Team Meeting Presentations In the Clinic - Gout Team Meeting Presentations

Risk Factors for Gout Hyperuricemia Male sex if <60 Obesity High purine diet (red meat; shellfish) Alcohol (esp beer and spirits) and high fructose drinks Medications (thiazides; cyclosporine) CKD Lead exposure Organ transplantation Specific diseases (htn, DM, hyperlipidemia, hematologic malignancies; genetics

Are there effective strategies for primary prevention of gout? Dietary modifications, weight loss Pharmacologic therapy is not recommended when hyperuricemia is assymptomatic Pharmocologic therapy is recommended in pts on chemo for hematologic malignancies Uric acid lowering drugs and hydration prevent secondary gout due to tumor lysis Without this treatment, uric acid nephropathy with tubular obstruction can develop

Is gout associated with increased risk for CV disease and can this be prevented? Both CV disease and gout are associated with serum markers of inflammation CV disease risk is increased in persons with gout or hyperuricemia Opinions differ on whether the association of an elevated serum urate level with increased CV disease is modifiable

What symptoms and physical findings suggest gout? Warmth, swelling, redness and severe joint pain Of first attacks, 90% are monoarticular Common sites of crystal deposition, tophus development: helix of the ear, lower extremities Other sites: periarticular structures (bursae, tendons) Crystals are more likely in previously diseased joints Other forms of arthritis increase gout risk

Symptoms and Findings Episodic self-limited joint pain, swelling, erythema Attacks often occur at night or in early morning Trauma may trigger release of crystals into joint space Attacks often subside in 3-14 days without treatment

Tests to Diagnose Gout Serum urate level- may be normal in acute flare CBC with differential Synovial fluid or tophus aspirate examination Polarizing scope, cell count culture Radiography – to r/o other causes or for findings suggestive of chronic gout

Podagra

Uric Acid Crystals

Radiograph – chronic gout

Value of radiography in the diagnosis of gout Early in course- to r/o other conditions Later in course – can show prominent, proliferative bony reaction Gout related tophi cause bone destruction away from the joint Gout less likely to cause joint space narrowing than psoriatic arthritis or rheumatoid arthritis

Differential Diagnosis of Gout Rheumatoid arthritis Symmetrical polyarthritis in small joints of hands and feet Hand involvement more likely than in gout Subcutaneous nodules in 20% XRAY – soft tissue swelling; diffuse joint space narrowing, marginal erosions of small joints, osteopenia

Differential Diagnosis of Gout Pseudogout – calcium pyrophosphate deposition disease Appears in unusual places - elbows, wrists – without trauma Affects 10-15% >65 XRAY – looks like RA or osteoarthritis but with bony repair Cartilage calcification Triangular cartilage - pathognomonic

Differential Dx of Gout – cont’d Septic Arthritis – Fever, arthritis, great tenderness Up to ½ have concomitant RA Source is often evident Diagnose and treat immediately to avoid joint destruction

Differential Diagnosis Gout- Cont’d Cellulitis – gout often mistaken for cellulitis also Erythema, swelling of the extremity, very tender, febrile Often previous surgery or infection at the site Xray – soft tissue swelling Staph/strep most likely

Differential Dx- Gout – Cont’d Osteoarthritis – bony enlargement without signif inflammation – usually – May often involve the halus valgus – as in gout Psoriatic arthritis – DIP’s often, nail changes – XRAY central erosions, subchondral sclerosis, bony repair signs;uric acid levels might be high due to proliferative skin changes Sarcoidosis – acute disease can involve ankles – look for subcut nodules, erythema nodosum Assoc parotits, uveitis, hilar adenopathy, lung involvement

When to consider hospitalizing a patient with gout? To distinguish gout from septic arthritis Joint fluid analysis Empiric antibiotics until diagnosis is clear Repeated synovial fluid analysis if needed for culture, urate crystals, cell counts To control pain Aspiration of joint fluid may help Gout is one of the most painful conditions

Non Drug Therapy in Gout Reduce high purine foods in diet Reduce alcohol and high fructose drinks Weight loss – to decrease urate levels Hydration Diet high in fiber, vitamin C, folate Replace medications that reduce uric acid excretion whenever possible

