2: Crystal Induced Arthropathies Flashcards
1
Q
what are four microcrystals associated with crystal induced arthropathies?
A
- monosodium urate (MSU)
- calcium pyrophosphate dihydrate (CPPD)
- calcium apatite (apatite)
- calcium oxalate (CaOx)
2
Q
what conditions are included in a ddx for crystal induced arthropathies?
A
- gout
- pseudogout: acute CPP crystal arthritis
- psoriatic arthritis
- reactive arthritis
- osteoarthritis
- rheumatoid arthritis
- septic arthritis
- cellulitis
3
Q
pathogenesis of gout
A
Hyperuricemia followed by extracellular deposition of uric acid crystals in synovia of joints, bursae, and/or tendons - then release of crystals into joint or bursae with accompanying inflammation (key involvement of IL-1)
4
Q
biochem associated with gout
A
- uric acid = end product of human purine metabolism
- humans cannot metabolize it- must be excreted
- serum [urate] determined by balance of urate production vs. elimination
5
Q
definition of hyperuricemia
A
> 6.8 mg/dl (limit of its solubility in serum)
at this level, there is an accumulation of MSU at levels that drive the precipitation of urate crystals
6
Q
some famous people with gout
A
- King Henry VIII
- Ben Franklin
- Jared Leto
- Ansel Adams
- Maurice Cheeks
7
Q
risk factors for gout
A
- age
- male; or PMS women
- HTN (thiazide diuretic use)
- obesity
- hyperlipidemia
- hyperuricemia
- dietary excess: meat, seafood, alcohol (highest with beer)
- dehydration
- trauma/surgery/transplant
- AMI/stroke
- urate lowering therapy
- Lesch-Nyhan syndrome (HGPRT def: orange, sandy urine; self mutilation, mental retardation)
8
Q
causes of hyperuricemia
A
- 90% secondary to underexcretion
- 10% secondary to overproduction
use 24h quantitative urine uric acid to help define pathophysiology (normal = 250-750mg/24h)
9
Q
4 causes of primary uric acid overproduction
A
- Lesch Nyhan (NGPRT deficiency)
- overactive PRPP
- G6PD deficiency
- F1P aldolase deficiency
10
Q
many causes of secondary uric acid overproduction
A
- myelo/lympho-proliferative disorders
- malignancies
- hemolytic diseases
- psoriasis
- obesity
- chemotherapy (tumor lysis)
- Down syndrome
- Glycogen storage disease (III, V, VII)
- excessive purine or fructose rich foods
- pancreatic extract, Nicotinic acid, B12 deficiency
- alcohol (mix of overproduction and underexcretion)
11
Q
relationship b/w hyperuricemia and alcohol
A
- alcohol needs ATP degradation to metabolize thus increased purine turnover and urate generation (overproduction)
- binging can cause elevated lactate levels and decreased renal excretion via URAT-1 (underexcretion)
- promotes diuresis via suppression of ADH causing dehydration, volume depletion, and urate retention (underexcretion)
12
Q
what alcohols affect purine levels?
A
beer, ale, and distilled spirits
wine does not!
13
Q
describe urate excretion
A
kidney:
1. glomerular filtration of all serum urate
2. PCT resorption of 99% filtered load
3. resecretion in descending of 50% resorbed load
4. resorption in ascending of 80% of resecreted load
5. excretion of about 10% of filtered load (about 600 mgms/d)
14
Q
primary causes of renal underexcretion
A
- hereditary deficiency in urate exporter
- medullary cystic kidney disease in kids
15
Q
secondary causes of renal underexcretion
A
- kidney disease
- lactic and diabetic or starvation ketoacidosis
- dehydration: fluid loss, heart failure
- hypoparathyroidism
- hypothyroidism
- sarcoidosis
- pre-eclampsia
- medications
16
Q
drugs that promote hyperuricemia
A
- diuretics: thiazide > loop
- organic acids: low dose salicylates, nicotinic acid, pyrazinamide
- cyclosporine
- ethambutol
- ethanol
- levadopa
- CSF?
- lead toxicity (lead nephropathy -> saturnine gout)
- laxative abuse (alkalosis)
- severe salt restriction
17
Q
presentation of acute gouty arthritis
A
- acute inflammation with pain, redness, and swelling
- max severity in hours, resolves in 3-10d
- 80% monoarticular, often podagra (great toe MTP)
- pain to even put sheet over foot
- inflammation can spread beyond joint, giving tenosynovitis mimicking cellulitis
- urate crystals in synovial fluid at time of inflammation
18
Q
diagnosis of acute gouty arthritis
A
- joint aspiration (hyperuricemia + joint effusion not enough)
- look at fluid under polarized light
- can mimic septic arthritis (fever, leukocytosis, high ESR)
19
Q
what imaging can be used to tentatively diagnose gout, and what will you see?
