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Diagnosis and Management of Gout

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Diagnosis and Management of Gout Powered By Docstoc
					Diagnosis and Management of
            Gout
  The best medicine I know for rheumatism is
      to thank the Lord that it ain't gout.
                Josh Billings
              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
                       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.
• 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.
               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, Paget’s
            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              •   Psoriasis
•   Drug usage            •   Poisoning
•   Renal failure         •   Obesity
•   Hematologic Disease   •   Hypertension
•   Trauma                •   Organ transplantation
•   Alcohol use           •   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
• Inflammatory
  – Rheumatic arthritis, Reiter’s 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)
      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
• CBC
   – Mild leukocytosis in acute attacks, but may be higher than 25,000/mm
• ESR
   –   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.
       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
• NSAIDs
  – 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
• 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
          Acute treatment cont’d
• Corticosteriods
   – 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
• ACTH
   – 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
                    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
• Nephrolithiasis
• Joint deformity
• Recurrent Gout
Case study #1
• 56yo postmenopausal female with sudden onset of acute pain in her right
  toe and knee . The patient reported that she has had 3 previous episodes
  of the same symptoms lasting 4-5 days and treated by ED physicians. PMHx
  HTN treated with thiazide diuretic and patient is trying to lose weight and
  currently on the Atkins diet. BP 138/86 BMI 32 PE remarkable for swollen
  and tender right great toe and knee. UA 8.3mg/dL, aspiration of her knee
  demonstrated cell count of 15K and presence of urate crystals.
• Treatment options for this patient include all of the folllowing except:
    – A. Starting Allopurinol at 300mg/day with an NSAID for acute pain control
    – B. Discuss risk factors for gout to include obesity, stopping the Atkins diet but
      continue with weight loss and switching HTN meds.
    – C. Start colchicine at 0.6mg bid and start anti-hyperuricemia therapy in 4 weeks
    – D. Start therapy for acute pain with NSAIDs, but hold any anti-hyperuricemia
      meds until the results of the following labs have been reviewed: 24hr urine
      collection, Cr, lipid panel
Answer Case Study #1

• A. Starting Allopurinol at 300mg/day with
 an NSAID for acute pain control
  – Starting urate-lowering therapy during an
    acute attack will prolong the attack.
Case Study #2
• 50yo AAM who presents for evaluation of his long-standing gouty arthritis.
  He states that he has several attacks a year but he usually can treat them
  with OTC NSAIDs. However, he states that the attacks have become more
  frequent and the NSAIDs are not controlling the pain as well. Only other
  medical problem is his HTN for which he takes captopril. On PE: BP 135/85,
  BMI 31, temp nl. No gait abnormalities and exam remarkable for a small
  effusion over right knee and tophi noted over bilateral olecranons. Labs
  include UA 7.5mg/dL, ESR 23mm/hr and nl WBC count. X-rays of his knees
  noted narrowing of joint space with effusion on right side.
• Best treatment option for this patient is:
    – A. Start colchicine 0.6mg po bid and urate lowering therapy with allopurinol
    – B. Advise patient to discontinue NSAID therapy and use low dose prednisone
      daily for prophylaxis
    – C. Start colchicine 0.6mg po bid and uricosuric therapy with Probenecid
    – D. Since patient is between attacks, just start urate lowering therapy.
Answer Case Study #2

