crystal arthritis

Question 1

precipitation of uric acid in the joints due to high serum uric acid levels

Answer 1

Inflammatory arthritis- Gout

Question 2

MOA of gout

Answer 2

uric acid (monosodium urate) crystals deposit into the joint

Question 3

once the urate crystals are deposited into the joint it causes an inflammatory reaction….

Answer 3

Crystal phagocytosis by PMNs or macrophages –> immune response —> recruit white blood cells

Question 4

uric acid is pro-iflammatory

Answer 4

yep- lysosomal enzymes are present

Question 5

prevalence of gout

Answer 5

it rises with age but there is a difference between men and women with men having a higher prevalence at a younger age but the gap closes once we reach about 55

Question 6

distribution of involvement of Gout

Answer 6

first MTP point (podagra) due to trauma and cooling reducing the solubility of uric acid
it will eventually affect other parts of joints such as knees, ankles, wrists

Question 7

Crystals become ___ inflammatory after cycles of ingestion and release, inflammation subsides over 10 ‑ 14 days

Answer 7

less

Question 8

X-ray imaging what do we see?

Answer 8

early in the disease we see not much of anything but with untreated we start to see boney erosions leading to a deforming chronic polyarthritis

RAT BITES

Question 9

three most common causes of monoarthritis

How can we differentiate between them?

Answer 9

1. infection
2. trauma
3. Gout

Differentiate by arthrocentesis / synovial fluid analysis

Question 10

Diagnosis of Gout

Synovial fluid under a polarizing microscope:

Answer 10

intracellular or extracellular uric acid crystals

Question 11

yellow, parallel and allopurionol

Answer 11

GOUT

crystals are needle shaped

Question 12

Gout and infection can co‑exist in a joint, and joint infection can precipitate a gout attack

Answer 12

yep, do both a crystal analysis and culture/gram stain

Question 13

People who develop gout have had hyperuricemia for years or decades

Answer 13

yep but only a fraction of persons with hyperuricemia develop gout (5-year risk 20% in serum uric acid > 8 mg/gL )

Question 14

serum uric acid level is influenced by

Answer 14

1. uric acid productio- higher cell turnover such as people with lyphoma, obesity…
2. uric acid ingestion (dietary)
3. renal excretion

Question 15

overproducers vs underexcretion of uric acid…

Answer 15

it is much more common to be an underexcretion- this is mainly due to renal failure while overproduction is usually due to a genetic cause such as HGPRT deficiency( lesch-nyhan syndrome) and PRPP synthetase (anzyme overactivity) or an acute illness that leads to increased ATP turnover

Question 16

lead posioning in GOUT

Answer 16

affects both overproducers (directly reduces uric acid solubility in synovial fluid) and underexcretion (kidneys under-excrete uric acid)

Question 17

Increased urate production (accelerated hepatic breakdown of ATP)
Decreased urate excretion due to lactic acid conversion
Beer contains purines
Associated renal and hepatic impairment

Answer 17

excessive alcohol

Question 18

if someone comes in with gout and they are less than 30 of age?

Answer 18

Suspect an underlying enzyme defect in purine metabolism in age < 30

Question 19

Renal manifestations in Gout:

1. most common
2. rare
3. even rarer

Answer 19

1. most common- kidney stones (uric acid or calcium stones)
2. rare- acute uric acid nephropathy due to a consequence of cytotoxic chemotherapy (pre-treat with a xanthine oxidase inhibitor)
3. even rarer - chronic uric acid nephropathy (hypertensive)

Question 20

treatment between acute vs chronic gout

Answer 20

Acute Gout Attack: Managing Inflammation

Chronic Hyperuricemia: Lowering Uric Acid

Question 21

Acute Gout treatment

Answer 21

1. NSAIDs

2. colchine and glucocorticoids are second line

Question 22

effective, but costly and can be toxic
ADRs : nausea and diarrhea, neuromyopathy
most effective during first 24‑48 h of an attack
Mechanism:
inhibits cell division by disrupting microtubules / mitotic spindle
Downregulates TNF and LTB4, affects neutrophil activation
Blocks COX2 and prostanoid synthesis

Answer 22

colchicine

Question 23

orally, intravenously, intramuscularly, or by intra‑articular injection

most effective way to control an attack‑‑within hours‑‑inject directly into joint

Rule out infection first!

