gout - familyphysician.centerforconferences.uiowa.edu · chronic/tophaceous gout •destructive,...
TRANSCRIPT
Case• 48 year old man presents with swollen, painful left toe that
started overnight. Didn’t hurt when he went to bed. No trauma,
never happened before. No fever, no family history of arthritis or
gout.
• PMH: Hypertension, Hyperlipidemia
• Meds: HCTZ 25 mg daily, atorvastatin 20 mg daily, aspirin 81
mg daily
• SH: No tobacco, ETOH – 5-10/week
• Exam:
– t36.8 p95 (increases to 115 when you use the word “needle”), bp148/91
– Rest (except right toe) unremarkable
– Left toe ….
Case (continued)
• CBC, Electrolytes, liver tests normal
• Serum Uric Acid 5.2 mg/dl
• X-ray of the foot shows only soft-tissue
swelling.
Now what? Next diagnostic step?
Arthrocentesis
• Demonstrate crystals
• Needled-shaped
– Intracellular
– Negatively
birefringent (“parallel-
yellow”)
• Rule out septic joint
Alternate scenario
• “…you want to poke a needle where?!! I came to see
you to make this better, not make it hurt worse! Come
on, can’t you tell me what this is without sticking a
needle into my already sore toe?”
• Your records indicate that when you started his
statin, he had a serum uric acid of 10.2 mg/dl.
• Can we make a diagnosis without aspiration?
Presumptive Diagnosis:(Unable to demonstrate crystals)
• Rapid development of severe pain (≤ 24 hrs)
• Pain, erythema, swelling – typical joint
• Hyperuricemia
• ~80% probability of having gout – Zhang w et al. Ann Rheum Dis 2006;65:1301
Dual Energy Computed Tomography(DECT)
• Identifies urate deposits– Using chemical properties of
urate
• Yield 85-90% • False negative scans:
– 1st episode of gout
– Symptom duration < 6 weeks
• False positive– Osteoarthritis
• Similar to conventional CT– Radiation exposure
– Expense
Durcan L et al. Semin Arthritis Rheum 2015, http://dx.doi.org/10.1016/j.semarthrit.2015.09.008
Ultrasound
• “Double Contour Sign”– Irregular echogenic line over the superficial layer of hyaline cartilage
• No radiation
• $ < than CT
• Performance– Specific
– Not sensitive
Durcan L et al. Semin Arthritis Rheum 2015, http://dx.doi.org/10.1016/j.semarthrit.2015.09.008
Case
• “… you mean, you knew I had high levels of
that gout chemical and you didn’t treat it?
Could you have prevented this pain in my
toe?”
• Should we treat asymptomatic
hyperuricemia?
(Asymptomatic) Hyperuricemia
• Onset:
– Men: puberty
– Women: menopause
• Level of SUA correlates with likelihood of
acute gout, renal stones BUT only 1-10% of
those with hyperuricemia will develop acute
gout
• Not treated
Baseline Recommendations
• Education, diet & lifestyle
recommendations
– Avoid high-purine foods,
alcohol overuse
– Encourage low/non-fat dairy
products and vegetables
– Weight loss
– Smoking cessation
– Increase exercise
• Secondary Causes
– Obesity
– Excessive alcohol
– Metabolic syndrome
– Hypertension
– Hyperlipidemia
– History of urolithiasis
– Chronic kidney disease
– Genetic/acquired cause of urate
overproduction
– Lead intoxication
NSAIDs
• Use any short-acting NSAID- Full dose
– FDA: indomethacin, naproxen, sulindac
– No functional difference in efficacy
• Use at onset of symptoms
– Keep Rx available so no need to call office
• Continue until attack resolves
• Usually better tolerated than colchicine
Colchicine:Oral
• 1.2 mg then 0.6 mg 1 hour later
• 12 hours later 0.6 mg qd or BID
• Mechanism:
– Inhibits microtubule formation
– Decreases inflammatory response
• Side Effects: NVD, marrow suppression, death,
hepatitis, seizures, respiratory depression, alopecia,
Joint Injection
• Rule out infection before injecting
steroids
• Not routinely done unless cultures
negative for 24-72 hours
Case
• Should we stop his HCTZ? – “The decision should be individualized, taking into consideration the degree to which the thiazide increases the
serum urate level, whether this increase can be managed without overly complicating the patient’s
hypouricemic therapy, and, most importantly, what effect switching to another drug will have on the control of
the patient’s hypertension.”
– “No study has directly addressed this issue.”
• Should we stop his aspirin?– “…aspirin in low doses for cardioprotection (81 mg daily) also need not be stopped in patients with
hyperuricemia or gout in an effort to better control the serum urate level. Low-dose aspirin increases the serum
urate level by about 0.3 mg/dL. Since patients with gout have a higher risk of having cardiovascular disease,
metabolic syndrome, and chronic kidney disease, many will benefit from low-dose aspirin therapy.”
