CLINICAL OVERVIEW  

Gout 
Elsevier Point of Care  (see details)
Updated 21 April 2020. Copyright Elsevier BV. All rights reserved.

Synopsis
Key Points Urgent Action
Acute gouty arthritis results from an inflammatory In patients with hot, swollen,
response to deposition of monosodium urate crystals in painful joints, evaluate
the joints, creating intense inflammation in the joints or immediately to determine if
other soft tissues
septic arthritis is present; if so,
Chronic tophaceous gout usually develops when acute refer urgently to an
gout and hyperuricemia (which results from orthopedic surgeon, infectious
disease specialist, or
overproduction or underexcretion of uric acid) chronically
rheumatologist
have not been controlled and when hyperuricemia is
severe and sustained

Acute gout attacks are characterized by sudden onset of severe pain, swelling, redness,
limitation of range of motion, and warmth of the involved area, lasting from days to weeks

Chronic gout includes painful, yellowish, subcutaneous nodules (tophi) in various stages of
inflammation

Presumptive diagnosis of gout is established on basis of history and physical examination

findings; it is confirmed by presence of negatively birefringent monosodium urate crystals in a
synovial fluid sample viewed under polarized light microscopy (gold standard) 1 2

Treatment of an acute attack is most effective when started within the first 24 hours, usually
with traditional NSAIDs, 6 colchicine, corticosteroids, or cyclooxygenase 2 inhibitors 3 4 5

In patients with recurrent gout, address treatment of hyperuricemia 3 4

Hypouricemic and uricosuric medications are used to lower serum uric acid levels in an effort
to prevent further attacks but are not used for treatment of acute attacks 3 4

Most cases of acute gout resolve within a few days of initiation of treatment, but recurrence is
common

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 Recurring attacks tend to occur at shorter intervals, last longer, and eventually show
incomplete resolution, resulting in slowly progressive chronic arthritis 2

Pitfalls
Treatment failure is rare and likely signals lack of adherence to medication regimen

Consider antihyperuricemic therapy only for patients with recurrent, severe attacks likely to
lead to joint damage or progression to chronic tophaceous gout; NSAID or colchicine
prophylaxis is particularly important during introduction of antihyperuricemic therapy to
prevent acute attacks that occur initially in response to altered uric acid levels

Colchicine prophylaxis is more effective than NSAIDs in preventing recurrence, but the dose
required for gout control is often associated with diarrhea

Neither NSAIDs nor colchicine prevent monosodium urate crystal deposition; tophi may still
form

Terminology
Clinical Clarification
Gout is crystal-induced arthropathy caused by monosodium urate monohydrate crystals
(negatively birefringent)

Acute gouty arthritis results from an inflammatory response to deposition of monosodium

urate crystals in joints, creating intense inflammation in joints or other soft tissues

Chronic tophaceous gout usually develops when acute gout and hyperuricemia (which results
from overproduction or underexcretion of uric acid) chronically have not been controlled and
when hyperuricemia is severe and sustained
Firm, swollen nodules (tophi) form as a result of uric acid crystal deposition, usually on
digits or over olecranon bursa or Achilles tendon

Diagnosis
Clinical Presentation
History

Most acute gout attacks occur in a single joint, with inflammation of the first
metatarsophalangeal joint (podagra) accounting for most cases 2

Acute gout attacks are characterized by sudden onset of severe pain, swelling, redness, limited
range of motion, and warmth of the involved area, lasting from days to weeks

Severe pain in the affected joint with little stimulation (eg, bed sheet touching affected area)

Increased sensitivity of overlying skin

Redness over joints

Pain in the big toe (podagra)

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 Joint swelling

Fever can occur

History of excessive alcohol consumption

Family history of gout

Physical examination

Joint swelling

Joint erythema

Joint tenderness

Limited range of motion

Warmth of the involved joint

Presence of a mass on the affected joint

In chronic gout, painful, yellowish, subcutaneous nodules (tophi) in various stages of

inflammation (most often very inflamed early in disease course); often occurs on fingertips,
ears, and extensor surfaces (sites of common minor trauma)

Causes and Risk Factors

Causes

Hyperuricemia 2
Due to excessive uric acid production and/or decreased renal excretion of uric acid

Results in deposition of monosodium urate crystals in joints, causing inflammation

Primary hyperuricemia results from an inborn error of metabolism

Secondary hyperuricemia may result from acquired disorders (eg, leukemia, end-stage renal
disease), use of certain drugs (eg, diuretics), or dietary intake (eg, alcohol)

