Beruflich Dokumente
Kultur Dokumente
allopurinol
probenecid
Hyperuricemia
colchicine
Crystals in tophi
1963
1961 McCarty
1950 Talbott et al
1848 Garrod
Gout
1814
1798 Wollastone
Urate crystal
History of Gout
Middle-Age
Genetics & Lifestyle
Purine metabolism, overproduction
(10%) or underexcretion (90%)
Urate crystalization
Hyperuricemia
Genetic factor
Environments
Presentation/Diagnosis
Aspiration of Synovial Fluid
needle-shaped monosodium urate
crystals with negative birefringence.
Diagnosis
24 hour uric acid level
>800 mg = overproduction
<600 mg = underexcretion
Normal uric acid in the blood:
( 2.5 6 mg/dl)
Definition of hyperuricemia
Mean serum urate concentration in normal
adult:
5.11.0mg/dl( ), 4.01.0mg/dl(
)
Limit of solubility of MSU
6.7mg/dl at 37 C
Hyperuricemia
> 7.0mg/dl(
), > 6.0mg/dl(
)
A Musculoskeletal disease
Low-Purine Diet
Avoid Vitamin C
High Dose Colchicine
Avoid HCT ( Hidrochlorthiazide):
diuretic
Gout 2011
Profound Metabolic Consequences!
linked to obesity, hypertension, dyslipidemia,
insulin resistance, hyperglycemia, and
coronary artery disease.[3]
NHANES III Metabolic Syndrome in 62.8%
with gout vs. 25.4% without
Framingham Study - independent 60%
increased risk of coronary artery disease in
men with gout, after controlling for other
factors.[5]
Mechanism?
Gouty Tophi
Incidence has decreased over last few decades
Seen in 25-50% of untreated patients (after 1020yrs)
Location: Olecranon, bursae, digits, helix of ear
Damages bone, periarticular structures and soft
tissues
Palpable measure of total body urate load
Other Extraarticular Complications
Renal
Uric acid calculi (seen in10-15% of gout pts)
Chronic urate nephropathy (in those with tophi)
Acute uric acid nephropathy (in pts undergoing
chemotherapy)
Hypertensive Renal disease is the most common cause
of renal disease in gout
Management of
Chronic tophaceus arthritis
Advise to correct predisposing condition
Prophylactic colchicine or low dose
NSAID
Longterm urate lowering Tx
Ix: frequent gouty attacks, tophi, urate
nephropathy
Goal: maintain serume urate at < 6.0mg/dl
Uric Acid
Random hyperuricemia gout (likely CRI, diuretic
use)
Acute attack: Urate levels may be normal, low or high
40-49% of acute gouty attacks normouricemic
Mechanism: increased excretion of uric acid
Probably mediated by IL-6, inflammation
Urano W, et al. J Rheumatol 29:1950-3, 2002
Schlesinger N, et al. J Rheumatol 24: 2265-6, 1997
TheAmericanDiet/fastfood&itsconsequences
Obesity, Metabolic
Syndrome
and
Gout
~ 1/3 of Americans meet
PRINCIPAL FEATURES OF
METABOLIC SYNDROME
ELEVATED CIRCULATING INSULIN LEVELS
INSULIN RESISTANCE
GLUCOSE INTOLERANCE OR TYPE II DM
ABDOMINAL (VISCERAL) OBESITY: defined as waist
circumference > 40 inches in men (>35 inches in females)
DYSLIPIDEMIA (Hypertriglyceridemia&low HDL chol)
HYPERTENSION
HYPERURICEMIA
INCREASED RISK OF ATHEROSCLEROSIS AND
COAGULATIVE ARTERIAL OCCLUSIVE EVENTS
Stimulates
Increased Renal
Sodium and
Urate
Reabsorption
A Mild Defect in
Renal Ammonium
Excretion
Associated with
IR Promotes Acid
Milieu for Uric
Acid Urolithiasis
Urate
pH
1.
2.
3.
4.
REVIEW
Prevention Prescription
Encourage weight loss and maintenance of a healthy
body mass index.
Decrease consumption of red meat and most seafood.
Increase intake of vegetables, legumes, nuts, and
vegetable proteins.
Decrease intake of sugar-containing beverages and
fructose.
Limit alcohol to no more than 1-2 drinks per day and
drink wine rather than beer or liquor.
