Gout and Pseudogout
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Gout is a type of crystal arthritis. The other main type of crystal arthritis is that in which calcium pyrophosphate crystals are formed (pseudogout).

Gout is a disorder resulting from high concentration of uric acid. However, not all patients with a high blood urate level get gout, and having a low blood urate level does not rule out gout as a diagnosis!
Therefore, during an acute attack, checking the serum urate to confirm that diagnosis is not usually useful.
However, serum urate levels can and should be used to monitor the effectiveness of long-term preventative management (usually allopurinol – see below)
Typically it presents in the 1st MTP (metatarsal – phalangeal joint) of the foot, but can affect any joint, and rarely, multiple joints can be affected simultaneously.
It is traditionally viewed as a ‘nuisance’ rather than a serious diagnosis, but it causes significant morbidity (typically lots of sick days from work) in a significant number of sufferers.
The initial diagnosis is often obvious (if in the 1st MTP and has risk factors) but it may be more difficult if other joints are affected (e.g. the knee) – and a joint aspirate may be required for the diagnosis.
Any joint that is warm, red and painful should be considered septic arthritis until proven otherwise.
  • Gout and pseudogout can be differentiated by examination of the fluid aspirate contents of a joint viewed under polarised red light:
  • Urate crystals – are negatively birefringent – they will appear a needle shaped crystals (image below).
Gout Crystals on Microscopy
Gout Crystals on Microscopy
  • Calcium phosphate crystals – are positively birefringent – they will appear as rhomboid shapes
  • This is often a question in MCQ in exams !
  • If the joint is septic (often the other main differentials – and the reason for joint aspiration) – then there are usually no crystals, but the aspirate may appear purulent, will contain raised white cells on microscopy and a culture will be positive.


  • More common in men (M:F – 10:1)
  • Affects about 1.5% of the population – but 10% of elderly men
  • Incidence is increasing in women due to the wider use of thiazide diuretics
  • Age of onset usually 40-60
  • Rare before puberty
  • Rare in premenopausal women
  • Urate levels in the blood rise naturally with age


  • Multifactorial. Genetic components, but other factors also involved. In a genetically susceptible individual, certain circumstances may trigger the condition.
    • Diet – red meat, seafood and alcohol 
    • Also, high sugar intake – particular large intake of sugary drinks
    • Other foods that have a high concentration of purine
  • Socio-economic status – more prevalent in richer populations – “Rich Man’s disease” – possibly because of its associations with alcohol and an expensive diet.
  • Body size – greater risk in larger body size
  • Drugs
    • Any diuretic, but particularly thiazide diuretics

Clinical features

  • Usually a monoarthritis
    • Only polyarthritis in 10% of cases
    • MTP is the joint affected in >65% of patients
    • Also often affects the PIP’s and DIP’s
  • Tophi – deposits of urate crystals in the skin. Chalky in texture. The MTP joint in the foot is the most common place for crystal deposition – gravity might play a role.
    • Typically the result of long-term, poorly controlled gout
    • Rare in the hip and knee
  • Inflammatory Arthritis and synovitis – due to urate crystal deposition in the joints. The urate crystals are phagocytosed by neutrophils, but in the process, these cells release inflammatory cytokines, attracting more neutrophils, and setting off an inflammatory reaction, resulting in an inflammatory arthritis.
    • The MTP of the first toe is most commonly affected.
    • This neutrophilic mechanism is the same is calcium phosphate crystal arthritis
    • The neutrophils quickly die off, and thus there is a rapid turnover of cells. This accelerates the inflammation. This is because the crystals are toxic to the cells.
  • Warm, tender, painful joints
  • Pyrexia is also often present
  • Stone formation aka urolithiasisin the kidney and bladder – may cause associated symptoms
    • There may also be secondary pyelonephritis, although renal insufficiency is not usually caused by gout, and any proteinuria is probably age related, mild, and non-progressive
Classical gout appearance 1st MTP
Classical gout appearance 1st MTP. This file is taken from wikimedia commons and is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.




