Crystal Arthropathy and Polymyalgia Rheumatica Flashcards
What are the common crystal deposition diseases characterised by?
Deposition of mineralised material within the joints and periarticular tissue
What substance is present in gout?
Monosodium urate
What substance is present in pseudogout?
Calcium Pyrophosphated DiHydrate (CPPD)
What substance is present in calcific periarthrtiis/tendonitis?
Basic calcium phosphate hydroxy-apatite (BCP)
What is tophus?
Massive accumulation of uric acid
Pathology of Lesch Nyan Syndromes
HGPRT deficiencies
- hypoxanthine guanine phosphonbosy transferase
- normally plays a role in recycling purine bases, hypoxanthine and guanine, into purine nucleotide pools
- in the absence of this, the purine bases are degraded and excreted as uric acid
- the synthetic rate for purines also accelerates
The failure of recycling together with increased synthesis of purines is the basis for the over production of uric acid
X linked recessive
Features of Lesch Nyan syndromes
Intellectual disability Aggressive and impulsive behaviour self mutilation gout renal disease
Who gets pseudogout?
The knee is to pseudogout as the toe is to gout
Elderly females
Causes of pseudogout
Idiopathic
Familial
metabolic
Triggers of pseudogout
Trauma
Intercurrent illness
Features of pseudogout
Erratic flares
Chondrocalcinosis
Pyrophosphate crystals
Treatment of pseudogout
NSAIDs
I/A steriods
Is there prophylactic therapy for pseudogout?
No
Pathology of gout
Purine metabolism
- endogenous production of uric acid from degradation of purines contributes to 2/3rds of body urate pool, remainder dietary in origin
- 70% of uric acid produced is excreted by the kidneys and the rest by the biliary tract and bacteria
- in the vast majority of people with gout, HYPERURICAEMIA RESULTS FROM REDUCED EFFICIENCY OF RENAL URATE CLEARANCE
Causes of hyperuricaemia
Overproduction - malignancy e.g. lymphoproliferative - severe exfoliative psoriasis - drugs, e.g. ethanol, cytotoxic drugs - inborn errors of metabolism - HGPRT deficiency Underexcretion - renal impairment - hypertension - hypothyroidism - drugs e.g. alcohol, low dose aspirin, cyclosporin - exercise - starvation - dehydration - lead poisoning
Why does alcohol increase the risk of gout?
Some alcoholic drinks are rich in purines, noteably beer
Metabolism of ethanol to acetyl CoA leads to the formation of a precursor of uric acid
Alcohol also raises the lactic acid level in the blood which inhibits the uric acid secretion
Who gets gout?
Older men (men have higher urate levels than women) Very rare in young women
Gout and women
Very rare in young women as oestrogen has a uricosuric effect
after menopause, urate levels rise and gout becomes increasingly prevalent
Ageing is a risk factor for both men and women for gout due to …..
Increase in sUA levels (mainly due to reduced renal function)
Increased use of diuretics and other drugs that are raised in sUA
Age related changes in connective tissues which may encourage crystal formation
Increased prevalence of OA
Treatment of gout/hyperuricaemia
Acute flare of gout
- NSAIDs
- Colchicine
- Steroids (I/A, I/M, oral)
Hyperuricaemia
- prophylactically prior to treating malignancies
- lowering uric acid
- xanthine oxidase inbihitor (allopurinol)
- febuxostat
- uricosuric agents (sulphinpyrazone)
- canakinumab
Lifestyle
- BP
- weight loss
- diet
- alcohol and smokingWhen is hyperuricaemia treated?
DO NOT TREAT IF ASYMPTOMATIC 1st attack not treated unless - single attack of polyarticular gout - tophaceous gout - urate calculi - renal insufficiency Treat if second attack in one year
Rules for 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 the urate level Is normal
Adjust allopurinol dose according to renal function
What is polymyalgia rheumatica?
An inflammatory condition of the elderly causing pain, stiffness and inflammation of muscles around the shoulders, neck and hips
What is polymyalgia rheumatica closely related to?
GCA
Symptoms of gout
Sudden severe pain
Swelling, redness and tenderness over joints
Where is gout pain often seen?
The base of the big toe
Who gets polymyalgia rheumatica?
rare <50, usually > 70 y/o
F > M 2:1
Presentation of polymyalgia rheumatica
Rapid onset < 1 month SUDDEN onset of shoulder +/- pelvic girdle stiffness Aching, morning stiffness in proximal limbs (NOT weakness) ESR usually > 45 often 100 Anaemia Malaise Weight loss Fever Night sweats Depression
Diagnosis of polymyalgia rheumatica
Compatible history Age > 50 ESR > 50 Dramatic steroid response *no specific diagnostic test*
Differential diagnosis for polymyalgia rheumatica
Myalgic onset inflammatory disease underlying malignancy - multiple myeloma - lung cancer Inflammatory muscle disease Hypo/hyperthyroidism Bilateral shoulder capsulitis Fibromyalgia
Treatment of polymyalgia rheumatica
Prednisolone 15mg per day daily 18-24 month course
Bone prophylaxis
Where is most commonly affected in pseudogout?
Knee
Wrist
Shoulder
How does colchicine work?
Inhibits microtubule polymerisation by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity
Classic side effect of colchicine
Diarrhoea
What does polymyalgia rheumatica NOT have?
Weakness
What are chemo patients at increased risk of and why?
Gout
Increased urate production
What should happen to allopurinol treatment if they are already on the treatment, but have an acute flare of gout?
Continue allopurinol on current dose
RFs for pseudogout
Hyperparathyroidism Hemochromatosis Acromegaly Low Magnesium Low phosphate Wilsons disease
What is seen on joint aspiration if have pseudogout?
Weakly-positively birefringent rhomboid-shaped crystals