• A. Start colchicine 0.6mg po bid and urate
 lowering therapy with allopurinol.
  – Meds for lower uric acid levels are indicated
    for patients who have frequent attacks a year
    and those who have tophi or erosive arthritis.
    As urate therapy can precipitate an attack,
    patients also needs prophylactic meds for
    several months.
Case Study #3
• 60yo male presenting with persistent gouty symptoms despite taking allopurinol daily
    at 100mg/day for the past year. He has a 20 year hx of gout usually manifested by
    mono- or oligoarthritis involving his lower extremities. Patient has been treated with
    NSAIDs for his acute flairs; however, once the attacks became more common, he
    was placed on chronic NSAID therapy. PMHx significant for HTN and chronic renal
    insufficiency- last Cr 1.6. On PE: BP 125/73 BMI 34. no acute musculoskeletal
    symptoms but he has chronic synovial changes over wrists, and left first MTP. Tophi
    are noted over olecranon. UA 9.5mg/dL
•   The best treatment options for this patient is:
     –   A. Replace NSAIDs for chronic prophylaxis with prednisone starting at 30mg/day and then
         tape. Do not change allopurinol dose
     –   B. Continue to increase allopurinol despite his renal issues to a dose that keeps UA level
         below 6.0mg/dL and replace NSAIDs with other prophylactic therapy.
     –   C. Continue NSAID therapy for prophylaxis. Counsel patient that long term NSAID use and
         HTN can contribute to increasing renal disease.
     –   D. Discontinue all current meds and replace them with Colchicine 0.6mg po bid
     –   E. None of the above
Answer Case Study #3
 – B. Continue to increase allopurinol despite his
   renal issues to a dose that keeps UA level
   below 6.0mg/dL and replace NSAIDs with
   other prophylactic therapy.
Questions?
                      References
• Klippel, JH.Primer on Rheumatic Diseases. 12th ed. Arthitis
    Foundation 2001; 307-323.
•   Schumacher HR, Chen LX. Newer Therapeutic Approaches: Gout.
    Rheumatic Disease Clinics of North America 2006;32.
•   Pittman, JR, Bross, MH. Diagnosis and Management of Gout.
    American Family Physician 1999;59
•   Monu JU, Pope TL. Gout: a clinical and radiologic review. Radiologic
    Clinics of North America. 2004;42
•   Goldman. Cecil Textbook of Medicine. 22nd ed. W.B. Saunders
    Company 2004;
•   Shen S, Wolfe R. Gout. Emergency Medicine Clinical Reviews. 2004
Review Question #1
• A 62yo male comes into your office with pain and swelling over left
   great toe at MTP joint. Exam shows it is erythematous, warm
   swollen, tender to touch. The patient has a history of DM controlled
   by diet and HTN. His medications include HCTZ 25mg daily. A CBC
   and blood chemistry profile are normal except for uric acid level of
   9.2 mg/dL(Nl 3.6-8.5).

• Which of the following is true in this situation?
    –   A. This attack should resolve spontaneously in 3-4 days
    –   B. Allopurinol therapy should be started
    –   C. The elevated uric acid level establishes diagnosis of gout
    –   D. Intra-articular injection should be avoided
    –   E. Stopping the HCTZ may control hyperuricemia
          Answer #1

• E. Stopping HCTZ may control
 hyperuricemia.
Question #2A
• A 32 year-old male visits your office complaining of pain of 12 hr
  duration in the MTP joint of large left toe. He states that the joint is
  very tender to touch and denies history of trauma. He is on no
  meds. Exam is within normal limits except for large area of
  erythema over his left large toe and up onto the dorsum of his foot.
  No lymphangitis is noted.
• Tests which would help establish a definitive diagnosis include which
  of the following?
    –   A gram stain of the fluid aspirated from the joint
    –   24hr urine collection for protein
    –   An X-ray of foot and ankle
    –   Microscopic examination for crystals in the synovial fluid aspirate
    –   Intravenous pyelography
Question #2 Answer
• Tests which would help establish a definitive
  diagnosis include which of the following?
  T: A gram stain of the fluid aspirated from the joint
  F: 24hr urine collection for protein
  F: An X-ray of foot and ankle
  T: Microscopic examination for crystals in the synovial
    fluid aspirate
  F: Intravenous pyelography
Question #2B
• Appropriate drug choices for the initial
  management of this acute gout attack include
  which of the following?
   –   A. Colchicine
   –   B. Probenecid
   –   C. Nafcillin
   –   D. Prednisone
   –   E. Indocin
   –   F. Allopurinol
Answer #2B
• Appropriate drug choices for the initial
  management of this acute problem include
  which of the following?
   –   T: Colchicine
   –   F: Probenecid
   –   F: Nafcillin
   –   T: Prednisone
   –   T: Indocin
   –   F: Allopurinol
Question#3
• You are able to aspirate synovial fluid from the
  joint, to establish diagnosis of gout, which of the
  following joint findings will establish the
  diagnosis of gout?
  –   A. Negatively birefringent needle shaped crystals
  –   B. Positively birefringent needle shaped crystals
  –   C. Snowball like aggregate crystals
  –   D. Dumbbell and octahedron shaped crystals
Answer #3

• A. Negatively birefringent needle shaped
 crystals
                                   Gout
• Introduction
• Etiology
     – Primary vs secondary gout
• Epidemiology
     – Age, gender and race
•   Pathophysiology
•   Predisposing factors
•   Associated conditions
•   Presentation
     – History, PE, Lab and Radiology work-up
• Differential Diagnosis
• Treatment Summary
     – Pharmacologic
     – Non-pharmacologic
        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
        Associated Conditions

• Cardiovascular Disease
• Paget’s disease
• Arthritis- rheumatoid and osteoarthritis
• Septic Arthritis
• Metabolic syndrome