SM 235a - Crystalline Diseases Flashcards
Which drugs are associated with increased risk of gout?
- Thiazides
- Cyclosporie
- Low-dose aminosalicylates
What kind of crystals are these?
Pseudogout
Rhoboid shaped, weakly positively birefringent
(Blue when parallel to the polarizer = positive biregringence)
Describe the synovial fluid in BCP crystal arthritis
Not inflammatory
(<2000 WBCs)
Describe the microscopic appearance of CPPD crystals
Rhomboid shaped
Weakly positively birefringent = Blue when parallel to the polarizer
Which crystaline disease does not have inflammatory characteristics?
BCP arthropathy
What conditions cause overproduction of uric acid?
What are the consequences?
- Alcohol use
- Enzyme abnormality (disease onset will be early)
- Hemolytic disease
- Myeloproliferative disease
-> increased uric acid -> GOUT
Serum ____________ concentration is associated with gout
Serum uric acid concentration is associated with gout
What agents are used for the chronic management of gout?
- Xanthine oxidase inhibitors
- Decrease production of urate
- Allopurinol (*Hypersensitivity rxn risk*)
- Febuxostat
- Uricosuric agents
- Increase excretion of urate
- Probenecid (*Kidney stone risk*)
- Lesinurad
- Pegloticase
- IV Uricase
- Converts uric acid into allantoin
What are the risk factors for developing gout?
- Increased alcohol consumption
- Increased ATP degradation = increased urate synthesis
- Increased lactic acid = urate excretion
- Beer has the highest purine content of the alcohols
- Obesity
- Metabolic syndrome
- Insulin resistance
What are the treatments for acute gout?
- Colchicine
- NSAIDs
- Intra-articular corticosteroids
Do not start new uric acid lowering treatment during an accute attack
Do not stop uric acid lowering treatment if already taking
What are the 3 main crystal types that can be found in synovial fluid?
- Basic calcium phosphate (BCP)
- Calcium pyrophosphate dihydrate (CPPD)
- Monosodium urate (gout)
What medications are used as prophylaxis for acute gout attacks?
NSAIDs, colchicine, steroids
These can also be used to alleviate pain during an acute attack
Long-term management agents are not prophylactic against acute attacks (although lowering uric acid levels on its own should be prophylactic?)
Which inborn errors of metabolism increase one’s susceptibility to gout?
Leschi-Nyhan
PRPP synthetase mutation
What kind of crystals cause gout?
Monosodium urate monohydrate
- Negatively birefringent (yellow when parallel to the polarizer)
- Needle shaped
What medication increases the excretion of urate?
What condition can this help manage?
Uricosuric agents: Probenecid and Lesinurad
Used for chronic management of gout
BCP crystals deposition in soft tissue causes _________.
What are the consequences?
BCP crystals deposition in soft tissue causes acute calcific periarthritis.
-> intense local inflammation
What is the major risk factor for Calcium Pyrophosphate Dihydrate (CPPD) arthropathy?
Aging
Presentation peaks at 65-75 y/o; F>M
- Tends to affect joints affected by osteoarthritis
What foods increase one’s risk of gout?
- Foods rich in purines
- Purine degradations -> uric acid production
- Meat, shellfish, ethanol, soft drinks, high-fuctose corn syrup
Describe the clinical presentation of gout
- Acute monoarthritis
- Usually involves the 1st MTP
- Any joint can be affected
- Pain often begins in the early AM
- Very acute
- Unable to tolerate teh bedsheets touching the affected joint
- First few attacks are usually self-limited
- Resolve after 7-10 days without therapy
- Subsequent attacks may be more freqent, severe, and resistant to therapy
- If hyperuricemia persists, disease may become chronic and polyarticular
This is an image of synovial fluid obtained from a patient with gout and shows negatively birefringent needle shaped crystals. Which way is the polarizer facing?
C
- Needle-shaped crystals will be yellow when parallel to the polarizer
- This means they are positively birefringent
- Monosodium urate monohydrate crystals cause gout
What are the indications for chronic gout therapy?
Begin chronic therapy if any of the following are present
- > 2-3 gout attacks in 1-2 years
- Renal stones
- Tophaceous gout
- Erosions on x-ray
The metabolism of ______ creates uric acid.
