Crystal arthropathies

Question 1

What do calcium pyrophosphate crystals look like in joint fluid?

Answer 1

Weakly positive birefringent crystals under polarized light microscopy
Can be rectangular, rod shaped or rhomboid

Question 2

What age group is affected by CPPD?

Answer 2

Elderly
Age 65-75 : 10-15%
Age over 85 : 30-50%

Question 3

What are the most common ways calcium pyrophosphate deposition disease can present?

Answer 3

1. Asymptomatic chondrocalcinosis
2. mono-oligoarthritis (Pseudo gout)
3. Chronic arthritis

May also mimic other Arthritis, RA, AS, Tophi, spinal stenosis, cervical myelopathy

Question 4

Radiographic features of CPPD

Answer 4

Chondrocalcinosis - deposition of punctate linear radiodensities in fibrocartilage and articular cartilage, typically menisci, symphysis pubis, radio ulnar, glenoid and acetabular cartilages

Degenerative changes - subchondral cysts, osteophytes, bone and cartilage fragmentation

Question 5

What conditions are associated with CPPD?

Answer 5

Ageing
Familial chondrocalcinosis (associated with ANKH gene)
Primary hyperparathyroidism
Haemochromatosis
Hypomagnesemia
Chronic gout
Gitelmans syndrome
Post menisectomy

Question 6

What are typical precipitants of an acute flare of CPPD?

Answer 6

Surgery - particularly parathyroidectomy
Trauma
Medical illness

Question 7

Treatments for CPPD

Answer 7

NSAIDs
Intra-articular joint injection
Consider low dose colchicine for prophylaxis
Surgery for joint replacement

Question 8

What are two other crystal arthropathies other than gout and CPPD?

Answer 8

Calcium hydroxyapatite deposition disease
- Periarticular deposits of hydroxyapatite
Calcium oxalate deposition disease

Question 9

Who does gout affect?

Answer 9

Middle aged and elderly men
Post menopausal women
NZ Maori have very high rates - 6.4% in 2002, probably higher now

Question 10

Signs of gout?

Answer 10

Severe pain, warmth, redness, swelling and disability
Often occurs at night
Typically single joint distribution (most common 1st MTP, knee, ankle)
- polyarticular gout tends to present following at least 10 years of gout

Question 11

Precipitants of acute gout?

Answer 11

Diet excess (meat and seafood) 
Trauma
Surgery
Alcohol 
Hypouricaemic therapy
Serious medical illness

Question 12

What is the target uric acid level?

Answer 12

Less than 0.36

Question 13

What are uric acid levels in an acute attack?

Answer 13

Can be normal or low due to uricosuric affect of cytokines

Question 14

What are the synovial fluid findings in gout?

Answer 14

Negative birefringent needle shaped crystals
Appear YeLLow when ParaLLel to polarised light
High white cells with neutrophil predominance

Question 15

XR findings in chronic gout?

Answer 15

Sub cortical bone cysts
Well defined erosions with sclerotic margins
Soft tissue masses

Question 16

Treatment options in an acute attack of gout?

Answer 16

FIRST LINE
• Option 1:NSAID
• Option 2:Colchicine
SECOND LINE
• Option3:Systemiccorticosteroid
• Option4:Intra‐articularcorticosteroid

Question 17

Side effects and interactions of colchicine

Answer 17

Diarrhoea and vomiting 
Abdo cramps
Reversible neuropathy 
Cytopenias
Rhabdomyolysis
Rash
Liver failure
Fatal in overdose
Caution with CYP3A4 and p-glycoprotein inhibitors

Question 18

Medications for prevention of gout

Answer 18

Allopurinol - XO inhibitor
Febuxostat - XO inhibitor
Uricosuric agents- probenecid, benzbromarone
Uricase agents - rasburicase, pegloticase

Question 19

What is the interaction between azathioprine and allopurinol?

Answer 19

Azathioprine and 6MP are also metabolized by xanthine oxidase
By blocking the enzyme azathioprine and 6MP are shunted more to 6TGN metabolites, which lead to significant toxicity and bone marrow suppression

Question 20

Side effects of allopurinol?

Answer 20

Rash 
Leukopenia
Thrombocytopenia
Diarrhoea
Drug fever 
Stevens Johnson's syndrome or TEN
Allopurinol hypersensitivity syndrome

Question 21

What is the genetic risk factor for Allopurinol hypersensitivity?

