GOUT

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GOUT

• Dr Bhupesh Dhananjayan
• MD MPH

2
Definition

• Heterogeneous group of diseases involving
• An elevated serum urate concentration
  (hyperuricemia)
• Recurrent attacks of acute arthritis in which
  monosodium urate monohydrate crystals are
  demonstrable in synovial fluid leukocytes
• Aggregates of sodium urate monohydrate crystals
  (tophi) deposited chiefly in and around joints,
  which sometimes lead to deformity and crippling
• Renal disease involving glomerular, tubular, and
  interstitial tissues and blood vessels
• Uric acid nephrolithiasis
• Hyperuricemia serum uric acid 7mg (males) and
  6mg (females)

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Epidemiology

• Prevalence of hyperuricemia
• 2.3 41.4 in various populations.
• Corresponds with serum creatinine /BUN
  levels, body weight, height, age, blood pressure,
  and alcohol intake. (Taiwan)
• Body bulk (as estimated by body weight,
  surface area, or body mass index) has proved to
  be one of the most important predictors of
  hyperuricemia in people of widely differing races
  and cultures.
• Incidence of Gout
• Varies depending on population studied 1.8
  /1000 3.2/1000
• RR for blacks slightly higher (1.3)

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1977 ACR criteria for acute gout

• The presence of characteristic urate crystals in
  the joint fluid, or a tophus proved to contain
  urate crystals by chemical means or polarized
  light microscopy, or the presence of 6 of the
  following 12 clinical, laboratory, and
  radiographic phenomena
• 1. More than one attack of acute arthritis
• 2. Maximum inflammation developed within 1 day
• 3. Monoarthritis attack
• 4. Redness observed over joints
• 5. First metatarsophalangeal joint painful or
  swollen
• 6. Unilateral first metatarsophalangeal joint
  attack
• 7. Unilateral tarsal joint attack
• 8. Tophus (proven or suspected)
• 9. Hyperuricemia
• 10. Asymmetric swelling within a joint on x
  ray/exam
• 11. Subcortical cysts without erosions on x ray
• 12. Monosodium urate monohydrate microcrystals in
  joint fluid during attack
• 13. Joint fluid culture negative for organisms
  during attack

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Classification of Hyperuricemia and Gout

• Primary Hyperuricemia and Gout with No Associated
  Condition
• Uric acid undersecretion(8090)
• Idiopathic
• Urate overproduction (1020)
• Idiopathic
• HGPRT deficiency
• PRPP synthetase overactivity

• Secondary Hyperuricemia and Gout with
  Identifiable Associated Condition
• Uric acid undersecretion
•   Renal insufficiency
•     Polycystic kidney disease
• Lead nephropathy  
•  Drugs(Diuretics,Salicylates (low
  dose), Pyrazinamide, Ethambutol,Niacin, Cyclospori
  ne, Didanosine )
• Urate overproduction
•   Myeloproliferative/ Lymphoproliferative
  diseases / Hemolytic anemias/ Polycythemia
  vera/Other malignancies
•     Psoriasis/Glycogen storage disease
• Dual mechanism  
•  Obesity, ETOH,Hypoxemia and hypoperfusion

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Outcomes in Gout

• Clinical outcomes
• 60 of untreated gout have attacks within 1 yr ,
  78 have recurrence in 2 yrs, only 7 have no
  attacks in 10 yrs.
• Chronic tophaceous gout develops after 10 -20 yrs
  of untreated gout.
• Incidence decreased from 14 in 1949 3
  in 1972.(Oduffy et al)------colchicine effect
• Hyperuricemia control superior to self medication
  alone.
• Humanistic outcomes
• Treatment outcomes decrease QOL in pts with gout.
  
• Adherence to allopurinol only 56. (Riedel et al
  , managed care study)
• Economic outcomes
• Direct burden annually is 27.4 million USD. (men
  only)
• Patients with acute gout miss 3-5 days of work
  annually.
• Average cost-effectiveness ratio for patients
  using urate-lowering drugs is 487 to 983
  compared with a cost of 5070 to 6571 for those
  not using these agents.

