Gout

Question 1

Gout in short

Answer 1

Most common cause of inflammatory arthritis in the US

Deposition of monosodium urate monohydrate crystals in synovial fluid and other tissues

Question 2

Pathogenesis of gout

Answer 2

Hyperuricemia is necessary but not sufficient

Urate is breakdown from purine metabolism…if you increase turnover, then increase urate

Genetic renal urate underexcretion

Beyond hyperuricemia, mediated by formation of MSU crystals and inflammatory response to crystals

Question 3

Demographic and diet contribution to gout

Answer 3

Male, older, obese (Tissue nucleuotide synthesis and metabolism)

Alcohol, red meat, shellfish, corn syrup (dietary purines)

Question 4

Dz and meds contributing to gout

Answer 4

Renal insufficient, organ transplant

Thiazide and loop diuretics, cyclosporine….mostly affect kidnyes

Question 5

Formation of crystals and effects

Answer 5

Lower temp and higher conecntrations (furthest from the body core)

Once they deposit, macros phagocytose the crystals and begin inflamm cascade

More immune cells recurtied

Respiratory burst and release of inflamm mediators

With continued hyperuricemia and crystals, inflammation becomes chronic

A tophus (deposit of MSU crystals surrounded by granulomatous inflammation) is a hallmark

Bone erosions due to chondrocyte cell death and osteoclast formation

Question 6

Gout epidemiology

Answer 6

MIddle age men

Most common inflam arthritis

Question 7

Acute gouty phase

Answer 7

Acute gouty arthritis - acute inflammatory monarthritis of the first MTP joint, insetp, ankle, or knee

INitially occur in distal locations and then more proimmally

Happens in the middle of the night and then joint appears red, swollen, etc.

Sx quikcly reach maximal severity then decrease over 1-2 weeks

Question 8

Stages of gout

Answer 8

Asymptomatic hyperuricemia

Acute gouty arthritis and intercritical gout

Chronic gouty arthritis

Question 9

Intercritical gout

Answer 9

After resolution of the initial attack

Second attakc within the next 2 years….overtime the attacks become more frequent and involve more proximal joints and upper extremities

Question 10

Chronic tophaceous gout

Answer 10

Tophi in connective tissue

Accumukation of solid urate between gouty attacks

Bony erosions and joint dsmage

Question 11

Dx of gout

Answer 11

Definitive from MSU in synovial fluid

POlarizing light microscopy looks like needle shaped negatively birefringent crystals

Can als oaspirate tophi

Question 12

Dz outside of aspiration

Answer 12

Serum urate usually evelated but may be normal during flare

Radiography can show chornic tophaceous gout but that’s about it

Ultrasound will show hyperechoic linear density (double contour sign) overlying suerface of joint cartialge

Question 13

Manamgnet of acute gouty arthritis

Answer 13

Anti-intflam

NSAIDs, colchicine, systemic GCs and intra-articular GCs…intitate ASAP

Question 14

After a flare, manamgnet

Answer 14

Avoid diet things

Weight loss

Urate lowering therapies

Question 15

Xanthine oxidase inhibitors

Answer 15

Allopurinol and febuxostat

First lin e

Inhibit conversion of hypoxanthine to uric acid

Do NOT start during acute gouty episode because could prolong

Allopurinol has more side effects

Severe HS rxn in 1/1000

Question 16

Uricosuric drugs

Answer 16

Probenecid and lesinurad

Increase efficiency of renal uric acid excretion and can improve hyperuricemia in individuals who under excrete uric acid

Second line agents or add on

Increased risk for uric acid stone formation so avoid is nephrolithiasis risk

Question 17

Uricase

Answer 17

Enzyme that catalyzes conversion of urate to allantoin (more H2O soluble)

Pgloticase is option for advanced and have failed

Question 18

Acute attacks and meds

Answer 18

Acute fall in serum urate concentration can precipitate epsiode of acute gouty arthritis

NEVER intiate urate lowering therpauy durign acute attack

Oftne give the urate-wlowering agents which colchicine prophylaxis to help prevent acute attack