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Gout

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Ovid: 5-Minute Sports Medicine Consult, The


Gout
Natalie Voskanian
Basics
  • Gout is an acute disease that eventually progresses to a chronic state.
  • Consists of painful inflammatory deposition of monosodium urate crystals into joints and, eventually, soft tissues (tophaceous gout)
  • Pseudogout is a similar but distinct entity in which the inflammatory process is instigated by calcium pyrophosphate dihydrate (CPPD) crystal deposition instead of monosodium urate.
Description
  • Gout has 3 stages:
    • Acute phase: Inflammatory monarthritis; resolves within several days to a week
    • Intercritical or interval phase: The patient is asymptomatic.
    • Chronic phase: Intermittent repeated flairs of monarticular or polyarticular gout and soft tissue deposition of tophi.
  • Common joints affected by gout: 1st metatarsophalangeal (MTP) joint (most common site of initial presentation; also known as podagra), olecranon, ankle, wrist, knee, tarsal joints, and interphalangeal joints of the hand
  • Much less commonly affected joints include shoul-der, sternoclavicular joint, spine, and sacroiliac joints.
  • Tophaceous gout can extend to periarticular structures (tendons and soft tissue) and rarely can affect visceral organs.
  • Up to 20% of gout patients may present with polyarticular or tophaceous gout at initial presentation.
Epidemiology
Incidence
  • Typically presents in middle-aged men (30–50 yrs old).
  • Seen 2nd most commonly in elderly men and postmenopausal women, typically in those with multiple medical comorbidities.
  • Predominant gender: Male > Female (2–4:1).
Prevalence
  • Prevalence of gout in U.S. is ∼1% and increases with increasing age (1).
  • Others have found a prevalence of 8.4/1,000 (2).
Risk Factors
  • Excessive alcohol intake (especially beer and spirits)
  • Chronic diuretic use
  • Recent trauma
  • Recent surgery
  • Hyperuricemic state (from either overproduction or underexcretion of uric acid)
  • Rapid changes in uric acid level
  • Diets high in purine-containing products
  • Diets low in dairy or high in meat or fish (hazard ratio up to 1.41 in high-quantity meat-eaters and 1.51 in high-quantity fish-eaters) (3); total protein intake is not correlated with risk for gout.
  • Risk factors for the presence of tophaceous gout at initial diagnosis:
    • Postmenopausal women
    • Coexisting chronic renal disease
    • Diuretic therapy
General Prevention
  • Factors that can reduce risk of gout:
    • High-quantity dairy product intake (hazard ratio of 0.56) (3)
    • Minimizing diuretic use and dose
    • Minimizing alcohol intake
  • Urate-lowering agents are used for the prevention of chronic gout. See “Medications.”
Etiology
  • Chronic hyperuricemia for many years results in concentrated extracellular deposition of monosodium uric acid.
  • This leads to a localized inflammatory process in which the body tries to eradicate the foreign crystals.
  • This inflammatory process results in localized pain, swelling, and erythema of the affected joint.
  • This disease process mimics infection.
Commonly Associated Conditions
  • Hypertension
  • Chronic diuretic therapy
  • Obesity
  • Hyperlipidemia
  • Chronic nephropathy and renal disease
  • Cardiovascular disease
  • Hyperuricemic syndromes such as myeloproliferative or lymphoproliferative disorders, psoriasis, cyclosporine A use (in organ transplant patients), and inherited defects in purine metabolism
  • Patients with gout are at increased risk for uric acid nephrolithiasis.