Risk factors and/or associations

Age

First attack of acute gouty arthritis usually occurs: 2

Between ages 40 and 60 years in men

After age 60 years in women

Sex

More common in men 2

Genetics

Increased risk with family history of gout 2

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Other risk factors/associations  
 High alcohol intake, 6 especially beer

Fructose-rich beverage intake

Diet high in purines

Found in red meat, poultry, oily fish, liver, kidney, heart, gizzard, sweetbreads, yeast
extracts, meat extracts, peas, beans, spinach, and lentils

Lima, soy, kidney, northern, white, and black-eyed beans have the highest purine content;
garbanzo beans have the lowest

Use of medications such as thiazide diuretics 6 or aspirin

Obesity

Metabolic syndrome

Diabetes

Hypertension

Hyperlipidemia

Diagnostic Procedures
  Primary diagnostic tools

Presumptive diagnosis is based on history and physical examination findings; diagnosis is

confirmed by presence of monosodium urate crystals in aspirated joint fluid 1 2

Aspiration of affected joint and analysis of joint fluid is usually the only laboratory
investigation indicated for patients in whom acute gout is suspected 1 2 7

Gold standard for diagnosis is presence of negatively birefringent monosodium urate

crystals in a synovial fluid sample viewed under polarized light microscopy 1 2 6

Radiography is not useful in diagnosing acute attacks; in chronic gout, radiographs of the
affected joints can help determine presence of typical gouty erosions and/or changes
indicative of osteoarthritis 1

  Laboratory

  Imaging

  Procedures

Differential Diagnosis
Most common

Septic arthritis
Infection of a joint space that can be caused by a wide variety
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of microorganisms, notably Neisseria gonorrhoeae,
 Staphylococcus aureus, group B streptococci, and Streptococcus
pneumoniae; viruses, mycobacteria, and fungi are also
potential causes

Infection most commonly results from hematogenous spread

Abrupt onset with swelling, erythema, and warmth over the

affected joint (most commonly the knee, hip, or shoulder
[usually monoarticular]) and such intense pain that movement
is often impossible

Fever and shaking chills are common

Differentiated with joint fluid analysis, including leukocyte

count, Gram stain, polarizing microscopy, and culture

Synovial fluid leukocyte count is usually elevated (greater

than 50,000 cells/mm³), with more than 75%
polymorphonuclear cells 8

May also occur in the presence of tophaceous gout

Pseudogout
Caused by deposition of calcium pyrophosphate dihydrate
crystals in articular cartilage, synovium, and periarticular
ligaments and tendons

Women are predominantly affected

Onset is abrupt, with swelling and erythema over the affected

joint

Affected joint is most commonly the knee, followed by the

wrist, shoulder, ankle, and elbow (usually monoarticular; very
rarely polyarticular)

Acute pain and restricted movement

Fever is common

Attacks are self-limiting

Differentiated by identification of positively birefringent

calcium pyrophosphate dihydrate crystals in joint fluid

Bursitis
Inflammation of a bursa, usually aseptic; most commonly
caused by acute trauma or chronic, repetitive trauma

Patients present with tenderness of the affected bursa and

Outline diffuse ache or pain when the ligaments or tendons are  
 stretched over it; there also may be minimal pain with limited
passive range of motion of the joint

Localized swelling is seen if bursa is near the surface and often

is infected, appearing red and hot (particularly in patients
with olecranon bursitis)

Unlike in gout, the soft tissue (bursa) is more affected than the
joint

Differentiated by history and physical examination

Cellulitis
Acute bacterial skin infection of dermal and subcutaneous
tissue that presents clinically with spreading skin erythema,
warmth, induration, and tenderness

Most commonly caused by group A streptococci or

Staphylococcus aureus

Patients with diabetes, immunodeficiency, or venous or

lymphatic compromise are most likely to be affected

Acute onset of pain, warmth, redness, and swelling of involved

skin area, with malaise and fever possible; fever and
constitutional signs are mild or absent in uncomplicated mild
to moderate cases

Lymphangitis and lymphadenopathy in proximal lymph nodes

may be present

Differentiated by history and physical examination

Atypical presentations of
Features of psoriasis are present; examine nails, hairline,
psoriatic arthritis
navel, and natal cleft

Dactylitis (inflammation of an entire toe or finger) frequently

occurs and may affect more than 1 digit; affected fingers or
toes may have a characteristic sausage shape

