Dr. A Sumathi - LINEARITY CONCEPT OF SIGNIFICANCE.pdf
Sabah ( Malaysia) rheumatology update gout 2016
1. Gout: Aim for SIX
Treating for CURE
Sabah Rheumatology Update 2016
2. Where are we in understanding the
optimal management of Gout?
• Above par
• Below par
• We are no where
• All of the above
3. To answer this question....
• Review 98 case notes from HRPZ II
record office on Upper
Gastrointestinal Bleed Secondary to
Chronic Ingestion of NSAIDs (2010-
February 2012)
• How many of them are taking NSAIDs
due to Gouty arthritis
5. Where are we in understanding the
optimal management of Gout?
• We have some knowledge however it is
not at par
• We don't want to say we are no where in
the treatment of gout
• We are not optimal in our management
of gout patients
6. Why SIX?
6 mg/dl ( 360 micromol/L)
• Saturation point of serum uric acid
• New crystals cannot form and existing crystals
are dissolved
- Freedom from gout attacks
- Shrinkage and disappearance of tophus
7. • 267 patients, 87% ULT: strong correlation between average
SUA and gout attacks ( p<0.001)
Shoji A et al: Retrospective study of the relationship of SUA and attacks of gout. Arthritis Rheum 2004
• Patients with SUA >6 mg/dl experienced mean 6 attacks/year
compared to mean of 1 attack and almost half had no attack
for 2 years
Li-Yu et al: Treatment of chronic gout, can we determine when urate stores are depleted. J Rheumato 2001
• Gout flares were almost completely eliminated by the second
year of ULT targeting SUA < 6mg/dl
Perez et al:Randomised controlled Treatment of chronic gout in Renal impairement. J Rheumatolo 1999
• The lower SUA level, the faster the decrease in tophus size
Perez et al: Effect of ULT on the velocity of size reduction of tophi in chronic gout. Arthritis Rheuma 2002
Evidence
9. Scope of Lecture
• Case discussion
• Management of Acute Gout
• Management of Chronic Gout
• Co morbidities
• Dietary advise
• Asymptomatic hyperuricemia
10. Clinical Case
• 32 years old, referred by GP
• Unemployed for 3 months
due to illness
• Recurrent joint pain over 10
years – initially over both 1st
Metatarsophalangeal joint
• On regular voltaren, IM
injections, traditional herbs
• had tophi excision and
passing out sandy urine past
3 years
11. Case continue.....
• Defaulted Allopurinol due to recurrence of
joint pain with allopurinol
• Medical illness: Hypertension, Hyperlipidemia
• Clinically wheel chair bound with multiple
infected tophus – bilateral 1st
MTPs, knees,
elbows and small joints of both hands
- Hypotensive with evidence of sepsis
12. 4C: Confirm, Causes, Complication and
Co morbidities
• Leukocytosis 19.9 with thrombocytosis 660
• Anemia 9.6 g/L
• Serum Uric Acid 660micromol/L ( 11mg/dL)
• Serum creatinine 85 micromol
• Blood culture: Staph aureus
• OGDS – no overt bleeding
• Ultrasound KUB: nephrocalcinosis, (L) renal
nephrolithiasis. No hydronephrosis
13. Diagnostic Criteria for Gout
• 2 of the following criteria are required for a clinical
diagnosis:
Presence of a clear history of at least 2 attacks of
painful joint swelling with complete resolution within
2 weeks
A clear history or observation of
podagra
Presence of a tophus
Rapid response to colchicine within 48 hours of
starting treatment
14. A definitive diagnosis can be made if crystals
of monosodium urate are seen in the
synovial fluid or in the tissues
15. How do you manage the acute gouty
arthritis in this patient ?
