Gout

Question 1

What are the 2 main types of crystal arthritis?

How can they be distinguished from each other?

Answer 1

• sodium urate crystals - seen in gout
• calcium pyrophosphate crystals - seen in pseudogout

they are distinguished by their different shapes and refringence properties under polarised light with a red filter

Question 2

Why is it not usually useful to check serum urate levels during an acute attack to diagnose gout?

Answer 2

gout results from high uric acid concentration

not all patients with a high blood urate level will develop gout, and having a low blood urate level cannot rule out gout

checking serum urate during an acute attack is not usually useful

Question 3

Which joint is most commonly affected by gout?

Answer 3

first metatarsalphalangeal (MTP) joint of the foot

but it can affect any joint, and can affect multiple joints simultaneously

Question 4

When diagnosing gout, when can it be obvious and when are further tests needed?

What other diagnosis should be considered?

Answer 4

• if it is the 1st MTP that is affected and other risk factors are present, it is likely to be gout
• it can be more difficult to diagnose if other joints are affected and a joint aspirate may be needed for diagnosis
• any joint is warm, red and painful should be considered septic arthritis until proven otherwise

Question 5

How do urate crystals appear when viewed under red polarised light?

Answer 5

they are negatively birefringent (appear yellow)

they appear as needle-shaped crystals

Question 6

What do calcium pyrophosphate crystals look like under red polarised light?

Answer 6

they are positively birefringent (appear blue)

they appear as rhomboid shapes

Question 7

How can a septic joint aspirate be distinguished from gout or pseudogout?

Answer 7

if the joint is septic, there are usually no crystals in the aspirate

the aspirate may appear purulent and will contain raised white cells on microscopy

a culture will also be positive

Question 8

Who is more likely to be affected by gout?

Answer 8

it is more common in men with a M : F ratio of 10 : 1

it affects 1.5% of the population but 10% of elderly men

age of onset is usually between 40 and 60

Question 9

In what groups is gout rarely seen and why?

Why is incidence increasing in women?

Answer 9

• rarely seen before puberty
• rarely seen in premenopausal women
• urate levels in the blood rise naturally with age (starts to rise after puberty)
• uric acid levels are higher in men than in women until the female menopause
• incidence is increasing in women due to wider use of thiazide diuretics

Question 10

What are the factors involved in the aetiology of gout?

Answer 10

it is multifactorial

in a genetically susceptible individual, certain circumstances can trigger the condition (usually diet related)

also body size, drugs and socio-economic status are involved

Question 11

What dietary factors are likely to be involved in triggering gout in a genetically susceptible individual?

Answer 11

• high protein diet, including seafood and red meat
• alcohol (particularly beer)
• high sugar intake (particularly high intake of sugary drinks)
• foods that have a high concentration of purine

Question 12

How can socio-economic status play a role in the aetiology of gout?

Answer 12

it tends to be more prevalent in richer populations

it is called a “rich man’s disease” because of its associations with alcohol and an expensive diet

Question 13

How can body size and drugs influence gout development?

Answer 13

there is a greater risk of developing gout in a larger body size

any diuretic increases risk of gout, but particularly thiazide diuretics

Question 14

What are the four clinical syndromes resulting from hyperuricaemia?

Answer 14

• acute urate synovitis (gout)
• chronic polyarticular gout
• chronic tophaceous gout
• urate renal stone formation

Question 15

What type of arthritis is gout usually?

Which joints tend to be affected?

Answer 15

it is usually a monoarthritis and is only a polyarthritis in 10% cases

the first metatarsalphalangeal (MTP) joint is affected in >65% cases

it also often affects the DIPs and PIPs

Question 17

How does acute urate synovitis (acute gout) tend to present?

Answer 17

tends to present in middle-aged men

there is a sudden onset of agonising pain

with swelling and redness of the first MTP joint

the attack occurs at any time but it is often precipitated by too much food or alcohol, dehydration or by starting a diuretic

Question 18

How long does an untreated acute gout attack last for?

What is recovery associated with?

Answer 18

untreated attacks typically last for 7 days

recovery is associated with desquamation of the overlying skin

(peeling skin)

Question 19

In severe attacks, what can make gout difficult to distinguish from cellulitis?

How can a diagnosis be made?

