Diagnosis and Management of

Gout
Dr Nadrizal, SpPD, FINASIM
 Objectives

• To review the etiology and

pathophysiology of gout
• To recognize predisposing factors for gout
• To review diagnostic criteria and
evaluation for gout
• To select appropriate treatment for a
patient presenting with gout
 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.
– Defined as 2 SD above mean usually 7.0 mg/dL. This concentration is
about the limit of solubility for (monosodium urate) MSU in plasma. At
higher levels, the MSU is more likely to precipitate in tissues.
 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.
Classification of Hyperuricemia
• Uric acid overproduction
– Accounts for 10% of hyperuricemia
– Defined as 800mg of uric acid excreted
– Acquired disorders
• Excessive cell turnover rates such as myleoproliferative disorders, Paget’s
disease, hemolytic anemias
– Genetic disorders: derangements in mechanisms that regulate purine
neucleotide synthesis.
• Deficiency HGPRT, or superactivity PRPP synthetase
• Uric acid underexcretion
– Accounts for >90% of hyperuricemia
– Diminished tubular secretory rate, increased tubular reabsorption,
diminished uric acid filtration
• Drugs, other systemic disease that predispose people to renal insufficiency
 Predisposing Factors
• Heredity • Psoriasis
• Drug usage • Poisoning
• Renal failure • Obesity
• Hematologic Disease • Hypertension
• Trauma • Organ transplantation
• Alcohol use • Surgery
 Stages of Classic Gout
• Asymptomatic hyperuricemia
– Very common biochemical abnormality
– Defined as 2 SD above mean value
– Majority of people with hyperuricemia never develop symptoms of uric acid
excess
• Acute Intermittent Gout (Gouty Arthritis)
– Episodes of acute attacks. Symptoms may be confined to a single joint or patient
may have systemic symptoms.
• Intercritical Gout
– Symptom free period interval between attacks. May have hyperuricemia and
MSU crystals in synovial fluid
• 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.
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
 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
 Differential Diagnosis
• Trauma
• Infections
– septic arthritis, gonococcal arthritis, cellulitis
• Inflammatory
– Rheumatic arthritis, Reiter’s syndrome, Psoriatic
arthritis
• Metabolic
– pseudogout
• Miscellaneous
– Osteoarthrtis
 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)
 Synovial Fluid Findings
• Needle shaped
crystals of
monosodium urate
monohydrate that
have been engulfed
by neutrophils
 Diagnostic Studies
• Uric Acid
– Limited value as majority of hyperuricemic patients will never develop
gout
– Levels may be normal during acute attack
• CBC
– Mild leukocytosis in acute attacks, but may be higher than 25,000/mm
• ESR
– mild elevation or may be 2-3x normal
• 24hr urine uric acid
– Only useful in patients being considered for uricosuric therapy or if
cause of marked hyperuricemia needs investigation
• Trial of colchicine
– Positive response may occur in other types of arthritis to include
pseudogout.
 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 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
 Acute treatment cont’d
• 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
• 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
• 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
• 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
– 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
• 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
Questions?