Crystal Arthritis - Gout + Pseudogout Flashcards
Describe the physiological pathway that leads to monosodium urate formation.
Purines -> hypoxanthine -> xanthine -> uric acid -> monosodium urate.
What enzyme converts hypoxanthine to xanthine and xanthine to uric acid?
Xanthine oxidase
What are crystal arthropathies?
A group of joint disorders caused by deposits of crystals in joints and the soft tissues around them.
What are the 2 main types of crystal account for the majority of crystal induced arthritis?
Describe each one.
- Monosodium urate crystals:
* Needle-shaped (long and thin) urate crystals
* Negatively bifringent under polarised light - Calcium pyrophosphate crystals:
* Small rhomboid brick-shaped pyrophosphate crystals
* Positively bifringent under polarised light
What is gout?
An inflammatory arthritis + a type of crystal arthropathy that is associated with hyperuricaemia (high levels of uric acid) and intra-articular monosodium urate crystals
What kind of crystals do you see in gout?
Monosodium urate crystals - negatively birefringent.
With which disease would you associate negatively birefringent crystals?
Gout - monosodium urate crystals that are thin and needle shaped.
Describe the epidemiology of gout.
- Gout is common
- Male > Females
- Rarely occurs before young adulthood
- Most common inflammatory arthritis in the UK
Give 5 factors that can lead to increased levels of monosodium urate.
- Increased intake e.g. alcohol, red meat, seafood.
- Cell turnover (increased production).
- Cell damage e.g. due to surgery.
- Cell death e.g. due to chemotherapy.
- Reduced excretion (renal problems).
- Drugs e.g. bendroflumethiazide - diuretics impair urate excretion.
- High insulin.
Give 3 risk factors for gout.
- High alcohol intake
- Obesity
- > 50 YO
- High purine diet (e.g. red meat - liver + seafood)
- FHx
- Thiazide diuretics
- Male
- Existing cardiovascular or kidney disease - IHD.
- High fructose intake (sugary drinks, cakes, sweets and fruit sugars) - reduces uric acid excretion
- High saturated fat diet
What foods have high purines?
- Red meat
- Seafood
- Alcohol
- Beans/lentils
- Mushrooms
- Carbonated drinks / fructose
Other than diet, give 2 causes of too much uric acid production.
Increased cell turnover, as in:
- Myeloproliferative disorders
- Psoriasis
- Tumour lysis syndrome
What drugs can impair uric acid excretion?
- Tacrolimus
- Aspirin
- Thiazides
Name a drug that can lead to increased monosodium urate.
Bendroflumethiazide.
Diuretics impair urate excretion.
What happens when urate crystals are deposited in the joint?
They activate phagocytes –> inflammation –> joint pain (gout)
Which joint is most commonly affected in gout?
1st MTPJ (metatarsalphalyngeal joint) - big toe
Describe the clinical presentation of an acute gout attack - 1 key symptom.
- Sudden onset of agonising pain, swelling, hot + redness of the first MTP joint - BIG TOE
- Usually just 1 joint affected but can sometimes be polyarthritic
e.g. ankle, foot, small joint of hand, wrist, elbow or knee
Give 3 precipitating factors of an acute gout attack.
- Excess alcohol
- Excess food e.g. red meat, shellfish
- Sudden cessation/starting of gout therapy
- Trauma
- Surgery
- Infection
- Dehydration or diuretic therapy
Describe the clinical presentation of chronic gout.
- 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 - Chronic joint pain
- Tophi may ulcerate.
What are tophi?
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.
Name 4 diseases that someone with gout might have an increased risk of developing.
- Hypertension.
- CV disease e.g. stroke.
- Renal disease.
- Type 2 diabetes.
- Osteoarthritic damage to joints.
Investigations for gout.
- Joint fluid aspiration & microscopy:
* DIAGNOSTIC
* Shows long needles-shaped crystals that are NEGATIVELY bifringent under polarised light - 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 - Serum urea and creatinine & eGFR:
- to monitor for signs of renal impairment
What do you see in the joint aspirate in gout?
Needle shaped crystals that are negatively birefringent.
What do you see on an x ray in gout?
How can you differentiate it from other arthritis?
Joint effusion.
Punched out lesions.
No loss of joint space.
No peri-articular osteopenia.
What is the aim of treatment for gout?
To get urate levels < 300μmol/L.
