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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Clinical Manifestations
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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Clinical Manifestations
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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Clinical Manifestations
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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Clinical Manifestations
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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Clinical Manifestations
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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Clinical Manifestations
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