Feeling the chapter on gout in HPIM didn't sufficiently capture the essence of managing gout, I felt the need to come up with a presentation discussing how best to manage the disease and cover some related topics such as allopurinol adverse events, diet and genetic testing prior to allopurinol use. This is my talk on gout which I gave to my IM residents last April 2019

1. Type to enter a caption.
Review: GOUT
Sidney Erwin T. Manahan MD FPCP FPRA
Section of Rheumatology, East Avenue Medical Center

2. Disclosures
Pfizer (Celebrex)
Ajanta Philippines (Atenurix)

3. Coverage
How to diagnose?
How to manage acute gout?
How to prevent gout flares?
How to start and proceed with ULT?
Controversies

4. Is it GOUT?
Joint Pains
AND
Hyperuricemia
means GOUT?
Joint Inflammation
AND
The Gout, James Gillray 1799

5. Is it GOUT? 1977 ARA Classification
Criteria
Urate crystals in SF, OR
Urate crystals in suspected
tophus, OR
Any 6 of the following 12
>1 episode of acute arthritis
Maximal inflammation <24h
Monoarthritis
Joint redness
Podagra
Unilateral MTP1 attack
Unilateral tarsal jt attack
Suspected tophus
Hyperuricemia
Asymmetric jt swelling on XR
Subcortical cysts without
erosions on XR
Negative SF culture
Wallace SL, et al. Arthritis 1977; 20: 895-900.

6. Is it GOUT? 2014 Nijmegen score
NOT GOUT <4
Uncertain >4 but <8
GOUT >8
FEATURES Score
Male 2
Previous attack 2
Onset within 1 day 0.5
Joint redness 1
Podagra 2.5
HPN or >1 CV disease 1.5
SUA >5.88 mg/dl 3.5
Kienhorst LB, et al. Rheumatology (Oxford) 2014; 16: epub.

7. Developments in Imaging
Ultrasound - Tophus
Sen 0.65 / Spe 0.80
Ultrasound - DCT
Sen 0.80 / Spe 0.76
Dual Energy CT (DECT)
Sen 0.87 / Spe 0.76
Type to enter a caption. Type to enter a caption.
Type to enter a caption.

8. Is it GOUT? from 2015 onwards
2015 ACR EULAR Classification
Criteria
Clinical parameters (4)
Laboratory (2)
Imaging modalities (2)
Maximum score is 23
For gout, need a score >8
Neogi T, et al. Ann Rheum Dis 2015; 74: 1789-98.

9. ACR EULAR 2015 Gout
ENTRY CRITERION: At least one episode of pain, swelling or
tenderness in a peripheral joint or bursa
SUFFICIENT CRITERIA: Presence of MSU crystals in a symptomatic
joint, bursa or tophus

10. ACR EULAR 2015 Gout Criteria
JOINT INVOLVEMENT
Other joints/ polyarthritis (0)
Ankle/ mid foot (1)
MTP1 (2)
CHARACTERISTICS
Erythema
Can’t bear touch or pressure
Great difficulty ambulating
None present (0)
One present (1)
Two present (2)
All three present (3)

11. ACR EULAR 2015 Gout Criteria
EVIDENT TOPHUS
Absent (0)
Present (4)
TYPICAL EPISODE
Maximal pain <24h
Resolution <14 days
No symptoms between attacks
No typical episode (0)
One typical episode (1)
Recurrent typical episode (2)

12. ACR EULAR 2015 Gout Criteria
URIC ACID LEVELS
<4 mg/dl (-4)
4 - <6 mg/dl (0)
6 - <8 mg/dl (2)
8 - <10 mg/dl (3)
>10 mg/dl (4)
SYNOVIAL FLUID ANALYSIS
MSU negative (-2)
Not done (0)
DECT/ ULTRASOUND
Absent OR Not Done (0)
Present (4)
RADIOGRAPHS
Absent Or Not Done (0)
Present (4)

13. Performance of Criteria
CRITERIA Sensitivity Specificity
2015 ACR EULAR full 0.92 0.89
2015 ACR EULAR clinical 0.85 0.78
1977 ARA full 1.00 0.51
1977 ARA survey 0.84 0.62

14. Case A
68F consults for podagra of 2
days. She’s had several episodes
in the past with maximal sx in
12h, resolves in 1 week,
asymptomatic in between. PE
reveals warm, erythematous,
tender R MTP1.
SUA 8 mg/dl
ST swelling on radiographs
MTP1 2
3 Characteristics 3
Recurrent eps 2
No tophus 0
SUA 8mg/dl 3
SF not done 0
No DECT / US 0
No XR 0