Describe the treatment for an acute attack of gout.
- NSAIDs - high dose OR COX inhibitor
e.g. Naproxen / Ibruprofen
e.g. Aspirin - 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 - Corticosteroids - IM or IA.
* IA = most effective, but can be painful
- e.g PREDNISOLONE
If NSAIDs cannot be used in an acute gout attack, what is the next step?
Give Colchicine
What is the main side effect of colchicine?
A notable side effect is gastrointestinal upset.
Diarrhoea is a very common side effect.
how would you prevent recurrent gout attacks?
- Lifestyle modifications
- Lose weight
- Less alcohol
- Avoid purine rich food e.g. liver and seafood e.g. shellfish
- Dairy can help reduce gout! - Stop diuretics (thiazides) -> switch to to angiotensin receptor
blocker
e.g. LOSARTAN = an uricosuric - promotes uric acid excretion - Allopurinol
- Wait until 3 wks after the attack (can precipitate an attack intially!)
- Xanthine oxidase inhibitor (stops the conversion of purines to uric acid)
What drug is 1st line for maintaining remission of gout / prevention of gout?
What is the mechanism of action?
Give 2 side effects.
Allopurinol.
Xanthine oxidase inhibitor = stops the conversion of purines to uric acid.
SE: rash, headache, hypersensitivity
Which drug should be used for gout prevention if allopurinol is contraindicated?
FEBUXOSTAT:
- Non purine Xanthine oxidase inhibitor
- Use if Allopurinol is contraindicated or due to side effects
What is the 2nd line treatment for gout?
When should it not be used?
Febuxostat.
Not for renal or hepatic impairment.
You see a patient with gout who is taking bendroflumethiazide. What drug might you replace this with to help treat their gout?
You would switch bendroflumethiazide to cosartan as bendroflumethiazide is a diuretic and so impairs urate excretion.
A patient presents with an acute mono-arthropathy of their big toe.
What are the 2 main differential diagnoses?
- Gout.
- Septic arthritis.
Exclude septic arthritis in any acute monoarthropathy!!
What is pseudogout?
A crystal arthropathy caused by the deposition of calcium pyrophosphate crystals in the joint, causing joint problems.
It is also known as chondrocalcinosis.
Describe the pathophysiology of pyrophosphate arthropathy (pseudogout).
Calcium pyrophosphate crystals are deposited on joint surfaces. The crystals elicit an inflammatory response.
What can cause pyrophosphate arthropathy (pseudogout)?
- Hypo/hyperthyroidism.
- Diabetes.
- Haemochromatosis.
- Magnesium levels.
- Old age
- Osteoarthritis
- Joint trauma/injury
Give 3 risk factors for pseudogout.
- Osteoarthritis
- Age
- Haemachromotosis
- High PTH
- Low phosphate
- Low magnesium
- Hypothyroidism
- Acromegaly
- Illness
- Surgery
- Trauma
What kind of crystals do you see in pseudogout?
Calcium pyrophosphate crystals - positively birefringent.
With which disease would you associate positively birefringent crystals?
Pseudogout - pyrophosphate crystals that are rhomboid shaped.
What joints does pseudogout affect?
Larger joints - knee/wrist/elbow/shoulder.
Symmetrical, if chronic.
Describe the clinical presentation of pseudogout.
Acute, hot + swollen joints - typically the wrist or knee
- Very painful attacks
- More common in elderly women
what disease must you assume a patient presenting with acute pseudo-gout has, until proven otherwise?
Septic arthritis
What investigations might you do in someone who you suspect might have pyrophosphate arthropathy (pseudogout)?
- 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
- X-ray:
* Shows chonedrocalcinosis - linear calcification parallel to the articular surfaces - Bloods:
- Raised WCC
What kind of crystals do you see in the joint aspirate in pseudogout?
Rhomboid shaped.
Positively birefringent.
What might you see on the X ray of pseudogout?
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)
Management for pseudogout.
- NSAIDs - high dose OR COX inhibitor
e.g. Naproxen / Ibruprofen
e.g. Aspirin - 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 - Corticosteroids - IM or IA (intra-articular)
* IA = most effective, but can be painful
- e.g PREDNISOLONE - Aspiration of the joint
= Reduced pain dramatically!!
How does pseudo-gout present differently from gout?
Usually occurs in larger joints (e.g. knee) - but pain is similar
