A Case Presentation

By Ann Dorsey, MD
Glendale Adventist Medical Center
Family Medicine Residency

GOUT: A Chronic Disease of

4 stages
Asymptomatic
Acute

hyperuricemia

Flares of crystallization

Intervals

between flares

Advanced

Gout & Complications

ACUTE GOUTY FLARES

Abrupt

onset of severe joint inflammation,

often nocturnal;

Warmth, swelling, erythema, & pain;

Possibly fever
Untreated?
80%

Resolves in 3-10 days

of initial attacks involve a single joint,

most often at the base of great toe
(podagra) or knee

SITES OF ACUTE FLARES

90%

of gout patients
eventually have
podagra : 1st MTP
joint

Can

occur in other
joints, bursa & tendons

INTERVALS WITHOUT
FLARES
Asymptomatic
If

untreated, may advance

Intervals
Crystals
Body

may shorten

in asx joints

urate stores increase

FLARE INTERVALS
Silent

tissue deposition & Hidden Damage

ADVANCED GOUT
The interval from the first gouty attack to the onset of
chronic arthritis or detectable tophi average about 12 yrs,
ranging from 5 to 40 yrs.
Chronic

Arthritis

X-ray

Changes

Tophi

(Solid urate deposits in tissues)

Acute

Flares continue

DIAGNOSING GOUT
Hx

& P.E.

Synovial
Not

fluid analysis

Serum Urate

For histologic examination of tophaceous gout: tissue

example should be fresh or frozen sections or preserved
in alcohol and later stained with a non-aqueous system
such as Wright-Giemsa stain. Aqueous stains, such as
hematoxylin and eosin, allow urate crystals to dissolve.

GOUT RISK FACTORS

Male

Surgery;

Postmenopausal

Alcohol

female

Older
Hypertension
Pharmaceuticals:

Diuretics, ASA,
cyclosporine

trauma

intake

Highest with beer

Not increased with
wine
High
Diet

BMI (obesity)

high in meat &

seafood

SYNOVIAL FLUID ANALYSIS

(Polarized Light Microscopy)
The

Gold standard

Crystals

intracellular during attacks

Needle

& rod shapes

Strong

negative

birefringence

SERUM URATE LEVELS

Not

reliable

May

be normal with flares

May

be high with joint Sx from other causes

The most accurate time for assessment of

serum uric acid (and establishment of
baseline value) is 2 weeks or more after
complete subsidence of an acute gout flare.

Hyperuricemia & gout

Serum Uric
Acid Level

Annual
Incidence

5-Year
Prevalence

> 10 mg/dl

70

30%

< 7 mg/dl

0.9

0.6%

Serum uric acid levels &

age
1
1
1
1

3
2
1
0
9
8
7
6
5
4
3

.0
.0
.0
.0
.0
.0
.0
.0
.0
.0
.0

G
N
G
N

1 0

2 0

3 0

4 0

5 0

A g e (y e a rs )

6 0

o
o
o
o

u ty M a le
rm a l M a le
u ty F e m a le
rm a l F e m a le

Treating acute gouty

arthritis

colchicine
NSAIDs
steroids
rest, analgesia, ice, time

Hyperuricemia

Hyperuricemia

results when production

exceeds excretion net uric acid loss
results when excretion exceeds

Net

uric acid loss results when excretion

exceeds production

Treating acute gouty

arthritis
colchicine
NSAIDs
steroids
rest, analgesia, ice, time

Colchicine - plant alkaloid

c o lc h ic u m
a u tu m n a le
(a u tu m n c ro c u s o r
m e a d o w s a ffro n )

Colchicine
only effective in gouty arthritis
not an analgesic
does not affect renal excretion of uric
acid
does not alter plasma solubility of uric
acid
neither raises nor lowers serum uric
acid

Colchicine
mechanism of action poorly understood
reduces inflammatory response to
deposited crystals
diminishes PMN phagocytosis of
crystals
blocks cellular response to deposited
crystals

