CHRONIC TOPHACEOUS GOUT IN ACUTE
EXACERBATION
IN Suarjana1, DE Arianti2
1
Ulin General Hospital Gout is defined as
Internist-Rheumatology heterogenic disease group that results
Consultant
2
Lambung Mangkurat from the deposition of monosodium
University Co- Assistant urate crystals in soft tissue and/or
Student
joints, or results from uric acid
supersaturation in extracelluler
fluid.1,2 According to the National
Health and Nutrition Examination
Survey III in 1988-1994, an
estimated 5.1 million people in the
United States suffer from gout and
the most common inflammatory
arthritis in adult males.3,4 Gout is
divided into 3 symptomatic phase.
There are: acute phase, characterized
by monoarticular arthritis that remit
after 1 to 2 weeks and recurs
periodically; intercritical gout that is
period between attacks; and chronic
phase, characterized by tophaceous
joints and deposit of urate in the skin
or bursa.2 European League Against
Rheumatism (EULAR)
recommendations and the American
College of Rheumatology (ACR)
criteria provide guidance for making
a clinical or presumptive diagnosis of
gout. The gold standard for
diagnosing gout remains synovial
fluid aspiration for monosodium
urate crystals finding.1,2,5
Management of gout consists of 3
stages: (1) treating the acute attack;
(2) lowering excess stores of uric
acid to prevent flares of gouty
arthritis and to prevent tissue
deposition of uric acid crystals; and
(3) providing prophylaxis to prevent
acute flares.6 The prognose of gout is
good as long as it is treated in good
management.
CASE REPORT
A 52-year-old man came to
Emergency room of Ulin Hospital,
Banjarmasin, South Kalimantan with
the main problem is the pains on his
both knee, left shoulder and foot
area. Patient had start this pain since
2 days ago in sudden at night and
gradually worsen until he was
entering the hospital. The pain was
more felt in the joint area that having
some bumps. The bumps came since
almost 6 years ago, but they became
swollen, more redness, and suddenly
painful since 2 days ago. The patient
felt more painful when patient came
for walking and worsen at night.
Patient started to complaint about
this problems since 1999, and had
hospitalize for several times in last
10 years.
Patient was confess for
uncontrolling dietary habit and
consuming high carbohydrate, fat,
and purines diet. Approximately
since a week before entering the
hospital, patient complain about pain
when urinating. He confessed the
urine color was still clear yellowish
and no complaint about frequence
and urine volume in his daily
urinating.
He was obese grade I, having
mild hypertension, and decreasing
range of motion in left shoulder, both
knee, both ankle, and left wrist. He
also had some bumps with redness,
swollen, painful, with diameter about
1
3-5cm in the joint of left shoulder, DISCUSSION
both knee, both ankle, left wrist, and
in first metatarsophalangeal joint. Gout is heterogenic disease
group that results from the deposition
Laboratory finding showed of monosodium urate crystals in soft
some decreasing level of tissue and/or joints, or results from
haemoglobin (9,4g/dL) and uric acid supersaturation in
hemotocryte (28vol%) and having extracelluler fluid. Two main
some elevating level of SGOT processes are involved in its
(54U/L), ureum (61mg/dL), development: the overproduction of
creatinine (1,7mg/Dl), and uric acid uric acid and the underexcretion of
(8,6mg/dL). Abdominal uric acid.
ultrasonography founded
nephrocalcinosis dextra. For There are three types of gout:
histopathology examination for acute gout, intercritical gout, and
synovial fluid aspiration, it was find chronic gout. During an acute attack,
monosodium urate monohydrate the affected joint becomes hot, red,
crystals. swollen, and extremely tender. These
symptoms may be accompanied by
Based on history, physical fever. The attack may resolve in a
examination, and supporting few hours or last from days to weeks.
examination, the patient was A period between first and second
diagnosed with chonic tophaceous attack is called intercritical gout.
gout in acute exacerbation with renal Second attack occurs within 6
insufficiency. The treatment that had months to 2 years of the first attack.
