Gout&Pseudogout Update

7/29/2019 Gout&Pseudogout Update

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GOUT AND

PSEUDOGOUT


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Definition Gout is a syndrome caused by the

inflammatory response to tissue

deposition of monosodium uratecrystals (MSU).


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Classification Acute gout.

Tophaceus Gout.

Asymptomatic Hyperuricemia.

Primary Gout.

Secondary Gout.


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Etiology Hyperuricemia is the common

denominator in gout.

Two-thirds of uric acid are excretedby the kidney and the rest in the GI

tract.

90% of cases of gout are

secondary to under-excretion.

Overproduction is secondary to

defects in the HGPRT or PRPP.


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Etiology The inflammatory response is

secondary to the response of the

leukocytes to the MSU crystals. Acute gout is most likely secondary

to the formation of new crystals.

Factors that precipitate gout

includes: surgery, trauma, alcohol,

starvation and medications.


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Pathology The most frequent sites of

deposition of MSU crystals are:

cartilage, epiphyseal bone,periarticular structures and the

kidney.

A tophus is a foreign body reaction

that includes the MSU crystalssurrounded by fibrous tissue.

In the kidney the deposition of

MSU crystals causes interstitialfibrosis and arteriosclerosis.


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Epidemiology The prevalence of asymptomatic

hyperuricemia is 5 to 8%.

The prevalence of gout is 13 casesper 1000 men and 6.4 cases per

1000 women.

The higher the uric acid, the higher

the risk to develop gout.

90% of patients with primary gout

are men.


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Epidemiology Women rarely develop gout before

the menopause, because

estrogens are thought to beuricosuric.

Peak incidence in men is in the

fifth decade.

Primary gout is associated with:

obesity, hyperlipidemia, diabetes

mellitus, hypertension and

atherosclerosis.


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Epidemiolgy

Causes of secondary gout include:

Excessive dietary purine intake,

increase nucleotide turnover (e.g.,lymphoproliferative disorders,

hemolytic anemia, psoriasis),

Glycogen storage diseases,

diminished renal function,ketoacidosis, lactic acidosis,

hyperparathyroidsm and

medications.


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Clinical Manifestations Acute gout: acute arthritis is the

most common manifestation. The

most common is the podagra. 50% of patients experience their

first attack in this joint.

80% of the attacks are

monoarticular and typically involve

the lower extremities. (MTPs,

ankle and knee).


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Clinical Manifestations

Less common sites of involvement

include wrist, fingers and elbow.

Differential diagnosis includesseptic arthritis, cellulitis or

thromboflebitis.

Attacks subside in 3 to 10 days.

Recurrent attacks can involve

more joints and usually persist

longer.


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Clinical manifestations

Repeated attacks could cause joint

erosions.

Polyarticular attacks are commonin patients with established poor

controlled disease.

These attacks could also involve

periarticular structures.


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Intercritical gout: It is the

asymptomatic period between

crises, but MSU crystals can stillbe recovered if necessary.

The duration of this period varies,

but untreated patients may have a

second episode within two years.

Some patients evolve to chronic

polyarticular gout without pain free

intercritical episodes.


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Chronic tophaceus Gout: The

clinical characteristic is the

deposition of solid urate in theconnective tissue.

It is associated with early age of

onset, long duration of untreated

disease, frequent attacks, upperextremity involvement, polyarticular

disease and elevated serum uric

acid.


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Transplant patients treated with

cyclosporine and/or diuretics have

an increased risk for tophaceusgout.

The most common sites for tophi

are: the olecranon, prepatellar

bursa, ulnar surface and Achillestendon.


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Tophi in the hands can cause joint

destruction.

Tophi can ulcerate the skin andexcrete a chalky material

composed of MSU crystals.

Tophi progress insidiously with

increased stiffness and pain.


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Renal disease: this includes

urolithiasis, urate nephropathy

(deposition of MSU crystals in theinterstitium), and uric nephropathy

( deposition of MSU crystals in the

collecting tubes).