Diet Issues High purine animal and fish sources Red meat, meat extracts, organ meats, seafood Yeast products – baked goods and beer Mushrooms, spinach, asparagus, cauliflower Legumes – peas, dried beans

Drugs for Acute Gout NSAIDS Colchicine (oral) First line –analgesic/antiinflammatory Ibuprofen and Naproxen better tolerated than indomethacin; don’t use aspirin Start at higher dose and taper over 1 week Side effects as usual Caution in elderly Don’t use in anticoagulated patients Colchicine (oral) Most effective if started 12-36 hours after onset Lower doses reduce side effects (0.6 mg tid) Side effects – GI, bone marrow suppression, myopathy, neuropathy, dermatitis, urticaria, alopecia, purpura Myelosuppression can be severe at high doses; reduced with a short course Caution when using other CYP3A4 inhibitors Reduce dose for renla or hepatic dysfunction; avoid if on dialysis

Drugs for Acute Gout Corticosteroids (oral) For polyarticular gout when NSAIDS contraindicated Side effects Corticosteroids (intraartiular injection) For monoarticular gout when NSAIDS not ideal Side effects – risk for damage to nerves, tendons, vascular structures; joint infection risk; usual oral steroid risks Rule out infectious cause before injecting join Opiates – For severe pain Oral combinations of oxycodone, hydrocodone, codeine Severe cases – morphine IV or SC Short term - until inflammation resolved

Drugs to Prevent Gout and Complications of Hyperuricemia To prevent growth of crystalliine deposits Deposits can lead to chronically stiff, swollen joints and debilitating arthritis To reduce tophi To prevent flare recurrence 60% flare again in 1 year, 78% within 2 Subsequent attacks may last longer, involve more joints To prevent uric acid stones Occurs in 10-40% of persons with gout Goal is to reduce urate <6 mg/dl

Drugs to prevent gout and complications of hyperuricemia Allopurinol Start 100-200 mg/d, increase by 100 mg.d every 1-4 weeks; reduced dose for CKD Not in acute attack, concurrent colchicine may reduce risk for flare Watch for hypersensitivity syndrome Other side effects – rash, fever, headache, uritcaria, interstitial nephritis LFTs and CBC monitored Febuxostat Start 40-80 mg/d; increase to achieve goal urate level Steady state urate after 2 week use LFT abn, diarrhea, headache, nausea, rash No dose adjustment needed in mild to mod CKD

Other Drugs to reduce Uric acid level Rasburicase To prevent tumor lysis Not if G6PD deficient Start 24 hours before chemo Probenicid 0.5-2 mg /day divided 2X/day, dose adjust until urate level normalizes Uricosuric – use only if underexreter Don’t use with aspirin Increases methotrexate toxicity Rare anaphylaxis Not effective in pts with signif CKD

Drugs to prevent Gouty attacks Colchicine (oral) Dose and use depends on cr clearance; avoid if <10 ml/min Continue for 6 months after serum urate <6 or until tophi disappear Use caution with other CYP3A4 inhibitors May need to dose reduce with calcium channel blockers Side effects GI intolerance, bone marrow suppression, dermatitis, urticaria, alopecia, purpura Myopathy, neuropathy may increase with renal disease or with statin use Avoid in severe liver disease

Indications for long term drug therapy to prevent gout and complications of hyperuricemia At least 2-3 acute attacks of gout Tophaceous gout Severe attacks or polyarticular attacks Radiographic evidence of joint damage from gout Nephrolithiasis Identifiable inborn metabolic deficiency causing hyperuricemia

When to think about referring for specialty consultation… Consult with a rheumatologist or orthopedist When joint sepsis is suspected When gout is poorly controlled When diagnosis is unclear When gout occurs with other forms of arthritis To aid in deciding on timing of initiation of meds or complicated regimens Consult with rheum in pts with inherited metabolic disease for patients aged <20 with gout Consult with nephrologist for help managing pts with CKD and/or urate nephropathy