Musculoskeletal System

Gout: Overview

Gout is characterized by the deposition of monosodium urate crystals in the extracellular fluid of the joints and other sites, due to disturbances of uric acid metabolism (i.e., either overproduction or underexcretion). This results in joint space destruction, bony erosion and damage to the surrounding ligaments and tendons.

Manifestations are either acute, characterized by severe mono- or polyarticular pain, redness, and swelling of the affected joint; or chronic, characterized by development of monosodium urate crystals in the soft tissues in and around the joints, giving rise to painless swellings referred to as "tophi".

Joint mobility is affected in both forms. In acute disease, this is due to severe pain limiting movement, and in the chronic form, due to longstanding destruction of the joint spaces.

Frequently affected joints include the first metatarsophalangeal joint (i.e. "podagra"), ankle, knee, wrist, finger and elbow. This pattern is due to the fact that urate is more li

kely to crystallize in the cooler areas of the body.

Gout: Radiography during acute attacks

In the early stages of acute gout, X-rays of the affected joint will often be normal, or only show subtle changes such as small erosions. Thus, they are not particularly helpful in establishing the diagnosis.

Gout: Serum urate levels during acute attacks

During an acute attack of gout, serum urate levels may be reduced or normal. The exact mechanism behind this is poorly understood but thought to be due to either increased excretion of uric acid, inflammatory reactions, or increased crystal formation. Therefore, serum urate levels should be rechecked about one to two weeks following resolution of an acute attack.

Gout: Arthrocentesis

Arthrocentesis involves the aspiration of synovial fluid from the joint space. The aspirate is then sent for macroscopic and microscopic analysis. This allows both confirmation of gout, as well as the exclusion of other differentials such as septic arthritis and pseudogout.

Gout: Negative birefringence

Under polarized light microscopy, monosodium urate crystals in synovial fluid exhibit negative birefringence. That is, they appear yellow when aligned parallel to the slow axis of red plate compensator, and blue when aligned in the direction of polarization.

Gout: Treatment of acute episodes

NSAIDs and colchicine are the most widely used drugs in the management of acute flares of gout.

NSAIDs exert their effects via their anti-inflammatory properties, whereas colchicine inhibits neutrophil migration from blood vessels into the joint space and interfering with interleukin 1b production, thereby limiting the development of an inflammatory reaction.

Selective COX-2 inhibitors (e.g. celecoxib) are also used in the management of acute gout. Second-line drugs include IL-1 inhibitors and corticosteroids (either oral, intravenous, or intraarticular).

Pharmacologic interventions for acute gout should be started as soon as possible, preferably within 12 hours of the onset of symptoms.

Gout: Urate lowering drugs

Following resolution of an acute episode of gout, urate lowering therapy may be considered, although this is not required in all patients. Key indications include:

  • At least two attacks in less than a one-year period
  • Presence of tophi
  • Gout related kidney injury (urate nephropathy)
  • A history of any type of nephrolithiasis
  • Destructive joint changes
  • Serum urate levels >8mg/dL

Pharmacologic interventions include the use of xanthine oxidase inhibitors (allopurinol and febuxostat), uricosurics (probenecid, benzbromarone, sulfinpyrazone), or urate oxidases (rasburicase); and stopping hyperuricemic drugs such as thiazide and loop diuretics, beta blockers, and ACE inhibitors. Target serum urate levels are <6mg/dL or <5mg/dL in severe tophaceous gout.

Non-pharmacologic interventions include lifestyle and dietary modifications such as increased physical activity, weight loss, reduced alcohol intake, reduced intake of fructose sweetened sodas, reduced meat and seafood intake, increased hydration, and increased intake of skimmed milk.

If urate lowering measures are embarked on, prophylaxis with low dose NSAIDs or colchicine is important prevent recurrences secondary to urate mobilization and dissolution.