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Diagnosis

• Clinical
• In men , initial attack monoarticular 1st MTP
  joint(50 of cases)
• Other jts involved instep/knees/wrists/
  olecranon bursa. Often begins at night. Usually
  abrupt , severely painful.
• Later attacks polyarticular , assoc with
  systemic signs., most often initial presenting
  complaint in women. (hands/tarsal jts/knees)
• Precipitants Minor trauma , ETOH, diuretic Rx,
  Surgery, severe medical illness, hypouricemic Rx.
• Tophi Classically , helix/ antihelix ,but rare
  more common , hands, feet, olecranon bursa.
  Complications ulceration/infection.
• Laboratory- GOLD STANDARD
• SF Analysis WBC ct 2000-100 000/ml
• MSU crystals-
  needle shaped , negatively birefringent.
• Serum Uric acid level important in monitoring
  treatment .(42 - normal levels)
• 24 hr uric acid collection useful in young pts
  with gout/ fam h/o

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Diagnosis

• Radiologic
• X RAY
• Punched out erosions only 45 of pts have them,
  takes 6 yrs to develop
• Martels sign
• CT/MRI/US/Bone scan
• Sensitive , non specific

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Treatment

• Acute gouty arthritis
• Anti- inflammatory drugs ( if s.creat no PUD)
• Colchicine preferred in pts without confirmed
  diagnosis of gout.
• Endpoints improvement in jt symptoms/ GI
  symptoms/ 10 doses taken.
• NSAIDs if diagnosis confirmed. Any NSAID can be
  used .
• Newer agents Etoricoxcib 120 OD comparable to
  indomethacin 50 TID.
• In c/o renal failure /PUD - IM ACTH , oral /iv
  prednisone.
• Avoid adjusting dosage of urate lowering agents.
• Prophylaxis
• Only indicated if patient is started on urate
  lowering Rx.
• Colchicine( 1-3 pills a day)/ NSAID( in
  colchicine intolerant).
• Does not alter crystal deposition and development
  of tophi.
• Continue till serum urate levels stabilize and no
  attacks for 3 6 mths.
• If long term prophylactic colchicine given, check
  CBC ,CK every 6 mths.

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Treatment (contd)

• Control of hyperuricemia
• Differing opinions regarding initiation esp.
  around 1st attack.
• Clear evidence if erosions on X-ray / chronic
  tophaceous gout/ 2 gout attacks per year.
• Goal s. urate levels
• Serial s. uric acid at least once every 6 mths
  upon initiation.
• Choice of agents
• Xanthine oxidase inhibitor
• Uricosuric agents.
• Equal efficacy in pts with normal renal function
  and who excrete

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Treatment (contd)

• Xanthine oxidase inhibitors
• Allopurinol- only prescription drug available.
• Renally excreted, therefore adjust dose if
  s.creat 2mg or CrCl
• Usually DOC in most patients.
• S/E GI / rash / sarcoid like reaction/Allopurino
  l hypersensitivity syndrome
• Drug interaction esp. with 6 MP/azathioprine/
  warfarin/theophylline.
• Desensitization protocols exist.
• Oxypurinol possible option
• Uricosuric agents
• Indications no h/o renal calculi , pts U.A excretion
• CI - nephrolithiasis, renal insufficiency
• Limit ASA to 81 mg/day
• Probenecid/ Benzbromarone

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Treatment (contd)

• Adjuvant Rx
• Control obesity ,ETOH intake, hyperlipidemia ,HTN
  
• Losartan / fenofibrate weakly uricosuric
• Diet moderation in purine intake. Makes a
  difference of up to 1mg in s. uric acid.
• Beer, other alcoholic beverages.
• Anchovies, sardines in oil, fish roes, herring.
• Yeast.
• Organ meat (liver, kidneys, sweetbreads)
• Legumes (dried beans, peas)
• Meat extracts, consommé, gravies.
• Mushrooms, spinach, asparagus, cauliflower

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Treatment (contd)

• Newer agents
• PEG- uricase
• Febuxostat
• Asymptomatic hyperuricemia
• Investigate cause
• No recommendations for Rx.

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THANK YOU