Crystal Arthropathy Flashcards
What are common crystal deposition diseases characterised by?
Deposition of mineralised material within joints and peri-articular tissue
What is the crystal responsible for gout?
Monosodium urate
What is the crystal responsible for pseudo gout?
Calcium pyrophosphate dihydrate (CPPD)
What is the crystal responsible for calcific periarthritis/tendonitis?
Basic calcium phosphate hydroxy-apatite (BCP)
What are the 2 most common crystal arthropathies?
Gout and pseudogout
What fractions of uric acid in the body comes from dietary purines?
- 1/3
- (2/3 - DNA, RNA, HGPRT)
What is the breakdown process for purines?
purines -> hypoxanthine -> xanthine -> plasma urate
How is uric acid excreted from the body?
- 70% via kidneys
- 30% into the biliary tract (subsequently converted by colonic bacterial uricase to allantoin)
How does hyperuricaemia occur in the vast majority of people with gout?
Reduced efficiency of renal urate clearance
What are the 2 causes of hyperuricaemia?
Overproduction and under-excretion
What are the underlying causes of overproduction?
- Malignancy e.g lymphoproliferative, tumour lysis syndrome
- Severe exfoliative psoriasis
- Drugs e.g. ethanol, cytotoxic drugs
- Inborn errors of metabolism
- HGPRT deficiency
What are the underlying causes of under-excretion?
- Renal impairment
- Hypertension
- Hypothyroidism
- Drugs e.g. alcohol, low dose aspirin, diuretics, cyclosporin
- Exercise, starvation, dehydration
- Lead poisoning
Why is alcohol thought to increase the risk of gout?
As the metabolism of ethanol to acetyl CoA leads to adenine nucleotide degradation resulting in increased formation of adenosine monophosphate, a precursor of uric acid
What is Lesch Nyan syndrome?
Genetic HGPRT deficiency
What are the features of Lesch Nyan syndrome?
•X-linked recessive •Intellectual disability •Aggressive and impulsive behaviour •Self mutilation •Gout •Renal disease
What is the importance of HGPRT deficiency?
- HGPRT - hypoxanthine-guanine phosphoribosyl transferase
- Plays a key role in the recycling of the purine bases (hypoxanthine and guanine) in the purine nucleotide pools
- In absence of HGPRT, the purine bases cannot be salvaged and they are degraded and excreted as uric acid
- There is also an increased synthesis of purines (presumably to compensate for purines lost) which also contributes to the over-production of uric acid
Who gets gout?
- Predominantly older men
- Men always > women
- Men have higher rate levels
How does oestrogen affect uric acid?
It has a uricosuric effect making gout very rare in younger women
How does ageing affect prevalence of gout?
- There is an increased in sUA levels mainly due to reduced renal function
- Increased use of diuretic and other drugs that raise sUA
- Age-related changes in connective tissues which may encourage crystal formation
- Increased prevalence of OA
How is gout diagnosed?
•History •Examination •Differential Diagnosis •Investigations
Where do gout episodes classically occur?
The 1st metatarsophalangeal joint
What is the history of a gout episode?
•Classically overnight onset •May have been on holiday - alcohol and dehydration •Erythema •Unbearably painful •Lasts 5-7 days •If severe - inflammation of the overlying skin •Potentially discharges f chalky material
What are tophi?
A tophus is a massive accumulation of uric acid
Where do tophi occur?
•Bony prominences •Ear
What is the gold standard in gout investigation?
- Aspirate the joint and look for crystals
- Aspiration is also important for differential diagnosis of sepsis
- Don’t usually aspirate the 1st MTP for gout as in so common in that location
How is an acute flare of gout treated?
- NSAIDs - some patients cannot take this
- Colchicine - has anti-inflammatory properties, perhaps slower onset, causes diarrhoea SPECIFICALLY FAVOURED IN GOUT
- Steroids - useful in renal impairments
When does a patient receive prophylactic intervention after a 1st attack of gout?
•Single attack of polyarticular gout •Tophaceous gout •Urate calculi •Renal insufficiency
What are other indications for prophylactic/long-term treatment of gout?
- Treat if 2nd attack within 1 yr
- Prophylactically prior to treating certain malignancies
How is long-term hyperuricaemia treated?
- Do not treat asymptomatic hyperuricaemia
- Xanthine oxidase inhibitor e.g. Allopurinol MOST COMMON
- Febuxostat - option for patients who are unable to tolerate allopurinol, can increase risk of cardiovascular death
- Uricosuric agents e.g. sulphinpyrazone, probenecid, benzbromarone
- Canakinumab - IL 1 antagonist, extremely expensive
How to allopurinol and febuxostat work?
They inhibit xanthine oxidase. Hypoxanthine -x> Xanthine -x> plasma urate
At what point should you attempt to reduce the urate level?
- Wait until the acute attack has settled
- Use prophylactic NSAIDs or low dose colchicine/steroids until urate level normal (poss. with allopurinol treatment)
- HOWEVER, if already on allopurinol during acute attack, continue treatment
What factor is important when using allopurinol?
•Adjust allopurinol dose according to renal function •Increase monthly until uric acid <300 and begin to wean off NSAIDs/colchicine
Where is pseudogout most commonly seen?
The knee
Who gets pseudogout?
Elderly females
What are the features of pseudogout?
- Erratic flares
- Triggers - trauma, intercurrent illness
What is the aetiology of pseudogout?
•Idiopathic •Familial •Metabolic
What is an x-ray feature of pseudogout?
Chondrocalcinosis
What are the crystals seen under the microscope in pseudogout?
Pyrophosphate crystals
What is the management of pseudogout?
- NSAIDs
- I/A steroids
What are the prophylactic therapies for pseudogout?
THERE ARE NONE
What is polymyalgia rheumatica?
- Inflammatory condition of the elderly
- Close relationship with giant cell arteritis (GCA)
What percentage of patients with polymyalgia rheumatic (PMR) have evidence of GCA?
20%
What percentage of patients with GCA may have PMR?
50%
How does PMR present?
- Sudden onset of shoulder +/- pelvic girdle stiffness
- Rare < 50y
- Usually > 70y
- F:M 2:1
- ESR usually > 45 often 100
- Anaemia
- Malaise, weight loss, fever, depression
- Arthralgia/synovitis occasionally
How is PMR diagnosed?
- Compatible history
- Age > 50
- ESR > 50
- Dramatic steroid response
- No specific diagnostic test
What are the differential diagnoses for PMR?
- Myalgiconset Inflammatory joint disease - rheumatoid arthritis
- Underlying malignancy e.g Multiple myeloma, lung cancer
- Inflammatory muscle disease
- Hypo/hyperthyroidism
- Bilateral shoulder capsulitis
- Fibromyalgia
What is the treatment for PMR?
- Prednisolone 15mg per day initially
- 18-24mthcourse
- Bone prophylaxis - >65 bone protection, <65 dexascan needed first