Involvement of upper limb joints is more likely than in

patients with gout

Differentiated by history and physical examination

Trauma Traumatic injury to a joint is typically apparent from history

or physical examination

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 In cases in which it is impossible to obtain a substantial history
(eg, in patients with loss of consciousness, cerebrovascular
accident, or cognitive or sensory deficit), differentiation is
more reliant on laboratory investigations

Erythema and warmth over the affected area are less likely to
be present than in patients with gout; however, the
presentation of an acute fracture with hematoma may be
similar to that of gout

Differentiated by history, physical examination, and, if

necessary, joint fluid analysis negative for gouty aspirate

Treatment
Goals
Rapidly resolve pain and inflammation

Prevent recurrence

Disposition
Recommendations for specialist referral

Referral to rheumatologist is recommended for any patient with gout who is younger than 30
years and for patients with the following:
Uncertain diagnosis

Severe gout attacks unresponsive to therapy

Recurrent gout attacks

Hyperuricemia unresponsive to therapy

Comorbid renal disease

Organ transplant along with gout

In patients with hot, swollen, painful joints, evaluate immediately to determine if septic
arthritis is present; if so, refer urgently to an orthopedic surgeon, infectious disease specialist,
or rheumatologist

Treatment Options
Treatment of an acute attack is most effective when started within the first 24 hours, usually
with traditional NSAIDs, 6 colchicine, corticosteroids, or cyclooxygenase 2 inhibitors 5

If not effective within 3 days, review and revise treatment 3 4

In patients with recurrent gout, address treatment of hyperuricemia 3 4

Outline  
 Neither NSAIDs nor colchicine prevent monosodium urate crystal deposition; tophi may still
form

Hypouricemic and uricosuric medications are used to lower serum uric acid levels in an effort to
prevent further attacks but are not used for treatment of acute attacks 3 4

American College of Physicians recommends against initiating long-term urate-lowering

therapy in most patients after a first gout attack or in patients with infrequent attacks 5

Consider antihyperuricemic therapy only for patients with recurrent, severe attacks likely to
lead to joint damage or progression to chronic tophaceous gout; NSAID or colchicine prophylaxis
is particularly important during introduction of antihyperuricemic therapy to prevent acute
attacks that occur initially in response to altered uric acid levels

Treatment failure is rare and likely signals lack of adherence to medication regimen

Dietary modification and weight loss also may help to prevent recurrent acute gout 3 4

Joint aspiration may relieve acute pain in affected joint 1 2

Drug therapy

Traditional NSAIDs 3 9
Most effective when administered within 24 hours of gout attack

Indomethacin
Indomethacin Oral capsule; Adults: 50 mg PO 3 times per day until pain is tolerable.
Reduce dose and/or discontinue therapy as soon as possible.

Indomethacin Oral capsule; Geriatric: Generally not recommended.

Ibuprofen
Ibuprofen Oral tablet; Adults: 400—800 mg PO 3—4x/day.

Ibuprofen Oral tablet; Geriatric: See adult dosage; elderly at higher risk of ADRs, treat with
lowest effective dose for shortest possible duration.

Naproxen
Naproxen Oral tablet; Adults: 750 mg PO, then 250 mg PO q8h PRN; treat with lowest
effective dose and for shortest duration; consider lower doses in geriatric patients.

Cyclooxygenase 2 inhibitors
Celecoxib 9 10
Off-label use

Most effective when administered within 24 hours of gout attack

For patients with contraindications to, or intolerance of, other NSAIDs 3

Celecoxib Oral capsule; Adults: 800 mg PO initially, then followed by an additional 400
Outline mg PO on the first day, if needed. On subsequent days, 400 mg PO twice daily for a total  
 of 7 days. Consider starting celecoxib at half the lowest recommended dose in patients
who are poor CYP2C9 metabolizers. 10

Colchicine 3
Used to treat acute gout attacks and prevent recurrent attacks

Most effective when administered within 24 hours of attack

Therapeutic window is narrow; cumulative amount that alleviates gout attack is similar to
the dose that triggers gastrointestinal symptoms (eg, vomiting, diarrhea)

American College of Physicians recommends clinicians use low-dose formulation of

colchicine to treat acute gout 5

Acute gout flare

Colchicine Oral tablet; Adults: 1.2 mg PO at the first sign of gout flare, followed by 0.6 mg
PO 1 hour later. Max total dose: 1.8 mg PO over a 1-hour period. Higher doses are not more
effective. Wait at least 3 days before repeating. In patients receiving colchicine
prophylaxis, wait 12 hours to resume the prophylactic dose. Coadministration of certain
drugs may need to be avoided or dosage adjustments may be necessary; review drug
interactions.

