Gout EBM Mark Lepsch 7292009

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Gout - EBMMark Lepsch7/29/2009
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Case 1

• A 31 year old family medicine resident presents
  to your clinic to discuss hair care products for
  his white mans afro. Additionally, he
  mentions that he has been struggling to reconcile
  the teachings he learned in medical school about
  under-excreters verus over-producers for
  gouty arthritis. He wants to know what the
  evidence is behind the workup and treatment, and
  how he should approach this clinical problem in
  the future.

Answer Soul Glo see Coming to America w/
Eddie Murphy for details.
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Gout - EBM

• Overview Pathology, Etiology, Epidemiology
• Overview Old School Teaching for Workup and
  RX
• Break into groups Construct plan for workup and
  Rx of a case, support with evidence.
• Reconvene compare group results w/ Level H
  evidence.
• Group Hug

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Gout - Overview

• Acute, intense, inflammatory monoarthritis caused
  by deposition of MSU (monosodium urate) crystals
  in a joint.
• Hyperuricemia (inc. uric acid) at some point is
  necessary, but not sufficient for diagnosis, as
  60 of people w/ elevated uric acid will never
  have an attack of gout.
• Onset usually after age 30 in men, after age 45
  in women.
• Men 8x women before menopause.
• Men 3x women after menopause.
• Gouty attacks are possible when serum uric acid
  levels are normal.

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Gout DDX
Trauma Infection (Strep, Staph, Gonorrhea) Gouty
Arthritis CPPD (Calcium pyrophosphate deposition
disease), aka Pseudogout Osteoarthritis Rheumatoid
Arthritis
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Gout - Biochemistry

• Allopurinol Alloxanthine (t1/218-30hrs)
• -
• Purines Xanthine Oxidase
• HypoXanthine Xanthine Urate (deposits in
• tissues as MSU crystals)
• Precipitation of MSU crystals level 8.0mg/dL
• Hyperuricemia level 7.0mg/dL
• Uric Acid Goal for Patients w/ Gout level 5-6mg/dL

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Gout Overproducers vs. Underexcreters

• Normal daily uric acid production 600mg/day
• Overproducer Person who excretes 800mg/day
• Assuming normal renal function and regular diet
  (no excessive purines)
• 60-80 of Uric acid is excreted renally.
• 20-40 of Uric acid is eliminated by GI tract.
• 90 of patients w/ primary gout have defects w/
  renal excretion of uric acid, thus 90 are
  Underexcreters.
• Uric acid filtered by glomeruli, resorbed in
  PCT, secreted in DCT

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Gout - Etiology

• Purine rich foods meat, kidney, liver, seafood,
  anchovies, oatmeal, certain vegetables (peas,
  beans, lentils, mushrooms, cauliflower, spinach),
  sweetbreads
• ETOH, Caffeine
• Drugs HCTZ, loop diuretics, NSAIDs,
  corticosteroids, Niacin, Sinemet, Cyclosporine,
  Salicylates, Ethambutol, Pyrazinamide
• Trauma
• Infection
• Other disease DM, HTN, vascular dx, renal dx,
  thyroid dx, sarcoidosis, etc.

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Gout History

• 90 present with acute, inflammatory, severe
  monoarticular pain.
• 50 present with podagra (inflammation of 1st
  MTP joint - big toe). Likely because MTP is
  susceptible to trauma and cooling
  (crystallization of MSU). 85-90 of patients w/
  gout will have podagra at some point in their
  life.
• Pain is so severe that patients cannot even
  tolerate a bedsheet on the affected joint.
• Abrupt dietary changes, i.e. acute fluctuations
  in purine intake.
• Peak of attack usually in 1-2 days, may last 7-10
  days if untreated.
• Why at Night? Water is reabsorbed from joint
  spaces, leaving supersaturated MSU
  concentrations.

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Gout PE

• Rubor
• Tumor
• Dolor
• Gouty tophi

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Gouty Tophi
Tophi masses of MSU crystals deposited in the
soft tissues (or bones) of body. Most commonly
in base of great toe, fingers wrist, hand,
olecranon bursae, or Achilles tendon.
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Acute Gout Workup

• Establish diagnosis w/ arthroscopy looking for
  MSU crystals (yellow, parallel, allopurinol)
• Needle shaped
• Negatively birefringent on polarized light
  microscopy
• From AAFP 4/1999
• Baseline labs should include BMP, U/A, CBC, and
  serum Uric Acid.

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Microscopy for MSU Crystals
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Acute Gout - Rx

• NSAIDs (unless CRI, CHF, PUD, etc.)

