Hey Doc, Ive Got the Gouch Diagnosis and Management of Gout

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Hey Doc, Ive Got the Gouch!Diagnosis and
Management of Gout

• Valerie Berger, M.D.
• January 15, 2001

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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.

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History

• Natures revenge for debauchery
• Most of the Roman emperors suffered from gout

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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

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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 1700s because it was thought to be
  poisonous.

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History

• Universally accepted in the 19th century after
  the French standardized the potency
• Ben Franklin
• King George IV
• Louis XVIII

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History

• Late 1800s brought the first uricosurics, but
  not widely used secondary to side effects
• 1950s - The first tolerable uricosurics and
  xanthine oxidase inhibitors

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Pathology

• Gout is associated with elevated serum uric acid
• Uric acid is the end product of purine metabolism
• Created by one of two pathways

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Pathology

• De Novo Pathway
• Uric acid created from non-purine precursors

• Salvage Pathway
• Uric acid created from the recapture of nucleic
  acid from breakdown products.

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Pathology
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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.

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Pathology

• Uric acid normally dissolves in plasma
• Poorly soluble in synovial fluid and precipitates
  out as MSU crystals

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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.

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Epidemiology

• Framingham Study, 1967
• 1st large population study
• prospective over 12 years
• uric acid levels
• x-ray findings
• clinical symptoms

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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

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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

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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

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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?

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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 gt6mg/dl in men and gt5.6mg/dl in females
  were arbitrarily picked as abnormal values

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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 gt5 attacks
• No difference in the mean uric acid levels in
  those with gt10 attacks versus the gouty
  population as a whole

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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.

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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

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Diagnosis

• 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

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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

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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?

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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.

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Diagnosis

• Do I need a twenty four hour urine if I think my
  patient has gout?

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Diagnosis

• 24 hour urines help discriminate between
  over-excreters and under-excreters among
  those patients with hyperuricemia

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Diagnosis

• 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

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Diagnosis

• gt800mg uric acid excretion
• Needs further workup to uncover etiology of
  hyperuricemia.
• Treated exclusively with xanthine oxidase
  inhibitor (allopurinol)

• lt800mg uric acid excretion
• No further work up needed
• May be treated with a uricosuric (probenecid) or
  xanthine oxidase inhibitor (allopurinol)

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Diagnosis

• 24 hour urine collection problems
• messy
• storage
• preservative
• precipitation of crystals

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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.

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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

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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

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Stages of Gout

• Asymptomatic Hyperuricemia
• Acute Attack
• Intercritical Period
• Chronic Gout

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Asymptomatic Hyperuricemia

• Do nothing unless they become symptomatic

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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

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Acute Attack

• The VA study
• 10 men given 800mg Motrin q8 hrs
• Dose decreased to 400mg q8 hrs after pain relief
• Questioned regarding pain relief, dyspepsia,
  nausea and vomiting.

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Acute Attack

• All men had significant reduction in pain at 24
  hours
• All had complete relief at 72 hours
• No side effects reported

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Acute Attack

• Sparked flury of other studies looking at every
  new NSAID that hit the market
• Basic conclusion from all of them is any short
  acting NSAID is effective in terminating an
  attack
• 800mg ibuprofen q6-8hrs
• However, there are side effects, primarily GI and
  renal

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Acute Attack

• Colchicine
• 0.6mg q1-2hrs times 16 doses
• Take until pain relief or side effects occur
• GI upset
• Diarrhea

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Acute attack

• Before 1987 there was no RCT proving that
  colchicine actually altered the course of acute
  gout.
• 42 pts with gout randomized to receive 1mg of
  colchicine followed by 0.5mg q2hrs until relief
  or toxicity, or placebo

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Acute Attack

• 2/3 of colchicine group reported pain relief
  versus 1/3 of placebo
• All patients receiving colchicine developed
  toxicity
• 91 reported developing it before relief of pain
• Study limited by inpatient population, small
  numbers and a mean 38hr delay between onset of
  symptoms and enrollment

