Gout Scott Smith PGY-1 1/11/2018 - PowerPoint Presentation

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Gout

Scott Smith PGY-1

1/11/2018

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Gout

Acute inflammatory arthritis caused by accumulation of monosodium urate

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Typical Features

Monoarticular

Rapid onset w/I 24

hrs

Incapacitating pain

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Pathophysiology

Uric Acid (product of purine degradation) accumulates to the point of precipitating into the joint

Precipitation of uric acid can be affected by variety of factors, including body pH and temperature

Hyperuricemia (serum urate >7mg/

dL

in men >6mg/

dL

in women) is the major risk factor

Precipitated urate crystals phagocytosed by macrophages

Crystals bins to cellular NLRP3

inflammasome

 Secretion of IL-1

IL-1 binds IL-1 receptor on synovial cells, secreting

proinflammatory

factors

Arrival of neutrophils and secretion of additional inflammatory factors causes inflammation and pain

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Pathophysiology

Understanding of pathophysiology presents targets

for control of disease

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Clinical Manifestations

Early gout is typically

monoarticular

, most frequently the MTP joint of 1

st

toe (

Podagra

)

Develops rapidly from asymptomatic to incapacitating pain in <25hrs

Joint is red, warm, swollen and exquisitely tender

Common sites 1

st

toe > arch of foot > ankle > knee

Wrist, elbow and shoulder involvement is more characteristic of more advanced gout

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Progression of Disease

After having years of disease a patient will have more frequent and more severe diseasePolyarticular GoutSoft tissue deposits of monosodium urate (tophi) esp. on auricle, extensor surface of hand/fingers, olecranon bursa and achilles tendonCan develop chronic arthritis as opposed to flares of acute goutErosive Arthropathy

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Gout Stages

Asymptomatic

hyperuricemia:

 majority never develop

This usually lasts for years-decades before developing acute gouty

arthritis

Acute gouty arthritis

:

monoarticular

pain (

podagra

, ankle, etc.); attacks last hours-2

week

Intercritical

gout

: completely asymptomatic between acute attacks

~65% will have another acute attack within 1-2 years

Presence of asymptomatic periods between

monoarthritic

attacks is almost unique to gout and used as a diagnostic

criterion

Chronic

tophaceous

gout

:

intercritical

periods are now symptomatic (chronic swelling and worsening pain) & develop subcutaneous

tophaceous

deposits of MSU; usually after >10y of acute intermittent gout

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Differential Diagnosis of Monoarthropathy

Gout

Pseudogout

Septic Arthritis

Hemorrhagic

Arthropathy

Reactive Arthritis

Traumatic

Arthropathy

Cellulitis

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Risk Factors - Demographics

Gender

Gout is more prevalent in men by a factor of 3 (6% vs 2%)

However Gap is narrowed in post-menopausal women

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Risk Factors - Demographics

Age

Increasing age brings heavier burden of disease to age cohort

1% prevalence in 20’s

3.3% prevalence in 40’s

12.6% prevalence in 80’s

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Risk Factors - Demographics

Ethnicity

More common in African Americans >

Causasians

> Mexican Americans

5% vs 4% vs 1.5%

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Risk Factors - Diet

Intuitively, a diet high in purines increases risk

Alcohol is also associated with higher risk, especially beer

Red meats and seafood

Caffeinated Coffee, low-fat dairy, Cherries are associated with lower risk

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Risk Factors - Diet

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Risk Factors - Clinical

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Diagnosis

Gold standard is arthrocentesis with microscopy

Aspirate in disease will be yellow vs. normal clear

Microscopy under polarized light shows needle-shaped, negatively birefringent crystals

Leukocyte count of 15,000

–

80,000 with neutrophil predominance

Soft Tissue Tophi

Shown to contain monosodium urate crystals under polarized microscopy

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Diagnosis

Arthrocentesis is not always feasibleClinical Criteria for diagnosisPut forth by American College of Rheumatology in 19776 or more is sufficient for diagnosis of gout

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Treatment of Acute Gout

Corticosteroids

Can be administered orally, IV or

intraarticularly

Rapid relief of symptoms 1-5 hours

Methylprednisolone dose pack (starting 24mg daily, reducing 4mg daily)

Prednisone starting 20-30mg daily, tapering in 1-2 weeks

Intra-articular injection of triamcinolone in

monoarticular

gout attack

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Treatment of Acute Gout

NSAID’s

Indomethacin most commonly used

Limited in many patients

PUD

CKD

Anticoagulation

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Treatment of Acute Gout

Colchicine

Commonly prescribed as 0.6mg tablets

Old Therapy included 1 tablet per hour until gout attack is improved

or until diarrhea develops

New Standard of 1.2mg dose followed by 0.6mg dose after an hour shown to be equal and less toxic

Can Impair Hematopoiesis, induce

neuromyotoxicity

, and is contraindicated in CKD

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Prevention of Gout Attacks

Eliminating precipitants

Certain Medications can increase serum Uric Acid

HCTZ

Immunosuppressant medications (Tacrolimus, Cyclosporine)

Low Dose aspirin

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Gout Prophylaxis

Criteria for prophylaxis

Based on clinical picture, not lab values

M

ore than one gout flare per year

Presence of

tophaceous

gout

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Gout Prophylaxis – Xanthine Oxidase Inhibitors

Allopurinol

Typically started at 300mg daily but can be lower at 50-100mg daily

Maximum dose of 600-800mg daily

Patients can rarely develop allopurinol hypersensitivity syndrome, more common in patients with impaired renal

function

Feboxistat

Relative indication is impaired renal function or other situation where allopurinol cannot be used

Metabolized by liver instead of kidney

Starting dose of 40mg daily maximum dose of 80mg daily

Should treat to goal serum uric acid level of <6mg/

dL

Both can precipitate new gout attack, so treatment should be started in conjunction with colchicine 0.6mg daily or naproxen 250mg 2x daily until steady dose is achieved

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Gout Prophylaxis – Colchicine

Can be used for prophylaxis at different dosage

0.6 or 1.2mg daily

Lower dosage should be considered in those with impaired renal function

Must monitor for drug-induced myopathy and neuropathy

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Gout Prophylaxis – Probenecid

Uricosuric

Agent

Inhibits reabsorption of uric acid in proximal renal tubule

Starting dose of 250mg 2x daily increased to 500mg 2x daily in one week

Ineffective in impaired renal function

Contraindicated in patient with prior urate nephrolithiasis

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Thank you!