Transcript GOUT AND PSEUDOGOUT

GOUT AND
PSEUDOGOUT
ANDRES QUICENO, MD
Rheumatology Division
Presbyterian Hospital of Dallas
Definition
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Gout is a syndrome caused by the
inflammatory response to tissue
deposition of monosodium urate
crystals (MSU).
Classification
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Acute gout.
Tophaceus Gout.
Asymptomatic Hyperuricemia.
Primary Gout.
Secondary Gout.
Etiology
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Hyperuricemia is the common
denominator in gout.
Two-thirds of uric acid are excreted
by 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.
Etiology
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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.
Pathology
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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 crystals
surrounded by fibrous tissue.
In the kidney the deposition of
MSU crystals causes interstitial
fibrosis and arteriosclerosis.
Epidemiology
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The prevalence of asymptomatic
hyperuricemia is 5 to 8%.
The prevalence of gout is 13 cases
per 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.
Epidemiology
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Women rarely develop gout before
the menopause, because
estrogens are thought to be
uricosuric.
Peak incidence in men is in the
fifth decade.
Primary gout is associated with:
obesity, hyperlipidemia, diabetes
mellitus, hypertension and
atherosclerosis.
Epidemiolgy
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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.
Clinical Manifestations
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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. (MTP’s,
ankle and knee).
Clinical Manifestations
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Less common sites of involvement
include wrist, fingers and elbow.
Differential diagnosis includes
septic arthritis, cellulitis or
thromboflebitis.
Attacks subside in 3 to 10 days.
Recurrent attacks can involve
more joints and usually persist
longer.
Clinical manifestations
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Repeated attacks could cause joint
erosions.
Polyarticular attacks are common
in patients with established poor
controlled disease.
These attacks could also involve
periarticular structures.
Clinical Manifestations
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Intercritical gout: It is the
asymptomatic period between
crises, but MSU crystals can still
be 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.
Clinical Manifestations
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Chronic tophaceus Gout: The
clinical characteristic is the
deposition of solid urate in the
connective tissue.
It is associated with early age of
onset, long duration of untreated
disease, frequent attacks, upper
extremity involvement, polyarticular
disease and elevated serum uric
acid.
Clinical Manifestations
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Transplant patients treated with
cyclosporine and/or diuretics have
an increased risk for tophaceus
gout.
The most common sites for tophi
are: the olecranon, prepatellar
bursa, ulnar surface and Achilles
tendon.
Clinical Manifestations
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Tophi in the hands can cause joint
destruction.
Tophi can ulcerate the skin and
excrete a chalky material
composed of MSU crystals.
Tophi progress insidiously with
increased stiffness and pain.
Clinical Manifestations
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Renal disease: this includes
urolithiasis, urate nephropathy
(deposition of MSU crystals in the
interstitium), and uric nephropathy
( deposition of MSU crystals in the
collecting tubes).
The prevalence of urolithiasis is
22% in primary gout and 42% in
secondary gout.
Clinical Manifestations
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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.
Diagnostic Tests
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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. Urinary
levels are normal below 750 mg/
24h.
Urinary levels above 750 mg/dl in
24h in gout or > 1100 mg/dl in
asymptomatic hyperuricemia
indicates urate overproduction.
Diagnostic tests
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Joint Fluid: in acute gout it is
inflammatory (>2000 cells/ml);
MSU crystals are identified with the
polarized light microscope. In
acute gout the crystals are usually
intracellular. The MSU crystals do
not exclude the possibility of septic
arthritis, for this reason it is also
recommended to request a Gram
smear.
Diagnostic Tests
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24 urine collection for uric acid
determination is useful in
assessing the risk of renal stones
and planning for therapy.
Radiological examination is helpful
to exclude other kinds of arthritis.
Long term gout shows erosive
arthritis with the characteristic
“punched-out” erosions.
Differential Diagnosis
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Acute Gout: septic arthritis,
pseudogout, Reactive arthritis,
acute rheumatic fever and other
crystalline arthropathies.
Chronic tophaceus gout:
Rheumatoid Arthritis, Pseudogout,
seronegative
spondyloarthropathies and erosive
osteoarthritis.
Therapy
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Usually there is no justification for
treatment of asymptomatic
hyperuricemia. But some
physicians treat if serum uric acid
is > 12 mg/dl and there is risk of
nephrolithiasis.
