Crystal arthropathies Flashcards
Diagnosis and Treatment of pseudogout
-what do the crystals look like?
What are the different crystals that can cause musculoskeletal manifestations?
Monosodium urate - gout
Calcium pyrophosphate - pseudogout
Calcium apatite
Calcium oxalate
What is gout? Who gets it? Risk factors?
- *Metabolic disease resulting in increased body pool of urate with hyperuricaemia**
- affects middle-aged and elderly men, and post-menopausal women
- Women only 5-20% of affected, usually in context of renal dysfunction and diuretics
- *Single biggest risk factor = high plasma uric acid**
- 10% overproduction, 90% underexcretion
- aspirin, thiazides, cyclosporine decrease excretion
Risk factors
- Obesity
- ETOH: beer > spirits
- Seafood, offal, fructose
- Metabolic syndrome
- Myeloproliferative disorders and chemotherapy
- Hyperparathyroidism
- Diuretics
- Severe psoriasis
Protective
- low fat dairy
- coffee
- vitamin C
- weight loss
Equivocal
- Purine rich vegeatbles
- wine
- tea
- diet soft drinks
- high fat dairy
How does gout present? What are the laboratory features?
Most common early manifestation is acute arthritis
- usually monoarticular initially, with polyarticular occuring subsequently if at all
- Warm, red, tender joint pain and swelling
- Early attacks resolve spontaneously in 3-10days as a rule
- Metatarsophalangeal joint of the 1st toe is the classic joint
- Tarsal, ankle, and knee joints commonly involved
- Digits involved in the elderly or advanced disease
A proportion develop a chronic asymmetric synovitis that can be confused with RA
- Less commonly chronic gouty arthritis will be the only manifestation
- Even less commonly tophaceous disease without synovitis will be the manifestation
Diagnosis
- even classic presentation should have joint aspiration to differentiate from acute septic, crystal associated, palindromic rheumatism, psoriatic arthritis
- Needle shaped strongly negatively birefringent needle shaped crystals
- Serum uric acid will be normal or low in acute attacks in ~50%: uricosuric effect of cytokines; hypouricaemic therapy precipitating an attack
- - ALmost always elevated at some point, important to follow the course of hypouricaemic therapy
- - 24hr urine collection for uric acid can be useful to delineate risk of stone, overproduction, undersecretion, and help assess for possibility of uricosuric therapy
- - >800mg/day uric acid suggest overproduction of purine
What are the xray features of gout?
- Punched out lytic lesions
- Well defined marginal and juxta-articular erosions with overhanging sclerotic margins
- Soft tissue masses - tophi pathognomonic
- Well preserved joint space
- No periarticular osteopoenia
What is calcium pyrophosphate deposition disease? Who gets it? Secondary causes?
Disease of the elderly
- >80% of pts >60yrs, 70% have pre-existing joint damage
- Likely due to biochemical changes related to aging or disease cartilage favouring crystal nucleation
May be associated with mutations in the ANKH gene
Presence <50yrs should prompt consideration of underlying metabolic disorder
How does calcium pyrophosphate deposition (CPPD) disease manifest? How is it treated?
- May be asymptomatic, acute, subacute, or chronic
- ~50% present with low grade fever, but it may be as high as 40
- May also mimic other arthritis, RA, AS Tophi, spinal stenosis, cervical myelopathy
- Age and joint damage the greatest risk factors
- look for metabolic causes in those presenting young
Multiple associations
- induction of severe destructive disease radiographically mimicing neuropathic arthritis
- chronic symmetric synovitis mimicing RA
- intervertebral disc and ligament calcification
- periarticular tophus like nodules
Most frequently affects the knee
- Polyarticular in 2/3
When chronically progressive it can be hard to differentiate from OA
- Look at joint distribution, e.g. OA rarely affects metacarpophalangeal, wrist, shoulder, elbow, ankles
Chondrocalcinosis is a classic radiographic finding
- punctate and/or linear radiodense deposits within fibrocartilaginous joint menisci or articular hyaline cartilage
- fibrocartilage -> menisci, wrist, symphysis pubis
Definitive diagnosis requires demonstration of crystals in synovial fluid or periarticular tissue
- weakly positive birefringent rectangular/rhomboidal/rod shaped crystals
Treatment
- Untreated can last from days to a month
- Rest, joint aspiration, NSAIDs, intraarticular steorids all result in more rapid improvement
- Severe polyarticular attacks require short courses glucocorticoids
- Frequent attacks may benefit from colchicine prophylaxis
- - NSAIDs, hydroxychloroquine, methotrexate all shown in uncontrolled studies to help persistent synovitis
What is calcium apatite deposition disease? What causes it? How does it present?