• NSAIDs and COX 2 inhibitors
• Colchicine
• Steroid
NO
YES definitely
YES
17. Terminating the Acute Gout Flare
Important issues:
•Early initiation of anti inflammatory
therapy to reduce pain and disability
•Adequate dosing
•Appropriate (brief) duration of therapy
•Consideration of patient co-morbidities
( renal impairment in up to 40% of gout patients)
18. Terminating the Acute Gouty flare
Options:
NSAIDs, including COX 2 inhibitors
Colchicine: low dose vs high dose regimens
Corticosteroids : oral, parenteral, or intraarticular
Interleukin 1 inhibitors: anakinra, canakinumab (off
label use)
19. Non selective or selective
Effective in relieving pain and reducing inflammation
•Non selective NSAIDs: diclofenac, indomethacine
•COX-2 inhibitors: celecoxib, etoricoxib
NSAIDs
In those at risk of peptic ulcer disease, intolerant of non
selective NSAIDs or those requiring a prolonged course
of NSAIDs treatment, COX-2 inhibitors are indicated
20. COLCHICINE
• Low dose regimens recommended
Tab Colchicine 0.6mg TDS
Helpful for prophylaxis before initiation of urate
lowering therapy
Maintenance
Tab Colchicine 0.6mg OD
Helpful for prophylaxis before initiation of urate
lowering therapy (ULT)
21. COLCHICINE
Renal impairment dose adjustment:
Creatinine Clearance ml/min Dose adjustment
More than 50 No dose adjustment
35-49 0.6 mg BD
10-34 0.6 mg EOD
Dialysis 0.3mg 2X/week
22. Role of STEROID during acute flare
• Considered in elderly patients and those with
renal insufficiency, hepatic dysfunction,
cardiac failure, peptic ulcer disease
• Short course oral prednisolone
• Low dose 0.3-0.5mg/kg BW for 4-10 days
• Intra articular injection especially
1 or 2 joints involvement
• Intramuscular and intravenous
No role of long term glucocorticoids in
the treatment of gout
23. Patients starting urate-lowering
therapy need to understand the
importance of prophylactic therapy
with colchicine or NSAIDs to reduce the
risk of ‘mobilization flares’ in the first
few months
24. Intra articular Triamcinolone 40mg + 1% lignocaine
injection done under aseptic technique to his left knee
Dramatic improvement of his symptoms and he was
discharge
Uric acid 620 micromol/liter after hydration
hemoglobin improves to 11.2 g/L
Left knee pain and swelling persisted despite Tramadol
and Tab Prednisolone 20mg OD
25. • What are the indications for urate lowering agent in
him?
• Will you start urate lowering agent Allopurinol?
• What is your aim of serum uric acid (SUA) level?
You saw him in your clinic after 3 weeks
Serum Uric acid of 670 micromol/L
Normal renal function
26. When do you start Urate Lowering
Therapy?
1. Frequent and disabling attacks of gouty arthritis
( 3 or more attacks/year)
2. Clinical or radiographic signs of erosive gouty
arthritis (Role of Ultrasound)
3. Presence of tophaceous deposits
4. Urate nephropathy
5. Urate nephrolithiasis
6. Impending cytotoxic chemotherapy or radiotherapy
for lymphoma and leukemia
27. How do we treat?
2 Principles:
1.Termination of crystal induced inflammation and
pain
2.Get Rid of Monosodium Urate crystals
Aim for serum uric acid level
less than 360 micromol/L
(<6.0mg/dL )
29. Allopurinol
• Current mainstay of urate lowering therapy
• Approve daily dose is 100- 800mg
• 95% of dosing is at < 300mg/day
• Many gout patients do not reach goal serum uric acid
< 360micromol/L (< 6.0 mg/dL) at 300mg/day
Intolerance in 10% and rare hypersensitivity
syndrome
Recurrent gout flares early in treatment
30. Allopurinol naive patients – don’t start
allopurinol when they come with acute gout
For those who have been on Allopurinol – don’t
stop or increase dose of allopurinol during acute
gout
31. Allopurinol dose reduction in CKD
• Widely employed
• No evidence that allopurinol is nephrotoxic
• Cautious titration of allopurinol dose with
monitoring of renal profile
• Cautious titration to serum uric acid goal has
been safe and successful
32. Creatinine Clearance
ml/min
Dose adjustment
More than 90 300-800mg OD
60-89 200mg OD
30-59 100mg OD
Less than 30 50-100mg OD
Allopurinol - Renal impairment dose
adjustment
Allopurinol - Renal impairment dose
adjustment
33. You saw him in your clinic after 3 weeks
Serum Uric acid of 670 micromol/L
Normal renal function
He was started on Tab Allopurinol 150mg OD
On Tab Colchicine 0.6mg mg OD
Within 3 months, Tab Allopurinol was increased to
450mg OD and SUA reduced to 382micromol/L
He was put on Tab Losartan for his BP control
34. • Recent review in January 2016
Serum Uric acid was 209micromol/L ( 3.4mg/dl)
