Crystal arthropathies Flashcards

1
Q

What do calcium pyrophosphate crystals look like in joint fluid?

A

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

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2
Q

What age group is affected by CPPD?

A

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

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3
Q

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

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

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

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4
Q

Radiographic features of CPPD

A

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

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5
Q

What conditions are associated with CPPD?

A
Ageing
Familial chondrocalcinosis (associated with ANKH gene)
Primary hyperparathyroidism
Haemochromatosis
Hypomagnesemia
Chronic gout
Gitelmans syndrome
Post menisectomy
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6
Q

What are typical precipitants of an acute flare of CPPD?

A

Surgery - particularly parathyroidectomy
Trauma
Medical illness

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7
Q

Treatments for CPPD

A

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

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8
Q

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

A

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

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9
Q

Who does gout affect?

A

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

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10
Q

Signs of gout?

A

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

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11
Q

Precipitants of acute gout?

A
Diet excess (meat and seafood) 
Trauma
Surgery
Alcohol 
Hypouricaemic therapy
Serious medical illness
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12
Q

What is the target uric acid level?

A

Less than 0.36

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13
Q

What are uric acid levels in an acute attack?

A

Can be normal or low due to uricosuric affect of cytokines

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14
Q

What are the synovial fluid findings in gout?

A

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

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15
Q

XR findings in chronic gout?

A

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

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16
Q

Treatment options in an acute attack of gout?

A
FIRST LINE
• Option 1:NSAID
• Option 2:Colchicine
SECOND LINE
• Option3:Systemiccorticosteroid
• Option4:Intra‐articularcorticosteroid
17
Q

Side effects and interactions of colchicine

A
Diarrhoea and vomiting 
Abdo cramps
Reversible neuropathy 
Cytopenias
Rhabdomyolysis
Rash
Liver failure
Fatal in overdose
Caution with CYP3A4 and p-glycoprotein inhibitors
18
Q

Medications for prevention of gout

A

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

19
Q

What is the interaction between azathioprine and allopurinol?

A

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

20
Q

Side effects of allopurinol?

A
Rash 
Leukopenia
Thrombocytopenia
Diarrhoea
Drug fever 
Stevens Johnson's syndrome or TEN
Allopurinol hypersensitivity syndrome
21
Q

What is the genetic risk factor for Allopurinol hypersensitivity?

A

HLA-B5801

Most common in Han Chinese population

22
Q

What are the features of Allopurinol hypersensitivity?

A

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

23
Q

What are the benefits of Febuxostat?

A

Can be used if Allopurinol intolerant

Hepatic metabolism - no dose reduction in renal impairment

24
Q

When should you consider uric acid lowering therapy?

A
tophi
erosions of x-ray
2+ attacks per year
urate calculi
rate nephropathy
  • not for asymptomatic hyperuricaemia (no evidence)
25
How common is gout following transplants and why?
Common 34 - 84% of solid organ transplants - caused by Cyclosporin and Tacrolimus Care to not co-prescribe Allopurinol with Azathioprine - OK with Mycophenalate
26
What are the risk factors for gout?
``` Metabolic syndrome insulin resistance obesity renal impairment - reduced excretion cardiac failure - diuretics organ transplantation - CNIs Myeloproliferate disorders (increased purine) ```
27
What foods increase the risk of gout?
``` Beer Alcohol Fructose - soft drinks, sweet fruit Red meat Shellfish/Seafood Butter ```
28
What lifestyle factors reduce uric acid?
``` Coffee vit C low fat dairy exercise and weight control possibly cherries ```
29
What is the pathogenesis behind an acute gout flare?
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
30
What is the clinical course of gout?
Asymptomatic hyperuricaemia Acute intermittent gout Chronic tophaceous gout
31
What are the common sites of acute gout flares?
``` 1st MTP (Podagra) ~90% of all individual with gout olecranon bursa, elbow wrist, fingers knee ankle subtalar mid foot ```
32
What are some (rare) causes of early onset of gout?
``` Purine pathway (HGPR Tdeficiency, PRPP increase) Glycogen Storage Diseases Sickle cell disease beta‐thalassaemia Non‐lymphocytic leukaemias ```
33
How does Colchicine work and what is the best dosing schedule?
Colchicine decreases leucocyte chemotaxis and phagocytosis give 1mg followed 1 hour later by 0.5mg then 0.5mg BD
34
What are the side effects of Colchicine?
``` really excreted nausea and diarrhoea neuromyopathy - proximal muscle weakness, absent reflexes, ascending paraesthesia - EMG/NCS: Mild axonopathy - Biopsy: vacuolar myopathy ```
35
What other disease does elevated uric acid level increase the risk of?
Cardiovascular disease
36
What renal complications of gout exist?
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
37
What is the pathogenesis of CPPD?
Trauma, OA, age, metabolic disease leads to cartilage damage which leads to CPPD deposition causing: - further cartilage damage - synovitis - mechanical wearing
38
How does Basic Calcium Phosphate Hydroxyapatite (BCP) disease present?
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
39
What is a Milwaukee shoulder and in what patient group does this occur?
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