Answer 19

overlying crystal cellulitis makes gout difficult to distinguish from infective cellulitis

a family/personal history of gout and a raised serum urate suggest the diagnosis

if in doubt, blood and other cultures should be taken

Question 20

In what types of people is chronic polyarticular gout seen in?

Answer 20

• eldery people on long-standing diuretic treatment
• renal failure
• men who have been started on treatment with allopurinol too soon after an acute attack

Question 21

How does chronic tophaceous gout present differently?

Answer 21

individuals have very high levels of urate

the sodium urate forms smooth white deposits / crystals (tophi) in the skin and around the joints

they tend to occur on the ear, the fingers or the Achilles tendon

Question 22

What can happen to tophi is they are not treated?

What are other features of chronic tophaceous gout?

Answer 22

large crystal deposits are unsightly and can ulcerate

there is also chronic joint pain and superimposed acute gouty attacks

Question 23

Are tophi present in all types of gout?

Answer 23

NO

deposits of urate crystals in the skin only tend to occur in long-term, poorly controlled gout

(chronic tophaceous gout)

Question 24

Why can inflammatory arthritis and synovitis occur in acute gout?

Answer 24

• there is urate crystal deposition in the joints
• the urate crystals are phagocytosed by neutrophils
• in this process, these cells release inflammatory cytokines, attracting more neutrophils
• this sets off an inflammatory reaction that leads to inflammatory arthritis

Question 25

Which joint is most commonly affected by inflammatory arthritis and synovitis in gout? Why is the inflammation particularly bad when associated with gout?

Answer 25

the **_MTP of the first toe_** is most commonly affected the neutrophils **quickly die off,** so there is **_rapid turnover_** of cells this accelerates the inflammation this occurs because the **crystals are _toxic_ to the cells**

Question 26

What systemic feature often accompanies a presentation of gout?

Answer 26

there are warm, painful tender joints these are accompanied usually by **_pyrexia_**

Question 27

How can chronic tophaceous gout be identified on an X-ray?

Answer 27

periarticular deposits (tophi) lead to a **_halo of radio-opacity_** on X-ray and clearly defined **_("punched out") bone cysts_**

Question 28

What factors influence the levels of uric acid in the blood?

Answer 28

Uric acid levels depend on the balance between **_purine synthesis_** and the **_ingestion_ of dietary purines** and the **_elimination of urate_** by the **kidney and intestine**

Question 29

Why does the levels of purine sythesis and ingestion influence uric acid levels?

Answer 29

uric acid is the last step in the **breakdown pathway of purines** the last two steps in this pathway are: conversion of **_hypoxanthine_** to **_xanthine_** conversion of **_xanthine_** to **_uric acid_** they are both catalysed by the enzyme **_xanthine oxidase_**

Question 30

In what form does uric acid travel in the blood? What happens when levels are high in gout?

Answer 30

in the blood, uric acid is mostly found as **_monosodium urate_** in gout, there are **extremely high levels** of monosodium urate this high concentration allows for **_monosodium urate crystal_ formation**

Question 31

What is the clinical limit that defines hyperuricaemia?

Answer 31

when levels of uric acid in the blood are **\>2 standard deviations above the mean** this is a uric acid level **_\>0.4 mmol/L_**

Question 32

How is uric acid excreted normally by the body?

Answer 32

* uric acid is **completely filtered** by the glomerulus * **98-100%** is reabsorbed by the **proximal tubule** * **50%** is then secreted by the **distal tubule** * some **post-secretory reabsorption** takes place * the result is around **_5-10%_** of the glomerular load being **_excreted in the urine_** * around 1/3 of uric acid is eliminated in the faeces

Question 33

In \>75% of cases of gout, what is the problem causing it?

Answer 33

In \>75% of cases, the problem is with **_excretion of uric acid_** by the kidney there is not a problem with overproduction of uric acid (which is a result of overproduction of purine)

Question 34

What % of people with a high uric acid level actually have gout?

Answer 34

many people have a uric acid level high enough to cause gout, but live happily without symptoms only **_5%_** of those with a **_uric acid level \>0.5 mmol/L_** will have symptoms

Question 35

What is the defect associated with inherited gout?

Answer 35

* **absence** of the enzyme **_hypoxanthine guanine phosphoribosyl_** (HGPRT) * **overproduction** of **_5-phosphoribosyl-1-pyrophosphate synthase_** (PRPP) * both of these defects lead to **increased purine synthesis**, and **increased production of uric acid**

Question 36

What causes primary gout?