given was: Triamcinolone acetonide If hyperuricemia and acute gout are
intraarticular injection, meloxicam left untreated, the interval between
tablet, colchicine tablet, and attacks may disappear, leaving
metylprednicolone tablet. patients with persistent low-grade
joint inflammation, joint deformity,
On the fourth day , the patient and tophaceous deposits of urate
had able to walk and the swelling of crystals in chronic gout. Tophi can
the bumps was decreasing. The pain occur at various locations, generally,
when urinating lost also. In but not always, within the same joint
laboratory examination, the uric acid affected by acute gout. The tophi
was undecreasing, but the level of may not be painful, but periodic
ureum was decreasing and creatinine acute inflammation can occur around
becoming normal on the second the site, causing intense pain.2
days.
According to the National
th
On his 8 day of Health and Nutrition Examination
hospitalization, the patient had no Survey III, 1988-1994, an estimated
more complaints, and was 5.1 million people in the United
recommend to undergo ambulatory States suffer from gout. According to
care and prescribe with colchisine, the National Institutes of Health
allupurinol, and meloxicam. (NIH), gout accounts for about 5% of

2
all cases of arthritis reported in the
United States. Gout is the most
common form of inflammatory
arthritis in men, affecting at least 1
percent of men in Westerncountries,
with a male:female ratio ranging
from 7:1 to 9:1.3,4
Hyperuricemia is central to
gout but does not inevitably cause
disease. A variety of conditions,
including renal disease, have been
implicated as causes of gout, but the
vast majority of cases are
idiopathic.1,2,3 The risk of developing
gout is increased by obesity, renal
insufficiency, hypertension, alcohol
ingestion, and inherited enzyme
deficiencies as outlined in Table 1.
Individual gout flares are often
triggered by acute increases or
decreases in urate levels that may
lead to the production, exposure, or
shedding of crystals that are not
coated with apo B or apo E.
Medications may precipitate gout by
interfering with renal excretion of
uric acid. 7,8,9
Table 1. Causes of hyperuricemia
1. Inherited enzyme defects:
a. Glucose-6-phosphatase deficiency
b. Hypoxanthine-guanine phosphoribosyltransferase
deficiency
c. Phosphoribosylpyrophosphate synthetase
overactivity
2. Myeloproliferative or lymphoproliferative diseases
3. Hypertension
4. Diabetic ketoacidosis
5. Lactic acidosis
6. Intrinsic renal disease
7. Other Malignancies
8. Alcohol use (including lead-contaminated
moonshine)
9. High purines diet
10. Obesity
11. Drugs:
a. Diuretics
b. Low-dose salicylates
c. Pyrazinamide
d. Levodopa
e. Cytotoxic drugs
f. Cyclosporine
The classic symptoms of
gouty arthritis are recurrent attacks
of acute, markedly painful
monoarticular or oligoarticular
inflammation, but polyarthritis and
chronic arthritis can occur. European
League Against Rheumatism
(EULAR) recommendations and the
American College of Rheumatology
(ACR) criteria (table.2) provide
guidance for making a clinical or
presumptive diagnosis of gout. When
it fulfills of 6 or more of the criteria
in ACR, it can be assumed that
patient having arthritis gout.1,2,5 In
this case, patient got 8 points of all
criteria which were: more than 1
attack of acute attack of acute
arthritis, maximum inflammation
develops within 1 day, redness over
joints, first metarsophalangeal joint
painful and in unilateral side, tophus,
hyperuricemia, and monosodium
urate monohydrate microcrystals in
joint fluid during attack.
