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Gouty Arthritis
Dr.noori
rheumatologist
Gout: Definitions
 Gout is a disease characterized by
hyperuricemia and monosodium urate
deposition in the body
 Gouty arthritis is joint inflammation
caused by monosodium urate crystals in
the synovial fluid and/or joint tissues
Gout is a metabolic disease
that most often affects
middle-aged to elderly men
and postmenopausal women.
It results from an increased body
pool of urate with
hyperuricemia. It typically is
characterized by episodic
acute and chronic arthritis
caused by deposition of MSU
crystals in joints and
connective tissue tophi and
the risk for deposition in
kidney interstitium or uric
acid nephrolithiasisn.
Women represent only 5–20% of all patients
with gout. Premenopausal gout is rare; it is seen
mostly in individuals with a strong family
history of gout. Kindreds of precocious gout in
young females caused by decreased renal urate
clearance and renal insufficiency have been
described. Most women with gouty arthritis are
postmenopausal and elderly, have osteoarthritis
and arterial hypertension that cause mild renal
insufficiency, and usually are receiving diuretics.
URATE, HYPERURICEMIA & GOUT
 Urate: end product of purine metabolism
 Hyperuricemia: serum urate > urate solubility (>
6.8 mg/dl):urate>7 men/urate>6 women
 Gout: deposition of monosodium urate crystals
in tissues
HYPERURICEMIA & GOUT
 Hyperuricemia caused by
Overproduction
Underexcretion
 No Gout w/o crystal deposition
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
Gout: Clinical Manifestations
 Acute gouty arthritis
 Intercritical gout
 Chronic tophaceous gout
 Miscellaneous other (e.g., gouty
nephropathy)
Stages of Classic Gout
 Asymptomatic hyperuricemia
 Very common biochemical abnormality
 Defined as 2 SD above mean value
 Majority of people with hyperuricemia never develop symptoms
of uric acid excess
 Acute Intermittent Gout (Gouty Arthritis)
 Episodes of acute attacks. Symptoms may be confined to a single
joint or patient may have systemic symptoms.
 Intercritical Gout
 Symptom free period interval between attacks. May have
hyperuricemia and MSU crystals in synovial fluid
 Chronic Tophaceous Gout
 Results from established disease and refers to stage of deposition
of urate, inflammatory cells and foreign body giant cells in the
tissues. Deposits may be in tendons or ligaments.
 Usually develops after 10 or more years of acute intermittent
gout.
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
ASYMPTOMATIC
 A- meaning without
indicates that there are
no symptoms
associated
 Patient will be unaware
of what is happening
 Gout can only be
determined with the
help of a physician
Management of Asymptomatic
Hyperuricemia
 Determine the cause
 Address contributing factors
 Hypertension
 Obesity
 Alcoholism
 Hyperlipidemia
 At this time, specific urate-lowering drugs are
not indicated
Clinical Course of Classic
Gout
Presenting Symptoms
 Systemic: fever rare but patients may have fever, chills
and malaise
 Musculoskeletal: Acute onset of monoarticular joint
pain. First MTP most common. Usually affected in 90%
of patients with gout. Other joints knees, foot and
ankles. Less common in upper extremities
 Postulated that decreased solubility of MSU at lower
temperatures of peripheral structures such as toe and ear
 Skin: warmth, erythema and tenseness of skin overlying
joint. May have pruritus and desquamation
 GU: Renal colic with renal calculi formation in patients
with hyperuricemia
Acute Gouty Arthritis:
Diagnosis
 Observation of monosodium urate crystals
in synovial fluid leukocytes
 Monosodium urate crystals are
 needle-shaped
 negatively birefringent
ACUTE gout
 Sever and sudden
onset
 Involve one or a few
joints
 Frequently starts
nocturnally
 Joint is warm, red, and
tender
Laboratory Diagnosis
diagnosis ideally should be confirmed by needle
aspiration of acutely or chronically involved joints or
tophaceous deposits. Acute septic arthritis, several of the
other crystalline-associated arthropathies, palindromic
rheumatism, and psoriatic arthritis may present with
similar clinical features. During acute gouty attacks,
needle-shaped MSU crystals typically are seen both
intracellularly and extracellularly .With compensated
polarized light these crystals are brightly birefringent with
negative elongation.
Synovial fluid leukocyte counts are
elevated from 2000 to 60,000/
L.
Effusions appear cloudy due to the
increased numbers of leukocytes. Large
amounts of crystals occasionally produce
a thick pasty or chalky joint fluid.
Bacterial infection can coexist with urate
crystals in synovial fluid; if there is any
suspicion of septic arthritis, joint fluid
must be cultured
SYMPTOMS
 Joint pain
 Affects one or more joints : hip, knee, ankle, foot,
shoulder, elbow,wrist, hand, or other joints
 Great toe, ankle and knee are most common
 Swelling of Joint
 Stiffness
 Warm and red
 Possible fever
 Skin lump which may drain chalky material
Synovial Fluid Findings
 Needle shaped crystals
of monosodium urate
monohydrate that
have been engulfed by
neutrophils
Diagnosis
 Definitive diagnosis only
possible by aspirating and
inspecting synovial fluid or
tophaceous material and
demonstrating MSU
crystals
 Polarized microscopy, the
crystals appear as bright
birefringent crystals that
are yellow (negatively
birefringent)
Diagnosis
 Definitive diagnosis only
possible by aspirating and
inspecting synovial fluid or
tophaceous material and
demonstrating MSU
crystals
 Polarized microscopy, the
crystals appear as bright
birefringent crystals that
are yellow (negatively
birefringent)
Serum uric acid levels can be normal or low at
the time of an acute attack, as inflammatory
cytokines can be uricosuric and effective
initiation of hypouricemic therapy can
precipitate attacks. This limits the value of
serum uric acid determinations for the
diagnosis of gout. Nevertheless, serum urate
levels are almost always elevated at some
time and are important to use to follow the
course of hypouricemic therapy.
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
Differential
Diagnosis
 Trauma
 Infections
 septic arthritis, gonococcal arthritis, cellulitis
 Inflammatory
 Rheumatic arthritis, Reiter’s syndrome, Psoriatic
arthritis
 Metabolic
 pseudogout
 Miscellaneous
 Osteoarthrtis
Predisposing Factors
 Heredity
 Psoriasis
 Drug usage
 Poisoning
 Renal failure
 Obesity
 Hematologic Disease
 Hypertension
 Trauma
 Organ transplantation
 Alcohol use
 Surgery
Less commonly, chronic gouty
arthritis will be the only
manifestation, and, more rarely, the
disease will manifest only as
periarticular tophaceous deposits in
the absence of synovitis
 Prevalence increasing
 May be signal for unrecognized
comorbidities : ( Not to point of
searching)
Obesity (Duh!)
Metabolic syndrome
DM
HTN
CV disease
Renal disease
INTERCRITICAL
 More concentration of
uric acid crystals
 Typically no need for
drug intervention at
the time.
CHRONIC GOUT
Chronic Gout-Radiographic
Features
Chronic Tophaceous Gout
CHRONIC GOUT
Chronic Tophaceous Gout
Questions?
Chronic Tophaceous Gout
CHRONIC
 Continuous or
persistent over a long
period of time
 Treatment required
 Not easily or quickly
resolved
Diagnostic Studies
 Uric Acid