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Diagnosis
History
  • Initially a severely painful, erythematous, and swollen joint (noninfectious monarthritis)
  • There is no significant trauma of the joint preceding the attack.
  • Rarely there may be polyarticular involvement at 1st onset.
  • Maximal pain reaches peak at 24–48 hr (4).
  • Often symptoms resolve within 5–7 days even without treatment (5).
Physical Exam
  • Gout:
    • Fever
    • Swelling, erythema, warmth, and tenderness of affected joint
    • Sometimes overlying skin can be erythematous and desquamated, resembling cellulitis.
  • Tophi:
    • Subcutaneous nodules (resembling rheumatoid arthritis) or a bulky mass overlying a joint
    • ±Tenderness or erythema of tophi
    • Aspirated tophi contents appear as white pasty or chalky material.
Diagnostic Tests & Interpretation
Lab
  • Distinction from an infectious process may be difficult.
  • CBC: Leukocytosis may be extremely high.
  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are often elevated as well.
  • Chemistry panel to assess renal function: Not only is renal impairment associated with gout, but chronic hyperuricemia can lead to urate nephropathy.
  • Uric acid level often will be high during an acute gout attack but may be normal.
    • Incidence of gout in patients with uric acid levels >9 mg/dL is 6 × greater than in patients at 7–8.9 mg/dL (5).
    • In a group of 339 patients with acute gout, 14% had uric acid levels ≤6 mg/dL and 32% were ≤8 mg/dL (6).
    • Thus uric acid level on its own cannot be used to diagnose or rule out gout, but a high uric acid level in the appropriate clinical context can be suggestive of gout (5,7)[B].
Imaging
  • Although sometimes helpful, imaging is not necessary to make a diagnosis of gout (8)[A].
  • Can be used to rule out alternate diagnoses such as rheumatoid arthritis
  • Chronic gout is often characterized by subcortical cysts, bony erosions, overhanging edges, and diffuse soft tissue calcifications on x-ray or MRI (8).
  • Large tophi can be identified on MRI but often will need to be aspirated to confirm the diagnosis (8)[A].
  • Pseudogout, on the other hand, does not typically have bony abnormalities but instead consists of chondrocalcinosis (calcification of cartilage).
Diagnostic Procedures/Surgery
  • The “gold standard” diagnosis of gout is made by aspiration (arthrocentesis) of the affected joint's synovial fluid (9)[A].
  • Characteristic needle-shaped negatively birefringent monosodium urate crystals are seen under polarized light microscopy.
  • In contrast, pseudogout consists of rhomboid-shaped crystals with weakly positive birefringence.
  • Aspirate: Check cell count, Gram stain, and bacterial culture to rule out infection (with a negative Gram stain and negative culture).
  • Aspirate WBC count: 2,000–50,000 seen in gout (also pseudogout or rheumatoid arthritis); >50,000 is suspicious for septic arthritis.
  • It is important to rule out septic arthritis, which can mimic gout (and rarely may coexist with gout).
Differential Diagnosis
  • Pseudogout
  • Rheumatoid arthritis
  • Septic arthritis
  • Osteoarthritis
  • Reactive arthritis
  • Osteomyelitis
  • Malignancy
  • Joint trauma
Treatment
Medication
First Line
  • NSAIDs are 1st-line therapy; typically naproxen (500 mg b.i.d.) or indomethacin (50 mg t.i.d.) is used (10)[A]. Should be given within 24–48 hr of symptom onset for best results (4)[B]
  • COX-2 inhibitors are equally effective according to recent studies (11)[B].

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  • Duration of treatment varies, often ranging from 3–10 days until the attack subsides.
  • Within several days of treatment, the dosing can be decreased if clinical improvement (5)[B].
  • Corticosteroids (IV, oral, or intra-articular) are an effective alternative 1st-line agent if NSAIDS are contraindicated (12)[A].
    • Begin oral prednisone at 30–40 mg/day × 2–3 days; then taper over total of 7–10 days (5,9)[C].
    • If doing intra-articular injection instead, can use methylprednisolone 20–40 mg (5,9)[C].
  • Septic arthritis is an absolute contraindication to intraarticular corticosteroid treatment.
Second Line
  • Colchicine is a very effective 2nd-line agent for treatment of acute gout (13,14)[A]. Colchicine has fallen out of favor as a 1st-line agent owing to its high side-effect profile and contraindication in renal disease (5,13).
  • Use oral colchicine 0.6 mg t.i.d. or b.i.d.; choose b.i.d. or daily regimen in patients with renal impair-ment or elderly patients (or avoid entirely) (5,9).
    • For best results, colchicine should be given within 24–48 hr of symptom onset (14)[B].
    • The hourly dosing of colchicine used in the past was poorly tolerated (nausea, vomiting, and diarrhea) and resulted in poor compliance (13).
  • IV colchicines should not be used and are no longer approved by the FDA owing to the high level of toxicity (14)[A].
  • In a randomized, controlled trial that compared colchicine with placebo, the number needed to treat (NNT) for colchicine was 3, whereas the NNT with resulting toxicity for colchicine was 2 (13).
Additional Treatment
  • Preventive therapy can substantially reduce future episodes but should be avoided during acute attacks (10,14)[B].
  • Indications for chronic preventative therapy include (7,15)[B]
    • Recurrent or disabling gout attacks (specifically >2 gout attacks/yr)
    • Persistent tophi
    • Joint damage noted on imaging
    • Uric acid nephropathy or nephrolithiasis
  • The symptom-free period required prior to starting prophylactic therapy once the acute attack has resolved is unclear.
    • Some advocate using concomitant colchicine treatment the 1st 3–6 mos of urate-lowering treatment (16)[C].
    • Some suggest waiting about 4–6 wks after the acute attack before starting prophylactic medication (5)[C].
  • If a gout attack occurs while on urate-lowering treatment, the urate-lowering medication should not be stopped (4)[B].
  • Uric acid level should be monitored for a goal of <6 mg/dL (355 µmol/L) because this is associated with a significantly lower incidence of gout (5)[B].
  • Allopurinol is a xanthine oxidase inhibitor that decreases uric acid production.
    • Used most commonly
    • Therapeutic dose is 100–300 mg/day: Start at a lower dose (50 or 100 mg/day), and titrate up slowly over several weeks (eg, by 100 mg every 2–4 wks) to target uric acid goal of <6 mg/dL (9)[C].
    • Patients with renal insufficiency require lower doses.
    • Periodic laboratory testing (liver enzymes and CBC) should be considered.
  • Febuxostat is a newer medication.
    • Cleared through the liver and therefore an appropriate alternative in renal disease.
    • Recent studies suggest that it might be superior to allopurinol, but more studies are needed (17).
  • Probenecid is a uricosuric agent that increases uric acid secretion.
    • 2nd-line medication for prophylaxis (10)
    • Ineffective in patients with impaired creatinine clearance
    • Avoid in patients with nephrolithiasis.
    • Caution for multiple medication interactions
  • NSAIDs (naproxen 250 mg b.i.d.) or colchicine (≤0.6 mg/day or b.i.d.) can be used as chronic suppression therapy in the place of or in addition to urate-lowering agents (4)[B].
  • Low-dose prednisone (≤10 mg) also can be considered, but it has long-term side effects (4)[B].
General Measures
  • See “Risk Factors” for what to avoid.
  • Therapy for gout includes diet modification (see “Risk Factors”), using medications that reduce overall uric acid levels (such as losartan and fenofibrate), and minimizing medications that are known to increase gout flairs (such as diuretics and aspirin) when appropriate.
Referral
  • Rheumatology if refractory condition, multiple comorbities, or unusual presentation
  • Orthopedics if suspected septic arthritis
In-Patient Considerations
  • Consider for severe cases of gout, especially if needed for pain control or for diagnostic confirmation.
  • Suspected septic arthritis requires IV antibiotics and orthopedic referral.

