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“Hey Doc, I’ve Got the Gouch!” Diagnosis and Management of Gout. Valerie Berger, M.D. January 15, 2001. History. Earliest evidence of gout is on an Egyptian mummy The Works of Hippocrates, 460-357BC A woman does not take the gout unless her menses are stopped.
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“Hey Doc, I’ve Got the Gouch!”Diagnosis and Management of Gout Valerie Berger, M.D. January 15, 2001
History • Earliest evidence of gout is on an Egyptian mummy • The Works of Hippocrates, 460-357BC • A woman does not take the gout unless her menses are stopped. • A youth does not get gout before sexual intercourse. • In gouty affections inflammation subsides within 40 days.
History • Nature’s revenge for debauchery • Most of the Roman emperors suffered from gout
History • The term gout comes from the 10th century Latin word “gutta” meaning “a drop” • The first classic, clinical description of gout by Thomas Snydenham, 1683 • Leeuwenhoek • 1848 Alfred Garrod identifies urate crystals in the blood
History • The advent of colchicine • Eber Papyrus mentions colchicine, dates to 1500BC • Derived from the Autumn crocus • Routine use was stopped from the Middle Ages until the mid 1700’s because it was thought to be poisonous.
History • Universally accepted in the 19th century after the French standardized the potency • Ben Franklin • King George IV • Louis XVIII
History • Late 1800’s brought the first uricosurics, but not widely used secondary to side effects • 1950’s - The first tolerable uricosurics and xanthine oxidase inhibitors
Pathology • Gout is associated with elevated serum uric acid • Uric acid is the end product of purine metabolism • Created by one of two pathways
De Novo Pathway Uric acid created from non-purine precursors Salvage Pathway Uric acid created from the recapture of nucleic acid from breakdown products. Pathology
Pathology • Enzymatic deficiencies and increased nucleic acid turnover account for only 10% of gout patients. • Remaining 90% are “primary gout” due to an unknown defect limiting the ability to excrete uric acid.
Pathology • Uric acid normally dissolves in plasma • Poorly soluble in synovial fluid and precipitates out as MSU crystals
Pathology • Acute attack is not related to the presence of crystals in the joint, but rather to a cascade of events that occurs after activation of synovial macrophages.
Epidemiology • Framingham Study, 1967 • 1st large population study • prospective over 12 years • uric acid levels • x-ray findings • clinical symptoms
Epidemiology • 5,127 subjects (2,283 men and 2,844 women) • Age 30-59 at time of enrollment • Biennial exam • average of 7 physical exams preformed
Epidemiology • Age had no effect on the mean serum uric acid level in men • But in women, there was an increase in mean uric acid levels between the ages of 40 and 50
Epidemiology • Average age of onset of gout • 47.7 in men • 54.1 in women • Prevalence of gout was 1.5% of the population • 2.8% of men • 0.4% of women
Epidemiology • What is the relationship between hyperuricemia and gout? • What is an abnormal uric acid level? • Gout screening • How low does the uric acid need to be?
Epidemiology • There was no specific level at which uric acid was abnormal • Many patients who are hyperuricemic do not have symptoms • Since there was no definitive cut off, uric acid levels >6mg/dl in men and >5.6mg/dl in females were arbitrarily picked as abnormal values
Epidemiology • Clinical features • 25% had only one attack during the study • The average number of attacks was 5 • 23% of men and 10% of women had >5 attacks • No difference in the mean uric acid levels in those with >10 attacks versus the gouty population as a whole
Epidemiology • Clinical features • 84% had at least one episode of podagra • 90% had podagra or attack involving the foot • Only 13% ever had an attack involving the upper extremities.
Diagnosis • No standard classification of gout until 1977 • Wallace, et al. did a chart review of 700 patients from Rheumatology clinics • gout • psuedogout • rheumatoid arthritis • septic arthritis
More than one attack Maximum inflammation in one day Monoarthritis Redness First MTP involved Unilateral first MTP Unilateral tarsal attack Tophus Hyperuricemia Asymmetric swelling Subcortical cysts MSU crystals in joint fluid Joint fluid culture negative Diagnosis
Diagnosis • The gold standard for diagnosis of gout is joint aspiration and crystal identification • Chart review revealed that not all gout patients had a tap • 50% of gout pts • 25% of RA pts • 80% of psuedogout pts • 70% of septic arthritis pts
Diagnosis • Is this because gout affected joints are difficult to tap? • Crystals were only found in 84.4% of those patients with gout • Can the diagnosis gout be made strictly by history?
Diagnosis • 6 out of 12 positive criteria provides best sensitivity and specificity • 6 out of 12 positive criteria plus identification of crystals identifies 97.8% of patients with gout.
Diagnosis • Do I need a twenty four hour urine if I think my patient has gout?
Diagnosis • 24 hour urines help discriminate between “over-excreters” and “under-excreters” among those patients with hyperuricemia
Over-excreters enzymatic deficiencies high metabolic turnover states excrete more than 800mg of uric acid/24hrs account for 10% of patients with gout Under-excreters Unknown defect excrete less than 800mg of uric acid/24hrs account for 90% of patients with gout Diagnosis
>800mg uric acid excretion Needs further workup to uncover etiology of hyperuricemia. Treated exclusively with xanthine oxidase inhibitor (allopurinol) <800mg uric acid excretion No further work up needed May be treated with a uricosuric (probenecid) or xanthine oxidase inhibitor (allopurinol) Diagnosis
Diagnosis • 24 hour urine collection problems • messy • storage • preservative • precipitation of crystals
Diagnosis • 1979 Simkin, et al. evaluated the utility of a spot urine for uric acid levels versus a 24 hour collection. • 19 physicians and health care workers collected 24 hour samples. • Compared these to several mid-morning spot urines from the controls, from 10 normal patients, and 36 men with gout and normal renal function.
Diagnosis • No significant difference in the mid-morning spot urine values and the 24 hour values. • Mean uric acid excretion among the normal men was 0.4+/-0.095mg/dl • Of the men with gout, only 8 excreted greater than 0.7mg/dl
Diagnosis • Conclusions • Crystal identification is the best • If crystals cannot be obtained, use the history • Determination of uric acid excretion is not mandatory unless underlying pathology is suspected (young age, signs of malignancy) or long-term antihyperuricemic agents are needed
Stages of Gout • Asymptomatic Hyperuricemia • Acute Attack • Intercritical Period • Chronic Gout
Asymptomatic Hyperuricemia • Do nothing unless they become symptomatic
Acute Attack • NSAIDS • Indomethacin • 150mg followed by 50mg q6-8 hours times 6-8 doses • then decrease to 25 mg q6-8 hours. • Symptoms usually resolve in 5-7 days