Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
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
Pathophysiology
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
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.
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, Pagets disease, hemolytic anemias
Predisposing Factors
Heredity Drug usage Renal failure Hematologic Disease Trauma Alcohol use Psoriasis Poisoning Obesity Hypertension Organ transplantation Surgery
Intercritical Gout
Symptom free period interval between attacks. May have hyperuricemia and MSU crystals in synovial fluid
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, Reiters 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)
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
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
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
ACTH
Peripheral anti-inflammatory effects and induction of adrenal glucocorticoid release 40-80IU IM followed by second dose if necessary
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
The best medicine I know for rheumatism is to thank the Lord that it ain't gout.
Josh Billings
Terima Kasih