Crystal Arthritis - Gout + Pseudogout

Question 1

Describe the physiological pathway that leads to monosodium urate formation.

Answer 1

Purines -> hypoxanthine -> xanthine -> uric acid -> monosodium urate.

Question 2

What enzyme converts hypoxanthine to xanthine and xanthine to uric acid?

Answer 2

Xanthine oxidase

Question 3

What are crystal arthropathies?

Answer 3

A group of joint disorders caused by deposits of crystals in joints and the soft tissues around them.

Question 4

What are the 2 main types of crystal account for the majority of crystal induced arthritis?
Describe each one.

Answer 4

1. Monosodium urate crystals:
   * Needle-shaped (long and thin) urate crystals
   * Negatively bifringent under polarised light
2. Calcium pyrophosphate crystals:
   * Small rhomboid brick-shaped pyrophosphate crystals
   * Positively bifringent under polarised light

Question 5

What is gout?

Answer 5

An inflammatory arthritis + a type of crystal arthropathy that is associated with hyperuricaemia (high levels of uric acid) and intra-articular monosodium urate crystals

Question 6

What kind of crystals do you see in gout?

Answer 6

Monosodium urate crystals - negatively birefringent.

Question 7

With which disease would you associate negatively birefringent crystals?

Answer 7

Gout - monosodium urate crystals that are thin and needle shaped.

Question 8

Describe the epidemiology of gout.

Answer 8

• Gout is common
• Male > Females
• Rarely occurs before young adulthood
• Most common inflammatory arthritis in the UK

Question 9

Give 5 factors that can lead to increased levels of monosodium urate.

Answer 9

1. Increased intake e.g. alcohol, red meat, seafood.
2. Cell turnover (increased production).
3. Cell damage e.g. due to surgery.
4. Cell death e.g. due to chemotherapy.
5. Reduced excretion (renal problems).
6. Drugs e.g. bendroflumethiazide - diuretics impair urate excretion.
7. High insulin.

Question 10

Give 3 risk factors for gout.

Answer 10

1. High alcohol intake
2. Obesity
3. > 50 YO
4. High purine diet (e.g. red meat - liver + seafood)
5. FHx
6. Thiazide diuretics
7. Male
8. Existing cardiovascular or kidney disease - IHD.
9. High fructose intake (sugary drinks, cakes, sweets and fruit sugars) - reduces uric acid excretion
10. High saturated fat diet

Question 11

What foods have high purines?

Answer 11

1. Red meat
2. Seafood
3. Alcohol
4. Beans/lentils
5. Mushrooms
6. Carbonated drinks / fructose

Question 12

Other than diet, give 2 causes of too much uric acid production.

Answer 12

Increased cell turnover, as in:
- Myeloproliferative disorders
- Psoriasis
- Tumour lysis syndrome

Question 13

What drugs can impair uric acid excretion?

Answer 13

1. Tacrolimus
2. Aspirin
3. Thiazides

Question 14

Name a drug that can lead to increased monosodium urate.

Answer 14

Bendroflumethiazide.

Diuretics impair urate excretion.

Question 15

What happens when urate crystals are deposited in the joint?

Answer 15

They activate phagocytes –> inflammation –> joint pain (gout)

Question 16

Which joint is most commonly affected in gout?

Answer 16

1st MTPJ (metatarsalphalyngeal joint) - big toe

Question 17

Describe the clinical presentation of an acute gout attack - 1 key symptom.

Answer 17

1. Sudden onset of agonising pain, swelling, hot + redness of the first MTP joint - BIG TOE
2. Usually just 1 joint affected but can sometimes be polyarthritic
   e.g. ankle, foot, small joint of hand, wrist, elbow or knee

Question 18

Give 3 precipitating factors of an acute gout attack.

Answer 18

1. Excess alcohol
2. Excess food e.g. red meat, shellfish
3. Sudden cessation/starting of gout therapy
4. Trauma
5. Surgery
6. Infection
7. Dehydration or diuretic therapy

Question 19

Describe the clinical presentation of chronic gout.

Answer 19

1. Tophi:
   = Subcutaneous deposits of uric acid (smooth white deposits on the skin)
   = Typically affecting the small joints and connective tissues of the fingers, elbows, ears & Achilles tendon
2. Chronic joint pain
3. Tophi may ulcerate.

Question 20

What are tophi?

Answer 20

Onion-like aggregates of monosodium urate crystals
with inflammatory cells.

• Smooth white deposits (tophi) in the skin and around joints, on
  the ear, fingers or the Achilles tendon
• Proteolytic enzymes are released -> erosion.

Question 21

Name 4 diseases that someone with gout might have an increased risk of developing.

Answer 21

1. Hypertension.
2. CV disease e.g. stroke.
3. Renal disease.
4. Type 2 diabetes.
5. Osteoarthritic damage to joints.

Question 22

Investigations for gout.

Answer 22

1. Joint fluid aspiration & microscopy:
   * DIAGNOSTIC
   * Shows long needles-shaped crystals that are NEGATIVELY bifringent under polarised light
2. Bloods - Serum uric acid is raised:
   * If it is not, it should be rechecked several weeks after the attack, as level fall immediately after an acute episode
3. Serum urea and creatinine & eGFR:
   - to monitor for signs of renal impairment

Question 23

What do you see in the joint aspirate in gout?

Answer 23

Needle shaped crystals that are negatively birefringent.

Question 24

What do you see on an x ray in gout?
How can you differentiate it from other arthritis?

Answer 24

Joint effusion.
Punched out lesions.

No loss of joint space.
No peri-articular osteopenia.

Question 25

What is the aim of treatment for gout?

Answer 25

To get urate levels < 300μmol/L.

