Gout Flashcards
Gout - history
- Severe pain, usually in single joint
- acute onset (<24 hours)
- episode lasts 1-2 weeks
- frequently involves 1st MTPJ, foot or ankle (may involve any joint especially if co-existent osteoarthritis)
Gout - examination
- tender, hot, red swollen joint
- tophi - chalky white deposits = markers of severe disease. Typically form in digits or over elbows.
Gout - investigations
- Baseline renal and liver functions
- convalescent serum urate (4-6 weeks after attack)
- Xray of symptomatic joints (characteristic erosion in established disease)
- Good practice recommends screening patients for cardiovascular risk factors
- synovial aspirate - usually not performed in primary care
Gout - diagnosis in primary care
Score equal to or above 8
Male - 2
Previous reported arthritis attack - 2
Onset within 1 day - 0.5
Joint redness - 1
First metatarsophalangeal joint involvement - 2.5
Hypertension or >/= 1 cardiovascular disease - 1.5
Serum uric acid >0.35 mmol/l - 3.5
Gout - when would referral be required?
Normally managed in primary care.
Urgent referral if suspect septic arthritis.
Consider routine referral if there is diagnostic uncertainty / genuine treatment resistance (note may be due to poor compliance to treatment)
Gout - differential diagnosis
- Septic arthritis
- Reactive arthritis
- pseudo gout secondary to chondrocalcinosis
- psoriatic arthritis
- infective cellulitis
What is gout?
- Inflammatory arthritis caused by immune reaction to uric acid crystals in joint
- incidence: 2.5% in UK
- driven by association with obesity, cardiovascular disease and ageing
- diet RF: alcohol, fructose, purine intake
What is a complication of gout?
Renal stones
Gout - What other abnormality may be noted on examination?
Tophi
- predilection for extensor surface of fingers, hands, forearm, elbows, achilles tendon and helix of ear
- white colour
- can ulcerate -> discharge white gritty material
- may become infected or induce a local inflammatory response with erythema and pus in absence of secondary infection
Gout - pathophysiology
Inflammatory arthritis caused by immune reaction to uric acid crystals in joint
- Urate crystals (monosodium urate) precipitate on articular cartilage of joints, on tendons and in surrounding tissue → provoking inflammatory reaction
- Urate = end product of purine metabolism / normal component of blood / poorly soluble
Over years if untreated – chronic articular damage develops leading to joint deformities and impaired function -> several joints may be affected (including those initially free of symptoms)
Deposits of crystals (tophi) develop → eventually can destroy underlying joint
Homeostasis
- Urate overproduction – rare cause
- Gut excretion (1/3 urate excretion)
- Renal excretion (2/3 urate excretion)
Decreased in 90% cases (May be hereditary or in patients on diuretics, decreased GFR)
- Alcohol – increases purine catabolism in liver & increases formation of lactic acid, blocks urate secretion by renal tubules
- Lead poisoning & immunosuppresants (tacrolimus & cyclosporine) given to transplant patients – irreversibly damage renal tubules -> urate retention
- 1/3 uric acid pool derived from dietary sources, 2/3 from endogenous purine metabolism
Gout - causes of hyperuricaemia
Diminished renal excretion o Increased tubular reabsorption o Renal failure o Lead toxicity o Lactic acidosis o Alcohol o Drugs: Thiazide and loop diuretics, low dose aspirin, ciclosporin, pyrazinamide
Increased intake o Game o Seafood o Offal o Red meat
Increased production
o Myeloproliferative and lymphoproliferative disease
o Psoriasis
o High fructose intake
o Glycogen storage disease
o Inherited disorders: Lech-Nyhan syndrome (HPRT mutations), Phosporibosyl pyrophosphate synthetase 1 mutations
Gout - treatment of acute attack
Focus on acute attack -> then give prophylaxis to lower serum uric acid
1st line = full strength NSAID – take promptly after attack
Cortico-steroid have equal efficacy to NSAID
- Prednisolone 30mg od for 5 days
- Consider IM or IA steroid
- Good in elderly – as increased risk due to NSAID or colchicine
If have recurrent episodes – can have NSAID, colchicine or prednisolone supply and take when first symptom appears until attack resolves
Joint aspiration can give pain relief – esp. if large joint affected & may be combined with intra-articular glucocorticoid injection (if know diagnosis & ruled out infection)
Colchicine
- Acute gout – 0.5mg BD 2-4 times daily
- Inhibits microtubule assembly in neutrophils
- SE: nausea, vomiting, diarrhoea
- Reduce dose to maximum tolerated dosage
- Contraindicated: renal / hepatic impairment and on P-glycoprotein inhibitor (ciclosporin, verapamil, quinidine), or strong CYP3A4 inhibitor (ritonavir, atazanavir, indinavir, clarithromycin, telithromycin, itraconazole, ketoconazole)
Gout - long term management
Long term management:
- If possible discontinue medications causing hyperuricaemia
- Lifestyle modification (weight loss, alcohol moderation)
Xanthine oxidase inhibitors – reduce formation of uric acid
- Allopurinol / febuxostat
Uricosurics – kidney excretion of uric acid
- Rarely used
- Sulphinpyrazone / Benzbromarone
Uricolytics – enzyme degrades uric acid
- Very expensive
- pegloticase
Offer flare prohpylaxis with initiation of ULT
- Flares may continue for 12 months after urate control & more common with aggressive urate lowering.
- Colchicine 500mcg b.d. for up to 6 months.
- Consider low dose NSAID in patients intolerant of colchicine
- Target <0.36 mmol/l
- Should prevent formation of new crystals, but still allows infrequent attacks, persistence of urate crystals in synovial aspirates, resolution of tophi is speeded in direct proportion to success of urate lowering
New diagnosis or patients with tophi – aim <0.3mmol/l
Annual monitoring of uric acid levels
Gout - allopurinol
1st line
Effective in majority of patients
To reduce paradoxical flares → start at low dose of 100mg daily, & increase monthly by 100mg until target is achieved (<0.3mmol/l)
Median dose = 400mg daily
Recheck SUA after 2 weeks of dose adjustment
Max. dose = 900mg od (only if normal renal function)
Gout - Febuxostat
2nd line - when allopurinol not tolerated/ineffective
Initially 80mg daily, can be increased to 120mg daily
Give 6 months prophylaxis with colchicine
Undergoes hepatic metabolism → safe in moderate renal impairment
Not recommended in patients with CV disease