A
US - superficial, hyperechoic, irregular band on surface of articular cartilage = “double contour sign” or “urate icing”
MRI/ CT - good for finding gouty erosions
20
Q
most important indication for arthrocentesis
A
to check for septic arthritis
21
Q
how can you determine if blood in aspirated synovial fluid is from hemarthrosis or from trauma from a poorly performed arthrocentesis?
A
- trauma: blood may remain unmixed with synovial fluid, appearing as red streaks in an otherwise yellow fluid
- hemarthrosis: synovial fluid is generally homogeneously bloody and does not form a clot
22
Q
how to differentiate MSU from CPPD crystals with polarized microscopy
A
MSU: yellow parallel, blue perpendicular
CPPD: blue parallel, yellow perpendicular
23
Q
how long can asymptomatic hyperuricemia last
A
up to 20 years
24
Q
3 stages of gout
A
- acute gout
- intercritical gout
- chronic tophaceous gout
25
describe the first gout attack
- usually monoarticular (big toe, instep, ankle, heel, knee, wrists, fingers, elbows)
- can get bursitis, tendinitis and tenosynovitis
- acute w/ intense pain and limited time
- men 40-60 y/o and women more than 60 y/o
26
describe intercritical gout
- after 1st attack there is "intercritical gout period"
- most untreated patients will have a second episode within 2 years
- trend if untreated:
- additional acute attacks
- progressively shorter asymptomatic periods
- increasingly severe, prolonged and polyarticular flares
27
describe chronic recurrent gout
- polyarticular acute exacerbations
- more commonly in upper extremities
- bony erosions and deformities
28
tophaceous gout
- solid urate deposits (tophi) in tissues
| - 75% with tophi after 20 years of untreated gout
29
factors that can precipitate a gout flare
- trauma
- surgery or hospital admission w/ IV fluids
- starvation
- dehydration
- increased alcohol consumption (but NOT wine)
- dietary indulgence
- acute changes in serum uric acid level
- stopping or starting medications for gout
30
gout treatment goals
- rapidly end acute flares
- protect against future flares for lifetime
- reduce change of crystal inflammation
- prevent disease progression (lower serum urate to less than 6 mg/dl)
- correct metabolic cause
31
specific treatments for acute gout
- rest, ice packs, elevation
- increase water consumption
- NSAIDs
- colchicine
- glucocorticoids
- IL-1B antagonists
32
does ending acute flares cure gout?
no- but it controls inflammation, relieves pain. but not a cure b/c crystals remain in joints
33
what steps can one take after a first attack to try to slow down/prevent future attacks?
- avoid dehydration
- modify meds
- reduce alcohol intake
- lose weight
- meds to increase excretion (probenecid)
- meds to reduce production (allopurinol, febuxostat, PEG-uricase)
- prophylaxis against attacks with colchicine and NSAIDs
34
reasons to start urate lowering therapy
- recurrent attacks
- urate nephrolithiasis
- tophaceous gout
- evidence of gout-induced joint damage
35
how do you choose what urate lowering therapy to use
base choice on whether pt is an overproducer or underexcreter:
700/24h = overproducer (10%) - use xanthine oxiase inhibitor
36
function of uricosuric agents
-increase secretion of urate into urine
37
examples of uricosuric agents
- probenecid
- benzbromarone
- losartan or fenofibrate (mild urisocurics)
38
two xanthine oxidase inhibitors and their MOA
- allopurinol: blocks conversion of hypoxanthine to uric acid
- febuxostat (didn't say MOA)
39
function of urate oxidase (UO)
catalyzes the oxidation of uric acid to 5-hydroxyisourate, which can then be converted to more soluble and excretable allantoin
(humans have a gene for this, but its non-functional)
40
calcium crystal disease involves what two crystal types
calcium pyrophosphate dihydrate (CPPD)
| basic calcium phosphate (BCP)
41
describe CPPD disease
- excessive cartilage pyrophosphate production leads to CPPD crystals depositing in joint articular cartilage (hyaline), fibrocartilage (menisci), and ligaments
- can be asymptomatic
- acute release of CPPD crystals into joint space - phagocytosis by macrophages - release of chemotactic and inflammatory substances - activating inflammasome
- can also cause mild chronic inflammation
42
XR diagnosis for CPPD disease
chondrocalcinosis - calcification of the cartilage and fibrocartilage
*high res US helpful b/c XR of CPPD not always detectable
43
describe the production of CPPD
- extracellular ATP 'scavenging' by nucleoside triphosphate pyrophosphate hydrolase yields PP
- OA cartilage matrix abnormal: favors Ca + PP deposition
44
epidemiology of CPPD
- both sexes equally affected
| - idiopathic with aging most common
45
causes of CPPD deposition
- idiopathic with aging most common**
- complication of primary osteoarthritis
- long term consequence from trauma/menisectomy
- familial chondrocalcinosis