Answer 23

glucocorticoid

Question 24

In patients with contraindications to 1st line treatments, frequent or refractory flares treatment

Answer 24

1. Anakinra (Il-1 receptor antagonist)***
2. Canakinumab (Il-1 beta inhibitor)
3. Rilonacept is still under FDA review.

Question 25

Management of Chronic Hyperuricemia

Answer 25

First Line: lifestyle changes , diet and exercise and management of comorbidities

Treatment depends on risk of another attack.

Question 26

Do not treat hyperuricemia if no previous history of gout or uric acid kidney stones.

Answer 26

yeppppppp

Question 27

People come to medical attention because of gout, but this is an opportunity to intervene in a much more deadly associated condition – metabolic syndrome – which does not generally bring people to see doctors.

Answer 27

sooo true

Question 28

Uric acid lowering treatments:

1, Uricosuric agents:

2. Xanthine Oxidase Inhibitors:
3. Pegloticase

Answer 28

1, Uricosuric agents: enhance renal excretion of uric acid by inhibiting renal reabsorption (through URAT-1). [probenecid and Lesinurad]
Contraindicated if history of kidney stones
Inefficiency in those with GFR < 60

2. Xanthine Oxidase Inhibitors: allopurinol and febuxostat
   reduce production of uric acid, increase production of xanthine, which is excreted

3. Pegloticase (other above meds are contraindicated)
Urate oxidase (enzyme)

Question 29

first line therapy for lowering uric acid
Efficacy
ease of use
generic availability
Build dose slowly based on uric acid and GFR, starting with 100 mg/d for patients with GFR > 60 ml/min.

Answer 29

allopurinol

Question 30

allopurinol toxicity (2) and contraindication

Answer 30

1. renal/hepatic dysfunction
2. DRESS
3. contraindicated with azathioprine

Question 31

HLA B*5801

Answer 31

genetic predisposition to severe toxicity for taking allopurinol .(Korean descent with CKD or Han Chinese and Thai descent regardless of GFR)

Question 32

Febuxostat

Answer 32

used instead of allopurinol but has some cardiac tox

Question 33

Bridging with colchicine

Answer 33

Small doses of oral colchicine for 6 months after starting the urate-lowering therapy and normalization of uric acid

Question 34

why do we need to bridge with colchicine?

Answer 34

Fluctuations in uric acid increase gouty attacks  colchicine decreases inflammation and risk of attack

Question 35

colchicine rare SE

Answer 35

neuromyopathy that mimics polymyositis. (age >60 and serum creatinine >2.0 mg/dl
Follow symptoms, strength, CK levels)

Question 36

All non‑allergic patients with tophi should take an _____________

Answer 36

XO inhibitor.

Question 37

Tophi :

Answer 37

Tophi : >10 or more years of gout

Question 38

Calcium Pyrophosphate Dihydrate (CPPD): (4)

Answer 38

Four forms of arthritis:

1. Pseudogout (20%): knee and wrist
2. PseudoRA (rare): wrist and metacarpophalangeal joints
3. PseudoOA (most common): knees and shoulders
4. CPPD leading to “ charcot” arthropathy: bone fragmentation associated with extensive, bizarre hypertrophic bony changes.

Question 39

Diagnosis of CPPD (2)

Answer 39

1. Characteristic x‑ray findings of linear calcifications in the cartilage –>chondrocalcinosis.
2. Synovial aspiration: rhomboid crystals and positve birefringent (blue)

Question 40

CPPD associated conditions

Answer 40

Usually occurs sporadically but associated conditions include:

1. Hyperparathyroidism
2. Hemochromatosis
3. Hypomagnesemia
4. Hypophosphatemia
5. familial hypocalciuric hypercalcemia

Question 41

Calcium pyrophosphate crystals (pseudogout) are positively birefringent – yellow when perpendicular to the axis of the red compensator, and blue when parallel.

Answer 41

yep

Question 42

Treatment of CPPD

Answer 42

DS, colchicine or corticosteroids (0ral or intraarticular)

** Colchicine has been shown to prevent pseudogout attacks and improve the more chronic forms of CPPD

Question 43

There is no way to reduce the pyrophosphate concentration in the joint, in the same way that allopurinol or uricosuric agents remove uric acid from the body.

Answer 43

unfortunately yes