Wilson’s Disease – How do I manage ?

Dr. Ashish BavdekarAssociate Professor

Consultant Ped. GastroenterologistK.E.M. Hospital, Punebavdekar@vsnl.com

Zn + penicillamine

Zn + trientine

Zn sulfate

Zn acetate

trientine

penicillamine

transplanted

EuroWilson: initial treatment

Why?

“Available in our countryCheapTried and testedWhat we’ve always used

“Not available in our countryKept as second lineNot as effective?

“expensive”

Wilson’s disease – management

- Low copper diet - Serving size (< 0.1mg, 0.1-0.2, > 0.2mg)

Wilson’s disease – management

- Low copper diet - Serving size (< 0.1mg, 0.1-0.2, > 0.2mg)

- Medications - D-Penicillamine

- Trientine

- Zinc

- Ammonium molybdate

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

DP Trientine Zinc

Chelator Chelator Induces MT

Easy availability Patient named basis

Easy availability

Reasonable cost V Expensive Cheap

Side effects Neurological

Minimal SE Gastric discomfort

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 TxTrientine + zinc‘bridge’

Modified Kings scoreTx if >11Trientine + zinc

Score Bilirubinmol/Lɥ

INR ASTIU/L

WCCx 109/L

Albuming/L

0 0-100 0-1.29 0-100 0-6.7 >451 101-150 1.3-1.6 101-150 6.8-8.3 34-442 151-200 1.7-1.9 151-300 8.4-10.3 25-333 201-300 2.0-2.4 301-400 10.4-15.3 21-244 >301 >2.5 >401 >15.4 <20

Modified King’s score

A score > 11 = urgent need for transplantationValidated in other centres; better than PELD

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 TxTrientine + zinc‘bridge’

Modified Kings scoreTx if >11Trientine + zinc

Zinc

Zinc – when to start?

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 TxTrientine + zinc‘bridge’

Modified Kings scoreTx if >11Trientine + zinc

Zinc

Zinc – when to start?

Trials needed

DP Trientine Zinc

Chelator Chelator Induces MT

Easy availability Patient named basis

Easy availability

Reasonable cost V Expensive Cheap

Side effects Neurological

Minimal SE Gastric discomfort

Initial therapy Initial therapy Initial Rx / co-RxMaintenance Rx

All except Severe t-peniaDP intoleranceNeurological

Initial co-RxMaintenance RxPresympt. cases

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

Monitoring in WD ?

• To determine clinical and biochemical improvement/deterioration

• Ensure compliance

• To identify adverse effects of medications

• To review diagnosis if necessary

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

DP Trientine ZincEarlyFever, RashBM suppression, Proteinuria, LNpathy

Avoid iron + TRashesHaem. GastritisSideroblastic ALoss of taste

GastritisLeucopeniaIncreased lipase and amylase

LateNephrotoxicityLupus like SEPSLoss of tasteV LateMyasthenia, PolymyositisRetinitis

Elastosis perforans serpiginosa

Zinc DP / Trientine

Initial Rx U Cu 100-500 ug/dS free Cu > 25 ug/dL

U Cu > 500ug/dS free Cu > 25 ug/dL

Good control U Cu < 75ug/dS free Cu < 15 ug/dL

U Cu 200-500 ug/dS free Cu < 15ug/dL

Non-compliance/Inadequate dose

U Zn < 2mg/d U Cu < 200 ug/dU Cu > 200 ug/dS free Cu > 15ug/dL

Over-treatment U Cu < 25 ug/d S. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin

U Cu < 200 ug/dS. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin

Urinary copper in Wilson’s disease

Zinc DP / Trientine

Initial Rx U Cu 100-500 ug/dS free Cu > 25 ug/dL

U Cu > 500ug/dS free Cu > 25 ug/dL

Good control U Cu < 100ug/dS free Cu < 15 ug/dL

U Cu 200-500 ug/dS free Cu < 15ug/dL

Non-compliance/Inadequate dose

U Zn < 2mg/d U Cu < 200 ug/dU Cu > 200 ug/dS free Cu > 15ug/dL

Over-treatment U Cu < 25 ug/d S. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin

U Cu < 200 ug/dS. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin

Urinary copper in Wilson’s disease

Summary

• Chelators are mainstay of treatment

• Diet has adjunct role

• Zinc has role in long-term Rx

• Monitoring is crucial

• Interpretation of UCu important