Wilson’s disease – how do i manage dr. ashish bavdekar

Talk: How do I manage a child with Wilson disease?
Speaker : Ashish Bavdekar

1. Wilson’s Disease – How do I manage ?

Dr. Ashish Bavdekar
Associate Professor
Consultant Ped. Gastroenterologist
K.E.M. Hospital, Pune
[email protected]

2. Zn + penicillam
ine
Zn + trientine
Zn sulfate
Zn acetate
trientine
penicillamine
transplanted
EuroWilson: initial treatment
Why?
“Available in our country
Cheap
Tried and tested
What we’ve always used
“Not available in our country
Kept as second line
Not as effective?
“expensive”

3. Wilson’s disease – management
- Low copper diet - Serving size (< 0.1mg, 0.1-0.2,
> 0.2mg)

5. Wilson’s disease – management
- Low copper diet - Serving size (< 0.1mg, 0.1-0.2,
> 0.2mg)
- Medications - D-Penicillamine
- Trientine
- Zinc
- Ammonium molybdate

6. Wilson’s Disease - therapy
1) Reduce Cu to sub-toxic threshold
- takes 6-12 months
- DP, Trientine
2) Maintain slightly negative Cu balance
- life long therapy
- DP, Trientine, Zn

7. DP Trientine Zinc
Chelator Chelator Induces MT
Easy availabilityPatient named
basis
Easy availability
Reasonable costV Expensive Cheap
Side effects
Neurological
Minimal SE Gastric
discomfort

8. Treatment: Hepatic cases
 acute liver failure with encephalopathy
 acute liver failure without encephalopathy
 intermediate severity
 Asymptomatic transaminitis
 Asymptomatic and normal LFTs
 Neonate detected by screening
List for Tx
Trientine + zinc
‘bridge’
Modified Kings score
Tx if >11
Trientine + zinc

9. Score Bilirubin
mol/L
ɥ
INR AST
IU/L
WCC
x 10
9
/L
Albumin
g/L
0 0-1000-1.29 0-100 0-6.7 >45
1 101-1501.3-1.6101-1506.8-8.334-44
2 151-2001.7-1.9151-3008.4-10.325-33
3 201-3002.0-2.4301-40010.4-15.321-24
4 >301 >2.5 >401 >15.4 <20
Modified King’s score
A score > 11 = urgent need for transplantation
Validated in other centres; better than PELD

10. Treatment: Hepatic cases
 acute liver failure with encephalopathy
 acute liver failure without encephalopathy
 intermediate severity
 Asymptomatic transaminitis
 Asymptomatic and normal LFTs
 Neonate detected by screening
List for Tx
Trientine + zinc
‘bridge’
Modified Kings score
Tx if >11
Trientine + zinc
Zinc
Zinc – when to start?

11. Treatment: Hepatic cases
 acute liver failure with encephalopathy
 acute liver failure without encephalopathy
 intermediate severity
 Asymptomatic transaminitis
 Asymptomatic and normal LFTs
 Neonate detected by screening
List for Tx
Trientine + zinc
‘bridge’
Modified Kings score
Tx if >11
Trientine + zinc
Zinc
Zinc – when to start?
Trials needed

12. DP Trientine Zinc
Chelator Chelator Induces MT
Easy availabilityPatient named
basis
Easy availability
Reasonable costV Expensive Cheap
Side effects
Neurological
Minimal SE Gastric
discomfort
Initial therapyInitial therapyInitial Rx / co-Rx
Maintenance Rx
All except Severe t-penia
DP intolerance
Neurological
Initial co-Rx
Maintenance Rx
Presympt. cases

13. Treatment of WD in pregnancy
•Treatment should not be stopped
•DP, Trientine, Zn allowed
•Zinc preferable, no dosage change
•DP, Trientine reduce dose to 25-50% esp in
last trimester

14. Monitoring in WD ?
•To determine clinical and biochemical
improvement/deterioration
•Ensure compliance
•To identify adverse effects of medications
•To review diagnosis if necessary

15. Monitoring plan (chelators)
•Clinical
–Liver status, neuro-psychiatric worsening
–KF ring annually
•Biochemical (USG)
–CBC, LFTs, Urine
–3, 6, 9, 12 days initially
–Weekly, biweekly, 1 mo, 3 mo, 6mo
•Urinary Cu, Serum free copper
–Initially 4 times per year
–Later 1-2 times

16. DP Trientine Zinc
Early
Fever, Rash
BM suppression,
Proteinuria,
LNpathy
Avoid iron + T
Rashes
Haem. Gastritis
Sideroblastic A
Loss of taste
Gastritis
Leucopenia
Increased lipase
and amylase
Late
Nephrotoxicity
Lupus like S
EPS
Loss of taste
V Late
Myasthenia,
Polymyositis
Retinitis

17. Elastosis perforans serpiginosa

18. Zinc DP / Trientine
Initial Rx U Cu 100-500 ug/d
S free Cu > 25 ug/dL
U Cu > 500ug/d
S free Cu > 25 ug/dL
Good control U Cu < 75ug/d
S free Cu < 15 ug/dL
U Cu 200-500 ug/d
S free Cu < 15ug/dL
Non-compliance/
Inadequate dose
U Zn < 2mg/d U Cu < 200 ug/d
U Cu > 200 ug/d
S free Cu > 15ug/dL
Over-treatmentU Cu < 25 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
U Cu < 200 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
Urinary copper in Wilson’s disease

19. Zinc DP / Trientine
Initial Rx U Cu 100-500 ug/d
S free Cu > 25 ug/dL
U Cu > 500ug/d
S free Cu > 25 ug/dL
Good control U Cu < 100ug/d
S free Cu < 15 ug/dL
U Cu 200-500 ug/d
S free Cu < 15ug/dL
Non-compliance/
Inadequate dose
U Zn < 2mg/d U Cu < 200 ug/d
U Cu > 200 ug/d
S free Cu > 15ug/dL
Over-treatmentU Cu < 25 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
U Cu < 200 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
Urinary copper in Wilson’s disease

20. Summary
•Chelators are mainstay of treatment
•Diet has adjunct role
•Zinc has role in long-term Rx
•Monitoring is crucial
•Interpretation of UCu important