Abnormal accumulation of basic calcium phosphates, usually with carbonate substituted apatite
- Occurs in damaged tissue, hypercalcaemic or hyperparathyroid states, and others
- Assoc conditions - ageing, OA, Milwaukee shoulder, tendinitis, hyperpth, renal failure, CTD
In chronic renal failure, hyperphosphataemia can contribute to extensive deposition in and around joints
Often found in Milwaukee shoulder
- Destructive chronic arthropathy of the elderly, most often in the shoulders
- Very large bloody effusions
Most commonly affects bursae and tendons in and around knees, shoulders, hips, fingers
Range of presentations
- asymptomatic radiographic changes
- acute synovitis/bursitis/tendinitis
- chronic destructive arthropathy
Diagnosis
- Usually low leukocyte count on aspiration with predominant mononuclear cells
- Crystals only visible on electron microscopy
- Clumps of crystals are nonbirefringent
- Calcification differentiates it from CPPD on xray (CPPD is linear)
- Yellow arrows show linear chondrocalcinosis in cppd (see attached)
Treatment
- nonspecific
- NSAIDs/colchicine/steroids all appear to shorten duration of symptoms
What are the principles of management of gout?
Acute attacks
- Anti-inflammatory drugs
- NSAIDs effective in 90%, with resolution in 5-8 days
- Colchicine (intermittent dose as effective as high dose) 0.6mg 8 hourly with tapering or 1.2mg then 0.6mg in 1hr with next day dosing depending on response. Discontinue at first sign of diarrhoea
- Systemic corticosteroids in polyarticular
- Intra-articular in single or few joints
- Anakinra not used commonly but very effective
Hypouricaemic therapy (generally not in acute attacks; should use symptom suppresant)
- Prevent attacks and tophaceous deposits
- - Aim for normal serum uric acid (<0.36mmol/L; <0.30 in tophaceous)
- - DON’T STOP IN ACUTE ATTACKS
Uricosuric
- probenacid blocks re-uptake in the nephron
- used in those who underexcrete and have good renal function
- <600mg/24hrs is underexcretion
Xanthine oxidase inhibitors
- For those who overproduce, form stones, or have poor renal function
- Allopurinol (inhibits azathioprine metabolism)
- Adverse effects: TEN, vasculitis, bone marrow suppression, granulomatous hepatitis, renal failure
- Febuxostat is chemically unrelated to allopurinol and so can be trialled in skin reactions
- hepatically cleared; inhibits both reduced and oxidised xanthine oxidase (allopurinol predominantly inhibits reduced)
- abnormal LFTs common
- superior to allopurinol at lowering serum uric acid, no difference in gout flares or tophi
- initial trials showed increased thromboembolic CV events, not borne out in subsequent RCT
What is calcium oxalate deposition disease?
Primary oxalosis is a rare heritable metabolic disorder
- >=2 enzyme defects lead to hyperoxalaemia and deposition of CaOx in tissues
Secondary oxalosis is much more common
- Seen in chronic renal disease that’s haemo or peritoneal dialysis dependent
Manifestations
- Deposition of CaOx in visceral organs, vessels, bones, cartilage
- One of many causes of arthritis in chronic renal failure
- presentation often not distinguishable from those caused by MSU/CPP/apatite
- aspiration usually non or mildly inflammatory
- crystals vary in shape and birefringence, most recognisable type is bipyramidal with strong birefringence
Treatment
- Nothing makes much difference
- In primary oxalosis liver transplantation significantly reduces crystal deposits
Management of Acute Gout
Urate Lowering Therapy in Gout
- Indication
- Target
- First line agent and most common SE, serious SE + who is at risk
- Second line agents
- Concurrent therapy required?
What birefringence does gout display? What about pseudogout?