Symptoms free
Tophus over both MTPs shrunken
Now working at furniture factory and helping
his wife selling nasi lemak
35. Case 2
• 50 years old lorry driver. Met during SOCSO
• Diagnosed Gouty arthritis for 9 years
• Initial presentation Left 1st
MTP
• Had 3-4 attacks per year
• Developed multiple tophi over the year
• No history of passing out sandy material
• Not known any medical illness
36. Does he has indication for ULT?
• He developed blistering skin lesion with mucosal
involvement with Allopurinol 50mg OD
• What will be your next option
37. Probenecid
• Alternative to allopurinol in patients
with normal renal function
• Make sure :
24H urate excretion is less than 800mg/day
No urate nephropathy or nephrolithiasis
Initial dose is 0.5-1 gram and can be increased to 1.5-
2 gram in divided doses
38. Case Continuation
• He was started on Tab Probenecid 500 mg OD
• His serum uric acid improves from 662 micromol/L to
481 micromol/L within 3 months
• Noted slight deterioration of renal function
• Presence of RBCs in urine microscopy
• Ultrasound KUB – bilateral medullary nephrocalcinosis
• It was changed to Febuxostat 40 mg OD ( later
increase to 80mg OD)
• His latest SUA 225 micromol/L with resolution of tophi
39. Febuxostat
• Xanthine oxidase Inhibitor
• 40mg and 80 mg
• Safe in:
mild to moderate renal ( CrCl 30-89mL/min)
mild to moderate liver impairment (Child-Pugh Class
A or B)
• Alternative to Allopurinol allergies
45. Progression of Gout
Asymptomatic
hyperuricemia
Male >420micromol/L
Female >360micromol/L
Progression to
clinical gout
20-30%
Acute Gout Urate lowering
agent indicated
Aim uric acid level
<360micromol/L
Lifestyle
measures
Frequent flares
Renal function
Monitor SUA
Stone disease
Co-mobidities
Suppress pain and
inflammation as soon
as possible
NSAIDs
Cox 2 inhibitor
Colchicine
corticosteroid
Lifestyle measures
46. Lifestyle Modification
• Weight reduction
• Restriction of alcohol intake
• Reduce intake of purine
rich foods
• Adequate water intake
of 2-3L/day
• Moderate intake of purine
rich foods and vegetables
47. Food Diary
Dietary Advise
High Purine
Internal Organs - brains, liver,
sweet bread, heart
Goose
Meat Extract
Mackerel, sardines, anchovies
Yeast
Moderate Purine
Red meat
Chicken
Shellfish
Seafoods
Fish
Vegetables – asparagus,
beans,
broccoli,spinach and
mushroom
48. Diabetes mellitus, hypertension, hyperlipidemia and
obesity are the common so-morbid conditions
associated with gout and they should be screened
for in individual with asymptomatic hyperuricemia
and gout – Grade C
Clinical Practive Guideline Management of
Gout,Malaysia Oct 2008
Isolated hyperuricemia has not been shown to be
associated with an increased risk of death from
CHD, CVD or all causes of death in men
49. Asymptomatic Hyperuricemia
A state in which SUA is abnormally high but
with neither signs nor symptoms of urate
deposition have occured
(male > 0.42 mmol/L (7.0 mg/dL)
(female > 0.36 mmol/L (6.0 mg/dL)
2/3 of individuals will remain
asymptomatic throughout their lives
50. • Hyperuricaemia is associated with three major
disorders: gout, urolithiasis and nephropathy.
Asymptomatic Hyperuricemia
Routine prophylactic treatment is not
needed in asymptomatic hyperuricaemic
individuals
51. The clinical manifestations of gout are due to
deposition of MSU crystals and if the crystals
are dissolved completely and no new crystals
can form, then the condition is cured.
GOUT: Aim for 6, Treating for Cure
Thank you
Editor's Notes
SUA should be linked to the saturation level of MSU rather than to the normal laboratory change
Lower target may be appropriate in patients with xtensive crystal deposition
Acute gout - only 7% of patients do not have a recurrence with the next 10 years
&gt; than 80% had second attack within 1st and 2nd year
Intercritical gout – periods in between attacks when the patient is asymptomatic
Chronic polyarticular gout – marked by polyarticular arthritis and formation of tophi
Usual course is intermittent attacks and remission, followed by a chronic phase
Intercritical history whereby patients are asymptomatic in between attacks put more weight for the diagnosis of gout
virtually all anti inflammatory agents have been used effectively
Studies have shown that etoricoxib has equal efficacy to indomethacin in the treatment of acute gout, with etoricoxib showing an improved safety profile