Limited value as majority of hyperuricemic patients will never develop
gout
 Levels may be normal during acute attack
 CBC
 Mild leukocytosis in acute attacks, but may be higher than 25,000/mm
 ESR

mild elevation or may be 2-3x normal
 24hr urine uric acid

Only useful in patients being considered for uricosuric therapy or if cause
of marked hyperuricemia needs investigation
 Trial of colchicine

Positive response may occur in other types of arthritis to include
pseudogout.
A 24-h urine collection for uric acid can, in some
cases, be useful in assessing the risk of stones,
elucidating overproduction or underexcretion of uric
acid, and deciding whether it may be appropriate to
use a uricosuric therapy (.Excretion of >800 mg of
uric acid per 24 h on a regular diet suggests that
causes of overproduction of purine should be
considered. Urinalysis, serum creatinine,
hemoglobin, white blood cell (WBC) count, liver
function tests, and serum lipids should be obtained
because of possible pathologic sequelae of gout and
other associated diseases requiring treatment and as
baselines because of possible adverse effects of gout
treatment.
MEDS- Decreased Urate Pool







High dose Salicylate
Losartan
Fenofibrate
Amlodipine
Vitamin C
Probenecid, sulfinpyrazone, benzbromarone
Allopurinol, uricase, febuxostat
Diagnostic Studies
 Uric Acid

