Gout

Question 1

What is gout?

Answer 1

This is a common disorder or uric acid metabolism

Monosodium urate crystals are deposited in soft tissues

Question 2

What are monosodium urate (MSU) crystals usually coated by and why are they coated?

Answer 2

Coated by serum proteins (apoE or apoB)

Coating inhibits the binding of MSU crystals to cell receptors

Question 3

What can trigger a gout attack?

Answer 3

• Uric acid levels elevate 20 years before the onset of gout
• The presence of urate crystals alone is not enough

Gout may be triggered by:

1. release of uncoated crystal (partial dissolution of microtophus due to changing serum urate levels)
2. precipitation of crystals in a supersaturated microenvironment

Question 4

What occurs after a gout attack has been triggered?

Answer 4

• make urate interacts with the intracellular and surface receptors of local dendritic cells and macrophages –> activates immune system
• interaction may be enhanced by binding of IgG
• MSU triggers receptors (TLRs and NALP3 inflammasomes) and receptors expressed on myeloid cells = production of IL-1
• cascade of pro-inflammatory cytokines
• neutrophil phagocytosis = burst of inflammatory mediators

Question 5

How do the crystals contribute to the pain and inflammation in gout?

Answer 5

The crystals are long and thin
Pierce the neutrophils = lysis
Release of contents from neutrophils attracts more WBCs and increases immune cells present
this causes the inflammation and pain

Question 6

Why does pH become lowered and what effect does this have?

Answer 6

Neutrophils release acid when phagocytosed/lysed

Lowering of pH results in more crystal precipitation

Question 7

What is podagra? How often is it seen in gout?

Answer 7

inflammation of the 1st MTP joint

Seen in 50% of gout cases

Question 8

What is the onset of gout like? How long does it last?

Answer 8

Onset is usually sudden and intensity peaks at 8-12 hours
- usually occurs 2-3am when body temp is low

1st attacks will resolve within 2 weeks and will not require treatment

Question 9

How does gout often present? what joints does it most often affect etc?

Answer 9

Common in men >30
Acute monoarticular in 90% of cases
Affects smaller, lower extremity joints
Joint will be red, hot, tender, and pain starts acutely and at night time

Question 10

What happens if a person has multiple gout attacks that go untreated?

Answer 10

• attacks become polyarticular
• more proximal and upper extremity joints are involved
• attacks are more frequent and long-lasting
• chronic polyarticular arthritis almost symmetrical
• can affect other synovial structures

Question 11

What are the main differences between an acute gout attack and chronic tophaceous gout?

Answer 11

Acute gout:

• phagocytosis of crystals
• cell swelling + inflammasome activation
• cytokines production + vasodilation
• neutrophil + monocyte influx

Chronic tophaceous gout:

• packaging of MSU crystals
• resolution of inflammation
• inactivation of inflammatory cytokines
• neutrophil death by NETosis

Question 12

What are tophi? What % of cases do they develop in?

Answer 12

Urate crystals in soft tissues
Foreign body type giant cell reaction to the deposited crystals

Develop in 50% of patients with untreated gout

Question 13

At what point is uric acid considered saturated?

Answer 13

At 6.8mg/dL

- often due to insufficient excretion rather than overproduction (90%)

Question 14

How is gout diagnosed?

Answer 14

> 6 out of 11 variables

SF analysis:

• inflammatory
• WBC count >2000/uL
• predominance of polymorphonuclear neutrophils
• urate crystals will be needle-like + high negatively birefringent

Serum uric acid:
- if higher than 11 mg/dL - should be treated

X-rays/US:

• soft tissue swelling/increased blood flow
• maintenance of joint space
• erosion outside joint capsule
• erosions have overhanging edges (rat-bite)

Dual energy computed tomography (DECT)

Question 15

What is the pharmacological treatment for acute gout?

Answer 15

1. NSAIDs
   - start with highest dose for 2-3 days
   - taper down over 2 weeks
   - gout symptoms should be gone for 2 days before stopping treatment
2. Colchicine (stops cell division)
3. Corticosteroids
   - if NSAIDs/colchicine cannot be used
4. IL-1 biologicals:
   - Rilanocept, canakinumab, anakinra
   - reduces length of attacks + recurrences
   - used for severe + frequent attacks

Question 16

How can acute gout be treated non-pharmacologically?

Answer 16

Lifestyle - low purine diet etc.

Question 17

How is chronic gout treated pharmacologically?

Answer 17

1. Allopurinol
   - blocks xanthine oxidase
   - reduces the generation or uric acid
2. Probenecid
   - increases uric acid excretion
   - fewer S/E than allopurinol
3. Rasburicase
   - catalyses conversion of uric acid to Allantoin

Question 18

What is pseudo gout?

Answer 18

AKA Calcium pyrophosphate (CP) deposition disease
- acute deposition of CP crystals around joints
It is a metabolic arthropathy
Causes chondrocalcinosis

Question 19

What joint is most commonly affected in pseudo gout?

Answer 19

Knee

Question 20

what can trigger pseudo gout?

Answer 20

trauma

rapid decrease in serum calcium levels

Question 21

How is pseudo gout diagnosed?

Answer 21

• SF = 10000-50000 WBCs/uL
• Rhomboid shaped crystals that are weakly birefringent
• US may show calcification
• Chondrocalcinosis of articular disc and atypical OA of hands

Question 22

How is pseudo gout treated?

Answer 22

intra-articular corticosteroids and NSAIDs

Question 23

In which condition is cholesterol crystals found? What is their appearance like? What causes them to occur?

Answer 23

Found in some cases of RA (rare)
Plate-like structure and notched
Caused by:
- defective drainage of SF back into venous system
- local destruction
- increased permeability of synovial membrane to LDL and HDL
- intra-articular bleeding