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 pre-
menopausal 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 Psoriasis
Drug usage Poisoning
Renal failure Obesity
Hematologic Disease Hypertension
Trauma Organ transplantation
Alcohol use 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 Macrophag, Neutrofil

(MSU)

IL-12

TNF IL-1

IL-6 Endotel IL-8 Low Neutral protease

vascular Moleculer Collagenase
Mediator Proteoglicanase
(PGE,POR,NO)
Acute
Phase
Protein Selection Chemostatic
febris HEV leukocyt Blood Flow

Systemic sign Local inflamation Heart damage

Febris
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
regulate purine neucleotide synthesis:
Deficiency HGPRT, or superactivity
PRPP synthetase
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/ Dose-dependent gastropathy, Peptic ulcer disease or bleeding Indomethaction 50mg TID for 2
prophylaxis nephropathy, liver dysfunction, ASA- Or NSAID-induced asthma, to 3 days, then tapered over 5 to 7
NSAIDs central nervous system urticaria, or allergic-type reactions. days; naproxen 750 mg, followed
dysfunction. May cause fluid by 250mg TID, then tapered over
overload in patients with 5 to 7 days, sulindac 200mg BID,
congestive heart failure. then tapered over 5 to 7 days.
Prophylaxis low daily doses.

Cox-2 selective inhibitors Less GI toxicity than Cautious use in patients with Etoricoxise 120 mg/d (available
(etoricoxib) conventional NASIDs renal advanced renal disease, history of outside the United States)
effecect similar to conventional ischemic heart disease, or history of
NSAIDs NSAID-induced asthma.

Colchicine Dose-dependent GI symptoms, Use cautiously in renal or hepatic 1.2mg initially then 0.6mg every
neuromyopathy; improve IV dysfunction. 1 to 2 hours until pain relief or
dosing can cause bone narrow abdominal discomfort/diarrhea
suppression, renal failure, develops (do not exceed 4 mg/d).
paralysis, and death. Prophylaxis 0.6 to 1.2 mg/d.

Corticosteroids Fluid detention, impaired Intra-articular;

Wound healing, psychosis methylprednisolone 10 to 20mg
Hyperglycemia hypothalamus for a small joint; 20 to 10 mg for
Pituitary axis suppression large joint. IM: triamcinolone
acetonide 60mg repeat after 24
Osteoporosis, potential for hours if necessary. PO:
Rebound inflammation. prednisone 30 to 60mg QD, then
tapered over 7 to 10 days.
 Table III. (Continued)

Agent Adverse Events Contraindications Regimen

ACTH Fluid retention, hypokalemia relapse of 40 to 80 IU IM, repeat every
gout, worse diabetes control 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 Renal dysfunction (CrCI 250mg BID for 1 to 2 weeks
nephritic syndrome, hepatic necrosis, <50mL/min) or renal calculi ny500mg increments every 1
aplastic anemia and hemolytic anemia. to 2 weeks until satisfactory
Reduced orate levels in control is achieved or maximal
underexcretors.Potential for numerous dose 3 g.
drug interactions because of
interference with excretion of many
medications.

Sulfinpyrazone Rash, headache, and GI symptoms, Renal dysfunction (CrCI 50mg BID; to 300 to 400
bone narrow suppression, minor <50mL/min) or renal calculi mg/d in 2 to 3 divided doses
hypersensitive. Possesses inherent maximum dose 800 mg/d.
antiplatelet activity.
 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, low-dose 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.