- gitelman syndrome
- systemic metabolic disease (primary hyperparathyroidism)
46
describe gitelman syndrome
autosomal recessive renal tubular disorder
- mimics chronic thiazide ingestion
- presents as older child/adult w/ hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and normal BP
- leg and arm cramps, weakness, polyuria, nocturia, and chondrocalcinosis
47
three possible presentations of CPPD disease
- asymptomatic CPPD crystal deposition
- acute CPP crystal arthritis (pseudogout)
- chronic CPP crystal inflammatory arthritis
48
describe pseudogout
- acute inflammatory mono or oligoarticular arthritis
- typically involves larger joints (knees most)
- lasts 1-3w
- flares after parathyroidectomy
49
describe chronic CPP crystal inflammatory arthritis
- pseudo-RA
- non-erosive, asynchronous, inflammatory arthritis with CPPD crystals in joint fluid of clinical joints, suggesting RA
- XR changes more typical of osteoarthritis than RA
50
MSU vs. CPPD crystals
MSU:
- gout
- needle-shaped, about size of PMN
- negatively birefringent (yellow parallel)
CPPD:
- pseudogout
- rhomboid, smaller than PMN
- positively birefringent (blue parallel)
51
how does aspirated fluid in CPPD differ from gout
fluid tends to be inflammatory - typically 15,000 to 30,000 WBCs (90% neutrophils)
52
XR findings of CPPD
- chondrocalcinosis
- subchondral cysts
- beak-like projections (2nd and 3rd metacarpal heads)
53
how an you diagnose CPPD when unable to prove crystals?
high res US:
- thin hyperechoic bands, parallel to surface of cartilage (knee)
- 'punctate' pattern w/ several thin hyperechoic spots (fibrous cartilage and tendons)
- homogenous hyperechoic nodular or oval deposits in bursae and articular recesses
54
treatment of pseudogout
- joint aspiration and intra-articular corticosteroid
- NSAIDs
- colchicine
- systemic corticosteroid
55
pseudogout prophylaxis
- necessary if more than 3 episodes/year
- low dose colchicine
- methotrexate or hydroxychloroquine for refractory chronic inflammation/synovitis
- IL-1B inhibitors for recurrent acute or severe attacks
56
describe BCP deposition
- closely tied to osteoarthritis
- can cause chondrocalcinosis on XR
- rarely causes acute inflammation- more of a chronic low grade destructive arthritis
57
what conditions can BCP be found in?
- advanced chronic renal failure (hyperphosphatemia)
- hypercalcemic metastatic calcification
- hyperparathyroidism
- areas of tissue damage (dystrophic calcification)
58
what is the most common BCP crystal
hydroxyapatite
| -primary mineral in bone/teeth (apatite is)
59
ID of hydroxyapatite crystals in BCP
- amorphous crystals not visible with polarized light*
- if in a clump, edge can be birefringent
- synovial fluid crystal stain w/ alizarin red to ID crystals
- absolute ID with EM
60
what does hydroxyapatite crystals cause
- cartilage and bone damage with chronic low grade inflammation
- synovial fluid WBC counts less than 2000
61
presentation of hydroxyapatite crystals
- associated with periarthritis, tendon calcifications
- knees, shoulders, hips, fingers
- acute onset pain and swelling or chronic low grade inflammation
62
what are hydroxyapatite crystals associated with?
- progressive rotatoe cuff degeneration
- elderly women: Milwaukee shoulder
- extremely destructive chronic arthropathy
- hemorrhagic shoulder effusions
- synovial fluid shows BCP crystals
63
treatment of BCP crystal deposition arthropathy
- NSAIDs or COX2 inhibitors
- intra-articular or periarticular corticosteroid injections
- local irrigation
- high frequency therapeutic US to degrade BCP crystal deposits
- agents to lower serum [phosphate] may lead to resorption of deposits in renal failure patients receiving hemodialysis
64
describe primary calcium oxalate deposition disease
- rare hereditary metabolic enzyme defect
- overproduction of oxalic acid
- oxalate crystals in tissue, nephrocalcinosis
- renal failure and death before age 20
65
describe secondary calcium oxalate deposition disease
- more common than primary
- metabolic abnormality complicating end-stage renal disease dependent on long-term peritoneal/hemodialysis who received ascorbic acid supplements
66
where do you find CaOx deposits?
- bone, articular cartilage, synovium, and periarticular tissues
- crystals may be shed, causing acute synovitis stimulating synovial cell proliferation and enzyme release, resulting in progressive articular destruction
- deposits in fingers, wrists, elbows, knees, ankles, feet
67
describe shape of CaOx crystals
- variable shape and variable birefringent to polarized light
- most easily recognizable ones are bipyramidal with strong birefringence and stain with alizarin red
68
treatment of CaOx arthropathy
- NSAIDs
- colchicine
- intra-articular glucocorticoids
- increased frequency of dialysis (only slight improvement)
- primary oxalosis, liver transplantation
