Table of Contents
- Described by Hippocrates
- Podagra was the foot goddess, a bad tempered virgin, who attacked victims after they overindulged.
- Autumn crocus used to Rx arthritis in 6th Century
- For many centuries, thought to be confined to men who had indulged in dietary or sexual excess.
- Benjamin Franklin's advice:
- “Be temperate in wine, eating, girls & sloth or the gout will seize you & plague you both”
- Sydenham wrote the classic description of the disease in 1684.
- colchicine isolated 1820
- Probenecid developed to inhibit penicillin excretion in 1951
pathophysiology & epidemiology:
- gout is deposition of uric acid crystals from a supersaturated extracellular fluid.
- risk of gout attacks correlates with serum uric acid levels although “healthy levels” of less than 0.42mM is not as important as whether the concentration places the patient at risk of crystal formation.
- only 20% of people with hyperuricaemia develop gout but the higher the level the greater the risk
- more than half of patients with acute gout have normal serum uric acid levels 1)
- the crystals are ingested by PMNLs resulting in inflammatory reaction
- uric acid can be over-produced (eg. myeloproliferative/lymphoproliferative diseases) or under-excreted by the kidneys.
- calcium channel blockers and Losartan appear to mildly reduce incidence of gout while other antihypertensives especially diuretics may increase the risk2)
- metabolism and immune systems developed hand-in-hand from an evolutionary and survival perspective as resisting starvation and mounting an immune response to pathogens was paramount, nutrients use the pathogen-sensing systems to trigger inflammatory responses. Most humans do not have to face food scarcity, thus, once beneficial, uric acid metabolism triggers the accumulation of fats and inflammation even without infection, a biological process driving renal impairment. A metabolomic analysis in 2023 found a characteristic metabolite profile for gout, in which 10 of 46 metabolites showed marked differences, and nearly all were related to metabolic inflammation: 3)
- DL-2-aminoadipic acid, an intermediate lysine metabolism metabolite, plays a key role in glucose and lipid metabolism, thus, its elevated concentrations promote fat consumption. However, that damages renal function in gout patients by enhancing their metabolism
- hypoxanthine could cause inflammation in the kidneys
- adenosine, a purine metabolite, bound different purinergic receptors to regulate interleukin-1beta (IL-1β) secretion and played an anti-inflammatory role in gout development and remission
- kynurenic acid (KYNA), a byproduct of the tryptophan metabolism, regulates immune system cells and several immune-mediated diseases - chronic stress or mild inflammation could promote KYNA production and immunomodulatory actions
- they suggest changes in the levels of metabolites, such as UA, hypoxanthine, adenosine, creatinine, and DL-2-aminoadipic acid, form the basis of gout development and confirmed the significance of metabolic inflammation in gout pathogenesis. The authors found that the signaling pathways used by metabolic and traditional inflammation were relatively consistent and originated from the energy metabolism pathways finding related biomarkers in the evolutionary journey, which could help detect or prevent gout attacks
risk factors include:
- obesity or weight gain in young adulthood
- alcohol consumption
- proximal loop diuretics
- thiazide diuretics
- lead exposure
- GTN infusions (? due to alcohol in mixture)
- post-menopausal women (oestrogens increase renal excretion of uric acid)
- renal insufficiency
precipitants of acute attacks:
- stress of illness or surgery
- alcohol or dietary excess
- organ transplant patients taking cyclosporine
acute gouty arthritis:
- occurs most commonly in middle-aged men & postmenopausal women
- increased serum uric acid levels are usually present for 20yrs before the 1st attack
- gouty attacks most often affect the 1st MTP jt (up to 75%), the tarsal joints, ankle & knee
- 40% have polyarticular involvement
- pain is excruciating at the onset & some cannot tolerate even the weight of a sheet on the joint
- fever may be present but serum uric acid level may be normal during acute attack
- without Rx, self-limiting lasting several days to weeks & followed by an intercritical period of wks-yrs.
- subsequent attacks get closer together, involve more jts & last longer
systemic inflammatory polyarticular gout syndrome (SIPGS)
- renal calculi
- tophi (foreign body granulomas with the crystal as the nidus)
- form in the musculotendinous unit:
- olecranon bursa, Achilles tendon, ulnar surface of forearm, hands, feet, toes, finger, helix of ear
- bone erosions with overhanging margins
acute gout attack:
- is it possible that joint is infected or is joint easy to aspirate? if so, aspirate joint looking for urate crystals (must be done within 24hrs of aspirate to avoid degradation)
- otherwise treat as gout:
- early Rx within hours is probably more important than which anti-inflammatory:
- non-steroidal anti-inflammatory drugs (NSAIDs) for 1wk after symptoms have settled if no C/I such as PU, renal/cardiac/liver failure; post-op. state, anticoagulant Rx or poorly controlled HT
- if C/I to NSAIDS then consider either:
- eg. oral prednisone 10mg bd for 3-5 days then taper
- intra-articular methylprednisolone if no sepsis on aspirate eg. 40mg for knee joint
- low dose colchicine 0.5mg bd if healthy adult over 50kg to prevent short term recurrence
- avoid colchicine in the elderly, weight < 50kg or severe liver or renal impairment.
- avoid changing anti-gout Rx as any sudden change in uric acid levels (esp. a fall) will exacerbate the attack.
- pts taking hypouricaemic Rx should continue and those not on any should not start until the acute attack is over.
- consider concurrent low dose colchicine 0.5mg bd to cover high risk starting phase of new hypouricaemic Rx
- Rx if either frequent attacks, tophi, joint destruction, or renal stones:
- take baseline U&E, uric acid level
- reduce alcohol consumption to reduce risk of acute attacks as there is dose-related risk:
- 1.36 (95% CI: 1.00 to 1.88) times higher for >1-2 alcoholic beverages/day
- 1.51 (95% CI: 1.09 to 2.09) times higher for >2-4 alcoholic beverages/day5)
- commence Rx to reduce uric acid levels:
- historically, the choice of drug is allopurinol starting at 200mg/day and increasing to 600mg/day
- assuming there is no evidence of acute gout but be aware of risks of allopurinol Rx:
- precipitation of acute gout attack
- rarely, a potentially fatal syndrome 1-6wks after starting Rx of:
- exfoliative rash
- renal failure
- NB. this syndrome is more likely if pre-existing renal insufficiency or concomitant diuretics
- in 2015, a new Rx, febuxostat was introduced and trials suggest it may be more effective than allopurinol but does risk cessation due to causing abnormal LFTs, and commencement needs to be covered with NSAIDs or colchicine for 6 months as flare ups at commencement are more likely.
- for patients with tophi, start at 40mg/d, if urate levels > 0.36mM after 2-4wks Rx, then increase to 80mg/d
- may also consider probenecid
- plus non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine 0.6mg bd for 6-12mths if frequent attacks
- BUT note that NSAIDs may have very limited efficacy for prevention of attacks
- Risk of no Rx:
- further exacerbation of gouty nephropathy
- renal stones
- gouty arthritic attacks
- further tophi
- joint destruction
gout.txt · Last modified: 2023/07/19 08:28 by gary1