Gout: Management of flares during urate lowering therapy

During urate lowering therapy, there is an increased risk of gout flares. This risk can be reduced with low dose NSAID or colchicine therapy. If a flare still occurs, the drug should be upgraded to the treatment dose, and the urate lowering agent continued at the existing dose.


  1. JORDAN KM, CAMERON JS, SNAITH M, ZHANG W, DOHERTY M, SECKL J, HINGORANI A, JAQUES R, NUKI G, BRITISH SOCIETY FOR RHEUMATOLOGY AND BRITISH HEALTH PROFESSIONALS IN RHEUMATOLOGY STANDARDS, GUIDELINES AND AUDIT WORKING GROUP (SGAWG). British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford) [online] 2007 Aug, 46(8):1372-4 [viewed 11 October 2016] Available from:
  2. SHIRTLIFF ME, MADER JT. Acute Septic Arthritis Clin Microbiol Rev [online] 2002 Oct, 15(4):527-544 [viewed 12 October 2016] Available from:
  3. VISSER S, TUPPER J. Septic until proven otherwise: Approach to and treatment of the septic joint in adult patients Can Fam Physician [online] 2009 Apr, 55(4):374-375 [viewed 12 October 2016] Available from:
  4. DHOBLE A, BALAKRISHNAN V, SMITH R. Chronic tophaceous gout presenting as acute arthritis during an acute illness: a case report Cases J [online] 2008 Oct 15:238 [viewed 12 October 2016] Available from:
  5. THISSEN CA, FRANK J, LUCKER GP. Tophi as first clinical sign of gout. Int J Dermatol [online] 2008 Nov:49-51 [viewed 12 October 2016] Available from:
  6. TAUSCHE AK, JANSEN TL, SCHRöDER HE, BORNSTEIN SR, ARINGER M, MüLLER-LADNER U. Gout—Current Diagnosis and Treatment Dtsch Arztebl Int [online] 2009 Aug 24, 106(34-35):549-555 [viewed 12 October 2016] Available from:
  7. BERNAL JA, QUILIS N, ANDRéS M, SIVERA F, PASCUAL E. Gout: optimizing treatment to achieve a disease cure Ther Adv Chronic Dis [online] 2016 Jan 12, 7(2):135-144 [viewed 12 October 2016] Available from:
  8. BURNS CM, WORTMANN RL. Latest evidence on gout management: what the clinician needs to know Ther Adv Chronic Dis [online] 2012 Nov, 3(6):271-286 [viewed 12 October 2016] Available from:
  9. VENA-WOODS C, HILAS O. Febuxostat (Uloric), A New Treatment Option for Gout P T [online] 2010 Feb, 35(2):82-85 [viewed 31 October 2016] Available from:
  10. UNDERWOOD M. Diagnosis and management of gout BMJ [online] 2006 Jun 3, 332(7553):1315-1319 [viewed 08 March 2018] Available from:
  11. KHANNA D, KHANNA PP, FITZGERALD JD, SINGH MK, BAE S, NEOGI T, PILLINGER MH, MERILL J, LEE S, PRAKASH S, KALDAS M, GOGIA M, PEREZ-RUIZ F, TAYLOR W, LIOTé F, CHOI H, SINGH JA, DALBETH N, KAPLAN S, NIYYAR V, JONES D, YAROWS SA, ROESSLER B, KERR G, KING C, LEVY G, FURST DE, EDWARDS NL, MANDELL B, SCHUMACHER HR, ROBBINS M, WENGER N, TERKELTAUB R. 2012 American College of Rheumatology Guidelines for Management of Gout Part II: Therapy and Anti-inflammatory Prophylaxis of Acute Gouty Arthritis Arthritis Care Res (Hoboken) [online] 2012 Oct, 64(10):1447-1461 [viewed 08 March 2018] Available from:
  12. RAGAB G, ELSHAHALY M, BARDIN T. Gout: An old disease in new perspective - A review J Adv Res [online] 2017 May 10, 8(5):495-511 [viewed 09 March 2018] Available from: