Gout

Dr.dr.Radiyati Umi Partan,SpPD,K-R,M.Kes

Divisi Reumatologi Ilmu Penyakit Dalam
Fakultas Kedokteran
Universitas Sriwijaya

Definition
Gout is a heterogeneous disorder that results in the
deposition of uric acid salts and crystals in and
around joints and soft tissues or crystallization of uric
acid in the urinary tract.
Uric acid is the normal end product of the
degradation of purine compounds.
Major route of disposal is renal excretion
Humans lack the enzyme uricase to break down
uric acid into more soluble form.
Metabolic Disorder underlying gout is hyperuricemia.

Epidemiology

Most common of microcrystalline arthropathy.

Incidence has increased significantly over the past
few decades.
Affects about 2.1million worldwide
Peak incidence occurs in the fifth decade, but can
occur at any age
Gout is 5X more common in males than premenopausal females; incidence in women increases
after menopause. After age 60, the incidence in
women approaches the rate in men.
People of South Pacific origin have an increased
incidence.

Predisposing Factors

Heredity
Drug usage
Renal failure
Hematologic Disease
Trauma
Alcohol use

Psoriasis
Poisoning
Obesity
Hypertension
Organ transplantation
Surgery

Pathogenesis of Gouty
Inflammation
Urate crystals stimulate the release of numerous
inflammatory mediators in synovial cells and
phagocytes
The influx of neutrophils is an important event for
developing acute crystal induced synovitis
Chronic gouty inflammation associated with cytokine
driven synovial proliferation, cartilage loss and bone
erosion

Figure 6. Chemical Mediator in acute

Inflamation
Stimulation
(MSU)

Macrophag, Neutrofil

IL-12
TNF

IL-6

Acute
Phase
Protein
febris

Systemic sign
Febris

IL-1

Endotel
vascular

IL-8

Selection
HEV

Chemostatic
leukocyt

Local inflamation

Low
Moleculer
Mediator
(PGE,POR,NO)

Neutral protease
Collagenase
Proteoglicanase

Blood Flow

Heart damage

Classification of
Hyperuricemia

1. Uric acid overproduction

Accounts for 10% of hyperuricemia
Defined as 800mg of uric acid
excreted
a. Acquired disorders
Excessive cell turnover rates
such as
myleoproliferative disorders,
Pagets
disease, hemolytic anemias
b. Genetic disorders

derangements in mechanisms
that

2. Uric acid underexcretion

Accounts for >90% of
hyperuricemia
Diminished tubular secretory rate,
increased tubular reabsorption,
diminished uric acid filtrat
Drugs, other systemic disease that
predispose people to renal
insufficiency

Stages of Classic Gout

1. Asymptomatic hyperuricemia
Very common biochemical abnormality
Majority of people with hyperuricemia never
develop symptoms of uric acid excess
2. Acute Intermittent Gout (Gouty Arthritis)
Episodes of acute attacks. Symptoms may be
confined to a single joint or patient may have
systemic symptoms.

Stages of Classic Gout

3. Intercritical Gout
Symptom free period interval between attacks.
May have hyperuricemia and MSU crystals in
synovial fluid
4. 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.

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

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)

Acute Gout Treatment

NSAIDs
Most commonly used.
No NSAID found to work better than others
Regimens:
Indocin 50mg po bid-tid for 2-3 days and then taper
Ibuprofen 400mg po q4-6 hr max 3.2g/day
Ketorolac 60mg IM or 30mg IV X1 dose in
patients<65
30mg IM or 15mg IV in single dose in patients
>65yo, or with patients who are renally impaired
Continue meds until pain and inflammation have
resolved for 48hr

Acute Treatment
Colchicine
Inhibits microtubule aggregation which disrupts
chemotaxis and phagocytosis
Inhibts crystal-induced production of chemotatic
factors
Administered orally in hourly doses of 0.5 to 0.6mg
until pain and inflammation have resolved or until GI
side effects prevent further use. Max dose 6mg/24hr
2mg IV then 0.5mg q6 until cumulative dose of 4mg
over 24hr

Indications for Antihyperuricemic Therapy in Gout

Frequent and disabling attacks of acute gouty arthritis

Clinical or radiographic signs of chronic gouty joint

disease
The presence of tophaceous deposits in soft tissues
or subchondral bone

Gout with renal insufficiency

Recurrent nephrolithiasis
Serum urate levels persistently in excess of 13 mg/dL
in men or 10 mg/dL in women

Urinary uric acid excretion exceeding 1100 mg/day

Impending cytotoxic chemotherapy or radiotherapy for
lymphoma or leukemia

Table III. Main medications used in the treatment and prophyaxis of gout .1-8,13,81

Agent

Adverse Events

Contraindications

Regimen

Acute therapy/
prophylaxis
NSAIDs

Dose-dependent gastropathy,
nephropathy, liver dysfunction,
central nervous system
dysfunction. May cause fluid
overload in patients with
congestive heart failure.

Peptic ulcer disease or bleeding

ASA- Or NSAID-induced asthma,
urticaria, or allergic-type reactions.

Indomethaction 50mg TID for 2

to 3 days, then tapered over 5 to 7
days; naproxen 750 mg, followed
by 250mg TID, then tapered over
5 to 7 days, sulindac 200mg BID,
then tapered over 5 to 7 days.
Prophylaxis low daily doses.

Cox-2 selective inhibitors

(etoricoxib)

Less GI toxicity than

conventional NASIDs renal
effecect similar to conventional
NSAIDs

Cautious use in patients with

advanced renal disease, history of
ischemic heart disease, or history of
NSAID-induced asthma.

Etoricoxise 120 mg/d (available

outside the United States)

Colchicine

Dose-dependent GI symptoms,
neuromyopathy; improve IV
dosing can cause bone narrow
suppression, renal failure,
paralysis, and death.

Use cautiously in renal or hepatic

dysfunction.

1.2mg initially then 0.6mg every 1

to 2 hours until pain relief or
abdominal discomfort/diarrhea
develops (do not exceed 4 mg/d).
Prophylaxis 0.6 to 1.2 mg/d.

Corticosteroids

Fluid detention, impaired

Wound healing, psychosis
Hyperglycemia hypothalamus
Pituitary axis suppression
Osteoporosis, potential for
Rebound inflammation.

Intra-articular;
methylprednisolone 10 to 20mg
for a small joint; 20 to 10 mg for
large joint. IM: triamcinolone
acetonide 60mg repeat after 24
hours if necessary. PO: prednisone
30 to 60mg QD, then tapered over
7 to 10 days.

Table III. (Continued)

Agent
ACTH

Adverse Events

Contraindications

Fluid retention, hypokalemia relapse of

gout, worse diabetes control

Regimen
40 to 80 IU IM, repeat every 12
hours as necessary.

Orate-lowering therapy
Allopuriol

Rash, GI symptoms, headache, urticaria,

and intestinal nephritis; rare potentially
fatal hypersensitivity syndrome, reduces
orate levels in over producers and
underexcretors.

Probenecid

Rash, headache, and GI symptoms; rare

nephritic syndrome, hepatic necrosis,
aplastic anemia and hemolytic anemia.
Reduced orate levels in
underexcretors.Potential for numerous
drug interactions because of interference
with excretion of many medications.

Renal dysfunction (CrCI

<50mL/min) or renal calculi

250mg BID for 1 to 2 weeks

ny500mg increments every 1 to
2 weeks until satisfactory
control is achieved or maximal
dose 3 g.

Sulfinpyrazone

Rash, headache, and GI symptoms, bone

narrow suppression, minor
hypersensitive. Possesses inherent
antiplatelet activity.

Renal dysfunction (CrCI

<50mL/min) or renal calculi

50mg BID; to 300 to 400

mg/d in 2 to 3 divided doses
maximum dose 800 mg/d.

Low Purine Diet

On a strict low purine diet, protein is derived principally from eggs

and cheese. Grains, most vegetables, fruits and nuts are acceptable.
The following should be AVOIDED
Animal-based proteins Meats, poultry, seafood,
Liver, kidney, heart, gizzard,
sweetbreads,
Meat extracts, yeast extract.
Vegetables

Peas, beans, spinach, lentils.

Beverages

Alcohol, beer, and beer products.

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

Acute treatment contd

Corticosteriods
Patients who cannot tolerate NSAIDs, or
failed NSAID/colchicine therapy
Daily doses of prednisone 40-60mg a day for
3-5 days then taper 1-2 weeks
Improvement seen in 12-24hr
ACTH
Peripheral anti-inflammatory effects and
induction of adrenal glucocorticoid release
40-80IU IM followed by second dose if
necessary

Acute treatment contd

Intra-articular injection with steroids

Beneficial in patient with one or two large
joints affected
Good option for elderly patient with renal or
PUD or other illness
Triamcinolone 10-40mg or Dexamethasone
2-10mg alone or in combination with
Lidocaine

Non- Pharmacologic Treatments

Immobilization of Joint
Ice Packs
Abstinence of Alcohol
Consumption can increase serum urate
levels by increasing uric acid production.
When used in excess it can be converted to
lactic acid which inhibits uric acid excretion
in the kidney

Non- Pharmacologic Treatments

Dietary modification
Low carbohydrates
Increase in protein and unsaturated fats
Decrease in dietary purine-meat and
seafood. Dairy and vegetables do not seem
to affect uric acid
Bing cherries and Vitamin C

Prophylaxis

Frequent attacks >3/year, tophi development or

urate overproduction
Avoid use of medications that contribute to
hyperuricemia: Thiazide and loop diuretics, lowdose salicylates, niacin, cyclosporine, ethambutol
Losartan promotes urate diuresis and may even
normalize urate levels. This action does not
extend to other members of the ARB class.
Useful in elderly with HTN and gout

Prophylaxis

Colchicine
Colchicine 0.6mg qd-bid
Use alone or in combination with urate
lowering drugs
Prophylaxis without urate lowering drugs
may allow tophi to develop

Prophylaxis
Urate Lowering drugs
Used for documented urate overproduction
Goal is for serum urate concentration to 6mg/dL or
less
Start of therapy can precipitate acute attack;
therefore, may need to use colchicine as a long as
six months
Xanthine oxidase inhibitors
Allopurinol: blocks conversion of xanthine to uric
acid. works for underexcretors and
overproducers.
Start typically 300mg/day and titrate weekly
100mg/day until optimal urate levels achieved.
Start lower doses with renally impaired patients

Prophylaxis

Uricosuric drugs
Probenecid or Sulfinpyrazone: increase
renal clearance of uric acid by inhibiting
tubular absorption
Side effects may prohibit use-GI and
kidney stones
Need measurement of 24hr urine in
anyone for whom Probenecid therapy is
initiated

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

Newer Therapies

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

Complications
Renal Failure
ARF can be
caused by
hyperuricemia,
chronic urate
nephropathy
Nephrolithiasis
Joint deformity
Recurrent Gout

X-ray

Acute
Soft tissue swelling
Chronic
chronic tophaceous gouty
arthritis, extensive bony
erosions are noted
throughout the carpal
bones
Sclerosis and joint-space
narrowing are seen in the
first metatarsophalangeal
joint, as well as in the
fourth interphalangeal
joint .

Treatment
Acute:
NSAIDs anti-inflammatory doses
Colchicine 0.5 mg po q2 hours, may require 6 mg.
Stop with response or side effect
Can be used for chronic disease, increased risk
for BM suppression
Aspirate followed by administration of
corticosteroids
Prednisone
ACTH 40-80 IM/IV or Solumedrol
Opiates and Tylenol

Treatment

Chronic:
Diet will decrease uric acid 1 mg/dL at best
Weight loss
Limit ETOH
Modification of medications
Avoid low dose ASA, diuretics, etc.

Treatment

Chronic
Uricosuric: for under-excretors
Probenicid:
Sulfinpyrazone: toxic side effects
Avoid with renal disease
Consider NSAIDs to avoid exacerbation of
gout

Treatment

Chronic
Indications for Allopurinol
Tophaceous deposites
Uric acid consistently >9
Persistent Sx with moderate UA levels
Impaired renal function
Prophylaxis for tumor-lysis syndrome
Consider NSAIDs to avoid exacerbation

Prognosis

Generally good
More severe course when Sx present < 30 y/o
Up to 50% progress to chronic disease if
untreated.
Surgical intervention may be required for tophi.