• Could we substitute losartan for HCTZ?– “Losartan is a weak uricosuric and can lower the serum urate level slightly, possibly making the addition of
another hypouricemic agent unnecessary, while still controlling the blood pressure with a single pill. This
decision must be individualized, taking into consideration the efficacy and cost of the alternative
antihypertensive drug, as well as the potential but as yet unproven cardiovascular and renal benefits of
lowering the serum urate with a more potent hypouricemic to a degree not likely to be attained with losartan
alone.”
Mandel B. Cleveland Clinic Journal of Medicine. 2014 February;81(2):83, 86
Case
• Same patient 10 years later…
• Managed his “attacks” by taking ibuprofen 800 mg three times
daily at the first “twinge” of toe pain for 5 days
• Frequency of attacks has been increasing over the past few
years – now he gets 4-5 attacks per year and the ibuprofen
doesn’t completely abate the attacks anymore.
• He returns to clinic for advice…
• Exam:
– T37.1 p82 bp 127/78
– Rest unremarkable (no tophi)
– CBC, Liver tests, electrolytes normal. Serum Uric Acid 10.4 mg/dl
Chronic/Tophaceous Gout
• Destructive,
chronic arthritis
• Rate of urate
deposition SUA
level
• Can be
polyarticular with
systemic features
Urate Lowering Therapy
• Indications– 1 gout attack & chronic kidney disease
– Tophi
– ≥ 2 attacks/year
– History of urolithiasis
• Medications– Xanthine Oxidase Inhibitors (XOI)
• Examples: Allopurinol, Febuxostat
• Stop purine metabolism (inhibit xanthine oxidase)
• Uric acid doesn’t form
– Uricosurics: • Example: Probenecid
• increase renal excretion of uric acid
– Urate Transporter (URAT1) inhibitor• Example: Lesinurad
• inhibits uric acid reabsorption
– Uricase: converts uric acid to allantoin
Overall Approach to Therapy
• Allopurinol or Febuxostat (XOI)
– Treat to at least ≤ 6.0 mg/dl (< 5.0 mg/dl if tophi)
– Increase intensity and re-evaluate
– If not successful, consider adding lesinurad
• Probenecid as alternative if XOI is contra-indicated or
not tolerated
• Add uricosuric with both agents titrate to max
appropriate dose
• If ineffective, consider pegloticase
Allopurinol• Xanthine oxidase (competitive) inhibitor • Consider HLA-B*5801 in Koreans with CKD 3, Chinese, Thai
• Dose
– Start 100 mg/day (50 mg/day in CKD 4)
– Titrate up q 2-5 weeks
– Max 800 mg/day
• Side Effects: TEN, NVD, marrow suppression, hepatitis,
fever, vasculitis, alopecia
• Drug interactions: azathioprine
• Any change in SUA can precipitate acute flare of gout
• Beware of allopurinol hypersensitivity – TEN can be fatal
Febuxostat
• Xanthine Oxidase inhibition (non-competitive)
• 40 mg qd (max 80 mg)
• Side Effects
– Cardiovascular (MI, CVA)
– Elevated LFTS
– Gout Flare
• Avoid combo with azathioprine
Probenecid
• Uricosuric – monotherapy or combo with XOI
• Rarely used anymore
• Ideal candidate:– XOI not tolerated
– < 60 years of age
– normal renal function (GFR > 30-60 ml/min)
– 24 hour urine uric acid < 800 mg
– no history of stones
– > 2 attacks/year
• 250 mg BID (max 3g/day)
• Side effects: rash, NVD, marrow toxicity
Lesinurad
• Urate transporter (URAT1) inhibitor
• 200 mg daily
• Used in combination with XOI
• Side Effects
– Renal failure (stop if CrCl < 45)
– Headache
– GERD
• Avoid with ASA, valproic acid, OCP
Other Options
• Pegloticase (uricase): Persistent activity
despite (or intolerance to) combination urate lowering
therapy
• IL-1 antagonists
Prophylaxis
• Colchicine (or NSAIDs) to prevent an acute
exacerbation while initiating hypouricemic
therapy
– Colchicine 0.6 mg qd - BID
– indomethacin 25 mg qd – BID
• Duration: Greater of…
– 6 months –or-
• 3 mos after target SUA (no tophi)
• 6 mos after target SUA (with tophi that resolved)
Take Home Points
• Diagnosis of gout:
– Crystal identification
– Presumptive Dx Criteria
– Dual Energy CT
– Ultrasound
• Asymptomatic
Hyperuricemia not
treated.
• Acute treatment:
– NSAIDs
– Colchicine
– Prednisone
• Allopurinol: – ≥ 2 attacks/yr,
– stones,
– GFR,
– tophi,
– TLL,
– Enzyme deficiency
Questions?
• References
– Neogi T. Clinical practice: gout. New Engl J Med 2011;364:443-52.
– Khanna D, et al. 2012 American College of Rheumatology Guidelines for
Management of Gout Part 1. Arthritis Care Res 2012;64(10): 1431-1446.
– Khanna D, et al. 2012 American College of Rheumatology Guidelines for
Management of Gout Part 2. Arthritis Care Res 2012; 64:1447-61.
– Mandel B. Cleveland Clinic Journal of Medicine. 2014 February;81(2):83, 86
– Zhang w et al. Ann Rheum Dis 2006;65:1301