The prevalence of urolithiasis is22% in primary gout and 42% in

secondary gout.


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Uric acid nephropathy may present

acutely in patients being treated for

malignancy. Urate nephropathy is slowly

progressive and associated with

hypertension and proteinuria.


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Diagnostic Tests

Uric Acid: normal values range

from 4.0 to 8.6 mg/dl in men to 3.0

to 5.9 mg/dl in women. Urinarylevels are normal below 750 mg/

24h.

Urinary levels above 750 mg/dl in

24h in gout or > 1100 mg/dl inasymptomatic hyperuricemia

indicates urate overproduction.


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Diagnostic tests

Joint Fluid: in acute gout it is

inflammatory (>2000 cells/ml);

MSU crystals are identified with thepolarized light microscope. In

acute gout the crystals are usually

intracellular. The MSU crystals do

not exclude the possibility of septicarthritis, for this reason it is also

recommended to request a Gram

smear.


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Diagnostic Tests

24 urine collection for uric acid

determination is useful in

assessing the risk of renal stonesand planning for therapy.

Radiological examination is helpful

to exclude other kinds of arthritis.

Long term gout shows erosivearthritis with the characteristic

punched-out erosions.


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Differential Diagnosis

Acute Gout: septic arthritis,

pseudogout, Reactive arthritis,

acute rheumatic fever and othercrystalline arthropathies.

Chronic tophaceus gout:

Rheumatoid Arthritis, Pseudogout,

seronegativespondyloarthropathies and erosive

osteoarthritis.


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Therapy

Usually there is no justification for

treatment of asymptomatic

hyperuricemia. But somephysicians treat if serum uric acid

is > 12 mg/dl and there is risk of

nephrolithiasis.

In the setting of malignancy, whentumor lysis can cause

hyperuricemia, allopurinol is

recommended.


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Therapy

Acute Gout: NSAIDs,

corticosteroids or oral colchicine

can be used. NSAIDs are the preferred

modality.

When NSAIDs are

contraindicated, corticosteroids areeffective.


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Therapy

Intra-articular corticosteroids are

an alternative when systemic

therapy is contraindicated. Colchicine has been the

medication traditionally used for

acute gout, but it has significant GI

toxicity and delayed onset ofaction.


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Therapy

Intercritical Gout: the focus in this

stage is prevention and

prophylaxis. Patients with only one or few

attacks it is acceptable to wait and

treat the acute attacks.

Patient with frequent attacksshould be offered medical therapy.


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Therapy

Diet is usually impractical,

ineffective and rarely adhered to in

clinical practice. Indications for pharmacological

therapy includes: inability to

reverse secondary causes,

tophaceus gout, recurrent acutegout and nephrolithiasis.


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Therapy

The pharmacological agents

indicated for gout include:

uricosuric (probenecid,sulfinpyrazone) or inhibitors of uric

acid production (allopurinol).

Uricosuric agents are indicated in

patients with normal renal function,under-excretion and no evidence

of tophi.


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Therapy

Patients taking uricosuric agents

are at risk for urolithiasis. This can

be decreased by ensuring highurinary output and by adding

sodium bicarbonate 1 gram TID.

The available agents include:

probenecid (1-2 g/day) andsulfinpyrazone (50-400 mg BID).

Dose should be increased to

decrease uric acid < 6.0 mg/ml


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Therapy

Allopurinol decreases uric acid in

overproducers and underexcreters;

it is also indicated in patients with ahistory of urolithiasis, tophaceus

gout, renal insufficiency and in

prophylaxis of tumor lysis

syndrome.


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Therapy

Allopurinol: usual dose is 300

mg/day. Maximal recommended

dose is 800 mg/day. In renal insufficiency dose should

be decreased to 200 mg/day for

creatinine clearance < 60ml/min

and to 100 mg/day if clearance

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