Gouty

Arthritis
Calvin Damanik
Departemen Penyakit Dalam
FK Universitas Methodist Indonesia Medan

Epidemiology
mean age of onset
incidence (age 32-64)

men
49
2.8%

women
60
1.5%

the lower incidence and later onset of gout in women is

attributed to more efficient urate excretion
attack before the age of 30 is rare and suggest a
genetic metabolic disorder

Pathophysiology
Gout is caused by disorders of purine
metabolism resulting in elevated levels
of uric acid
> 7 mg/dl in men
> 6 mg/dl in women

prolonged hyperuricemia leads to

formation of monosodium urate
monohydrate crystals

Serum Urate Level

any sudden change in serum urate
concentration can provoke an acute
gouty attack
sudden increase favors formation of new
crystals
sudden decrease promotes shedding of
previously formed crystals from the synovial
membrane

Serum Urate Level

during a gouty attack, serum urate
levels are normal in about 20% of
cases
repeat blood tests eventually
detect hyperuricemia

Gout: Pathophysiology
Uric acid: overproduction vs.
underexcretion
Mechanisms of urate production
cellular nucleoproteins/nucleotides (~ 66%)
diet (~33%)

Mechanisms of urate excretion

kidney (~66%)
gut (~33%)

Renal Excretion of Uric Acid

Completely filtered by the glomerulus
Completely (essentially) reabsorbed in the
proximal tubule
Approximately 50% is secreted back into the
tubule in the descending loop
Approximately 80% (of the 50% now in the
loop) is reabsorbed in the ascending loop
Net excretion = 10% of filtered load

Urate Excretion
hOAT3- human
renal organic
anion transporter
hUAT1
hUAT2
URAT 1

OAT
OAT
URAT1 mutations
implicated in
familial renal
hypouricemia
Proximal tubule
Suppressed by
uricosurics and
losartan, high dose
salicylate
Lasix may increase
its fxn
Bieber JD et al. Gout-On the Brink of Novel Therapeutic Options for an
Ancient Disease. 50 (8). August 2004, p2400-2414.

Diet
12 year prospective study of 47,150 men with
no h/o gout
730 new cases of gout
Conclusions:
High levels of meat and seafood increased risk
High levels of dairy decreased the risk
Moderate intake of purine-rich vegetable or protein
not associated with increase risk of gout

Choi HK, et al. Purine-Rich Foods, Dairy and Protein Intake, and the Risk
of Gout in Men. NEJM 350(11). March 2004. 10931103.

Asymptomatic Hyperuricemia
Hyperuricemia alone does NOT make a
diagnosis of gout
-only a subset of people with hyperuricemia
will develop gout
-probability of gout increases with higher uric
acid levels

Asymptomatic hyperuricemia generally

requires no treatment

Conditions Associated
With Hyperuricemia

Lymphomas (esp. Hodgkins disease)

Myeloproliferative disorders
Diabetes
Psoriasis
Sarcoid
Glycogen storage disease

Acute Gouty Arthritis:

Clinical Features
Acute onset (hours) of severe arthritis
Usually monarticular
almost any joint can be affected
1st MTP joint (podagra) most common (50%)
Other joints (in decreasing frequency): midfoot,
ankle, heel, knee, wrist, fingers, elbow

Associated findings: fever, WBC,

ESR
Typically resolves over days or weeks,
regardless of treatment

Acute Gouty Arthritis

Acute Gouty Arthritis:

Precipitating Factors
Surgery
Alcohol
Fluctuation of uric acid level
initiation of therapy to lower uric acid level
diuretics (esp. hydrochlorothiazide)
aspirin
low doses raise uric acid levels
high doses lower uric acid levels

Acute Gouty Arthritis:

Diagnosis
Observation of monosodium urate
crystals in synovial fluid leukocytes
Monosodium urate crystals are
needle-shaped
negatively birefringent

Manifestations of Hyperuricemia
subcutaneous tophaceous deposits
urolithiasis
nephrolithiasis
renal diseases involving the
tubules, interstitium, or glomeruli

Treatment

NSAIDs
colchcine
allopurinol
steroids
to prevent recurrent attacks,
serum urate levels should be
kept < 6 mg/dl

Intercritical Gout
Symptom-free period between attacks
(may be months or years)
If untreated, episodes of acute gouty
arthritis become more frequent, last
longer, and often involve more joints
(polyarticular)

Chronic Tophaceous Gout:

Clinical Features
Tophi are deposits of urate crystals in
tissue
Common sites:
synovium
subchondral bone
olecranon bursae
infrapatellar
Achilles tendon

Chronic Tophaceous Gout:

Clinical Features
Frequent attacks of acute gouty
arthritis
Bone destruction and degenerative
arthritis are common in advanced
cases

Chronic Tophaceous Gout

Chronic Tophaceous Gout

Chronic Tophaceous Gout

Chronic Gout-Radiographic Features

Chronic Tophaceous Gout:

Treatment Options
Control and prevent acute gouty
arthritis

Non-steroidal antiinflammatory drugs

Colchicine
Steroids
Analgesics

Reduce serum uric acid levels (< 4.0

mg/dL)

decrease uric acid production (inhibit xanthine

oxidase)
increase uric acid excretion (uricosuric drugs)

Xanthine Oxidase Inhibition:

Allopurinol
Blocks conversion of hypoxanthine to
xanthine, and xanthine to uric acid
Accumulation of hypoxanthine inhibits
de novo purine biosynthesis (negative
feedback)
DO NOT USE allopurinol with
azathioprine or 6-mercaptopurine

Uricosuric Agents:
Probenecid
Blocks renal tubular resorption of uric
acid
Most effective when urine pH basic and
flow relatively high
Used less frequently than allopurinol

Differential Diagnosis
pseudogout
Gout
negative birefringent needle-shaped
intraleukocytic crystals
yellow when parallel
blue when perpendicular

Pseudogout
rod- or rhomboid-shaped crystals with
opposite refractive properties

Differential Diagnosis
Septic Arthritis
Septic and gouty arthritis present with
many of the same signs and symptoms
fever and monoarthritis

Beware: both septic and gouty arthritis

may present in the same joint

Differential Diagnosis
synovial fluid analysis

WBC
PMNs

gout
> 50 k
> 90%

septic
15 k (5 to 80k)
~70%