In the setting of malignancy, when
tumor lysis can cause
hyperuricemia, allopurinol is
recommended.
Therapy
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Acute Gout: NSAID’s,
corticosteroids or oral colchicine
can be used.
NSAID’s are the preferred
modality.
When NSAID’s are
contraindicated, corticosteroids are
effective.
Therapy
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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 of
action.
Therapy
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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 attacks
should be offered medical therapy.
Therapy
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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 acute
gout and nephrolithiasis.
Therapy
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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.
Therapy
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Patients taking uricosuric agents
are at risk for urolithiasis. This can
be decreased by ensuring high
urinary output and by adding
sodium bicarbonate 1 gram TID.
The available agents include:
probenecid (1-2 g/day) and
sulfinpyrazone (50-400 mg BID).
Dose should be increased to
decrease uric acid < 6.0 mg/ml
Therapy
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Allopurinol decreases uric acid in
overproducers and underexcreters;
it is also indicated in patients with a
history of urolithiasis, tophaceus
gout, renal insufficiency and in
prophylaxis of tumor lysis
syndrome.
Therapy
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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 <
30 ml/min).
Therapy
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Start with small doses of
allopurinol to reduce the risk of
precipitating an acute gout attack.
Most common side effects are rash
(2% of patients) but rarely patients
can develop exfoliative dermatitis
that can be lethal.
Chronic use of colchicine (0.6-1.2
mg/day) is used as prophylaxis for
acute attacks.
PSEUDOGOUT
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Calcium pyrophosphate Crystal
Deposition Disease (CPPD) is the
syndrome secondary to the
calcium pyrophosphate in articular
tissues.
This includes: Chondrocalcinosis,
Chronic CPPD and Pseudogout.
Pseudogout
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Etiology: It is unknown, but can be
secondary to changes in the
cartilage matrix or secondary to
elevated levels of calcium or
inorganic pyrophosphate.
Pathology: CPPD crystals are
found in the joint capsule and
fibrocartilaginous structures.
There is neutrophil infiltration and
erosions.
Pseudogout
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Demographics: It is
predominantly a disease of the
elderly, peak age 65 to 75 years
old. It has female predominance
(F:M, 2-7:1).
Prevalence of chondrocalcinosis is
5 to 8% in the general population.
Pseudogout
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Disease Associations:
hyperthyroidsm, hypocalciuria,
hypercalcemia, hemochromatosis,
hemosiderosis, hypophosphatasia,
hypomagnesemia, hypothyroidsm,
gout, neuropathic joints,
amyloidosis, trauma and OA.
Pseudogout
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Clinical Manifestations
Pseudogout: Usually presents
with acute self-limited attacks
resembling acute gout. The knee
is involved in 50% of the cases,
followed by the wrist, shoulder,
ankle, and elbow.
Pseudogout
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In 5% of patients gout can coexist
with pseudogout.
The diagnosis is confirmed with the
synovial fluid analysis and/or the
presence of chondrocalcinosis in
the radiographs.
Acute Pseudogout primarily affects
men.
Psedogout
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Chronic CPPD: predominately
affects women; it is a progressive,
often symmetric, polyarthritis.
Usually affects the knees, wrists,
2nd and 3rd MCP’s, hips, spine,
shoulders, elbows and ankles.
Chronic CPPD differs from
pseudogout in its chronicity,
involvement of the spine and
MCP’s.
Pseudogout
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Chondrocalcinosis: Generally is an
incidental finding in XRays.
Diagnostic Tests: Inflammatory
cell count in the synovial fluid.
Rhomboidal or rodlike intracellular
crystals. Imaging studies reveal
chondrocalcinosis usually in the
knee, but can be seen in the radial
joint, symphisis pubis and
intervertebral discs.
Pseudogout
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Differential Diagnosis: Includes
septic arthritis, gout, inflammatory
OA, Rheumatoid Arthritis,
neuropathic arthritis and
Hypertrofic Osteoarthropathy.
Pseudogout
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Therapy: It is similar to gout and
includes intrarticular
corticosteroids. Colchicine can be
used in acute attacks and also in
prophylaxis. There is no specific
treatment for chronic CPPD. It is
important to treat secondary
causes and colchicine could be
helpful.