This contributes to the pathologenesis of which crystaline disease?
The metabolism of purines creates uric acid.
Buildup of uric acid leads to gout
What medication decreases the production of urate?
What condition can this help manage?
Xanthine oxidase inhibitors
Ex: Allopurinol, febuxostat
Used for chornic management of gout
What medication is the enzyme uricase given intraveneously?
What condition does this medication treat?
Pegloticase
Converts urate into allantoin
Used for the chronic management of gout
What are the indications for colchicine?
Acute management of CPPD and Gout
Prophylaxis againt acute gout attacks
Where do basic calcium phosphate (BCP) crystals deposit?
What pathologies does this cause?
Remember the ABC’s of BCP
- Soft tissue -> Acute calcific periarthritis
- Joints -> BCP arthropathy
- Tendons -> Calcific tendonitis
BCP deposition in the tendons causes ________.
What are the consequences?
BCP deposition in the tendons causes Calcific Tendinitis.
- Most commonly seen in the shoulder
- Buritis, impingement syndrome
- Can also involve other joints
- Hand, wrist, hip, knee, foot, neck
BCP crystal deposition in joints causes ____________.
What are the consequences?
BCP crystal deposition in joints causes BCP Arthropathy.
- Shoulder -> Milwaukee shoulder syndrome
- Severe degenerative arthritis of the shoulder joint
- Loss of rotator cuff, cannot abduct arm, huge swelling
- Bilateral involvement is common
- Finger -> Philadelphia finger
- Same thing but in the finger
- Can affect other joints as well
Describe the goals of management for an acute gout attack.
How are they achieved?
- Rapid and safe pain relief: decrease inflammation
- NSAIDs
- Colchicine
- Corticosteroids
- Prevent further attacks
- Xanthine oxidase inhibitors (Decrease urate production)
- Uricosuric agents (Increase urate excretion)
- Pegloticase (Convert uric acid into allantoin
- Anakinra (Anti-IL1)
- Prevent the formation of tophy and destructive arthritis: keep uric acid levels low
What conditions cause underexcretion of uric acid?
What are the consequences?
- Alcohol consumption
- Drugs
- Decreased renal function
-> hyperuricemia -> GOUT
Describe the clinical presentation of CPPD
CPPD = pseudogout
- Most often presents the same way gout does
- Can also present as chronic polyarthritis (like RA), or progressive osteoarthritis
- May be asymptomatic
What are the 4 stages of Gout?
- Asymptomatic hyperuricemia
- Acute gouty arthritis
- Intercritical gout
- Quiescent intervals between gout attacks
- Chronic tophaceous gout
- After ~10 years of uncontrolled disease
What kind of crystals are these?
Which disease are they associated with?
Monosodium urate monohydrate crystals
Gout
- Needle-shaped
- Yellow when parallel to the polarizer
What is the treatment for CPPD?
- NSAIDs
- Intra-articular or oral steroids
- Colchicine
- There is no true prophylaxis; can only treat acute attacks
What kind of crystals are these?
How do you know?
Basic Calcium Phosphate (BCP)
- “Shiny coins” on ordinary light microscopy
- Not birefringent on polarized light microscopy
- Alizarin red stain
Monosodium urate monohydrate crystals are associated with which disease?
Gout
What characterizes all crystalline arthropathies?
- Inflammation in the joint
- Synovial fluid will have WBC cound 2000-50,000, just like other inflammatory joint conditions
- Except BCP crystals - not inflammatory
- Crystals in the synovial fluid
What causes gout?
Hyperuricemia
- Underexcretion (most common cause)
- Alcohol use
- Decreased renal function
- Drugs
- Diuretics (thiazides), cyclosporine, ethambutol, ASA
- Overproduction
- Alcohol use
- Enzyme abnormality (disease onset will be early)
- Hemolytic disease
- Myeloproliferative disease
Why do men <60 years old have a higher prevalence of gout than women <60 years old?
Uric acid levels start to increase in men at puberty
- Estrogen is uricosuric => it is protective against gout
- Prevalence in males and females equalizes post-menopause
What is the treatment for BCP arthropathy?
Treat if symptomatic
- NSAIDs
- Physical Therapy
- Intra-articular steroids
- Surgery if indicated