  • Uric acid is a breakdown product of metabolism
  • Small amounts are also taken up in the diet
  • In the blood, it is mostly in the form monosodium urate. In gout, levels of monosodium urate are extremely high. This high concentration allows monosodium urate crystal formation.
  • In the inherited form of the disease there is often an absence of the enzyme HGPRT – hypoxanthine guanine phosphoribosyl, OR, an overproduction of PRPP – 5-phosphoribosyl-1-pyrophosphate.
  • in >75% of cases, the problem is a problem with excretion of uric acid by the kidney, and not a problem with overproduction of uric acid (which is the result of overproduction of purine)
  • Many patients have a uric acid level high enough to cause gout, but live happily without symptoms.
    • Only 5% of those with a uric acid level >0.5mmol/L will have symptoms

Types of gout

  • Primary gout – may result from an inherited (X-linked) gene. Is either due to excess de novo purine synthesis, or reduced renal excretion of uric acid. Enzyme defects resulting in excess de novo synthesis are associated with:
    • Gout before the age of 20
    • FH of gout that presents at an early age
    • Uric acid lithiasis is present at presentation, particularly in a young person
  • Secondary gout – results from:
    • Any condition in which there is increased lysis of cells – e.g. in chemotherapy treatment. This releases lots of nucleic acids (Which are subsequently broken down into uric acid) in the bloodstream
    • Most chemotherapy patients are now treated prophylactically with a xanthene oxidase inhibitor.
    • Disorders of decreased uric acid excretion, which can be:
    • Idiopathic – accounts for 75% of all cases of gout (primary gout)
    • Secondary to THIAZIDE DIURETICS, or CHRONIC RENAL FAILURE (secondary gout)


Acute gout – will typically last about 7 days, and may resolve itself if left untreated. With effective treament, symptoms often subside within a couple of days
  • Acute monoarthritis – usually in a distal joint – e.g. hand or foot. MTP of the big toes is affected in >50% of patients. Sometimes also occurs in the knee elbow and wrist. Other joints are not affected.
  • Pain may be so severe it wakes the patient during the night
  • Hot, red, swollen, tender joint
  • Will usually resolve within a couple of weeks, with few remaining signs.
  • Some patients may only ever have one attack
  • Most patients have a second attack within 18 months. If patients are left untreated, they will often suffer more regular attacks as time goes on.
  • Arthritis, bursitis and cellulitis may be associated with these repeated acute attacks.


Chronic (tophaceous) gout – occurs after many attacks. Some patients may never have remission.

  • Asymmetrical polyarthritis
  • After many attacks, there may be:
    • Cartilage and bone erosion
    • Deposition of urate crystals – resulting in tophi
    • Secondary OA
    • Restriction of joint movements
  • The severity of the tophi, and the rate of joint damage are proportional to the severity of the disease
  • Tophi are only usually seen after 10+ years of untreated/unresponsive gout
  • They often develop more quickly in secondary gout – e.g. due to thiazide diuretics
  • Tophi are usually white. They may get caught on things as the patients move around, in which case, the discharge is usually chalky.
  • If you feel them under the skin, they have a texture like toothpaste
  • The white appearance of the tophi can help differentiate them from rheumatoid nodules.


  • Serum Urate – will only be raised in 60% of cases – NOT useful in the acute setting
  • WCC – often raised
  • ESR – often raised
  • Synovial fluid
    • Negatively birefringent
    • High leucocyte count
    • Exclude bacterial infection
  • x-ray – may be used in patients with long-standing disease, to assess joint damage. Sings can include:
    • ‘Punched-out erosions’ – look a little bit like something has taken a bit out of the side of a bone!
    • Flecked calcifications