Crystal-induced
inflammation
h y p e r u r ic e m ia

in f la m m a tio n

c r y s t a l d e p o s it io n

c r y s t a ls e n g u lf e d

p r o t e in b in d in g

i n f l u x o f P M N s

r e c e p t o r b in d in g

c y t o k in e r e le a s e

P M N is c r itic a l
com ponentof
c r y s ta lin d u c e d
in f la m m a t io n

Colchicine - indications
D ose

In d ic a tio n

h ig h

tr e a tm e n t o f a c u te g o u ty a r th r itis

lo w

p r e v e n t io n o f r e c u r r e n t g o u t y a r t h r it is

Colchicine - toxicity
gastrointestinal (nausea, vomiting,
cramping, diarrhea, abdominal pain)
hematologic (agranulocytosis,
aplastic anemia, thrombocytopenia)
muscular weakness

Hyperuricemia mechanisms
e x c e s s iv e
p r o d u c t io n

in a d e q u a t e
e x c r e t io n

h y p e r u r ic e m ia

Decreased excretion is about 85 to 90% of

hyperuricemia.

Urate-lowering drugs
b lo c k
p r o d u c t io n

enhance
e x c r e t io n

n e t r e d u c t io n in t o t a l b o d y p o o l o f
u r ic a c id

Gout - urate-lowering
therapy
prevents arthritis, tophi & stones by
lowering total body pool of uric acid
not indicated after first attack
initiation of therapy can worsen or
bring on acute gouty arthritis
no role to play in managing acute
gout

Allopurinol (Zyloprim)
inhibitor of xanthine oxidase
effectively blocks formation of uric
acid
how supplied - 100 mg & 300 mg
tablets
pregnancy category C

Uric acid metabolism

d ie ta r y in t a k e

x a n t h in e o x id a s e
c a t a ly z e s
h y p o x a n t h in e t o
x a n t h in e &
x a n t h in e t o u r ic
a c id

p u r in e b a s e s

h y p o x a n t h in e

x a n t h in e

u r ic a c id

c e ll
b re a k d o w n

Allopurinol
90% absorption from the gut
metabolized to oxypurinol
once daily dosing
lowers serum uric acid levels
lowers urine uric acid levels
side effects rare, but potentially lethal

Allopurinol - usage
indications
management of hyperuricemia of
gout
management of hyperuricemia
associated with chemotherapy
prevention of recurrent calcium
oxalate kidney stones

Allopurinol - common
reactions
diarrhea, nausea, abnormal liver tests
acute attacks of gout
rash

Allopurinol - serious
reactions
fever, rash, toxic epidermal necrolysis
hepatotoxicity, marrow suppression
vasculitis
drug interactions (ampicillin,
thiazides, mercaptopurine,
azathioprine)

Febuxostat (Uloric)
oral xanthine oxidase inhibitor
chemically distinct from allopurinol
94% of patients reached urate < 6.0
mg/dl
minimal adverse events
can be used in patients with renal
disease

Pegloticase (Kystexxa)

Porcine uricase

For patients who failed urate-lowering agents

used

Uricosuric therapy
probenecid
blocks tubular reabsorption of uric
acid
enhances urine uric acid excretion
increases urine uric acid level
decreases serum uric acid level

Uricosuric therapy
moderately effective
increases risk of nephrolithiasis
not used in patients with renal disease
frequent, but mild, side effects
some drugs reduce efficacy (e.g.,
aspirin

Uricosuric therapy
contra-indications
history of nephrolithiasis
elevated urine uric acid level
existing renal disease
less effective in elderly patients

Other uricosuric therapy

Losartan: ARB, modest uricosuric effect that

plateau at 50 mg/day
Fenofibrate: a fibric acid used for treatment of
hyperlipidemia; 200 mg/day -->19% reduction in
serum urate & 36% increase in uric acid renal
clearance
Vitamin C: may have mild but persistent uratelowering effect, 500 mg/day 0.5 mg/dL
decreased in urate levels.

Choosing a uratelowering drug

e x c e s s iv e
p r o d u c t io n
x a n th in e
o x id a s e
in h ib ito r

in a d e q u a t e
e x c r e t io n
u r ic o s u r ic
agent

h y p e r u r ic e m ia

References

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