Comprehensive Management in

Treating Gout Arthritis

Gout Pathophysiology and
Etiology
Pathophysiology

Rees, F. et al. (2014) Optimizing current treatment of gout

Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.32
Risk Factors
• High Purine Diet (Red • Obesity
Meat, Fatty Poultry, High • Drugs (Allopurinol,
Fat Dairy, Seafood) uricosuric agents,
• Alcohol Consumption thiazides, loop diuretics,
• Trauma low dose aspirin)
• Osteoarthritis • Renal Impairment
• Surgery • Genetic Mutations
• Starvation (SLC22A9, SLC22A12,
• Dehydration ABCG2)
 Monosodium urate crystals

needle shape

negative
birefringence

polarized light red compensator

Hyperuricemia

hyperuricemia results when production exceeds excretion

 Hyperuricemia

net uric acid loss results when excretion exceeds production

 Classifying hyperuricemia
• serum uric acid level
• urine uric acid excretion (24-hour)

overproduction underexcretion
serum uric acid high high
urine uric acid high normal/ low
Stages of Gout
• Asymptomatic tissue deposition
• Acute Gouty Arthritis
• Intercritical Gout
• Chronic Articular and Tophaceous Gout
Primer on the Rheumatic Diseases. 12th ed. Arthritis Foundation; 2001:313.
 Asymptomatic Hyperuricemia
 Urate levels rise in the
blood, but produces no
symptoms
 Over time, high serum
urate levels lead to gout
 However vast majority
of people with
hyperuricemia never
develop symptoms.

Campion et al. Am J Med. 1987;82:421-426

 Acute Gout
• Single joint or • Fever and leukocytosis
multiple joints in the • Maximal severity
lower extremities: reached within 12-24
First MTP (podagra; hours
50%), midtarsal, • Even without treatment,
ankle, knee joints attacks subside within
days to several weeks
• Pain, erythema,
swelling and warmth,
desquamation of skin.
Description of acute attack:
• The victim goes to bed and sleeps in good health. About 2 am
he is awakened by a severe pain in the great toe; more rarely
in the heel , ankle, or instep. The pain is like that of a
dislocation, and yet the parts feel as if cold water were poured
over them…..Now it is a violent stretching and tearing of the
ligaments…. So exquisite and lively meanwhile is the feeling
of the part affected , that it cannot bear the weight of
bedclothes nor the jar of a person walking in the room.
Primer on the Rheumatic Diseases. 12th ed. Arthritis Foundation; 2001:313.
Thomas Sydenham, 17th century
ACUTE STAGE
 INTERCRITICAL STAGE

• symptom-free intervals between gout

episodes. Most people have a second
attack from six months to two years,
while others are symptom-free for
five to 10 years.
 Chronic Tophaceous Gout
• Characterized by chronic arthritis and tophi,
resulting in chronic inflammatory and
destructive changes
 Renal Complications
• Nephrolithiasis
 Risk factors: increase uric
acid excretion, reduced urine
volume, and low urine pH
• Chronic urate
nephropathy
 Urate crystals can deposit in
renal medullary interstitium
producing inflammatory
changes and fibrosis
 Clinical features are non
specific: renal function
impairment, bland
urinary sediment, mild
proteinuria and serum
urate concentrations
often higher than
expected for the degree
of renal impairment.
 Biopsy confirms
diagnosis
Drugs used to treat gout

Acute Arthritis Drugs Urate Lowering Drugs

colchicine allopurinol

steroids probenecid

NSAID’s febuxostat

rest + analgesia + time

Treating acute gouty arthritis
• colchicine
• NSAID’s
• steroids
• rest, analgesia, ice, time
 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
• mechanism of action
poorly understood
• reduces inflammatory
response to deposited
crystals
• diminishes PMN
phagocytosis of crystals
• blocks cellular response to
deposited crystals
Colchicine - indications

Dose Indication

high treatment of acute gouty arthritis

prevention of recurrent gouty

low
arthritis
Colchicine - toxicity
• gastrointestinal (nausea, vomiting,
cramping, diarrhea, abdominal pain)
• hematologic (agranulocytosis, aplastic
anemia, thrombocytopenia)
• muscular weakness
adverse effects dose-related & more common when
patient has renal or hepatic disease
 NSAIDs (Selective or non- selective )

• Inhibit pain & inflammation.

• Inhibit urate crystal phagocytosis by
decreasing the migration of granulocytes
into the inflammatory area.
• They are commonly used now & may
replace colchicine ( Except aspirin &
paracetamol)
Anti-Inflammatory Prophylaxis for Gout
Flares
Non-pharmacologic
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

JANGAN DIBERIKAN ULT SEWAKTU

SERANGAN AKUT
Management of Gout Pharmacologic
EULAR Recommendations for
Treating to Target
2012 ACR Gout Guidelines
Indications for Pharmacologic Urate-Lowering
Therapy
2012 ACR Gout Guidelines
Current Recommendations for Urate-Lowering
Therapy
2012 ACR Gout Guidelines
Allopurinol as First-Line Urate-Lowering Therapy
Allopurinol - serious reactions
• fever, rash, toxic epidermal necrolysis
• hepatotoxicity, marrow suppression
• vasculitis
• drug interactions (ampicillin, thiazides,
mercaptopurine, azathioprine)
• death
Stevens-Johnson syndrome

target skin lesions

mucous membrane
erosions
epidermal necrosis
with skin detachment
Allopurinol – black box warning

THIS IS NOT AN INNOCUOUS DRUG. IT IS

NOT RECOMMENDED FOR THE
TREATMENT OF ASYMPTOMATIC
HYPERURICEMIA

ALLOPURINOL SHOULD BE
DISCONTINUED AT THE FIRST
APPEARANCE OF SKIN RASH OR
OTHER SIGNS OF AN ALLERGIC
Urate-Lowering Therapy
Febuxostat
Urate-Lowering Therapy
Uricosuric Agents
Continuing to Manage Gout
Closing Comments