GOUT

Objective

 Definition
 Epidemiology
 Pathogenesis
 Clinical manifestation
 Complications
 Treatment
What is that?
 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.
 Gout  Hiperurisemia
L > 7 mg /dl
w > 6 mg/dl
 Prevalensi 2% → dunia

 Indonesia  bervariasi:

Sinjai  pria 10%, wnt 4%,

Minahasa  pria 34,3% Wnt 23,31%
 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.
Clinical Manifestation

 Artritis gout bisa with tophy

 Urinary stone

 Nephropaty gout
 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, Paget’s
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
 Stadium Gout

 Hiperurisemia asimptomatik
Hiperurisemia tanpa adanya G/ klinik
Fase ini berakhir dg adanya serangan akut u/
pertama kali

 Gout intermiten akut (Gouty Arthritis)

Di jumpai adanya serangan akut.
Mungkin dpt mengenai 1 sendi
 Gout Interkritikal
Std diantara 2 serangan akut tanpa
menimbulkan G/

 Gout Tophus kronik

 Biasanya terjadi stlh > 10 th menderita gout
intermiten.
 Sendi bengkak dan tdk nyaman scr persisten
 tophus bisa dimana-mana : jari, siku, telinga,
lutut, bursa olekranon.
Diagnosis

Kriteria klasifikasi artritis gout

A. Adanya kristal as.urat yg khas di cairan
sendi, atau tofus dan atau
B. Adanya 6 dr 12 tanda klinis:
1. > 1serangan artritis akut
2. Inflamasi maksimal yg berkembang dlm
1 hr
3. serangan monoartritis
4. sendi yg terkena warna merah
5. nyeri atau bengkak sendi pd sendi pertama
metatarsofalangeal
6. Inflamasi unilateral yg mengenai sendi pertama
metatarsofalangeal
7. Serangan pd sendi tarsal unilateral
8. Tophi
9. Hiperurisemia
10. Pembengkakan sendi asimetris yg tampak dg
pemeriksaan rontgen
11. Kista subkortikal tanpa erosi pd pem.rontgen
12. Kultur bakteri cairan sendi negatif
 Pem lab
 ditemukanya kristal MSU pd cairan sendi
atau tofus
 hiperurisemia

 Radiologis
 tdk spesifik

 akut→ pembengkakan jar lunak sekitar

sendi.
 Kel tulang dan sendi dp dijumpai bila sdh
berlangsung tahunan
 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 .
Penatalaksanaan

 Edukasi
 Program diet
 Istirahat sendi
 Fisioterapi
 Penanganan medis
 Kerusakan sendi dan kerusakan ginjal
Penanganan medis
 Akut →
- Kolkisin: 0,5 mg/jam
sp nyeri dan inflamasi hilang.
Dihentikan bl toksisitas
- NSAID
- Kortikosteroid→ bila ada kontraindikasi
kolkisin dan NSAID.
Prednison : 40mg/hr atau ekivalennya
3-4 hr lalu diturunkan perlahan 1-2 mg
 Fase lanjutan : profilaksis dg memodifikasi diet
dan gaya hidup, menghindari alkohol

 Target asam urat < 6,0/dl

 Obat : allopurinol dg dosis max 300 mg/hr, atau

agen urikosurik ( probenecid, Sulpipyrazone atau
brenzbromaro)
 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
– Preventing chronic kidney disease and
cardiovasculer complications
Management of gout (ACR)
 An acute gouty arthritis attack should be treated
with pharmacologic therapy, initiated within 24
hours of onset.
 Established pharmacologic urate-lowering therapy
should be continued, without interruption, during
an acute attack of gout.
 Nonsteroidal antiinflammatory drugs (NSAIDs),
corticosteroids, or oral colchicine are appropriate
first-line options for treatment of acute gout,
andcertain combinations can be employed for
severe or refractory attacks.
 Pharmacologic antiinflammatory prophylaxis is
recommended for all gout patients when
pharmacologic urate lowering is initiated, and
should be continued if there is any clinical evidence
of continuing gout disease activity and/or the
serum urate target has not yet been achieved.
 Oral colchicine is an appropriate first-line gout
attack prophylaxis therapy, including with
appropriate dose adjustment in chronic kidney
disease and for drug interactions, unless there is a
lack of tolerance or medical contraindication.
 Low-dose NSAID therapy is an appropriate choice

for first-line gout attack prophylaxis, unless there is a

lack of tolerance or medical contraindication.
Management
Differential Diagnosis
 Septic arthritis
 CPPD
 Acute Rheumatic fever
 Palindromic Rheumatism
 Psoriatic arthritis
 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 Meats, poultry, seafood,

proteins： Liver, kidney, heart, gizzard,
sweetbreads,
Meat extracts, yeast extract.
Vegetables Peas, beans, spinach, lentils.

Beverages Alcohol, beer, and beer

products.
 Agent Adverse Events
Acute therapy/ Dose-dependent gastropathy,
prophylaxis nephropathy, liver
NSAIDs dysfunction, central nervous
system dysfunction. May
cause fluid overload in
patients with congestive
heart failure.
Cox-2 selective inhibitors Less GI toxicity than
(etoricoxib) conventional NASIDs renal
effecect similar to
conventional NSAIDs
Colchicine Dose-dependent GI
symptoms, neuromyopathy;
improve IV dosing can cause
bone narrow suppression,
renal failure, paralysis, and
death.
Corticosteroids Fluid detention, impaired
Wound healing, psychosis
Hyperglycemia hypothalamus
Pituitary axis suppression
Osteoporosis, potential for
Rebound inflammation.
Contraindications
Peptic ulcer disease or bleeding
ASA- Or NSAID-induced asthma,
urticaria, or allergic-type
reactions.
Cautious use in patients with
advanced renal disease, history
of ischemic heart disease, or
history of NSAID-induced
asthma.
Use cautiously in renal or
hepatic dysfunction.
Regimen
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.
Etoricoxise 120 mg/d
(available outside the United
States)
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.
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.
 Agent Adverse Events Contraindications Regimen
ACTH Fluid retention, hypokalemia relapse 40 to 80 IU IM, repeat every
of 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; Renal dysfunction (CrCI 250mg BID for 1 to 2
rare nephritic syndrome, hepatic <50mL/min) or renal weeks↑ ny500mg
necrosis, aplastic anemia and calculi increments every 1 to 2
hemolytic anemia. Reduced orate weeks until satisfactory
levels in underexcretors.Potential for control is achieved or
numerous drug interactions because maximal dose 3 g.
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 mg/d in 2 to 3 divided doses
hypersensitive. Possesses inherent calculi maximum dose 800 mg/d.
antiplatelet activity.
 Acute treatment

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 cont’d

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
 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.
 THANK YOU