Answer 36

it results from an **inherited (X-linked) gene** this is either due to **_excess de novo purine synthesis_** or **_reduced renal excretion_** of uric acid

Question 37

What are enzyme defecrs resulting in excess de novo synthesis of purines in primary gout associated with?

Answer 37

* gout **before the age of 20** * **family history** of gout that presents at a young age * **_uric acid lithiasis_** present at presentation, particularly in a young person

Question 38

What does secondary gout result from?

Answer 38

any condition in which there is **_increased lysis of cells_** e.g. chemotherapy treatment cell lysis releases lots of **_nucleic acids_** into the bloodstream these are subsequently **broken down into _uric acid_**

Question 39

What prophylactic treatment is given to chemotherapy patients to prevent secondary gout?

Answer 39

**xanthene oxidase inhibitor**

Question 40

What conditions leading to decreased uric acid secretion cause primary and secondary gout?

Answer 40

disorders of uric acid excretion that are **_idiopathic_** cause **_primary gout_** this accounts for **75%** of all cases of gout decreased uric acid excretion can occur **_secondary_** to **_thiazide diuretics_** or **_chronic renal failure_** (secondary gout)

Question 41

When do patients often have a second gout attack? What happens if they are left untreated?

Answer 41

most patients have a second attack **_within 18 months_** if they are left untreated , they often suffer **more regular attacks** as time goes on

Question 42

What other conditions are associated with repeat acute attacks?

Answer 42

* arthritis * bursitis * cellulitis

Question 43

What features may develop after many acute attacks as part of chronic gout?

Answer 43

**_asymmetrical polyarthritis_** after many acute gout attacks, there may be: * **cartilage and bone erosion** * deposition of urate crystals, resulting in **tophi** * **secondary osteoarthritis** * restriction of **joint movements**

Question 44

After how many years are tophi typically seen? How does the severity of them reflect on severity of disease?

Answer 44

tophi are usually only seen after **_10+ years_** of **untreated / unresponsive gout** the severity of the tophi, and the rate of joint damage, are proportional to the severity of the disease

Question 45

What do tophi look / feel like? In what type of gout are they more likely to develop quickly?

Answer 45

* they are usually **_white_** with a texture like **toothpaste** * if they get caught on something, the discharge is **_white and chalky_** * they develop more quickly in **_secondary gout_** * their appearance helps to differentiate them from rheumatoid nodules

Question 46

What 5 investigations are used in gout?

Answer 46

**Serum urate:** * NOT useful in acute setting as it is only raised in 60% cases **WCC:** * often raised **ESR:** * often raised **Synovial fluid:** * ***_negatively birefringent_*** * high leucocyte count * can exclude bacterial infection **X-ray**

Question 47

When might an X-ray be used to investigate gout? What signs are looked for?

Answer 47

used to assess joint damage in patients with long-standing disease * **"punched out" / "rat bite" erosions** - looks like a bite has been taken out of the bone * **flecked calcifications**

Question 48

What other blood tests may be taken when investigating gout?

Answer 48

**serum urea and creatinine** to assess for signs of renal impairment

Question 49

What is the first line treatment for acute gout?

Answer 49

**NSAIDs** high doses rapidly (within hours) reduces pain and swelling

Question 50

What are the initial doses of 3 NSAIDs that are commonly prescribed for acute gout?

Answer 50

**_NAPROXEN:_** * 750mg immediately * then 500mg every 8 - 12 hours **_DICLOFENAC:_** * 75 - 100mg given immediately * then 50mg every 6 - 8 hours **_INDOMETACIN:_** * 75mg given immediately * then 50mg every 6 - 8 hours after 24-48 hours, reduced doses are given for a further week

Question 52

What medication is used in conjunction with NSAIDs or as a replacement in people who cannot tolerate NSAIDs? Who should not be given NSAIDs?

Answer 52

**_COLCHICINE_** typical dose is **1.2g stat**, followed by **600mg** every **12-24 hours** for up to **2-3 days** until symptoms resolve it is given to people with renal impairment or history of peptic ulceration it can cause GI upset

Question 53

When may steroids be used to treat acute gout?