15. Case B
56M consults for knee pain of 2
weeks duration. No prior
episodes. PE reveals a warm,
swollen, erythematous left knee
that is tender to touch. Knee is
kept in a flexed position.
SUA 9 mg/dl
ST swelling on radiographs
Knee 0
3 Characteristics 3
No typical episode 0
No tophus 0
SUA 9mg/dl 3
SF not done 0
No DECT / US 0
(-) Knee XR 0

16. Goals of GOUT Management
Acute Intercritical Chronic Tophaceous
Prevent further gout flares
Terminate an attack
Prevent
Complications
Reverse
Complications

17. Terminating ACUTE GOUT
VAS < 7/10 OR
few small joints OR
1-2 large joints
VAS > 7/10 OR
Polyarthritis OR
1-2 large joints
Monotherapy
Combination
Therapy
RESPONSE?
VAS >20% in <24H and >50% in >24H
RE-EVALUATE
DIAGNOSIS
Khan na D, et al. Arth Care & Res 2012: 64 (10): 1447-61.

18. Treatment Options: ACUTE GOUT
COLCHICINE NSAIDs STEROIDS
1 mg INITIALLY then 0.5 mg
AFTER 1 hour then
0.5 mg TID 12 hours later
Ibuprofen 2400 mg/d
Diclofenac 150 mg/d
Naproxen 1000 mg/d
Indomethacin 150 mg/d
Etoricoxib 120 mg/d
Celecoxib 400 mg/d
ALL FOR <8 DAYS
INTRA-ARTICULAR
INTRA-MUSCULAR
Prednisone 0.5-1 mkd for 5-
10 days
ACTH 25-40 IU SC
x 1-2 doses

19. Treatment Options: ACUTE GOUT
NSAIDs COLCHICINE Sys STEROIDS
IA Steroids AND any of the three

20. Considerations for TREATMENT
Condition Colchicine NSAIDs Steroids
CKD stage 3-5 👎* 👎
Heart Failure 👎 👎
Liver Cirrhosis 👎 👎
Peptic Ulcer Disease 👎 👎**
Diabetes 👎
Infections 👎
Anticoagulants 👎 👎
* Colchicine avoided if GFR <10; reduced dose if GFR 15-30
** Consider COXIBs; Celecoxib + PPI if high risk PUD

21. Preventing GOUT ATTACKS
COLCHICINE NSAID STEROID
0.5 mg OD-BID Naproxen 250 mg BID Prednisone <10mg/d
6 months of NO FLARES and TARGET SUA
(traditional)
If non-tophaceous gout, 3 months of NO FLARES
and TARGET SUA
If tophaceous gout, 6 months of NO FLARES,
TARGET SUA and RESOLUTION OF ALL TOPHI

22. Indications for Starting ULT
After the second flare (EULAR 2017)
Presence of tophi
Presence of UA Nephrolithiases
Radiographic evidence of gout
Co-morbid conditions that would complicate
management of gout (CKD, CV disease)
SUA >11 mg/dl (SUA>8, mg/dl EULAR 2017)

23. What is our GOAL?
TARGET SUA
• American College of
Rheumatology (ACR)
• British Society of
Rheumatology (BSR)
• European League Against
Rheumatism (EULAR)
• Philippine Rheumatology
Association (PRA)
SYMPTOM FREE
• American College of
Physicians (ACP)

24. Target for ULT
< 6 mg/dl
if no tophi
Reduces risk of gout
flares
< 5 mg/dl
if with tophi
Reduces risk of gout flares
Reduces tophus size (1 mm/mo)
Stone dissolution
? Improvement in renal function

25. When Do We Start ULT?
10 - 14 days AFTER the gout attack
resolves (PRA)
May be started DURING an acute attack
provided ADEQUATE anti-inflammatory
treatment is given (ACR)
25% chance of worsening, recurrent or
prolonged flare.

26. Treatment Options: ULT
Uricosurics
Xanthine Oxidase
Inhibitors (XOIs)
Uricase
Probenecid
Sulfinpyrazone
Benzbromarone
Lesinurad
Losartan
Fenofibrate
Amlodipine*
Allopurinol
Febuxostat
Pegloticase
Rasburicase
* Amlodipine showed uricosuric action in the setting of cyclosporine induced hyperuricemia

27. How do we proceed with ULT?
Start Allopurinol 100 mg OD
Increase by 100 mg/d
every 4 weeks until TARGET
Start Febuxostat 40 mg OD
Add uricosuric
Increase by 40 mg/d
every 2-4 weeks until
TARGET
Add uricosuric
Have you achieved your target SUA 2-4 weeks later?
Have you achieved your target SUA on follow up?

