g Multiple myeloma, lung cancer
> Inflammatory muscle disease
> Hypo/ hyperthyroidism
> Bilateral shoulder capsulitis
> Fibromyalgia
Treatment of polymylagia rheumatica?
Rapid response to corticosteroids e.g. prednisolone 15mg day initially for 18-24 months
Bone prophylaxis