Table 2. American College of Rheumatology
criteria for the classification of acute arthritis of
primary gout
1. More than 1 attack of acute arthritis
2. Maximum inflammation develops within 1 day
3. Monoarthritis attack
4. Redness over joints
5. First metatarsophalangeal joint painful or
swollen
6. Unilateral first metatarsophalangeal joint
attack
7. Unilateral tarsal joint attack
8. Tophus (proven or suspected)
9. Hyperuricemia
10. Assymetric swelling within a joint in
radiography
11. Subcortical cysts without erosion on
radiography
12. Monosodium urate monohydrate microcrystals
in joint fluid during attack
13. Joint fluid culture negative for organism during
attack
A definitive diagnosis
requires the direct identification of
urate crystals in the joint and the
exclusion of infection.4 Although the
3
presence of urate crystals in the soft
and synovial tissues is a prerequisite
for a gouty attack, the fact that urate
crystals can also be found in synovial
fluid in the absence of joint
inflammation suggests that the mere
presence of intrasynovial urate
crystals is not sufficient to cause
flares of gouty arthritis. One
explanation for this may lie in the
observation that clumps or
microtophi of highly negatively
charged and reactive MSU crystals
are normally coated with serum
proteins (apolipoprotein [apo] E or
apo B) that physically inhibit the
binding of MSU crystals to cell
receptors. A gout attack may be
triggered by either a release of
uncoated crystals (e.g., due to partial
dissolution of a microtophus caused
by changing serum urate levels) or
precipitation of crystals in a
supersaturated microenvironment
(e.g., release of urate due to cellular
damage). From either source, naked
urate crystals are then believed to
interact with intracellular and surface
receptors of local dendritic cells and
macrophages, serving as a danger
signal to activate the innate immune
system.10,11
This interaction may be
enhanced by immunoglobulin G
(IgG) binding. Triggering of these
receptors, including Toll-like
receptors, NALP3 inflammasomes,
and the triggering receptors
expressed on myeloid cells (TREMs)
by MSU, results in the production of
interleukin (IL)–1, which in turn
initiates the production of a cascade
of pro-inflammatory cytokines,
including IL-6, IL-8, neutrophil
chemotactic factors, and tumor
necrosis factor (TNF)–alpha.
Neutrophil phagocytosis leads to
another burst of inflammatory
mediator production. Subsidence of
an acute gout attack is due to
multiple mechanisms, including the
clearance of damaged neutrophils,
recoating of urate crystals, and the
production of anti-inflammatory
cytokines including, IL-1RA, IL-10,
and transforming growth factor
(TGF)–beta.10,11
Patient confessed having high
purines dietary habit that lead to
hyperuricemia condition. Humans
generate about 250 to 750 mg of uric
acid per day that almost all of uric
acid comes from dietary purines and
the rest id from the breakdown of
dying tissues. The exact cause of
gout is not yet known, although it
may be linked to a genetic defect in
purine metabolism. Uric acid, the
most insoluble of the purine
substances, is a trioxypurine
containing three oxygen groups. The
pathogenesis of gout starts with the
crystallization of urate within the
joint, bursa, or tendon sheath, which
leads to inflammation as a result of
phagocytosis of monosodium urate
crystals. Specifically, uric acid is a
breakdown product of the purines
adenine, guanine, hypoxanthine, and
xanthine. Adenine and guanine are
found in both DNA and RNA.
Hypoxanthine and xanthine are not
incorporated into the nucleic acids as
they are being synthesized, but they
are important intermediates in the
synthesis and degradation of the
purine nucleotides. Both
undissociated uric acid and
monosodium salt, which is the
4
primary form found in the blood, are
only sparingly soluble.12
The amount of urate in the
body depends on the balance
between dietary intake, synthesis,
and excretion. Statistically, normal
uric acid levels in men and
premenopausal women are 7mg/dL
and 6mg/dL that are close to the
limits of urate solubility
(approximately 7 mg/dL at 37°C) in
vitro, imposing a delicate
physiologic urate balance. In people
with primary gout, defects in purine
metabolism lead to hyperuricemia, or
high levels of uric acid in the blood.
This can be caused by increased
production of uric acid, abnormal
retention of uric acid, or both. Urate
in the blood can accumulate either
through an overproduction or an
underexcretion of uric acid. The
majority of patients with endogenous
overproduction of urate have the
condition as a result of salvaged
purines arising from increased cell
turnover in proliferation and
inflammatory disorders, from
pharmacologic intervention resulting
in increased urate production, and
from tissue hypoxia.12
The renal mechanism for
handling urate is one of glomerular
filtration followed by partial tubular
reabsorption. The final fractional
excretion of uric acid is about 20%
of what was originally filtered. Uric
acid levels independently predict
renal failure in patients with
preexisting renal disease.