Acute gout
  • NSAIDscan cause rapid (within hours) relief of symptoms. !st line treatment
  • Colchicine – is also sometimes used in conunction with NSAIDs and is especially useful in those who can’t tolerate NSAIDs. It can cause GI upset. Typical reccomended dose is 1.2g stat, followed by 600mg dose every 12-24 hours for up to 2-3 days until symptoms resolve.
  • Steroids – e.g. prednisone – often effective, but more likely to cause side effects than colchicine and NSAIDs. Usually reserved as second line where the above have been inneffective, or are contra-indicated
  • Allopurinol – or other uric acid lowering drugs traditionally not recommended during the acute attack – as these drugs have been thought to make the symptoms worse during the attack. However, recent evidence suggests that if they are started with acute treatment for gout, there is no increased risk of worsening the attack. BUT starting this medication outside of an acute attack does increase the risk of having an acute attack
  • Analyse and remove any triggers, e.g.:
    • Alcohol
    • Dietary excess
    • Drugs – Diuretics & Uric acid lowering drugs
    • Fasting or severe dieting
    • Surgery
    • Trauma
    • Unusual physical exercise
Long Term
Allopurinol – prevents urate acid synthesis, by inhibiting the enzyme xanthene oxidase.
Remember – starting allopurinol (or other similar urate lowering medications) can provoke an acute attack of gout. Some guidelines recommend a prophylactic course of NSAIDs when starting allopurinol to reduce this risk (reduces risk of attack by about 2/3rds).
Some guidelines now also state that it is safe to start allopurinol during an acute attack – as long as appropriate gout treatment is given – as there doesn’t seem to be a link between starting allopurinol and worsening the symptoms of the acute attack.
  • Always check renal function before giving the medication – lower doses are required in patients with reduced renal function
  • Start at a low dose (e.g. 50-100mg daily)
  • Titrate up to an effective dose – maximum of 900mg daily
  • Monitor serum urate level every 3 weeks to check effectiveness – aim for serum urate <0.36mmol/L


  • Renal disease


This is essentially deposition of calcium pyrophosphate dehydrate (CPPD)crystals. The crystals tend to deposit themselves in articular cartilage. It usually presents as a monoarthritis of the elderly.
  • It is also sometimes referred to as CPPD arthritis

Epidemiology and Aetiology

  • Age related – crystal deposition generally increases with age
  • Chondrocalcinosis seen in:
    • 5% under age 70
    • 30% over age 85
  • Slightly more common in women
  • Often accompanies OA
  • Can be secondary to phosphate metabolism disorders

Clinical features

  • Monoarthritis; usually elderly
  • Knee most commonly affected; particularly the menisci and articular cartilages
  • Acute attacks:
    • Attacks can last from a few days, up to 4 weeks
    • Joint swelling / effusion
    • Acute onset
    • Tenderness
    • Severe joint pain
    • Joint feels warm
    • Joint may be erythematous
    • Differentials:
      • Joint sepsisany hot, red swollen joint is sepsis until proven otherwise!
      • Gout
  • Chondrocalcinosis – seen radiographically as white horizontal lines in the cartilage – most commonly in x-rays of the knee
  • Chronic presentation is more common than the acute. There are two main types of chornic presentation:
    • Persistent sub-acute inflammatory arthritis – may resemble Rheumatoid Arthritis
    • Very long history, similar to OA – often punctuated by acute attacks
  • Joint affected:
    • Knees
    • Wrists
    • Shoulders
    • Elbows
    • MCP’s
    • Hips
    • Tarsal joints
  • Severe destruction of joints is rare, but can occur – usually presenting with subluxation of the affected joints


  • Joint aspiration
    • Examination of fluid under polarised light for CPPD crystals – which are rhomboid shaped, and thus can be distinguished from the needle-like crystals of gout. The crystals are positively birefringent.
    • Microbiology of aspirated fluid – to check for joint sepsis.
  • Radiographs – may show chondrocalcinosis


  • The standard NSAID treatment of gout is not as effective in cases of pseudogout.
  • Intra-articular injections of steroids – are useful at treating the acute presentation
  • Sometimes systemic steroids may be used
  • Long-term specific treatments to prevent organ damage are not widely used


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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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