diagnosis of gout

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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 1998;41:778-799.Mikuls TR, et al. Ann Rheum Dis 2005;64:267-272.

Zhang W et al, Ann Rheum Dis, 2006;65:1301-1311

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EULAR evidence based recommendations for gout

Zhang W, et al. Ann Rheum Dis 2006;65(10):1301-1311.

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EULAR recommendations 2006for gout: diagnosis


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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.

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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

Wallace SL, et al. Arthritis and Rheumatism 1977;20(3):895-900.

By kind permission of L. Punzi, Rheumatology Unit, University of Padua

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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 2006;65:1301-11.Richette P, et al. Lancet 2010;375:318-328.

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Differential diagnosis of ankle gout

• Sarcoidosis

• Reactive arthritis

• Psoriatic arthritis

• Enteroarthritis


• 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 2006;65:1301-1311.Richette P, et al. Lancet 2010;375:318-328.

De Leonardis F, et al. Rheumatol Int 2007;28:1-7.

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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


– basic calcium phosphate (pseudogout-like) By kind permission of L. Punzi,

Rheumatology Unit, University of Padua

Ning TC, et al. Curr Opin Rheumatol 2010;22(2):181-187.

.

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• Algoneurodystrophy

• Pitting oedema

– polymyalgia rheumatica

– psoriatic arthritis


• Other crystal-induced arthritides or bursitis


Differential diagnosis of hand-wrist gout


Richette P, et al. Lancet 2010;375:318-328.De Leonardis F, et al. Rheumatol Int 2007;28:1-7.

Ning TC, et al. Curr Opin Rheumatol 2010;28:181-187.

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Chronic arthritis: gout or not gout?

Gout or psoriatic arthritis? Gout or rheumatoid arthritis?

Gout or osteoarthritis (Heberden’s nodes)? By kind permission of L. Punzi,

Rheumatology Unit, University of Padua

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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.

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12Zhang W, et al. Ann Rheum Dis 2006;65(10):1301-1311.

13Zhang W, et al. Ann Rheum Dis 2006;65:1301-1311.

Likelihood ratio (HR) for various featuresin the diagnosis of gout

14Punzi L, et al. Ann NY Acad Sci 2009;1154:152-158.

15Grassi W, et al. Ann Rheum Dis 1999;58:595-597.

Ultrasound-guided arthrocentesis

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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



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• To detect whether there are any crystals

The technique for detection of MSU and CPPD differs

If so: to identify what type they are

Steps to follow:

Synovial fluid analysis for crystals

Steps to follow:


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Identification of MSU crystals

Monosodium Urate (MSU)

• Acicular

• Intense birefringence

• Negative elongation

Ordinary light Polarised light

First order red compensator

axis


Richette P, et al. Lancet 2010;375:318-328.Pascual E, et al. Ann Rheum Dis 2009; 68: 3-7.

Sivera F, et al. Ann Rheum Dis 2008;67:273-275.

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MSU crystals from tophi

Polarised light First order red compensator


Richette P, et al. Lancet 2010;375:318-328.Pascual E , et al. Ann Rheum Dis 2009;68:3-7.

Sivera F, et al. Ann Rheum Dis 2008;67:273-275.

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Identification of MSU crystals from asymptomatic joints may allow definite diagnosis in intercritical periods.

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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 (p<0.001).

Pascual E, et al. Ann Intern Med 1999;131:756-759.

MSU crystals in synovial fluid during intercritical periods

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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.

23Yu KH, et al. Rheumatol 2003;42:1062-1066.

24Yu KH, et al. Rheumatol 2004;43:518-521.

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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

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Follow-up of 2046 men, free of gout at the onset, over 14.9 years

Campion EW. Am J Med 1987;82:421-426.

Normative Aging Study

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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 2002;29(9):1950-1953. Agudelo CA, et al. Arthritis Rheum 1984;27(4):443-448

Wu VC, et al. Am J Kidney Dis 2005;45(1):88-95.

Inflammation… effects on serum UA

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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

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Although radiographs may be useful for differential diagnosisand may show typical features in chronic gout, they are not useful

in confirming the diagnosis of early or acute gout.

30Zhang W, et al. Ann Rheum Dis 2006;65:1301-1311.

Likelihood ratio (HR) for radiographic features in the diagnosis of gout

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Radiographic features of gout

DIP

PIP Big toes


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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).

diagnosis of gout

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