- Indomethacin 50mg tid - Naproxen 825mg once,
then 275 q8hr - Sulindac 200mg bid
Corticosteroids (Intra-articular if one joint,
systemic if multiple joints)
- 20-30mg/day if systemic used
- Most beneficial in first 12-36 hours of an
attack - 1mg initially, then 0.5mg qhr until
either symptoms relieved or GI side fx
(N/V/diarrhea) or 7mg total given - Renal
dosing - If Cr clearance If Cr clearance
Colchicine (adjust dose in patients w/ renal
insufficiency)
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Intercritical Gout - Rx
Education, Lifestyle/Diet modification,
Pharmacotherapy modification
Allopurinol toxicity?
Allopurinol therapy if - Recurrent attacks
despite diet chg/etc. - Hx of nephrolithiasis -
Serum creatinine 2.0 - Serum uric acid
11.0 - 24 hr urine uric acid 800mg/dL - Tophi
present
Colchicine

• Failing therapy?

Probenecid if - Recurrent attacks and 24hr
urine uric acid
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Asymptomatic Hyperuricemia

• Indications for Rx include
• 24hr Urinary Uric Acid Excretion 1100mg
• Serum uric acid Men 13mg/dL, Women 10mg/dL
• Nephrolithiasis
• Any hx of symptoms of gout, especially w/
  worsening renal function
• Presence of gouty tophi in bone or soft tissues
• Radiographic signs of gouty arthritis
• Impending chemotherapy or radiotherapy for
  leukemia or lymphoma

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Gouty Arthritis - Radiographs
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Case

• A 57 y.o. AA male w/ hx of HTN, DM (elevated FPG
  2 years ago, pt. lost to follow up), and self
  reported hx of the gout presents to your clinic
  with intermittent knee pain for the last year,
  now severe for the last week. Patient has
  history of intermittent compliance w/ medicines
  (HCTZ 25, Atenolol 25), pt. has occasional
  episodes of binge drinking (beer), pt. does not
  smoke. Pt. has been seen a total of 3 times in
  the last 10 years and has not had any
  preventative health screening. He is a
  self-paying patient who works construction
  (mostly concrete) and does often kneel on hard
  surfaces, but wears knee-pads. He denies any
  specific trauma or prior knee injuries. He says
  he has had a prior episode of podagra years ago
  but no arthrocentesis was ever done. He was
  prescribed Allopurinol 5 years ago but has never
  taken it. All other hx negative.
• PE BP 172/98. R knee warm, red, swollen, no
  breaks in skin, tender w/ flexion/extension,
  antalgic gait.
• Question What do you do today in clinic (1)
  Diagnostics (2) Rx? be specific, include
  dosages.

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Case

• Pt. returns in 2 weeks to your clinic. His labs
  were as follows
• - CBC normal
• - BMP notable for Glucose 220, BUN 27, Creatinine
  1.7, else nl
• - U/A 1 protein, TR LE, TR blood
• - Serum Uric Acid 8.4mg/dL
• - Knee fluid notable for negatively bi-refringent
  crystals
• The patient took Indomethacin 50mg tid for 3
  days, then has been taking it prn (between 0 and
  2 times a day). His knee pain is now a 4/10
  (down from an 8/10). He is ambulating with only
  a mildly antalgic gait. His knee is
  normotensive, not swollen, and only mildly tender
  to flexion/extension.
• Question What do you do today in clinic (1)
  Diagnostics (2) Rx? be specific, include
  dosages.

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Allopurinol

• Trade name Zyloprim
• 300mg daily reduces serum urate patients
• Renal dosing
• CrCl 40-60, max of 200mg/day
• CrCl 20-40, max of 150mg/day
• CrCl 10-20, max of 100mg/day
• CrCl
• Toxicities include
• Skin rash, potentially Stevens-Johnson and TEN
• Leukopenia
• GI intolerance
• Initiation can precipitate gout attack

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Colchicine

• Mechanism binds to microtubules, blocks
  phagocytosis of uric acid crystals by PMNs,
  blocks release of chemotactic factor thus
  decreasing inflammatory response.
• Works best early in attack once inflammation
  exists it is less effective
• Side fx include
• GI intolerance
• Bone marrow suppression
• Renal damage
• Hepatic damage
• Axonal neuropathy
• Irreversible azospermia

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Probenecid

• Trade name Benemid
• Typical dosing
• Start 500mg bid, max of 2-3g/day
• Dose of 1-2g/day achieves control in 60-85 of
  patients
• Renal dosing
• Contraindicated if hx of nephrolithiasis or CrCl
  
• Use limited by physiologic decline in CrCl w/
  aging
• Side fx include
• GI intolerance
• Aplastic anemia, Hemolytic anemia, Hepatic
  necrosis
• Blocks excretion of other organic acids, thus may
  increase plasma concentrations of PCN,
  Cephalosporins, Sulfonamides, and Indomethacin

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Indomethacin

• 10-40x more potent anti-inflammatory than ASA
• Side fx
• CNS effects (HA, dizzyness, confusion, tinnitus)
  in up to 50
• GI side effects potentially severe w/ prolonged
  use (ulcers, GI bleed)

Quiz Question In what neonatal disease is this
medicine commonly used?
Answer PDA (Patent Ductus Arteriosus)
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The End