Crystal arthropathy (gout, pseudogout)

Question 1

How long does a flare of gout last?

Answer 1

~5 days - this is less than most other forms of inflammatory arthritis

Question 2

Who is most affected by pseudogout?

Answer 2

Older women

Question 3

Which joints are most affected by pseudogout?

Answer 3

Wrists and knees

Question 4

What dermatological side effect is associated with allopurinol use?

Answer 4

SJS - if any rash appears then start Febuxostat instead (XO inhibitor)

Question 5

How do you manage an acute flare of pseudogout?

Answer 5

Intra-articular corticosteroid injection

NB: there is no role for allopurinol or hydroxychloroquine in management of calcium pyrophosphate dihydate deposition arthritis

Question 6

What is the regimen for starting allopurinol?

Answer 6

Allopurinol 100mgs OD, escalating by 100mgs every two weeks to 300mgs OD

+ colchicine 500mcg BD (because allopurinol alone can precipitate flares)

Question 7

What is the EULAR classification of CPPD?

Answer 7

They do not use the term ‘pseudoarthritis’

• Type A - acute CPP arthritis usually mono-articular, affecting large joints
• Type B - chronic CPP inflammatory arthritis, affecting large and small joints
• Type C - OA with CPP attacks with inflammation
• Type D - OA with CPP but no inflammation
• Type E - ianthanic/asymptomatic
• Type F - pseudo-neuropathic which is destructive

Question 8

What is deposited in pseudogout? Which joints are affected?

Answer 8

Calcium pyrophosphate

Knees, wrists, shoulders, ankles, elbows, or hands can be affected typically in older people.

Question 9

What is seen on a radiograph in pseudogout?

Answer 9

Chondrocalcinosis - although this alone will miss 60% of cases

Question 10

What is calcium pyrophosphate produced by?

Answer 10

Chondrocytes

CPP crystals can be shed from cartilage into the articular space to cause an inflammatory response.

Question 11

What are the risk factors for pseudogout?

Answer 11

• Advanced age
• Injury esp meniscal
• Hyperparathyroidism
• Haemochromatosis
• FH
• Hypomagnesaemia
• Hypophosphatasia

Question 12

What are the clinical features of pseudogout?

Answer 12

• Painful and tender joints
• OA-like involvement of joints (wrists, shoulders)
• Sudden worsening of OA
• Red and swollen joints
• Joint effusion and fluctuance

Other:

• Fever and malaise - uncommon

Question 13

What investigations would you do for pseudogout?

Answer 13

Bloods/bedside:

• Serum calcium
• Serum parathyroid hormone
• Iron studies
• Serum magnesium
• Serum ALP - to exclude hypophosphatasia

Imaging/invasive:

• Arthrocentesis with synovial fluid analysis
• XR joints

Question 14

What is seen on synovial fluid analysis in pseudogout?

Answer 14

Intracellular or extracellular positively birefringent rhomboid-shaped crystals under polarised light confirms CPPD; fluids are often bloody

Question 15

What is the mangement of pseudogout?

Answer 15

1st line:

• Simple analgesia e.g. paracetamol
• Intra-articular steroids - preferred for an acute attack ; triamcinolone hexacetonide is the longest-acting and most used.

2nd line: NSAIDs - COX-2 have lower GIT side-effects but same CVD risk

For those with polyarticular disease = systemic steroids

Surgery - in recurrent involvement associated with severe joint degeneration

Question 16

What are the complications of pseudogout and its management?

Answer 16

Intra-articular corticosteroid-related adverse effects e.g. bleeding and bruising around injection site

Question 17

What is the prognosis in pseudogout?

Answer 17

Most will recover over days to weeks but many will relapse

Question 18

Define gout.

Answer 18

Gout is a syndrome characterised by:

• hyperuricaemia and deposition of urate crystals causing attacks of acute inflammatory arthritis;
• tophi around the joints and possible joint destruction;
• renal glomerular, tubular, and interstitial disease;
• and uric acid urolithiasis.

