1. Gout
Scott Smith PGY-1
1/11/2018

2. Gout
Acute inflammatory arthritis caused by accumulation of monosodium urate

3. Typical Features Monoarticular Rapid onset w/I 24 hrs
Incapacitating pain

4. 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

5. Pathophysiology
Understanding of pathophysiology presents targets for control of disease

6. Clinical Manifestations
Early gout is typically monoarticular, most frequently the MTP joint of 1st toe (Podagra)
Develops rapidly from asymptomatic to incapacitating pain in <25hrs
Joint is red, warm, swollen and exquisitely tender
Common sites 1st toe > arch of foot > ankle > knee
Wrist, elbow and shoulder involvement is more characteristic of more advanced gout

7. Progression of Disease
After having years of disease a patient will have more frequent and more severe disease
Polyarticular Gout
Soft tissue deposits of monosodium urate (tophi) esp. on auricle, extensor surface of hand/fingers, olecranon bursa and achilles tendon
Can develop chronic arthritis as opposed to flares of acute gout
Erosive Arthropathy

8. 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

9. Differential Diagnosis of Monoarthropathy
Gout
Pseudogout
Septic Arthritis
Hemorrhagic Arthropathy
Reactive Arthritis
Traumatic Arthropathy
Cellulitis

10. 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

11. 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

12. Risk Factors - Demographics
Ethnicity
More common in African Americans > Causasians > Mexican Americans
5% vs 4% vs 1.5%

13. 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

14. Risk Factors - Diet

15. Risk Factors - Clinical

16. 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

18. Diagnosis Arthrocentesis is not always feasible
Clinical Criteria for diagnosis
Put forth by American College of Rheumatology in 1977
6 or more is sufficient for diagnosis of gout

19. 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

20. Treatment of Acute Gout
NSAID’s
Indomethacin most commonly used
Limited in many patients
PUD
CKD
Anticoagulation

21. 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

22. Prevention of Gout Attacks
Eliminating precipitants
Certain Medications can increase serum Uric Acid
HCTZ
Immunosuppressant medications (Tacrolimus, Cyclosporine)
Low Dose aspirin

23. Gout Prophylaxis Criteria for prophylaxis
Based on clinical picture, not lab values
More than one gout flare per year
Presence of tophaceous gout

24. Gout Prophylaxis – Xanthine Oxidase Inhibitors
Allopurinol
Typically started at 300mg daily but can be lower at mg daily
Maximum dose of mg 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

25. 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

26. 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

27. Thank you!