TOC  |  Rheumatology  

 Gout Arthritis         SX  |  DX  |  RX                  Outlines in  Clinical Medicine  on Physicians' Online 2003  
A. Introduction

1. Most common cause of acute mono- or oligoarthritis or bursitis
   1. Initially usu presents with monoarticular involvement
   2. Chronic disease may have polyarticular flares
   3. Alcohol, aspirin or diuretic use may precipitate gouty flares
2. Gout Variants
   1. Hyperuricemia without symptoms
   2. Monoarticular disease, episodic
   3. Polyarticular disease, multiple joints and several episodes
   4. Tophaceous gout, often with joint destruction
3. Almost all patients are men (post-menopausal woman may also get gout)
   1. Most patients have elevated serum urate (>7.0mg/dL; >416µmol/L)
   2. Gout can occur rarely, however, without hyperuricemia
4. Etiology
   1. Most patients are underexcreters of uric acid
   2. ~10% are overproducers
   3. Hyperproliferative diseases lead to overproduction of uric acid
   4. Hyperproliferative diseases include inflammatory (psoriasis) and neoplastic (leukemia, lymphoma, others) disorders
   5. Regardless of etiology, most patients are treated long term by suppression of synthesis
   6. Loss of hormone production at menopause may contribute to elevated uric acid
5. Hyperuricemia
   1. Associated with cardiovascular disease, nephropathy, urolithiasis, gout
   2. Hyperuricemia also associated with diabetes, hypertension, stroke, preelampsia
   3. Treatment only with high risk or history of gout, renal dysfunction
   4. Consider treatment for high levels in patients with severe vascular disease

B. Symptoms                

1. Presentation
   1. Painful, red swollen joint or bursa
   2. May have appearance of cellulitis or septic joint
   3. Fever, leukocytosis may also occur
   4. Most common initial joint is first MTP ("Podagra")
2. Formation of uric acid deposits
   1. Tophi may occur in chronic cases
   2. Usually occur in "coldest" areas on body
   3. Cold makes it more likely that monosodium urate will precipitate
   4. Common in distal joints, bursa, pinnae of ears
3. Drugs associated with Gout Flares
   1. Any drugs which change uric acid concentrations
   2. Aspirin - low doses lower urate, higher doses raise urate
   3. Alcohol - reduces uric acid excretion
   4. Thiazide Diuretics - raise serum uric acid; Other diuretics - lower serum uric acid
   5. Cyclosporine - probably due to decreased GFR and tubular inhibition

C. Evaluation / Diagnosis          

1. Joint / Bursa Fluid Analysis is essential     
   1. Rule out infection or superinfection with gram stain and culture
   2. Crystals commonly seen: needle shaped, negatively birefringent (yellow is parallel)
   3. Fluid may contain >50K/µl PMN
   4. Difficult to rule out coinfection even with crystals
   5. Therefore, Gram stain and cultures must be obtained
   6. Synovial fluid from asymptomatic joints in patients with active gout often contain uric acid crystals
   7. herefore, synovial fluid from the knee may be diagnostic and easiest to obtain
   8. Superinfection may occur (usually Staphylococci or Streptococci)
2. Other laboratory tests
   1. Serum urate useful for eventual initiation or adjustment of allopurinol, probenecid
   2. Elevated serum urate level is a risk factor for cardiovascular disease
   3. Serum calcium, phosphate useful for possible CPPD
   4. Complete blood count including white cell count with differential
   5. Blood cultures may be needed in selected cases
   6. Serum TSH for hypothyroid screening (up to 15% gout cases)
3. Radiograph may be useful
   1. Evaluate for chondrocalcinosis (CPPD; see below)
   2. Bone destruction usually without osteoporosis
   3. Joint effusion with joint space preservation
   4. Asymmetric nodular soft tissue mass (tophus)
   5. Erosions usually eccentric, round or oval in shape
   6. Intraosseous calcification and secondary osteoarthritis
4. Differential Diagnosis      
   1. Septic arthritis
   2. Pseudogout - calcium pyrophosphate dihydrate deposition disease
   3. Uncommon: Hemearthrosis, trauma, pigmented vilonodular synovitis (PVNS)
   4. Hydroxyapatite crystal disease (resolves spontaneously)

D. Treatment Strategy          

1. Depends on stage and symptoms of disease and
2. Acute Gout - anti-inflammatory agents or glucocorticoids may be used
3. Initial prevention of recurrent and chronic attacks (interim prophylaxis) - colchicine
4. Long term prophylaxis: Uric acid lowering agents (often with colchicine)
5. Uric acid reduction in patients with symptoms, gout, urate nephropathy, urolithiasis
6. Consider aggressive uric acid reductions in severe vascular disease