Question 26

Describe the treatment for an acute attack of gout.

Answer 26

1. NSAIDs - high dose OR COX inhibitor e.g. Naproxen / Ibruprofen e.g. Aspirin 2. Colchicine if NSAIDs are ineffective. - Used in patients with renal impairment or significant heart disease - Targets uric acid crystallisation - Very toxic in overdose - Side effects: diarrhoea and abdominal pain 3. Corticosteroids - IM or IA. * IA = most effective, but can be painful - e.g PREDNISOLONE

Question 27

If NSAIDs cannot be used in an acute gout attack, what is the next step?

Answer 27

Give Colchicine

Question 28

What is the main side effect of colchicine?

Answer 28

A notable side effect is gastrointestinal upset. Diarrhoea is a very common side effect.

Question 29

how would you prevent recurrent gout attacks?

Answer 29

1. Lifestyle modifications - Lose weight - Less alcohol - Avoid purine rich food e.g. liver and seafood e.g. shellfish - Dairy can help reduce gout! 2. Stop diuretics (thiazides) -> switch to to angiotensin receptor blocker e.g. LOSARTAN = an uricosuric - promotes uric acid excretion 3. Allopurinol - Wait until 3 wks after the attack (can precipitate an attack intially!) - Xanthine oxidase inhibitor (stops the conversion of purines to uric acid)

Question 30

What drug is 1st line for maintaining remission of gout / prevention of gout? What is the mechanism of action? Give 2 side effects.

Answer 30

Allopurinol. Xanthine oxidase inhibitor = stops the conversion of purines to uric acid. SE: rash, headache, hypersensitivity

Question 31

Which drug should be used for gout prevention if allopurinol is contraindicated?

Answer 31

FEBUXOSTAT: - Non purine Xanthine oxidase inhibitor - Use if Allopurinol is contraindicated or due to side effects

Question 32

What is the 2nd line treatment for gout? When should it not be used?

Answer 32

Febuxostat. Not for renal or hepatic impairment.

Question 33

You see a patient with gout who is taking bendroflumethiazide. What drug might you replace this with to help treat their gout?

Answer 33

You would switch bendroflumethiazide to cosartan as bendroflumethiazide is a diuretic and so impairs urate excretion.

Question 34

A patient presents with an acute mono-arthropathy of their big toe. What are the 2 main differential diagnoses?

Answer 34

1. Gout. 2. Septic arthritis. Exclude septic arthritis in any acute monoarthropathy!!

Question 35

What is pseudogout?

Answer 35

A crystal arthropathy caused by the deposition of calcium pyrophosphate crystals in the joint, causing joint problems. It is also known as chondrocalcinosis.

Question 36

Describe the pathophysiology of pyrophosphate arthropathy (pseudogout).

Answer 36

Calcium pyrophosphate crystals are deposited on joint surfaces. The crystals elicit an inflammatory response.

Question 37

What can cause pyrophosphate arthropathy (pseudogout)?

Answer 37

1. Hypo/hyperthyroidism. 2. Diabetes. 3. Haemochromatosis. 4. Magnesium levels. 5. Old age 6. Osteoarthritis 7. Joint trauma/injury

Question 38

Give 3 risk factors for pseudogout.

Answer 38

1. Osteoarthritis 2. Age 3. Haemachromotosis 4. High PTH 5. Low phosphate 6. Low magnesium 7. Hypothyroidism 8. Acromegaly 9. Illness 10. Surgery 11. Trauma

Question 39

What kind of crystals do you see in pseudogout?

Answer 39

Calcium pyrophosphate crystals - positively birefringent.

Question 40

With which disease would you associate positively birefringent crystals?

Answer 40

Pseudogout - pyrophosphate crystals that are rhomboid shaped.

Question 41

What joints does pseudogout affect?

Answer 41

Larger joints - knee/wrist/elbow/shoulder. Symmetrical, if chronic.

Question 42

Describe the clinical presentation of pseudogout.

Answer 42

Acute, hot + swollen joints - typically the wrist or knee - Very painful attacks - More common in elderly women

Question 43

what disease must you assume a patient presenting with acute pseudo-gout has, until proven otherwise?

Answer 43

Septic arthritis

Question 44

What investigations might you do in someone who you suspect might have pyrophosphate arthropathy (pseudogout)?

Answer 44

1. Joint fluid aspiration & microscopy: * Small rhomboidal crystals under microscopy * Positively bifringent crystals under polarised light - REMEMBER since Pseudogout = Positively bifringent * Joint fluid look purulent so should be sent for culture to exclude septic arthritis 2. X-ray: * Shows chonedrocalcinosis - linear calcification parallel to the articular surfaces 3. Bloods: - Raised WCC

Question 45

What kind of crystals do you see in the joint aspirate in pseudogout?

Answer 45

Rhomboid shaped. Positively birefringent.

Question 46

What might you see on the X ray of pseudogout?

Answer 46

Chondrocalcinosis: - It appears as a thin white line in the middle of the joint space caused by the calcium deposition. Calcification of cartilage. (neither is specific)

Question 47

Management for pseudogout.

Answer 47

1. NSAIDs - high dose OR COX inhibitor e.g. Naproxen / Ibruprofen e.g. Aspirin 2. Colchicine if NSAIDs are ineffective. - Used in patients with renal impairment or significant heart disease - Targets uric acid crystallisation - Very toxic in overdose - Side effects: diarrhoea and abdominal pain 3. Corticosteroids - IM or IA (intra-articular) * IA = most effective, but can be painful - e.g PREDNISOLONE 4. Aspiration of the joint = Reduced pain dramatically!!

Question 48

How does pseudo-gout present differently from gout?

Answer 48

Usually occurs in larger joints (e.g. knee) - but pain is similar