Answer 21

HLA-B5801

Most common in Han Chinese population

Question 22

What are the features of Allopurinol hypersensitivity?

Answer 22

DRESS - drug rash, eosinophilia and systemic symptoms including hepatitis and interstitial nephritis
- mortality is 25%

Question 23

What are the benefits of Febuxostat?

Answer 23

Can be used if Allopurinol intolerant

Hepatic metabolism - no dose reduction in renal impairment

Question 24

When should you consider uric acid lowering therapy?

Answer 24

tophi
erosions of x-ray
2+ attacks per year
urate calculi
rate nephropathy

• not for asymptomatic hyperuricaemia (no evidence)

Question 25

How common is gout following transplants and why?

Answer 25

Common 34 - 84% of solid organ transplants
- caused by Cyclosporin and Tacrolimus

Care to not co-prescribe Allopurinol with Azathioprine
- OK with Mycophenalate

Question 26

What are the risk factors for gout?

Answer 26

Metabolic syndrome
insulin resistance
obesity
renal impairment - reduced excretion
cardiac failure - diuretics
organ transplantation - CNIs
Myeloproliferate disorders (increased purine)

Question 27

What foods increase the risk of gout?

Answer 27

Beer
Alcohol
Fructose - soft drinks, sweet fruit
Red meat
Shellfish/Seafood
Butter

Question 28

What lifestyle factors reduce uric acid?

Answer 28

Coffee
vit C
low fat dairy
exercise and weight control
possibly cherries

Question 29

What is the pathogenesis behind an acute gout flare?

Answer 29

rapid change in urate level
reduced pH (urate crystals less soluble)
micro crystals released and phagocytosed
Inflammasome is activated (NLRP3)
IL-1beta secretion which triggers synovial inflammatory mediators (TNF alpha, IL-6)
PMN cells recruited and complement activated

Question 30

What is the clinical course of gout?

Answer 30

Asymptomatic hyperuricaemia
Acute intermittent gout
Chronic tophaceous gout

Question 31

What are the common sites of acute gout flares?

Answer 31

1st MTP (Podagra) ~90% of all individual with gout
olecranon bursa, elbow
wrist, fingers
knee
ankle
subtalar
mid foot

Question 32

What are some (rare) causes of early onset of gout?

Answer 32

Purine pathway (HGPR Tdeficiency, PRPP increase)
Glycogen Storage Diseases
Sickle cell disease
beta‐thalassaemia
Non‐lymphocytic leukaemias

Question 33

How does Colchicine work and what is the best dosing schedule?

Answer 33

Colchicine decreases leucocyte chemotaxis and phagocytosis

give 1mg followed 1 hour later by 0.5mg then 0.5mg BD

Question 34

What are the side effects of Colchicine?

Answer 34

really excreted
nausea and diarrhoea
neuromyopathy
- proximal muscle weakness, absent reflexes, ascending paraesthesia
- EMG/NCS: Mild axonopathy
- Biopsy: vacuolar myopathy

Question 35

What other disease does elevated uric acid level increase the risk of?

Answer 35

Cardiovascular disease

Question 36

What renal complications of gout exist?

Answer 36

1. Acute uric acid nephropathy: tumour lysis syndrome
2. Uric acid nephrolithiasis
   - 10-25% all patients with gout
   - Correlates strongly with urate level
3. Chronic urate nephropathy
   - Deposition of crystals in medulla and pyramids

Question 37

What is the pathogenesis of CPPD?

Answer 37

Trauma, OA, age, metabolic disease leads to cartilage damage which leads to CPPD deposition causing:

• further cartilage damage
• synovitis
• mechanical wearing

Question 38

How does Basic Calcium Phosphate Hydroxyapatite (BCP) disease present?

Answer 38

1) Asymptomatic
2) Acute synovitis
3) Chronic monoarthritis
4) OA
5) Large joint destructive arthropathy
- Milwaukee shoulder

Present with tendinitis, bursitis, periarthritis
Shoulder/rotator cuff, hip, knee, elbow, wrist, ankle

Question 39

What is a Milwaukee shoulder and in what patient group does this occur?

Answer 39

Large destructive arthropathy caused by Basic Calcium Phosphate Hydroxyapatite (BCP) disease
- reduced ROM of the shoulder with massive blood stained effusion

Occurs in elderly women