Prophylaxis
Colchicine Oral capsule; Adults: 0.6 mg PO once or twice daily. Max: 1.2 mg/day PO.
Coadministration of certain drugs may need to be avoided or dosage adjustments may be
necessary; review drug interactions.

Corticosteroids 3
Treatment of acute gouty arthritis
Intra-articular injection is most often used if only 1 or 2 joints are inflamed

Oral doses are most often used in patients with polyarticular involvement, patients with
attacks lasting more than several days, and patients who cannot tolerate NSAIDs or
colchicine

Rebound attacks of gout are relatively common after withdrawal of oral corticosteroids

Methylprednisolone
Methylprednisolone Acetate Suspension for injection; Adults: 10 to 80 mg at the
appropriate site, depending on degree of inflammation and size and location of affected
area. Repeat doses usually not required for 1 to 5 weeks. Dose ranges for large joints: 20 to
80 mg; medium joints: 10 to 40 mg; small joints: 4 to 10 mg. Suggested intralesional dose
range: 20 to 60 mg.

Methylprednisolone Oral tablet; Adults: 4 to 48 mg/day PO, administered in 4 divided

doses. Adjust to response and severity of condition.

Triamcinolone
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 Triamcinolone Acetonide Suspension for injection; Children and Adolescents: 2.5 mg to 5
mg for smaller joints and from 5 mg to 15 mg for larger joints, depending on the specific
disease entity being treated. Other regimens have been described: 2 mg/kg for large joints
(knees, hips, and shoulders) and 1 mg/kg for smaller joints (ankles, wrists, and elbows). For
the hands and feet, 2 to 4 mg/joint (metacarpo- or metatarpo-phalangeal) or 1.2 to 2
mg/joint (proximal interphalangeal).

Triamcinolone Acetonide Suspension for injection; Adults: 2.5 mg to 5 mg for smaller joints
and from 5 mg to 15 mg for larger joints, depending on the specific disease entity being
treated. For adults, doses up to 10 mg for smaller areas and up to 40 mg for larger areas
have usually been sufficient. Single injections into several joints, up to a total of 80 mg,
have been given.

Prednisone
Prednisone Oral tablet; Adults: Titrate to response. Usual dose ranges from 5 mg to 30 mg
PO once daily.

Allopurinol 4
Hypouricemic agent of choice in patients predisposed to uric acid calculi

Allopurinol Oral tablet; Adults: 100 mg PO once daily initially, then increase by 100 mg/day
each week until serum urate concentrations decrease to 6 mg/dL or less. Usual dose: 200 to
300 mg/day for milder disesase; 400 mg to 600 mg/day for moderate-severe tophaceous gout.
Doses more than 300 mg/day are given in divided doses. Max: 800 mg/day PO.

Febuxostat 4
Used to treat hyperuricemia in patients with gout

Can be used to treat hyperuricemia after resolution of an acute gouty attack, but
administration in combination with an NSAID or colchicine is advisable to prevent recurrent
flares of gouty arthritis

Because of the increased risk of cardiovascular mortality, should only be used in patients

who have an inadequate response to a maximally titrated dose of allopurinol, who are
intolerant to allopurinol, or for whom treatment with allopurinol is not advisable

Febuxostat Oral tablet; Adults: 40 mg PO once daily. May increase to 80 mg PO once daily if
the serum uric acid concentration is more than 6 mg/dL after 2 weeks of therapy. Max:
Usually 80 mg/day PO. Up to 120 mg/day has been studied in clinical trials.

Uricosuric agents 4
Treat hyperuricemia by enhancing renal clearance of uric acid

Lack analgesic and antiinflammatory properties and thus are not effective for treatment of
acute gout attacks

Lowering serum uric acid levels may precipitate an acute gouty attack; administer NSAIDs
or colchicine before, during, and after treatment with drugs that lower serum acid levels
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 Probenecid
Probenecid Oral tablet; Adults: 250 mg PO twice daily for 1 week, followed by 500 mg PO
twice daily. Some degree of renal dysfunction may be present; a daily dosage of 1,000 mg
may be adequate for such patients. May increase daily dose by 500-mg increments every 4
weeks within tolerance if symptoms are not controlled or the 24-hour uric acid excretion
is not above 700 mg. Usual Max: 2,000 mg/day PO, given as 500 mg PO 4 times per day.

