1. Scott Vogelgesang, M.D. Division of Immunology: Rheumatology & Allergy
Gout 2.0
Scott Vogelgesang, M.D.
Division of Immunology: Rheumatology & Allergy

2. 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 ….

3. Case (continued) Now what? Next diagnostic step?
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?

4. Arthrocentesis Demonstrate crystals Needled-shaped
Intracellular
Negatively birefringent (“parallel-yellow”)
Rule out septic joint

5. 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?

6. 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

7. 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,

8. Ultrasound “Double Contour Sign” No radiation $ < than CT
Irregular echogenic line over the superficial layer of hyaline cartilage
No radiation
$ < than CT
Performance
Specific
Not sensitive
CT = computed tomography
Durcan L et al. Semin Arthritis Rheum 2015,

9. 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?

10. (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

11. Choices depend on severity and number of joints
Case - Management
Choices depend on severity and number of joints

12. 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

13. NSAIDs Use any short-acting NSAID- Full dose Use at onset of symptoms
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

14. 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,

15. Prednisone 0.5 mg/kg x 5-10 days then stop –or-
0.5 mg/kg x 2-5 days then taper over 7 days

16. Joint Injection Rule out infection before injecting steroids
Not routinely done unless cultures negative for hours

17. Case Should we stop his HCTZ? Should we stop his aspirin?
“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 February;81(2):83, 86

18. 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

19. Chronic/Tophaceous Gout
Destructive, chronic arthritis
Rate of urate deposition  SUA level
Can be polyarticular with systemic features

20. 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
New!

21. 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

22. Allopurinol Xanthine oxidase (competitive) inhibitor Dose
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

23. 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

24. Probenecid Uricosuric – monotherapy or combo with XOI
Rarely used anymore
Ideal candidate:
XOI not tolerated
< 60 years of age
normal renal function (GFR > 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

25. 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

26. Other Options
Pegloticase (uricase): Persistent activity despite (or intolerance to) combination urate lowering therapy
IL-1 antagonists
IL-1 = Interleukin-1

27. 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)

28. 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

29. Questions?
References
Neogi T. Clinical practice: gout. New Engl J Med 2011;364:
Khanna D, et al American College of Rheumatology Guidelines for Management of Gout Part 1. Arthritis Care Res 2012;64(10):
Khanna D, et al American College of Rheumatology Guidelines for Management of Gout Part 2. Arthritis Care Res 2012; 64:
Mandel B. Cleveland Clinic Journal of Medicine February;81(2):83, 86
Zhang w et al. Ann Rheum Dis 2006;65:1301