Hyperuricemia causes interstitial and
glomerular changes that are
independent of the presence of
crystal.12,13
Three treatments were
prescibe to the patient that were
colchicine, corticosteroid, and non
steroidal antiinflammatory drug.
Basically, management of gout
consists of 3 stages: (1) treating the
acute attack; (2) lowering excess
stores of uric acid to prevent flares of
gouty arthritis and to prevent tissue
deposition of uric acid crystals; and
(3) providing prophylaxis to prevent
acute flares.6 Colchicine has been
used for hundreds of years as an anti-
inflammatory agent for acute arthritis
and is the most specific known
treatment for acute attacks of gout.
The benefit of colchicine in treating
gout is related principally to its
ability to inhibit phagocytosis of
urate crystals by neutrophils.
Colchicine forms a tubulin–
colchicine dimer that caps the
assembly end of the microtubules,
interfering with the transport of
phagocytosed material to lysosomes.
Colchicine also blocks the release of
chemotactic factor, reduces the
mobility and adhesion of
polymorphonuclear leukocytes, and
inhibits tyrosine phosphorylation and
the generation of leukotriene B4.1,2
But recently, colchisine is less
favored than past, because the
therapeutic ratio of benefits to
adverse effects is usually poorer for
colchicine than for other treatments.
Serious adverse effects, including
bone marrow suppression, may occur
even with the use of low doses (less
than 2 mg), especially of using with
intravenous colchicine in patients
with renal insufficiency and
hepatobiliary obstruction,
particularly in those over 70 years of
age, since these conditions and aging
impair the elimination of colchicine.
5
Colchicine cannot be extracted by
dialysis, and treatment of established
colchicine intoxication is primarily
based on supportive care.4,14
Corticosteroid was given in
this case, with intraarticular injection
with Flamicort, and oral medication
with metyl prednisolon.
Corticosteroids inhibit prostaglandin
synthesis and decrease the activity of
collagenase and other enzymes.
Their major mechanism of benefit in
osteoarthritis, however, remains
unclear. Saxne et al, measured the
release of proteoglycans into
synovial fluid to monitor the effects
of therapy on cartilage metabolism.
Their data strongly suggest that intra-
articular corticosteroid injections
reduce the production of interleukin-
1, tumor necrosis factor alpha, and
proteases that may degrade the
cartilage.15
For additional analgetic agent
in this case was meloxicam.
Meloxicam is an non streoidal
antiinflammatory drug that more
selective to inhibit COX-2 than
COX-1, which is supposed to have
fewer gastrointestinal side.
Meloxicam concentrations in
synovial fluid range from 40% to
50% of those in plasma. The free
fraction in synovial fluid is 2.5 times
higher than in plasma due to the
lower albumin in synovial fluid as
compared to plasma. It may account
for the fact that it performs
exceptionally well in treatment of
arthritis. However, NSAIDs must be
avoided in patients with chronic
renal insufficiency, anticoagulation,
congestive heart failure or gastric
ulcers.7
Allopurinol is also prescribed
in this case because of chronic case
itself and patient had no complaint
about pain anymore. Allopurinol is
uricosuric agent that works by
blocking production of uric acid and
affecting the system that
manufactures uric acid in the body. It
is used to prevent gout attacks, not to
treat them once they occur. In fact,
allopurinol should not be used during
an acute attack- it may make the
attack worse. 10,11,12 The patient also
got motivation for continuing routine
drug therapy and lifestyle
modifications that can significantly
decrease gout attack in the future.
SUMMARY
Has reported a case with a
diagnosis chronic tophaceous gout in
acute exacerbation. Patient presents
with pain and tophus in left
shoulder, both knee, both ankle, left
elbow, left wrist, and foot area.the
attack was come especially at night
and patient unable to be walk. From
symptoms obtained from the
anamnesis and physical examination,
laboratory and radiology finding is
performed is known that symptoms
specific to the diagnosis of chronic
tophaceous gout in acute
exacerbation. Patients had received
conservative treatment. After the 8th-
day care for the patients showed
improvement and was recommend to
undergo ambulatory care.
6
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