Crystal arthropathies Flashcards
What do calcium pyrophosphate crystals look like in joint fluid?
Weakly positive birefringent crystals under polarized light microscopy
Can be rectangular, rod shaped or rhomboid
What age group is affected by CPPD?
Elderly
Age 65-75 : 10-15%
Age over 85 : 30-50%
What are the most common ways calcium pyrophosphate deposition disease can present?
- Asymptomatic chondrocalcinosis
- mono-oligoarthritis (Pseudo gout)
- Chronic arthritis
May also mimic other Arthritis, RA, AS, Tophi, spinal stenosis, cervical myelopathy
Radiographic features of CPPD
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
What conditions are associated with CPPD?
Ageing Familial chondrocalcinosis (associated with ANKH gene) Primary hyperparathyroidism Haemochromatosis Hypomagnesemia Chronic gout Gitelmans syndrome Post menisectomy
What are typical precipitants of an acute flare of CPPD?
Surgery - particularly parathyroidectomy
Trauma
Medical illness
Treatments for CPPD
NSAIDs
Intra-articular joint injection
Consider low dose colchicine for prophylaxis
Surgery for joint replacement
What are two other crystal arthropathies other than gout and CPPD?
Calcium hydroxyapatite deposition disease
- Periarticular deposits of hydroxyapatite
Calcium oxalate deposition disease
Who does gout affect?
Middle aged and elderly men
Post menopausal women
NZ Maori have very high rates - 6.4% in 2002, probably higher now
Signs of gout?
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
Precipitants of acute gout?
Diet excess (meat and seafood) Trauma Surgery Alcohol Hypouricaemic therapy Serious medical illness
What is the target uric acid level?
Less than 0.36
What are uric acid levels in an acute attack?
Can be normal or low due to uricosuric affect of cytokines
What are the synovial fluid findings in gout?
Negative birefringent needle shaped crystals
Appear YeLLow when ParaLLel to polarised light
High white cells with neutrophil predominance
XR findings in chronic gout?
Sub cortical bone cysts
Well defined erosions with sclerotic margins
Soft tissue masses
Treatment options in an acute attack of gout?
FIRST LINE • Option 1:NSAID • Option 2:Colchicine SECOND LINE • Option3:Systemiccorticosteroid • Option4:Intra‐articularcorticosteroid
Side effects and interactions of colchicine
Diarrhoea and vomiting Abdo cramps Reversible neuropathy Cytopenias Rhabdomyolysis Rash Liver failure Fatal in overdose Caution with CYP3A4 and p-glycoprotein inhibitors
Medications for prevention of gout
Allopurinol - XO inhibitor
Febuxostat - XO inhibitor
Uricosuric agents- probenecid, benzbromarone
Uricase agents - rasburicase, pegloticase
What is the interaction between azathioprine and allopurinol?
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
Side effects of allopurinol?
Rash Leukopenia Thrombocytopenia Diarrhoea Drug fever Stevens Johnson's syndrome or TEN Allopurinol hypersensitivity syndrome
What is the genetic risk factor for Allopurinol hypersensitivity?
HLA-B5801
Most common in Han Chinese population
What are the features of Allopurinol hypersensitivity?
DRESS - drug rash, eosinophilia and systemic symptoms including hepatitis and interstitial nephritis
- mortality is 25%
What are the benefits of Febuxostat?
Can be used if Allopurinol intolerant
Hepatic metabolism - no dose reduction in renal impairment
When should you consider uric acid lowering therapy?
tophi erosions of x-ray 2+ attacks per year urate calculi rate nephropathy
- not for asymptomatic hyperuricaemia (no evidence)
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
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)
What foods increase the risk of gout?
Beer Alcohol Fructose - soft drinks, sweet fruit Red meat Shellfish/Seafood Butter
What lifestyle factors reduce uric acid?
Coffee vit C low fat dairy exercise and weight control possibly cherries
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
What is the clinical course of gout?
Asymptomatic hyperuricaemia
Acute intermittent gout
Chronic tophaceous gout
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
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
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
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
What other disease does elevated uric acid level increase the risk of?
Cardiovascular disease
What renal complications of gout exist?
- Acute uric acid nephropathy: tumour lysis syndrome
- Uric acid nephrolithiasis
- 10-25% all patients with gout
- Correlates strongly with urate level - Chronic urate nephropathy
- Deposition of crystals in medulla and pyramids
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
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
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