E. Treatment of Acute Gout Attack

1. NSAIDs are generally first line      
   1. Effective pain control and anti-inflammatory activity
   2. Contradindications include coumadin therapy, GI bleeding/intolerance, renal disease
   3. Caution should be used in patients on high dose diuretics or ACE inhibitors
   4. Examples: Indomethacin 25-50mg po tid-qid, Naproxen 500 po bid-tid, others
   5. Avoid salicylates which decrease uric acid excretion and may precipitate attacks
   6. Consider use of concomitant H-2 therapy to protect stomach
   7. COX-2 selective NSAIDS (such as celocoxib, Celebrex®) are safe on stomach
2. Glucocorticoids   
   1. First line therapy in patients intolerant or not improved with NSAIDs
   2. Prednisone - 20-40mg po initially continue for 3-5 days then taper
   3. Methylprednisolone 30-40mg iv qd (may divide doses) can be substituted for prednisone
   4. Taper usually slowly over 1-2 weeks to prevent flare
   5. Colchicine begun at 0.6mg po qd-bid during taper should also be started to prevent flare
   6. Low dose prednisone, 5-10mg/d, can also be used as flare prophylaxis (see below)
3. Colchicine
   1. Now considered 3rd line treatment for acute gout
   2. Dose: 0.2-0.6mg po q 1/2-2 hrs until nausea or diarrhea occurs
   3. Total acute dose should not exceed 6mg (in first 12-24 hours)
   4. Colchicine should then be given 0.6mg po qd-bid for about 1month
4. Agents which alter serum urate concentration are contraindicated in acute attacks
   1. Specific uric acid lowering agents:  Allopurinol, probenicid, sulfinpyrazone
   2. Other drugs: aspirin (changing dose), thiazides, other diuretics
   3. Initiation of agents may precipitate severe gouty attack, often with tophus formation
   4. If patient is on a uric acid lowering agent and has an acute attack, do not change dose

F. Interim Prophylaxis

1. Agent to prevent attacks must be given prior to starting uric acid lowering therapy
   1. Continue this agent for 2-12 months while uric acid lowering therapy is initiated
   2. Uric acid metabolism and serum levels must be stabilized before stoppping this agent
2. Colchicine
   1. Recommended first line for interim prophylaxis
   2. Dose is 0.6mg po bid; renal insufficiency dose 0.3-0.6mg po qd (creatinine >1.5mg/dL)
   3. Generally well tolerated at these doses
3. Other Agents
   1. Low dose NSAIDs - requires GI protective agent (or COX-2 selective) if used >1 month
   2. Low dose prednisone - well tolerated, minimal side effects at 10mg/day for < 1year
   3. Prednisone use should be preceded by PPD (MTB) test in most patients

G. Long Term Prevention

1. Lowering serum uric acid is most effective long term preventatitve strategy
2. Also permits resolution (slowly) of tophi
3. Uric acid lowering agent
   1. Allopurinol
   2. Probenecid
   3. HRT in postmenopausal women    
   4. Sulfinpyrazone (rarely used)
4. Allopurinol
   1. Inhibitor of xanthine oxidase; decreases blood uric acid concentration
   2. Dose 100-300mg po qd; 100mg po qd in renal insufficiency
   3. Many patients, with normal renal function, will respond to 100mg po qd
   4. Caution should be used as allopurinol reactions are serum level dependent
   5. In patients with rash in whom allopurinol must be used, desensitization can be done [7]
   6. In some patients with allopurinol allergy, oxopurinol can be obtained
   7. Goal serum uric acid for uncomplicated gout is <7mg/dL
   8. Goal serum uric acid for patients with tophaceous gout is probably <6mg/dL
5. Probenecid
   1. Increases urinary excretion of uric acid, called a "uricosuric"
   2. Generally effective only in underexcretors (defined by 24hr urine collection)
   3. Normal urinary excretion of uric acid is 250-750mg/day
   4. Contraindicated in patients with history of uric acid renal stones
   5. Initiate at 500mg po bid and increase as needed
   6. Monitor 24hr urinary uric acid excretion
   7. May be used in conjunction with allopurinol
   8. Will not work in patients with creatinine >2.0mg/dL
   9. Can increase risk of uric acid stones

References

1. McCarty DJ. 1994. JAMA. 271(4):302
2. Sumino H, Ichikawa S, Kanda T, et al. 1999. Lancet. 354(9179):650
3. 10. Dicker HE, Dincer AP, Levinson DJ. 2002. Clev Clin J Med. 69(8):594
4. 8. Pascual E, Batlle-Gualda E, Martinez A, et al. 1999. Ann Intern Med. 131(10):756
5. 9. Fang J and Alderman MH. 2000. JAMA. 283(18):2404
6. 4. Emmerson BT. 1996. NEJM. 334(7):445
7. Fam AG, et al. 1992. Am J Med. 93:299

Updated on: Aug 18, 2002   Database by OutlineMed Inc.