Crystalline Arthropathies Flashcards
What are the three main crystal types in arthropathies?
basic calcium phosphate (BCP)
calcium pyrophosphate dihydrate (CPPD)
monosodium urate (gout)
What is BCP? Where does it deposit?
aka calcium hydroxyapatite - calcium-containing mineral found in bone
deposit in:
- soft tissues (Acute calcific periarthritis) - first MTP in young men (pseudo-podagra)
- joints (BCP arthropathy) - Milwaukee Shoulder Syndrome
- tendons (calcific tendinitis) - shoulder, most commonly in supraspinatous tendon
acute calcific periarthritis
BCP crystals shed from calcific deposit - intense local inflammation, looks like gout on exam, but in “wrong type” of patients
comes on quickly, near the joint, not in the joint
BCP arthropathy
Milwaukee Shoulder Syndrome
inflammation leading to severe degenerative arthritis of the shoulder joint
destruction of rotator cuff, cannot abduct arm, huge swelling
BCP crystals identified
common in women >70
bilateral involvement common but can affect other joints such as knees, hips, and fingers (Philadelphia finger)
calcific tendinitis
most commonly seen in the shoulder
up to 5% of shoulder x-rays
usually in the muscles that abducts and stabilizes the shoulder
bursitis, impingement syndrome
hand, wrist, hip, knee, foot and neck
What are the features of BCP histology?
shiny choins on ordinary light microscopy
not birefringent, not seen on polarized light microscopy
joint aspirate staned for alizarin red
electron microscopy diagnostic
ABCs of BCP
A - Acte calcific periarthritis, Alizarin red stain, Atypical gout
B - BCP arthropathy, not Birefringent, Beer (Milwaukee Shoulder Syndrome)
C - Calcific tendinitis, Cuff (supraspinatous), Coints “shiny” on light microscope
Calcium Pyrophosphate Dihydrate (CPPD) Crystal Disease
results from pyrophosphate dihydrate salts depositing
in cartilage appears as chondrocalcinosis on radiographs
in joint space as pseudogout, pseudo-rheumatoid arthritis
spectrum of presentations
Crowned Dens syndrome - calcific deposit on the top of the dens
What is the spectrum of presentation in CPPD?
asymptomatic (lanthanic) - most common
30% population has chondrocalcinosis on x-rays by 90 years of age
pseudogout
polyarticular arthritis
osteoarthritis with superimposed atacks of pseudogout (Crowned Dens Syndrome)
overlap between various forms
pseudogout
fever, malaise
acute onset of joint pain, swelling with effusion, erythema over joint, tenderness, warmth
usually less painful than gout and takes longer to peak intensity
large joints affected mostly
diagnosis - aspirate, inflammatory, crystals within PMNs
knee and wrist are the most common joints
What are factors associated with secondary CPPD?
advanced age (>50)
OA
long-term consequences of mechanical knee joint trauma
familial (manifests third and fourth decades)
associated with systemic metabolic disease such as hyperparathyroidism, dialysis-dependent renal failure
hemochromatosis
hypomagnesemia
ochronosis
ochronosis
genetic lack of homogenistic oxidase enzyme, leading ot increased levels of endogenous phenols and hydroxyapatite
treatment of BCP and CPPD
NSAIDs
intraarticular steroid injections
anakinra (IL-1 inhibitor), inhibits the inflammasone
glucocorticoids
can only treat acute attack, no prevention
What is the epidemiology of gout?
prevalence increases with age
more men than women (3/4:1) - disappears after menopause (1:1)
estrogen has uricosuric effects
risk factors for gout
obesity, metabolic syndrome, insulin resistance
diet (rich in purines: meat, shellfish, ethanol (esp. beer), soft drinks and high fructose syrup)
drugs - thiazide cyclosporine, low dose ASA (<1g/day)
renal insufficiency
organ transplantation
inborn errors of metabolism: Lesch Nyhan, PRPP syndrome
hyperuricemia
due to overproduction or underexretion - taking in too many purines, increased cell production such as malignancy
occurs when concentration >6.8 mg/dL
treatment goal < 6.0 mg/dL for both
many people are hyperuricemic and never develop gout
What are the general methods of uric acid accumulation?
most people are both udnerexcretor and overproducer
others are underexcretors, which require higher serum urate level for renal excretion
overpreoducers are rare except for cancer where there is increased cell turnover
How does urine concentrations reflect the mechanism of uric acid build-up?
can get 24 hour collection for uric acid and creatinine
if >1000 mg then overproducer
if <1000 mg then underexcretor
What are the four stages of gout?
asymptomatic hyperuricemia - only 15% of hyperuricemic people develop gout
acute gouty arthritis - monoarticular acute inflammatory arthritis
intercritical gout - asymptomatic intervals between acute attacks
chronic tophaceous gout - uric acid deposits accumulate in the soft tissues
acute gout treatment
NSAIDs
Colchiciene 0.6 mg - inhibitor of mitotic spindle fibers
intraarticular steroid injections
Anakinra (IL-1 inhibitor)
glucocorticoids
next generation IL-1 inhibitors coming up - Canakinumab, Rilonacept
What are the methods of prevention for chronic gout?
xanthine oxidase inhibitors - Allopurinol and Febuxostat (Uloric) block hypoxanthine into xanthine and xanthine into uric acid
uricosurics - Probenecid (not used a lot now because need to take 4 times a day)
Uricases - Pegloticase/Krystexxa (humans don’t produce uricase, but most creatures do)
When should preventative gout therapy be initiated?
patients with hyperuricemia:
- >/= 2 acute gout attacks
- presence of tophi
- coexisting illness (nephrolithiasis)
patient preference
start 2-4 weeks after resolution of acute gout attack
allopurinol
purine analog xanthin oxidase inhibitor
metabolized to oxypurinol
lowers srum urate in the order of 20%
not to be started or stopped during acute attacks
rash in 2% - can attempt oral desensitization
Allopurinol Hypersensitivity Syndrome
GI intolerance a problem
can cause vasculitis
Febuxostate (Uloric)
non-purine analog xanthine oxidase inhibitor
decreases production of uric acid
can lead to paradoxical gout flares like allopurinol
more cardiovascular events
in HD and CHF - transaminitis in 2-3%
superior to allopurinol for safety (rash)
