TOC |
Rheumatology
Gout Arthritis
SX |
DX | RX
Outlines in Clinical Medicine
on Physicians' Online 2003
A. Introduction
-
Most common cause of acute mono- or oligoarthritis or bursitis
-
Initially usu presents with monoarticular involvement
-
Chronic disease may have polyarticular flares
-
Alcohol, aspirin or diuretic use may precipitate gouty flares
-
Gout Variants
-
Hyperuricemia without symptoms
-
Monoarticular disease, episodic
-
Polyarticular disease, multiple joints and several episodes
-
Tophaceous gout, often with joint destruction
-
Almost all patients are men (post-menopausal woman may also get gout)
-
Most patients have elevated serum urate (>7.0mg/dL; >416µmol/L)
-
Gout can occur rarely, however, without hyperuricemia
-
Etiology
-
Most patients are underexcreters of uric acid
-
~10% are overproducers
-
Hyperproliferative diseases lead to overproduction of uric acid
-
Hyperproliferative diseases include inflammatory (psoriasis) and neoplastic
(leukemia, lymphoma, others) disorders
-
Regardless of etiology, most patients are treated long term by suppression
of synthesis
-
Loss of hormone production at menopause may contribute to elevated uric acid
-
Hyperuricemia
-
Associated with cardiovascular disease, nephropathy, urolithiasis, gout
-
Hyperuricemia also associated with diabetes, hypertension, stroke, preelampsia
-
Treatment only with high risk or history of gout, renal dysfunction
-
Consider treatment for high levels in patients with severe vascular disease
B.
Symptoms
-
Presentation
-
Painful, red swollen joint or bursa
-
May have appearance of cellulitis or septic joint
-
Fever, leukocytosis may also occur
-
Most common initial joint is first MTP ("Podagra")
-
Formation of uric acid deposits
-
Tophi may occur in chronic cases
-
Usually occur in "coldest" areas on body
-
Cold makes it more likely that monosodium urate will precipitate
-
Common in distal joints, bursa, pinnae of ears
-
Drugs associated with Gout Flares
-
Any drugs which change uric acid concentrations
-
Aspirin - low doses lower urate, higher doses raise urate
-
Alcohol - reduces uric acid excretion
-
Thiazide Diuretics - raise serum uric acid; Other diuretics - lower serum
uric acid
-
Cyclosporine - probably due to decreased GFR and tubular inhibition
C.
Evaluation / Diagnosis
-
Joint / Bursa Fluid Analysis is essential
-
Rule out infection or superinfection with gram stain and culture
-
Crystals commonly seen: needle shaped, negatively
birefringent (yellow is parallel)
-
Fluid may contain >50K/µl PMN
-
Difficult to rule out coinfection even with crystals
-
Therefore, Gram stain and cultures must be obtained
-
Synovial fluid from asymptomatic joints in patients with active gout often
contain uric acid crystals
-
herefore, synovial fluid from the knee may be diagnostic and easiest to obtain
-
Superinfection may occur (usually Staphylococci or Streptococci)
-
Other laboratory tests
-
Serum urate useful for eventual initiation or adjustment of allopurinol,
probenecid
-
Elevated serum urate level is a risk
factor for cardiovascular disease
-
Serum calcium, phosphate useful for possible CPPD
-
Complete blood count including white cell count with differential
-
Blood cultures may be needed in selected cases
-
Serum TSH for hypothyroid screening (up to 15% gout cases)
-
Radiograph may be useful
-
Evaluate for chondrocalcinosis (CPPD; see below)
-
Bone destruction usually without osteoporosis
-
Joint effusion with joint space preservation
-
Asymmetric nodular soft tissue mass (tophus)
-
Erosions usually eccentric, round or oval in shape
-
Intraosseous calcification and secondary osteoarthritis
-
Differential Diagnosis
-
Septic arthritis
-
Pseudogout - calcium pyrophosphate dihydrate deposition disease
-
Uncommon: Hemearthrosis, trauma, pigmented vilonodular synovitis (PVNS)
-
Hydroxyapatite crystal disease (resolves spontaneously)
D.
