Gout and Pseudogout
Gout is a type of crystal arthritis. The other main type of crystal arthritis is that in which calcium pyrophosphate crystals are formed (pseudogout).
- You can tell the difference between the two types if you aspirate the contents of a joint, and then view it under polarised red light:
- Urate crystals – are negatively birefringent – they will appear a needle shaped crystals (image below).
- Calcium phosphate crystals - are positively birefringent – they will appear as rhomboid shapes
- This is often a question in MCQ in exams !
Gout is a disorder resulting from high concentration of uric acid in the blood stream. 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!
- More common in men (M:F – 10:1)
- 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 bit like diabetes in that in a genetically susceptible individual, certain circumstances may trigger the condition.
- Diet – meat and alcohol increase the risk
- 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
- 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.
- 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.
- Warm, tender, painful joints
- Pyrexia is also often present
Stone formation aka urolithiasis – in 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
- 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.
- The clinical definition is usually when levels of uric acid in the blood are >2 standard deviations above the mean.
- Clinically, this is a uric acid level >0.4mmol/L
- 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.
- 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
- WCC – often raised
- ESR – often raised
- 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
- NSAIDs – can 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.
- Allopurinol – or other uric acid lowering drugs should not be commenced until after the episode has passed! – as these drugs can actually can actually make the symptoms worse during the attack.
- Analyse and remove any triggers, e.g.:
Allopurinol – prevents urate acid synthesis, by inhibiting the enzyme xanthene oxidase.
- Always check renal function before giving the medication
- 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
- Monoarthritis; usually elderly
- Knee most commonly affected; particularly the menisci and articular cartilages
- Acute attacks:
- 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:
- Tarsal joints
- Severe destruction of joints is rare, but can occur – usually presenting with subluxation of the affected joints
- 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