GOUT By: Sunit tolia, PGY III

Gout Affects > 5 million people in the United States alone MCC of inflammatory arthritis in men. Is caused by monosodium urate (MSU) crystals formed in joints and tissues when serum urate levels exceed 6.8 mg/dL. Gout usually occurs only after many years of hyperuricemia. It is not currently recommended to treat asymptomatic hyperuricemia to prevent the disease. Needle-shaped, Negatively birefringent crystals on polarized microscopy.

Risk Factors Hyperuricemia (MOST IMPORTANT RF) Medications (i.e. thiazides or cyclosporine) Male sex if younger than 60 years Renal insufficiency Obesity Lead exposure Diet high in purines (i.e. red meat, shellfish) Organ transplantation Specific diseases increase the risk for gout (i.e. HTN, DM, HLD, metabolic syndrome, hematologic malignant conditions) Consumption of alcohol (i.e. beer and spirits) and high fructose drinks (i.e. sodas, some juices) Genetic risk factors Common diseases that increase risk for gout include diabetes, the metabolic syndrome, hyperlipidemia, hypothyroidism, and hypertension.

Symptoms Episodic self-limited joint pain, swelling, and erythema Recent trauma which may have triggered the pain Attacks often begin in the middle of the night or early morning.

Physical Examination Joint involved may be: Warm Swollen Red Severe joint pain is common complaint Joints that are usually involved are either previously diseased joints or more distal joints (i.e. midfoot, first metatarsophalangeal joint, ankle, or knee) First attacks are monoarticular and chronic gout can present w/ involvement of various joints.

DDX of Gout RA Calcium Pyrophosphate Deposition Disease (Pseudogout) Septic Arthritis Cellulitis Reactive Arthritis Fracture / Trauma OA Psoriatic Arthritis Sarcoidosis

DDX of Gout Pseudogout Septic Arthritis RA Cellulitis Reactive Arthritis Fracture / Trauma OA Psoriatic Arthritis Sarcoidosis

Pseudogout Chondrocalcinosis (calcium deposits in cartilage) Parameter Pseudogout Risk factors Hypothyroidism Hemochromatosis Renal osteodystrophy Hyperparathyroidism and/or recent parathyroidectomy Wilson's disease Affected joints Knee (most common) Wrist Hip Synovial fluid Positively birefringent crystals, linear or rhomboidal Calcium pyrophosphate crystals 50,000-100,000/mm3 WBC Chondrocalcinosis (calcium deposits in cartilage) Dx of CPPD is suggested radiographically by showing chondrocalcinosis and/or synovial fluid showing positively birefringent crystals under polarized light microscopy.

Septic Arthritis Fever, arthritis, great tenderness. Joint sepsis most commonly occurs in previously abnormal joints. Radiography generally shows swelling and effusion. If not treated promptly it causes diffuse joint-space narrowing and joint destruction. Diagnosis is usually suggested by synovial fluid showing elevated leukocytes (50,000-150,000 cells/µL), positive Gram stain, and positive fluid culture. However, synovial fluid Gram stain can be negative in 20-30% of septic arthritis cases, especially with gram-negative bacteria. Blood cultures are positive in 50% of patients and must always be obtained prior to antibiotic therapy. Treatment consists of IV antibiotics and joint drainage. This patient should be monitored clinically and started on IV antibiotics until culture results return.

What tests can diagnose gout? Serum urate level CBC with differential (if considering septic arthritis) Serum creatinine Examination of synovial fluid or tophus aspirate Radiography (to rule out other causes)

What are the components of the synovial fluid… Gross appearance: (clarity, color, viscosity) Microscopic examination: WBC and differential Crystals Gram stain Culture Synovial fluid tubes:  From left to right,  normal noninflammatory (e.g., osteoarthritis) inflammatory (e.g., rheumatoid arthritis) septic (e.g., gonococcal septic arthritis) hemorrhage (e.g., trauma, hemophilia A)

Joint Fluid Characteristic…

CRYSTALS… Gout crystals (left) and pseudogout crystals (right) under the microscope. Urate crystals have sharp, needle-like ends, while CPPD crystals are shaped more like rods or rhombuses.