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Acute Attack

• Colchicine is effective in aborting an attack
• Side effects must be contended with
• Best used at the first sign of an impending attack

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Acute Attack

• Intra-articular corticosteroid injections
• Can aspirate fluid at the same time
• Good option for those who cant take NSAIDS or
  tolerate colchicine

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Acute Attack

• Systemic Steroids
• 30-60mg Prednisone tapered over 7-10 days
• again good for patients who cant tolerate NSAIDS
  or colchicine

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Acute Attack

• ACTH
• Less commonly used
• 40-80 units IM twice a day for two days then
  daily for 2-3 days.

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Intercritical Gout

• Joint aspiration will often find uric acid
  crystals, but no accompanying inflammation
• Typically no need for drug intervention at this
  time

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Intercritical Gout

• Antihyperuricemic therapy indicated if
• Multiple attacks per year
• Multiple joints are involved at one time
• Extreme hyperuricemia (gt12mg/dl)
• Evidence of bone or joint destruction

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Intercritical Gout

• Colchicine
• 0.6mg qd, bid, or tid
• May be used in the short term to prevent an acute
  attack when starting probenecid or allopurinol

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Intercritical Gout

• Uricosurics
• Probenecid and sulfinpyrazone
• Used to lower serum uric acid levels
• Promotes uric acid excretion by blocking renal
  tubular reabsorption
• Best in patients with normal renal function and
  uric acid excretion lt800mg/day

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Intercritical Gout

• Probenecid
• Starting dose is 0.5g twice a day
• Then increase to a total 1.5g per day up to a max
  of 2g per day in divided doses
• GI distress, hypersensitivity rxn, precipitation
  of stones and an acute attack
• Never start in an acute flare
• Use NSAIDS and colchicine to stop any inflammation

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Intercritical Gout

• Xanthine Oxidase Inhibitors
• Reduces serum uric acid by inhibiting the
  production of it
• Allopurinol
• Can be used in both under and over-excreters
• Safe in patients with creatinine clearance lt50
  of normal

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Intercritical Gout

• Allopurinol
• Starting dose is 200mg per day
• Increase over the next 2-3 weeks until urate
  level decreases
• Max dose is 800mg/day but doses gt600mg/day
  increase risk of side effects

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Intercritical Gout

• Allopurinol
• Side effects include rash, hepatitis, vasculitis,
  and bone marrow suppression
• Hypersensitivity reaction
• TEN
• fever
• hepatitis
• eosinophilia
• worsening renal function

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Intercritical Gout

• Allopurinol
• More likely to have side effects if renal
  function is poor
• Can desensitize
• Dont use in an acute flare
• Can precipitate an acute attack

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Intercritical Gout

• Prevention
• Trauma
• Surgery
• Dehydration
• Alcohol
• Certain foods

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Intercritical Gout

• Organ meats
• Wild game
• Seafood
• Lentils
• Peas
• Asparagus
• Yeast
• Beer

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Chronic Gout

• Rare
• Continuous symptoms despite treatment
• Morning stiffness, synovial thickening, and joint
  deformity.
• Gouty erosions on x-ray
• Tophi

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Chronic Gout

• Continue treatment with antihyperuricemic agents
• Continue treatment for acute flares.

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Future Therapy

• 1988 Chua, et al. published a case report
• Pt with lymphocytic lymphoma and hypersensitivity
  to allopurinol.
• Urate was lowered using PEG-uricase

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Future Therapy

• Uricase oxidizes uric acid to allantoin which is
  much more soluble than uric acid
• Humans and birds lack this enzyme
• Uricase can reduce serum uric acid if given to
  species that lack the enzyme
• Efficacy diminishes over time due to the
  formation of antibodies

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Future Therapy

• Antigenicity may be reduced by the attachment of
  monomethoxypolyethylene glycol (PEG) to the
  uricase
• 2001 Duke University enrolling subjects with
  severe gout, lymphoid malignancies organ
  transplants to receive PEG-uricase