Increase intake of low-fat dairy, up to two servings per
day.
Maintain adequate hydration.
Fructose
present in honey and fruit
50% of sugar (sucrose = 1 glucose +
1 fructose molecule)
55% of HFCS ( high fructose corn
sryup)
Results
1 servings a day increased
risk by 45%
Suggests that the risk posed by free fructose intake , is as great as that of
the intake of purine rich food
ATP
fructose
Fructokinase
Fructose -1-
ADP
AMP
phosphate
AMP
Deaminase
IMP
URIC ACID
Liver Cell
ATP
fructose
Fructokinase
Fructose -1-
ADP
AMP
AMP
Deaminase
phosphate
IMP
Aldolase B
DHA phosphate
URIC ACID
Liver Cell
NSAIDs
1st choice
Rapid acting (naproxen, indomethacine) preferred
Continued until 48h after absence of inflammation
2. Colchicine
Alternative, out-dated
Time limit: effective between 12-36h of an attack
0.6mg q 1h up to 10 doses until relief of joint Sx or G-I
Sx
3. Intraarticular corticosteroid:
Effective in monoarticular gout
4. Systemic corticosteroid
When NSAIDs are not effective or contraindicated
Colchicine
Corticosteroid
P.O;20-40mg/day for 34days, then taper one to
2 weeks
Intraarticular injection:
triamcinolone 10-40mg or
deaxamethasone 2-10mg
with lidocaine
In:
recalcitrant acute gout
hepatopathy
elderly patients with
renal insufficiency
Correction of hyperuricemia
Indications
Quercetin
Inhibits xanthine oxidase
Decreases BP and oxidized LDL
onions, apples, berries, grapes, green
and black tea, citrus fruits, capers,
tomatoes, broccoli, and leafy greens
Supplement with 500mg
Turmeric
EFAs
Ginger
Rosemary
Nuts
Greens
Tea
Citrus
Rosemary
Cherries
Cold-Water Fish, Flax, Walnuts, Leafy
Greens
Onions, apples, berries, tea, broccoli,
tomatoes, grapes.
Pineapple
Acupuncture
Needles Vs. Allopurinol +
Indomethacin
93% effective vs. 80%
Greater reductions in serum uric acid
Fewer adverse effects
Ice
Most arthritic conditions benefit from
heat
patients with gout prefer ice.[38]
Treatment: MEDS
Prevention
SUMMARY
The disease burden of gout remains substantial and
may be increasing.
As more scientific data on modifiable risk factors and
comorbidities of gout become available, integration
of these data into gout care strategy may become
essential, similar to the current care strategies for
hypertension and type 2 diabetes.
Recommendations for lifestyle modification to
treat or to prevent gout are generally in line with
those for the prevention or treatment of other major
chronic disorders
Weight control, limits on red meat consumption, and
daily exercise are important foundations of lifestyle
modification recommendations
Plant-derived -3 fatty acids or supplements of
eicosapentaenoic acid and docosahexanoic acid
instead of consuming fish for cardiovascular benefits.
SUMMARY
Further riskbenefit assessments in each
specific clinical context would be helpful.
Daily consumption of nuts and legumes as
recommended by the Harvard Healthy
Eating Pyramid (32) may also provide
important health benefits without increasing
the risk for gout.
Similarly, a daily glass of wine may benefit
health without imposing an elevated risk for
gout, especially in contrast to beer or liquor
consumption.
These lifestyle modifications are inexpensive
and safe and, when combined with drug
therapy, may result in better control of gout.
SUMMARY
Effective management of gout risk factors (for
example, hypertension) and the
antihypertensive agents with uricosuric
properties (for example, losartan or
amlodipine could have a better risk benefit
ratio than diuretics for hypertension in
hypertensive patients with gout.
Similarly, the uricosuric property of fenofibrate
may be associated with a favorable risk
benefit ratio among patients with gout and the
metabolic syndrome.
SUMMARY
The recently elucidated molecular mechanism of renal
urate transport has several important implications in
conditions that are associated with high urate levels.
In particular, the molecular characterization of the
URAT1 anion exchanger has provided a specific target
of action for well known substances affecting urate
levels.
Genetic variation in these renal transporters or upstream
regulatory factors may explain the genetic tendency to
develop conditions associated with high urate levels and
a patients particular response to medications.
Furthermore, the transporters themselves may serve as
targets for future drug development.