Treatment of Gout

Xanthine Oxidase Inhibitors Tx for Gout Acute Tx NSAIDS Colchicine Corticosteroids Oral Intra-articular Corticotropin Chronic Tx Xanthine Oxidase Inhibitors Uricase Rasburicase Pegloticase Uricosuric

Treatment of Acute Gout Will usually last about 1 week w/o any medical intervention. NSAIDS usually the first-line therapy because of combined analgesic and anti-inflammatory effects. Two to 10 days of NSAIDS is usually enough to treat a gout attack. Ibuprofen and naproxen seem to be as effective as indomethacin but better tolerated. To hasten the antiinflammatory action, start the NSAID at a higher dose and taper over about 1 week. Gastrointestinal toxicity from NSAIDs is an important concern. PPIs can reduce NSAID ulcers by more than 50%

Treatment of Acute Gout Colchicine: a mainstay treatment of acute gout Oral colchicine treatment is most effective when initiated 12 to 36 hours after the start of an acute gouty attack Doses should be reduced for renal or hepatic dysfunction. It should be avoided in elderly persons, and should not be administered with other strong CYP3A4 inhibitors. Regularly check CBC, CK, AST/ALT in patient w/ CKD on colchicine on any dose. Avoided in patient who are on hemodialysis as this drug is not removed by dialysis or by exchange transfusion.

Treatment of Acute Gout Corticosteroids are the preferred treatment for acute gout in patients with renal insufficiency or other contraindications to NSAIDs Use w/ caution in patient w/ hyperglycemia or CHF. May be used in moderate-to-severe renal impairment. Prednisone 40mg q day until a day after the acute attack resolves and then taper over another 7-10days. Intra-articular steroid injections: Useful in tx of acute gout if limited to single joint or bursa. One needs to confirm that the joint is not infected.

In Summary: Tx for Acute Gout Treatment Indications Contraindications Side Effects NSAIDs First-line therapy Peptic ulcer disease CKD Heart failure GI bleeding Acute kidney injury Sodium retention, edema Colchicine NSAID intolerance CKD Diarrhea, abdominal cramps Neuromyopathy Steroids Intra-articular: 1-2 inflamed joints NSAID/colchicine contraindication Drug hypersensitivity No major systemic side effects Steriods Systemic: >2 joints involved Risk of rebound attacks Elevated blood pressure Elevated blood sugar Fluid retention

When do you recommend treatment for hyperuricemia… At least 2 or 3 acute attacks of gout Tophaceous gout Severe attacks or polyarticular attacks Radiographic evidence of joint damage from gout Identifiable inborn metabolic deficiency causing hyperuricemia Nephrolithiasis

Treatment for Chronic Gout Uricosurics Is warrented for underexcretion of uric acid (if they excrete less than 600-700mg/d while on low-purine diet). Probenecid is the only uricosuric durg available in the US. Contraindicated in patient with nephrolithiasis and a CrCl <30mL/min.

Treatment for Chronic Gout … Xanthine Oxidase Inhibitors… Avoid if the patient is on azathioprine or 6-mercaptopurine because these drug metabolized by xanthine oxidase. Allopurinol: Can be used in patient w/ urea overproduction or underexcretion. Monitor LFTs, CMP, CBC, and uric acid level before and after starting tx. Reduce the dose of allopurinol in patients with renal insufficiency Adverse Effect: rash Febuxostat For those who have CI or an inadequate response to allopurinol or uricosuric therapy. Does not require dose adjustment for mild-to-moderate renal impairment. But limited data on the use of this drug if the CrCl<30mL/min When starting these medications the acute episode of gout should be resolved.

Start low, go slow to avoid a flare… In patient w/ normal kidney function the FDA recommend slow upward titration of allopurinol , starting at 100-200mg/day anddose is increased by increments of 100mg/day at intervals of 1 week until the serum urate level is lower than 6mg/dL. Concurrent colchicine prophylaxis may help decrease flares.

Flare prophylaxis during initiation of urate-lowering therapy… Colchicine: Should be combined with allopurinol or probenecid Dosing is based on renal function Not to be used in patients with severe renal insufficiency or hepatobiliary dysfunction. Tx is continued for atleast 6 months after the serum urate level is less than 6 mg/dL or until tophi disappear.

How can patients reduce their risk for gout? Weight Loss Decrease the intake of high-purine foods such as: Red meat (beef, pork, lamb) Meat extracts (broth, gravy) Organ meats (such as sweetbreads, liver, and kidney) Seafood (shrimp, anchovies, mussels, scallops, sardines, herring, fish roe, canned tuna, shrimp, and lobster) Yeast products (beer and baked goods) Reduce the intake of high fructose foods & drinks Reduce the alcohol intake Avoid medications like: Thiazide Low – to – moderate levels of aspirin Pyrazinadmine, Ethambutol, Pyrazinoate. Cyclosporine. Staying hydrated

When to consult a Rheumatologist? Joint sepsis Poorly controlled gout Gout along w/ other forms of arthritis

QUESTIONS…