Question 19

Which joints are most affected in gout?

Answer 19

• first toe (podagra),
• foot,
• ankle,
• knee,
• fingers,
• wrist,
• elbow;

However, it can affect any joint.

Question 20

How common is gout?

Answer 20

Affects 3% to 6% of men and 1% to 2% of women

Gout is rare in pre-menopausal women

Question 21

What are the risk factors for gout?

Answer 21

• older age
• male sex
• use of drugs including aspirin, ciclosporin (cyclosporine), tacrolimus, or pyrazinamide
• consumption of meat, seafood, or alcohol
• genetic susceptibility
• conditions with a high cell turnover rate

Question 22

What are the causes of gout?

Answer 22

Aetiology is hyperuricaemia

Hyperuricaemia is due to renal under-excretion of urate in 90% of cases and to over-production in 10%,

Question 23

What medications increase uric acid levels?

Answer 23

Increasing uric acid re-absorption:

• aspirin
• ciclosporin
• tacrolimus
• pyrazinamide

Reduced excretion of uric acid:

• diuretics

Increased uric acid production:

• chemotherapy
• haematological cancers

Question 24

Why does gout commonly present as podagra?

Answer 24

Solubility of urate in the joints depends on temperature, pH, non-aggregated proteoglycans, and other factors.

1st MTP is a cool part of the body

Question 25

What are the clinical features of gout?

Answer 25

• Monoarticular/few affected joints
• Sudden onset to maximum pain within 1 day - patients can often indicate hour, most severe pain experienced
• Erythema and warmth
• Redness over joints
• Limited range of movement - due to pain
• Joint stiffness- morning
• Foot involvement
• Tophi - hard subcutaneous nodules (tophi) over extensor surface of elbows, knees, Achilles, hands, feet, helix of ears.

Question 26

What is the management of acute gout?

Answer 26

1st line:

• NSAIDs e.g. naproxen 500mg BD for 2 weeks
• OR Corticosteroids - oral or injections
• OR Colchicine - minimal effective dose

2nd line: IL-1 inhibitors e.g. anakinra, canakinumab - only usefd in acute flare where patients are refractory/intolerant to other treatments.

Question 27

What is the management of chronic gout?

Answer 27

1st line:

• Allopurinol + NSAIDs/colchicine - 100 mg orally once daily initially, increase by 100 mg/day increments every week according to serum urate level, maximum 800 mg/day;prophylactic NSAID/colchicine when initiating/tapering allopurinol, continued for 3-6 months

2nd line:

• Febuxostat + NSAID/colchicine - XOi, should not be taken during acute attack; as above

3rd line:

• Probenecid/sulfinpyrazone + NSAID/colchicine - uricosuric drugs

4th line

• Pegloticase +NSAID/colchicine - pegylated recombinant mammalian uricase, if all else fails

Question 28

What measures should be taken to prevent gout?

Answer 28

Avoid excessive alcohol consumption, diuretic use, and weight gain.

Question 29

What investigations should be done for gout?

Answer 29

Clinical diagnosis in those with reliable history of recurrent acute monoarthritis of the 1st MTP. Confirm with arthrocentesis.

• Uric acid level
• Arthrocentesis with synovial fluid analysis - shows WCC >2x10^9/L and strongly negatively birefringent needle-shaped crystals under polarised light
• XR - not useful but may show periarticular erosions with overhanging edge or punched-out appearance

Question 30

What are the complications of gout?

Answer 30

Acute uric acid nephropathy - usually only with very high levels of uric acid e.g. in those treated with cytotoxic agents

Nephrolithaisis - may be over 10% prevalence

Question 31

What is the prognosis with gout?

Answer 31

If not treated risk of recurrence after the first attack is 62%, 78%, and 84% during the first, second, and third year, respectively

Untreated gout can cause tophi and severe debilitating arthritis (usually both 20yrs after first attack)

Question 32

Which HLA is associated with risk of allopurinol hypersensitivity reaction?

Answer 32

HLA-B*58:01 - common in Korea, Han Chinese, Thai