Treatment Strategy
-
Depends on stage and symptoms of disease and
-
Acute Gout - anti-inflammatory agents or glucocorticoids may be used
-
Initial prevention of recurrent and chronic attacks (interim prophylaxis)
- colchicine
-
Long term prophylaxis: Uric acid lowering agents (often with colchicine)
-
Uric acid reduction in patients with symptoms, gout, urate nephropathy,
urolithiasis
-
Consider aggressive uric acid reductions in severe vascular disease
E. Treatment of Acute Gout
Attack
-
NSAIDs are generally first line
-
Effective pain control and anti-inflammatory activity
-
Contradindications include coumadin therapy, GI bleeding/intolerance, renal
disease
-
Caution should be used in patients on high dose diuretics or ACE inhibitors
-
Examples: Indomethacin 25-50mg po tid-qid, Naproxen
500 po bid-tid, others
-
Avoid salicylates which decrease uric acid excretion and may precipitate
attacks
-
Consider use of concomitant H-2 therapy to protect stomach
-
COX-2 selective NSAIDS (such as celocoxib, Celebrex®) are safe on stomach
-
Glucocorticoids
-
First line therapy in patients intolerant or not improved with NSAIDs
-
Prednisone - 20-40mg po initially continue
for 3-5 days then taper
-
Methylprednisolone 30-40mg iv qd (may divide doses) can be substituted for
prednisone
-
Taper usually slowly over 1-2 weeks to prevent flare
-
Colchicine begun at 0.6mg po qd-bid during taper should also be started to
prevent flare
-
Low dose prednisone, 5-10mg/d, can also be used as flare prophylaxis (see
below)
-
Colchicine
-
Now considered 3rd line treatment for acute gout
-
Dose: 0.2-0.6mg po q 1/2-2 hrs until nausea or diarrhea
occurs
-
Total acute dose should not exceed 6mg (in first 12-24 hours)
-
Colchicine should then be given 0.6mg po qd-bid for about 1month
-
Agents which alter serum urate concentration are contraindicated in acute
attacks
-
Specific uric acid lowering agents:
Allopurinol, probenicid,
sulfinpyrazone
-
Other drugs: aspirin (changing dose), thiazides, other diuretics
-
Initiation of agents may precipitate severe gouty attack, often with tophus
formation
-
If patient is on a uric acid lowering agent and has an acute attack, do not
change dose
F. Interim Prophylaxis
-
Agent to prevent attacks must be given prior to starting uric acid lowering
therapy
-
Continue this agent for 2-12 months while uric acid lowering therapy is initiated
-
Uric acid metabolism and serum levels must be stabilized before stoppping
this agent
-
Colchicine
-
Recommended first line for interim prophylaxis
-
Dose is 0.6mg po bid; renal insufficiency dose 0.3-0.6mg po qd (creatinine
>1.5mg/dL)
-
Generally well tolerated at these doses
-
Other Agents
-
Low dose NSAIDs - requires GI protective agent (or COX-2 selective) if used
>1 month
-
Low dose prednisone - well tolerated, minimal side effects at 10mg/day for
< 1year
-
Prednisone use should be preceded by PPD (MTB) test in most patients
G. Long Term Prevention
-
Lowering serum uric acid is most effective long term preventatitve strategy
-
Also permits resolution (slowly) of tophi
-
Uric acid lowering agent
-
Allopurinol
-
Probenecid
-
HRT in postmenopausal women
-
Sulfinpyrazone (rarely used)
-
Allopurinol
-
Inhibitor of xanthine oxidase; decreases blood uric acid concentration
-
Dose 100-300mg po qd; 100mg po qd in renal
insufficiency
-
Many patients, with normal renal function, will respond to 100mg po qd
-
Caution should be used as allopurinol reactions are serum level dependent
-
In patients with rash in whom allopurinol must be used, desensitization can
be done
[7]
-
In some patients with allopurinol allergy, oxopurinol can be obtained
-
Goal serum uric acid for uncomplicated gout is <7mg/dL
-
Goal serum uric acid for patients with tophaceous gout is probably <6mg/dL
-
Probenecid
-
Increases urinary excretion of uric acid, called a "uricosuric"
-
Generally effective only in underexcretors (defined by 24hr urine
collection)
-
Normal urinary excretion of uric acid is 250-750mg/day
-
Contraindicated in patients with history of uric acid renal stones
-
Initiate at 500mg po bid and increase as
needed
-
Monitor 24hr urinary uric acid excretion
-
May be used in conjunction with allopurinol
-
Will not work in patients with creatinine >2.0mg/dL
-
Can increase risk of uric acid stones
References
-
McCarty DJ. 1994. JAMA. 271(4):302
-
Sumino H, Ichikawa S, Kanda T, et al. 1999. Lancet. 354(9179):650
-
10. Dicker HE, Dincer AP, Levinson DJ. 2002. Clev Clin J Med.
69(8):594
-
8. Pascual E, Batlle-Gualda E, Martinez A, et al. 1999. Ann
Intern Med. 131(10):756
-
9. Fang J and Alderman MH. 2000. JAMA. 283(18):2404
-
4. Emmerson BT. 1996. NEJM. 334(7):445
-
Fam AG, et al. 1992. Am J Med. 93:299
Updated on: Aug 18, 2002 Database
by OutlineMed Inc.