Limited value as majority of hyperuricemic patients will never develop
gout
 Levels may be normal during acute attack
 CBC
 Mild leukocytosis in acute attacks, but may be higher than 25,000/mm
 ESR

mild elevation or may be 2-3x normal
 24hr urine uric acid

Only useful in patients being considered for uricosuric therapy or if cause
of marked hyperuricemia needs investigation
 Trial of colchicine

Positive response may occur in other types of arthritis to include
pseudogout.
Diagnosing Gout
 X-rays
 Arthrocentesisextraction of joint fluid
 Examination of joint
 Patient medical history
Radiographic Features
Early in the disease radiographic studies may
only confirm clinically evident swelling. Cystic
changes, well-defined erosions with sclerotic
margins (often with overhanging bony edges),
and soft tissue masses are characteristic features
of advanced chronic tophaceous gout.
Ultrasound, CT and MRI are being studied and
are likely to become more sensitive for early
changes
RADIOLOGIC SIGNS
X-RAYS
X-RAYS
Complications
 Renal Failure
 ARF can be caused by
hyperuricemia, chronic
urate nephropathy
 Nephrolithiasis
 Joint deformity
 Recurrent Gout
Questions?
Treatment Goals
 Gout can be treated without complications.
 Therapeutic goals include




terminating attacks
providing control of pain and inflammation
preventing future attacks
preventing complications such as renal stones,
tophi, and destructive arthropathy
Treatment: Gout
Acute Gouty Arthritis
The mainstay of treatment during an acute attack is
the administration of anti-inflammatory drugs such
as nonsteroidal anti-inflammatory drugs (NSAIDs),
colchicine, or glucocorticoids. NSAIDs are used
most often in individuals without complicating
comorbid conditions. Both colchicine and NSAIDs
may be poorly tolerated and dangerous in the elderly
and in the presence of renal insufficiency and
gastrointestinal disorders. Ice pack applications and
rest of the involved joints can be helpful.
The end
. Colchicine given orally is a traditional and effective
treatment if used early in an attack. One useful regimen is one
0.6-mg tablet given every 8 h with subsequent tapering. This
is generally better tolerated than the formerly advised hourly
regimen. The drug must be stopped promptly at the first sign
of loose stools, and symptomatic treatment must be given for
the diarrhea. Intravenous colchicine has been taken off the
market. NSAIDs given in full anti-inflammatory doses are
effective in
90% of patients, and the resolution of signs
and symptoms usually occurs in 5–8 days. The most effective
drugs are any of those with a short half-life and include
indomethacin, 25–50 mg tid; naproxen, 500 mg bid;
ibuprofen, 800 mg tid; and diclofenac, 50 mg tid
Hypouricemic Therapy
Ultimate control of gout requires correction of the basic
underlying defect: the hyperuricemia. Attempts to
normalize serum uric acid to <300–360
mol/L (5.0–
6.0 mg/dL) to prevent recurrent gouty attacks and
eliminate tophaceous deposits entail a commitment to
long-term hypouricemic regimens and medications that
generally are required for life
Colchicine given orally is a traditional and effective treatment if used early in an attack. One useful ir
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Hypouricemic Therapy
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SERUM URATE LEVELS
 Not reliable
 May be normal with flares
 May be high with joint Sx from other causes
Hypouricemic Therapy
Ultimate control of gout requires correction of
the basic underlying defect: the hyperuricemia.
Attempts to normalize serum uric acid to
<300–360
mol/L (5.0–6.0 mg/dL) to
prevent recurrent gouty attacks and eliminate
tophaceous deposits entail a commitment to
long-term hypouricemic regimens and
medications that generally are required for life.
Hypouricemic therapy should be considered when,
as in most patients, the hyperuricemia cannot be
corrected by simple means (control of body
weight, low-purine diet, increase in liquid intake,
limitation of ethanol use, decreased use of
fructose-containing foods and beverages, and
avoidance of diuretics
the decision to initiate hypouricemic therapy usually is made taking
into consideration the number of acute attacks (urate lowering may
be cost-effective after two attacks), serum uric acid levels
[progression is more rapid in patients with serum uric acid
>535
mol/L (>9.0 mg/dL)], the patient's willingness to commit
to lifelong therapy, or the presence of uric acid stones. Uratelowering therapy should be initiated in any patient who already has