28. How do we proceed with ULT?
100 mg
200 mg
500 mg
300 mg
400 mg
600 mg
700 mg
800 mg
900 mg
40 mg
80 mg
120 mg
PNDF Drug
Non PNDF
Drug
Which is BETTER?
NO DIFFERENCE in
incidence of gout
flares, adverse events
and discontinuation
rates
Allopurinol 300 mg =
Febuxostat 40mg

29. ULT in the setting of CKD
ALLOPURINOL
Starting dose of 50 mg/d or 100
mg EOD when CKD stage 4-5
Titrate by 50mg every 4-5 weeks
Maximum dose is as tolerated by
patient’s kidney and liver
50% of dose given as
supplement after HD
FEBUXOSTAT
Starting dose of 20 mg/d when
eGFR <30 ml/min
Titrate by 20 mg every 4 weeks
Maximum dose 40-60 mg/d
Use not defined in HD

30. Can we give allopurinol > 300 mg/d
in patients with CKD?
Guarded YES.
EDUCATE patients of possible
adverse events
MONITOR for pruritus, rash,
increased LFTs, eosinophilia

31. Allopurinol Hypersensitivity Reactions
Interface between Rheumatology and Allergology

32. Spectrum of Allopurinol AEs
Median time: 3 weeks
90% occurred within 8-
9 weeks of starting
allopurinol
AHSSCAR
DRESS
SJS/
TENS
Stamp LK & Barclay ML. Rheumatology 2018; 57: i35-i41.

33. Features of Allopurinol AEs
Reaction Liver Renal Fever
Eosin
ophili
a
Leucocytosis Others
Allopurinol
Hypersensitivity
Syndrome
Yes
Drug Reaction with
Eosinophilia and
Systemic Symptoms
Atypical
lymphocytosis
Inflammation of internal
organs (inc. interstitial
pneumonitis, pleuritis &
ARDS)
TENS/ SJS
Atypical lymphocytosis
generally do not occur
Sore throat, conjunctivitis,
arthralgia, GI or respiratory
tract may be affected
Stamp LK & Barclay ML. Rheumatology 2018; 57: i35-i41.

34. Risk Factors for Allopurinol AEs
Stamp LK & Barclay ML. Rheumatology 2018; 57: i35-i41.
Recent
initiation of
Allopurinol
HLA-B*5801
Dose
Renal function
Diuretic use
TIME GENETICS
DRUG
CONCENTRATION

35. Who are likely to have HLA B*5801
COMMON
Han Chinese (13.3 - 20.4%)
Korean (12.2%)
Thai (8.1%)
LESS COMMON
Japanese (0.61%)
European (1.5 - 5.2%)
Would you give him
Allopurinol?

36. Impact of Dose on AHS
Allopurinol - intolerant Allopurinol - tolerant
Mean Starting Dose 183.5 mg/d 112.2 mg/d
> 1.5 mg/ml/min Allopurinol 91% 36%
> 2 mg/ml/min Allopurinol 79% 53%
SUGGESTION: Start Allopurinol at 1.5 mg x ml/min GFR
Chung WH, et al. Ann Rheum Dis 2015: 74: 2157-64.

37. Diuretics Concerns in Gout
Known risk factor for AHS/
SCAR
Increase urate levels (HCTZ)
Increase oxypurinol levels
Stamp LK & Barclay ML. Rheumatology 2018; 57: i35-i41.

38. Do we treat asymptomatic
hyperuricemia?
To reduce risk of gout, NO.
To prevent UA nephrolithiases, YES if SUA
>11 mg/dl.
To reduce CV events, need larger well
designed RCTs. (Allopurinol is still the
preferred drug, Febuxostat might increase
CV risks, review CARES)
To protect the kidneys, NO FURTHER
benefit after 1 year of use.

39. Do we still advise a low purine diet?
Type to enter a caption.
If a patient is able to strictly adhere to a low purine diet,
serum urate levels will only go down by 0.5-1 mg/dl.

40. Gout will make
a comeback!

41. Genes contribute
more to
hyperuricemia than
the food we eat.
Major TJ, et al. BMJ 2018;
363: k3951.

43. What food impacts on SUA
RAISE URIC ACID LEVELS LOWERS URIC ACID LEVELS
Beer
Liquor
Wine
Potatoes
Poultry
Softdrinks
Meat (beef, pork or lamb)
Eggs
Peanuts
Cold cereal
Skimmed milk
Cheese
Brown bread
Margarine
Non citrus fruit

44. Practical Dietary Advice
Weight loss if overweight/ obese
Limit alcohol intake to red wine
Avoid sugar sweetened
beverages (and anything with
corn syrup/ fructose)
Avoid food triggers if present
(until urate levels controlled).

45. Summary
Diagnosis of gout
Management tailored to stage of
disease
Discussed concerns over
allopurinol adverse events,
asymptomatic hyperuricemia
and dietary advice.

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