Answer 53

often prednisolone effective, but more likely to cause side effects than colchicine or NSAIDs reserved for second line treatment when the others are contra-indicated or have been ineffective

Question 54

Should allopurinol (or other uric acid lowering drugs) be used for an acute attack? Why?

Answer 54

they are traditionally **_NOT recommended_** during the acute attack they have been thought to **make symptoms worse** during the attack 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 i_ncreases the risk_ of an attack***

Question 55

What triggers should be analysed and removed to try and prevent acute gout attacks?

Answer 55

* **_alcohol_** * particularly **beer** as it is high in purines * **_dietary excess_** * including too much food that is **high in purines** * lowering cholesterol and calorie intake * **fasting or severe dieting** * drugs - **_diuretics_** & **_uric acid lowering_** drugs * physical activity * surgery / trauma

Question 56

Under what conditions should allopurinol be used?

Answer 56

* only when attacks are **frequent and severe** * despite dietary changes * or when attacks are associated with **renal impairment** or **tophi** * or when the patient finds **NSAIDs or colchicine difficult to tolerate**

Question 57

What medication is sometimes recommended to be taken when starting allopurinol? Why?

Answer 57

a **_prophylactic course of NSAIDs_** for the **first 2-4 weeks before** and **4 weeks after** starting allopurinol starting allopurinol can provoke an acute attack of gout this will **reduce the risk of an attack by 2/3rds**

Question 58

How does allopurinol work?

Answer 58

* it blocks the enzyme **_xanthene oxidase_** * xanthene oxidase converts xanthene to urate * this **rapidly _reduces serum urate levels_**

Question 59

What should be checked before giving allopurinol? What initial dose should be given?

Answer 59

check **_renal function_** as lower doses (50 - 100mg) are required in patients with reduced renal function start at a low dose of **_50-100mg daily_** this can be titrated up to an effective dose - maximum of **_900mg daily_**

Question 60

What should be monitored to check the effectiveness of allopurinol?

Answer 60

**_serum urate level_** should be monitored **_every 3 weeks_** the aim is for serum urate to be **_\<0.36 mmol/L_**

Question 61

What is pseudogout and how does it usually present itself?

Answer 61

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**

Question 64

Who tends to be affected by pseudogout?

Answer 64

* it is **age related** - crystal deposition increases with age * slightly more common in **women** * often accompanies **osteoarthritis** * can be secondary to **phosphate metabolism disorders**

Question 65

Which joint is affected most commonly by pseudogout?

Answer 65

it presents as a **_monoarthritis_**, typically in the **elderly** it usually affects the **_knee_** particularly the **menisci** and the **articular cartilages**

Question 66

What are the symptoms associated with an acute attack of pseudogout? How long does an attack usually last for?

Answer 66

* acute onset of severe joint pain * joint swelling / effusion * tenderness * joint feels warm * joint may be erythematous attacks can last from a **few days** up to **4 weeks**

Question 67

What are the differentials for pseudogout?

Answer 67

* _gout_ * **_JOINT SEPSIS_** any red, hot swollen joint is treated as sepsis until proven otherwise

Question 68

What radiographic feature is seen in pseudogout?

Answer 68

**_CHONDROCALCINOSIS_** seen as **_horizontal white lines_** in the cartilage most commonly seen on X-rays of the knee

Question 69

What are the 2 different types of chronic presentation of pseudogout?

Answer 69

Chronic presentation is more common than acute and includes: * **persistent sub-acute inflammatory arthritis** * **​**this tends to resemble rheumatoid arthritis * very long history, similar to OA - often punctuated by acute attacks

Question 70

Which joints can be affected by pseudogout?

Answer 70

* knees * wrists * shoulders * elbows * MCPs * hips * tarsal joints severe destruction of joints is rare, but can occur and usually presents with subluxation of the affected joints

Question 71

What is the main investigation used to diagnose pseudogout?

Answer 71

**_JOINT ASPIRATION_** fluid is examined under **polarised red light** for **CPPD crystals** these are **_rhomboid shape_** and **_postively birefringent_** (appear blue)

Question 72

What is involved in the treatment of pseudogout? How is this different from conventional gout?

Answer 72

* the standard NSAID treatment of gout is not as effective * for the acute presentation, **intra-articular injections of steroids** are effective * sometimes systemic steroids are used