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Diagnosis of gout
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Background

• Gout is a severe inflammatory disease caused by
  the deposition of monosodium urate (MSU) crystals
  in joints and other tissues
• Gout is the most frequent inflammatory arthritis
  in men
• The incidence and prevalence of gout are rising
  in post-menopausal women
• 1-2 of adults are affected
• The prevalence of gout increases with age
• Gout is often misdiagnosed or diagnosed late in
  its clinical course

Lawrence RC, et al. Arthritis Rheum
199841778-799. Mikuls TR, et al. Ann Rheum Dis
200564267-272. Zhang W
et al, Ann Rheum Dis, 2006651301-1311
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EULAR evidence based recommendations for gout
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
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EULAR recommendations 2006 for gout diagnosis
In acute attacks the rapid development of severe
pain, swelling and tenderness that reaches its
maximum within just 6-12 hours, especially with
overlying erythema, is highly diagnostic of
crystal inflammation though not specific for
gout. For typical presentations of gout (such
as recurrent podagra with hyperuricemia) a
clinical diagnosis alone is reasonably accurate
but not definitive without crystal confirmation.
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
1.
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Acute gout classical clinical picture

• Acute, very painful,monoarticular inflammation
  usually affecting the big toe (podagra)(70)
  (less frequently other foot joints, ankle, knee,
  finger, wrist, elbow)
• Typical rapid development of severe pain,
  swelling and tenderness that reaches its maximum
  within just 6-12 hours, especially with overlying
  erythema
• As inflammation disappears, the skin over the
  joint often peels
• Attacks often start at night or in the early
  morning
• Attack usually resolve within 5-10 days

By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
Wallace SL, et al. Arthritis and Rheumatism
197720(3)895-900.
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• Often typical gout is gout but not always
• Not rarely what does not look like gout is gout

Differential diagnosis of big toe gout (podagra)

• Pseudogout (acute calcium pyrophosphate
  arthropathy)
• Pseudogout-like (basic calcium phosphate)
  (pseudopodagra)
• Reactive arthritis
• Psoriatic arthritis
• Septic arthritis
• Sarcoidosis
• Others

Zhang W, et al. Ann Rheum Dis 2006651301-11. Ric
hette P, et al. Lancet 2010375318-328.
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Differential diagnosis of ankle gout

• Sarcoidosis
• Reactive arthritis
• Psoriatic arthritis
• Enteroarthritis
• Septic arthritis
• Other crystal-induced arthritides
• acute pyrophosphate arthropathy (pseudogout)
• basic calcium phosphate (pseudogout-like)

By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
Zhang W, et al Ann Rheum Dis 2006651301-1311. R
ichette P, et al. Lancet 2010375318-328. De
Leonardis F, et al. Rheumatol Int 2007281-7.
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Differential diagnosis of elbow gout or bursitis

• Septic arthritis or bursitis
• Post-traumatic bursitis
• Rheumatoid nodules with bursitis
• Other crystal-induced arthritides or bursitis
• acute pyrophosphate arthropathy (pseudogout)
• basic calcium phosphate (pseudogout-like)

By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
Ning TC, et al. Curr Opin Rheumatol
201022(2)181-187. .
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Differential diagnosis of hand-wrist gout

• Algoneurodystrophy
• Pitting oedema
• polymyalgia rheumatica
• psoriatic arthritis
• Septic arthritis
• Other crystal-induced arthritides or bursitis
• acute pyrophosphate arthropathy (pseudogout)

By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
Richette P, et al. Lancet 2010375318-328. De
Leonardis F, et al. Rheumatol Int
2007281-7. Ning TC, et al. Curr Opin Rheumatol
201028181-187.
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Chronic arthritis gout or not gout?
Gout or psoriatic arthritis?
Gout or rheumatoid arthritis?
Gout or osteoarthritis (Heberdens nodes)?
By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
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EULAR recommendations 2006 for gout diagnosis
Demonstration of monosodium urate (MSU) crystals
in synovial fluid or tophus aspirates permits a
definitive diagnosis of gout. A routine
search for MSU crystals is recommended in all
synovial fluid samples obtained from undiagnosed
inflamed joints.
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
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Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
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Likelihood ratio (HR) for various features in the
diagnosis of gout
Zhang W, et al. Ann Rheum Dis 2006651301-1311.
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Punzi L, et al. Ann NY Acad Sci 20091154152-158.
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Ultrasound-guided arthrocentesis
Grassi W, et al. Ann Rheum Dis 199958595-597.
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MSU crystals are always found in