Lesinurad
Not recommended for patients taking allopurinol doses less than 300 mg/day (or less than
200 mg in patients with estimated creatinine clearance less than 60 mL/minute) 11

Lesinurad Oral tablet; Adults: 200 mg PO once daily in the morning, at the same time as
the morning dose of xanthine oxidase inhibitor. If treatment with the xanthine oxidase
inhibitor is interrupted, lesinurad should also be interrupted. Do not use lesinurad as
monotherapy.

Nondrug and supportive care

Dietary modification 3 4 6

Reduced alcohol intake (maximum of 2 drinks per day)

Increased fluid intake; advise patients to drink enough to keep the urine pale

A low-purine diet is considered impractical

Weight loss if overweight

Topical ice application 3

Procedures

Joint aspiration 8
General explanation

Provides rapid pain relief by reducing tense effusion

Indication

Treatment of acute pain in affected joint

Contraindications

Overlying skin infections or lesions

Coagulopathy or use of anticoagulant medications (safety not established)

Bacteremia (relative contraindication)

Comorbidities

Renal disease is both a predisposing factor for gout and a result of undertreated gouty
arthropathy 2
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 Monitoring
After an initial acute gout attack, observe patients periodically to review adherence with
prevention measures to help avoid recurrence

Complications and Prognosis

Complications
Recurrent painful gout attacks, with a significant effect on lifestyle

Chronic uric acid nephropathy and renal failure may result from hyperuricemia and recurrent
untreated gout attacks; uric acid nephrolithiasis is seen in some patients with gout

Tophaceous deposits, which are a nuisance and may become infected (septic arthritis)

Joint damage from tophi, which may become irreversible; early osteoarthritis in affected joints

Prognosis
Most cases of acute gout resolve within a few days of initiation of treatment, but recurrence is
common

Recurring attacks tend to occur at shorter intervals, last longer, and eventually show
incomplete resolution, resulting in slowly progressive chronic arthritis 2

Severe disease with significant tophi formation can require long-term treatment and prognosis
tends to be poorer

REFERENCES
1: Dalbeth N et al: Gout. Lancet. 388(10055):2039-52, 2016
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/27112094)

2: Burns CM et al: Clinical features and treatment of gout. In: Kelley's Textbook of Rheumatology.
9th ed. Saunders; 2013:1554-75.e5
View In Article

3: Khanna D et al: 2012 American College of Rheumatology guidelines for management of gout.
Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res
(Hoboken). 64(10):1447-61, 2012
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/23024029)

4: Khanna D et al: 2012 American College of Rheumatology guidelines for management of gout.
Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to
hyperuricemia. Arthritis Care Res (Hoboken). 64(10):1431-46, 2012
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/23024028)

5: Qaseem A et al: Management of acute and recurrent gout: a clinical practice guideline from
the American College of Physicians. Ann Intern Med. 166(1):58-68, 2017
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/27802508)
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 6: Mirmiran R et al: Joint clinical consensus statement of the American College of Foot and Ankle
Surgeons and the American Association of Nurse Practitioners: etiology, diagnosis, and treatment
consensus for gouty arthritis of the foot and ankle. J Foot Ankle Surg. 57(6):1207-17, 2018
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/30368431)

7: Qaseem A et al: Diagnosis of acute gout: a clinical practice guideline from the American
College of Physicians. Ann Intern Med. 166(1):52-7, 2017
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/27802479)

8: Matteson EL et al: Infections of bursae, joints, and bones. In: Goldman L, ed: Goldman-Cecil
Medicine. 25th ed. Elsevier; 2016:1805-10
View In Article

9: van Durme CM et al: Non-steroidal anti-inflammatory drugs for acute gout. Cochrane Database
Syst Rev. 9:CD010120, 2014
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/25225849)

10: Schumacher HR et al: Efficacy and tolerability of celecoxib in the treatment of acute gouty
arthritis: a randomized controlled trial. J Rheumatol. 39(9):1859-66, 2012
View In Article | Cross Reference   (https://pubmed.ncbi.nlm.nih.gov/22859357)

11: Ironwood Pharmaceuticals Inc: Zurampic - lesinurad tablet, film coated [prescribing
information]. National Library of Medicine DailyMed website. Updated December 18, 2018.
Accessed April 20, 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef9e7711-
f478-4e35-bf4e-6021c8457e3b
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