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An introduction to gout


Gout – an introduction

The amount of evidence concerning gout is surprisingly limited. This essay examines what is common knowledge from contemporary textbooks, to be supplemented by searching for evidence on treatment from systematic reviews, or clinical trials.

What is gout?

Gout describes a group of metabolic disorders where crystals of sodium urate (the sodium salt of uric acid) deposit in tissue. This usually follows a prolonged period where uric acid levels in blood are raised.

Uric acid is the end product of purine metabolism, and humans and higher apes lack an enzyme, urease, that further degrades uric acid. Two thirds of the uric acid formed each day is eliminated in the gastrointestinal tract or kidneys.

The increase in blood uric acid results from increased purine intake (purines are precursors of uric acid), or increased turnover or production, or from decreased uric acid elimination by the kidneys, or a combination of all these (Figure 1). Though higher purine intake may play a part in high blood uric acid levels, excretion by the kidney should increase to compensate. In most (75%-90%) people with gout, clearance of uric acid by the kidney is significantly reduced. Increased uric acid production or decreased renal clearance can be secondary to other disorders (Table 1).

Figure 1: Purines and uric acid

Table 1: Increased uric acid production and decreased elimination

Increased uric acid production

Decreased uric acid excretion





Specific enzyme defects Specific enzyme defects Idiopathic Chronic renal mass
  myelo or lyphoproliferative disorders Familial juvenile gouty nephropathy Kidney injury
Infectious mononucleosis   Volume depletion
Chronic haemoolytic anaemia Hypertension
Gaucher's disease Sickle cell anaemia
Severe proliferative psoriasis Hypothyroidism
  Down's syndrome
Beryllium or lead poisoning
Drugs like diuretics, low dose aspirin

The problems that can results are:

High blood uric acid

High blood uric acid is defined as a serum urate level more than two standard deviations from the mean, or 0.42 mmol/L (7 mg/100 mL) for adult males and 0.36 mmol/L (6 mg/100 mL) for adult females. Serum is saturated with sodium urate at 0.42 mmol/L, but higher concentrations of urate can remain stable in solution in a super-saturated state. When something triggers it, the supersaturated solution in blood or tissue (including joints) produces crystals.

Diagnosing gout

The American College of Rheumatology has 11 criteria, and the presence of six more or less suggests that gout is present. The 11 criteria are:

  1. More than one attack of active arthritis
  2. Maximum inflammation develops within one day
  3. Oligoarthritis attack
  4. Redness observed over joint
  5. First metatarsalophalangeal joint painful or swollen
  6. Unilateral first metatarsalophalangeal joint attack
  7. Unilateral tarsal joint attack
  8. Tophus (proven or suspect)
  9. Hyperuricaemia
  10. Asymetrical swelling within a joint on radiography
  11. Complete termination of an attack

Who gets gout?

Older men and women after the menopause, though it is always more common in men (10:1). In men the number of cases rises with age from 2/1,000 in men aged 18-44, and 34/1,000 in men between 45 and 65. In a population of 100,000 people there will be about 30 new cases a year with about 250 cases in total.

The natural history of gout

Gout, if untreated, evolves through four stages:

1 Asymptomatic hyperuricaemia

Crystals probably take a long time (months or years) to accumulate, most commonly in peripheral connective tissues in and around synovial joints, especially in the lower limbs. During this period there may well be no symptoms whatsoever. About 95% of people with hyperuricaemia will remain asymptomatic throughout their lives.

2 Acute attacks

A single peripheral joint is almost always involved in all initial episodes, and most often this is the metatarsalophalangeal joint between wrist and finger. Typically local irritation and aching proceeds to tissues becoming swollen, red, hot, shiny and extremely painful. The pain is often describes as the worst ever experienced. By 24 hours inflammation is maximal, and it then resolves slowly over a week or so, often with itching and flaking of overlying skin.


3 Intercritical gout

These are asymptomatic periods between attacks. Some never have a second attack, or perhaps after many years, but in most the second attack occurs with a year. The frequency of attacks and number of sites then increase with time, leading eventually to joint damage and chronic pain, after an average of about 10 years.

4 Chronic tophaceous gout

Large crystal deposits, or tophi, produce irregular firm nodules, predominantly around the upper surfaces of the fingers and hands, but other places as well, including forearms or Achilles tendons or ears. When untreated, these can lead to severe deformity.

Primary and secondary gout

Table 2 shows the circumstances that likely define primary and secondary (often diuretic-induced) gout. Primary gout develops most often in men between 30 and 60 years. Secondary gout usually results from chronic diuretic therapy and presents in older subjects, often older than 65 years.

Table 2: Primary and secondary gout




Sex Male much more than female Male = female
Age Middle aged Elderly
Acute attacks Common Uncommon
Tophi Develop late Develop early
Associations Obesity, hypertension, hyperlipidaemia, high alcohol intake Renal impairment, osteoarthritis

Treating gout

Treating acute attacks

Here treatment aims to reduce pain and inflammation, usually with nonsteroidal antiinflammatory drugs (NSAIDs) given in full dosage. Oral colchicine is also used, but produces severe diarrhoea, cramps and nausea accompany effective doses. Joint aspiration and lavage are also used to treat acute attacks.

Long-term management

The aims here are to try and eliminate any modifiable factors that cause high blood uric acid, and then use treatments to reduce high uric acid levels in serum.

Lifestyle changes in early primary gout involve weight loss, reduction in alcohol consumption and avoidance of toxins like low-dose aspirin and lead. With diuretic-induced gout stopping the diuretic may be possible and be all that is required.

The usual choice for reducing uric acid levels is allopurinol, because it inhibits xanthine oxidase and can depress new purine synthesis. Probenecid prevents proximal tubular reabsorption of urate.


Gout has little in the way of a strong evidence-base in the form of systematic reviews. Bandolier could find none on searching. Yet there is a strong empirical base of experience that Bandolier will seek to bolster through finding what evidence it can.