tophi or chronic gouty arthritis. Uricosuric agents such as
probenecid can be used in patients with good renal function who
underexcrete uric acid, with <600 mg in a 24-h urine sample. Urine
volume must be maintained by ingestion of 1500 mL of water every
day. Probenecid can be started at a dose of 250 mg twice daily and
increased gradually as needed up to 3 g per day to maintain a serum
uric acid level <360
mol/L (6 mg/dL). Probenecid is generally
not effective in patients with serum creatinine levels
>177
mol/L (2 mg/dL
Benzbromarone is another uricosuric
drug that is more effective in patients
with renal failure. Some agents used to
treat common comorbidities, including
losartan, fenofibrate, and amlodipine,
have some mild uricosuric effects.
The xanthine oxidase inhibitor allopurinol is by far the
most commonly used hypouricemic agent and is the
best drug to lower serum urate in overproducers, urate
stone formers, and patients with renal disease. It can be
given in a single morning dose, 100–300 mg initially
and increasing up to 800 mg if needed. In patients with
chronic renal disease, the initial allopurinol dose
should be lower and adjusted depending on the serum
creatinine concentration; for example, with a creatinine
clearance of 10 mL/min, one generally would use 100
mg every other day. Doses can be increased gradually
to reach the target urate level of 6 mg/dL; however,
more studies are needed to provide exact guidance.
Toxicity of allopurinol has been recognized
increasingly in patients who use thiazide diuretics
and patients allergic to penicillin and ampicillin. The
most serious side effects include life-threatening
toxic epidermal necrolysis, systemic vasculitis, bone
marrow suppression, granulomatous hepatitis, and
renal failure. Patients with mild cutaneous reactions
to allopurinol can reconsider the use of a uricosuric
agent, undergo an attempt at desensitization to
allopurinol, or take febuxostat, a new, chemically
unrelated specific xanthine oxidase inhibitor
Febuxostat is approved at 40 or 80 mg once a day and
does not require dose adjustment in mild to moderate
renal disease. Patients can also pay increased attention
to diet and should be aware of new alternative agents
(see below). Urate-lowering drugs are generally not
initiated during acute attacks but after the patient is
stable and low-dose colchicine has been initiated to
decrease the risk of the flares that often occur with
urate lowering. Colchicine anti-inflammatory
prophylaxis in doses of 0.6 mg one to two times daily
should be given along with the hypouricemic therapy
until the patient is normouricemic and without gouty
attacks for 6 months or as long as tophi are present.
Febuxostat is approved at 40 or 80 mg once a day and
does not require dose adjustment in mild to moderate
renal disease. Patients can also pay increased attention
to diet and should be aware of new alternative agents
(see below). Urate-lowering drugs are generally not
initiated during acute attacks but after the patient is
stable and low-dose colchicine has been initiated to
decrease the risk of the flares that often occur with
urate lowering. Colchicine anti-inflammatory
prophylaxis in doses of 0.6 mg one to two times daily
should be given along with the hypouricemic therapy
until the patient is normouricemic and without gouty
attacks for 6 months or as long as tophi are present.
Colchicine should not be used in dialysis
patients and is given in lower doses in
patients with renal disease or with P
gylcoprotein or CYP3A4 inhibitors such as
clarithromycin that can increase toxicity or
colchicine. Pegloticase is a new uratelowering biologic agent that can be effective
in patients allergic to or failing xanthine
oxidase inhibitors. New uricosurics are
undergoing investigation.
“Disease of Kings”
Rich foods have a higher concentration
of protein. This could cause major
problems for a person afflicted with
gout.
 ORGAN MEATS
 WILD GAME
 SEAFOOD
 LENTILS
 PEAS
 ASPARAGUS
 YEAST
 BEER
Newer Therapies
 Uricase


Enzyme that oxidizes uric acid to a more soluble form
Natural Uricase from Aspergillus flavus and Candida utilis under
investigation
 Febuxostat
 New class of Xanthine Oxidase inhibitor


More selective than allopurinol
Little dependence on renal excretion
 Losartan

ARB given as 50mg/dL can be urisuric. When given with HCTZ, it can
blunt the effect of the diuretic and potentiate its antihypertensive action
 Fenofibrate

Studies note when used in combo with Allopurinol produced additional
lowering of the urate