• Synovial fluid samples from inflamed joints
• Previously inflamed joints of patients untreated
  with urate-lowering drugs
• Material from tophi
• Joints of treated patients before they dissolve

By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
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Synovial fluid analysis for crystals
Steps to follow
Steps to follow

• To detect whether there are any crystals
• The technique for detection
• of MSU and CPPD differs
• If so to identify what type they are

Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
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Identification of MSU crystals
Richette P, et al. Lancet 2010375318-328. Pascua
l E, et al. Ann Rheum Dis 2009 68 3-7. Sivera
F, et al. Ann Rheum Dis 200867273-275.
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MSU crystals from tophi
Richette P, et al. Lancet 2010375318-328. Pascua
l E , et al. Ann Rheum Dis 2009683-7. Sivera F,
et al. Ann Rheum Dis 200867273-275.
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EULAR recommendations 2006 for gout diagnosis
Identification of MSU crystals from asymptomatic
joints may allow definite diagnosis in
intercritical periods.
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
1.
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MSU crystals in synovial fluid during
intercritical periods

• Aspiration of 101 asymptomatic gouty joints
• 80 knees
• 21 first MTP joints
• All had previously been inflamed and had been
  free of inflammation
• over two months.
• MSU crystals were found in
• 43/43 joints from untreated patients
• 34/48 (71) joints from patients on
  urate-lowering drugs (plt0.001).

Pascual E, et al. Ann Intern Med 1999131756-759.
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EULAR recommendations 2006 for gout diagnosis
Gout and sepsis may coexist, so when septic
arthritis is suspected gram stain and culture of
synovial fluid should still be performed even if
monosodium urate crystals are identified.
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
1.
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Yu KH, et al. Rheumatol 2003421062-1066.
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Yu KH, et al. Rheumatol 200443518-521.
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EULAR recommendations 2006 for gout diagnosis
While being the most important risk factor for
gout, serum uric acid levels do not confirm or
exclude gout since many people with
hyperuricaemia do not develop gout, and during
acute attacks serum levels may be normal
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
1.
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Normative Aging Study
Follow-up of 2046 men, free of gout at the onset,
over 14.9 years
Campion EW. Am J Med 198782421-426.
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Inflammation effects on serum UA
Inflammation effects on serum UA

• During a gout attack, serum uric acid drops
  because of an increase of its renal excretion
• For example 50 of gouty patients have normal
  or low UA levels during attacks
• Diseases with persistent inflammation have a
  negative association with hyperuricaemia and gout
• For example Rheumatoid arthritis
• Serum acid uric is an inverse acute phase
  substance?

Urano W, et al. J Rheumatol 200229(9)1950-1953.
Agudelo CA, et al. Arthritis Rheum
198427(4)443-448 Wu VC, et al. Am J Kidney Dis
200545(1)88-95.
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EULAR recommendations 2006 for gout diagnosis
Urinary uric acid excretion should be determined
in selected gout patients, especially those with
a family history of young onset gout, onset of
gout under age 25, or with renal calculi
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
1.
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EULAR recommendations 2006 for gout diagnosis
Although radiographs may be useful for
differential diagnosis and may show typical
features in chronic gout, they are not useful in
confirming the diagnosis of early or acute gout.
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
1.
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Likelihood ratio (HR) for radiographic features
in the diagnosis of gout
Zhang W, et al. Ann Rheum Dis 2006651301-1311.
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Radiographic features of gout
By kind permission of L. Punzi, Rheumatology
Unit, University of Padua
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EULAR recommendations 2006 for gout diagnosis
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Risk factors and associated co-morbidity can be
assessed during the diagnosis of gout, including
features of the metabolic syndrome (obesity,
hyperglycaemia, hyperlipidaemia, hypertension).
Zhang W, et al. Ann Rheum Dis 200665(10)1301-131
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