Gout Scott Smith PGY-1 1/11/2018

Gout Acute inflammatory arthritis caused by accumulation of monosodium urate

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

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

Pathophysiology Understanding of pathophysiology presents targets for control of disease

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

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

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

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

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

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

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

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

Risk Factors - Diet

Risk Factors - Clinical

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

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

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

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

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

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

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

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

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

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

Thank you!