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Ongoing Care
Prognosis
60% of patients undergoing a gout attack will have another one within 12 mos (18).
Complications
  • It takes, on average, about 10 yrs for chronic top-haceous gout to develop after the initial attack (4).
  • Chronic gout can lead to joint damage and destruction.
  • Frequent attacks can be very painful and disabling and have a negative impact on quality of life.
References
1. Wallace KL, Riedel AA, Joseph-Ridge N, et al. Increasing prevalence of gout and hyperuricemia over 10 yrs among older adults in a managed care population. J Rheumatol. 2004;31:1582–1587.
2. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum. 2008;58:26–35.
3. Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004;350:1093–1103.
4. Keith MP, Gilliland WR. Updates in the manage-ment of gout. Am J Med. 2007;120:221–224.
5. Eggebeen AT. Gout: an update. Am Fam Physician. 2007;76:801–808.
6. Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. J Rheumatol. 2009.
7. Zhang W, Doherty M, Pascual E, et al. Eular evidence based recommendations for gout—Part I Diagnosis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006.
8. Schumacher HR, Becker MA, Edwards NL, et al. Magnetic resonance imaging in the quantitative assessment of gouty tophi. Int J Clin Pract. 2006;60:408–414.
9. Terkeltaub RA. Clinical practice. Gout. N Engl J Med. 2003;349:1647–1655.
10. Zhang W, Doherty M, Bardin T, et al. EULAR Evidence based recommendations for gout— part II management: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006.
11. Wortmann RL. Recent advances in the management of gout and hyperuricemia. Curr Opin Rheumatol. 2005;17:319–324.
12. Janssens HJ, Janssen M, van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet. 2008;371:1854–1860.
13. Schlesinger et al. Cochrane database of systemic reviews: Colchicine for acute gout. CD006190, Issue 4, 2006.
14. Terkeltaub RA. Colchicine Update: 2008. Semin Arthritis Rheum. 2008.
15. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum. 2004;51:321–325.
16. Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol. 2004;31:2429–2432.
17. Becker MA, Schumacher HR, Macdonald PA, et al. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009.
18. Gutman AB. The past four decades of progress in the knowledge of gout, with an assessment of the present status. Arthritis Rheum. 1973;16:431–445.
Additional Reading
Li-Yu J, Clayburne G, Sieck M, et al. Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? J Rheumatol. 2001;28:577–580.
20. Sutaria S, Katbamna R, Underwood M. Effectiveness of interventions for the treatment of acute and prevention of recurrent gout—a systematic review. Rheumatology (Oxford). 2006.
Codes
ICD9
  • 274.00 Gouty arthropathy, unspecified
  • 274.01 Acute gouty arthropathy
  • 274.9 Gout, unspecified
Clinical Pearls
  • Gout is an acute inflammatory arthritis that can mimic infection and progresses to a chronic disease.
  • A painful, warm, erythematous, swollen joint should be aspirated to rule out septic arthritis versus gout.
  • Tophaceous gout is the chronic form of gout that, in rare cases, can present acutely as well.
  • Prophylactic treatment should be considered in recurrent patients because it has been shown to reduce chronic flairs and joint damage.
  • Many medications that treat gout have side effects, and care must be taken in choosing the right medication while maintaining close follow-up.
  • Pseudogout is a disease that is distinct from gout but has various similarities, is less debilitating, and is less common.


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