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Diagnosis and Management of Gout

Dr. Krishna W. Sucipto, Sp.PD-KEMD

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

Primary gout is caused by inborn defects in purine metabolism or inherited defects of the renal tubular secretion of urate. Secondary gout is caused by acquired disorders that result in increased turnover of nucleic acids, by defects in renal excretion of uric acid salts, and by the effects of certain drugs

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.

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, Pagets 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 Drug usage Renal failure Hematologic Disease Trauma Alcohol use Psoriasis Poisoning Obesity Hypertension Organ transplantation 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

Rheumatic arthritis, Reiters syndrome, Psoriatic arthritis



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

Mild leukocytosis in acute attacks, but may be higher than 25,000/mm

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.

Associated Conditions
Cardiovascular Disease Pagets disease Arthritis- rheumatoid and osteoarthritis Septic Arthritis Metabolic syndrome

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

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
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 contd

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

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

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

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
Enzyme that oxidizes uric acid to a more soluble form Natural Uricase from Aspergillus flavus and Candida utilis under investigation

New class of Xanthine Oxidase inhibitor More selective than allopurinol Little dependence on renal excretion

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

Studies note when used in combo with Allopurinol produced additional lowering of the urate

Renal Failure
ARF can be caused by hyperuricemia, chronic urate nephropathy

Nephrolithiasis Joint deformity Recurrent Gout

The best medicine I know for rheumatism is to thank the Lord that it ain't gout.
Josh Billings

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