eMedicine Specialties > Gastroenterology > Systemic Disease

Wilson Disease: Treatment & Medication

Author: Rahil Shah, MD, Consulting Staff, Department of Gastroenterology, University Medical Center
Coauthor(s): Michael H Piper, MD, FACG, FACP, Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates PLC
Contributor Information and Disclosures

Updated: Aug 25, 2009

Treatment

Medical Care

The mainstay of therapy for Wilson disease is pharmacologic treatment with chelating agents.

Surgical Care

  • The use of surgical decompression or transjugular intrahepatic shunting (TIPS) in the treatment of portal hypertension is reserved for individuals with recurrent or uncontrolled variceal bleeding that is unresponsive to standard conservative measures.
  • Orthotopic liver transplantation is a potentially curative treatment of Wilson disease.
    • Transplantation is primarily reserved for treatment of patients with fulminant liver failure or end-stage liver cirrhosis, which progresses despite chelation therapy.
    • The selection of patients for transplantation may be facilitated by determination of a prognostic index, which is based on the degree of abnormality of serum aspartate aminotransferase, bilirubin, and prothrombin time and appears to accurately predict a fatal or nonfatal outcome.
    • In the absence of severe hepatic disease, liver transplantation is generally not recommended for treatment of refractory extrahepatic manifestations.

Consultations

  • Consider consultation with gastroenterologists with specialty training in hepatology for any patient with Wilson disease, especially when evidence of hepatic insufficiency is present.
  • Consultation with surgeons may be sought for liver transplantation when deemed necessary.

Diet

Patients should generally avoid eating foods with a high copper content, such as liver, chocolate, nuts, mushrooms, legumes, and shellfish (especially lobster). Drinking water from atypical sources (eg, well water) should be analyzed for copper content and replaced with purified water if the copper content is greater than 0.2 parts per million.

Medication

The mainstay of therapy for Wilson disease is the use of chelating agents and medications that block copper absorption from the GI tract.

Chelating agents

Bind excess copper. Ammonium tetrathiomolybdate is being used under the investigational new drug approval of the US Food and Drug Administration at the University of Michigan as an initial treatment for those who present with neurologic or psychiatric manifestations. This drug works as both a chelating agent and an inhibitor of copper absorption from the GI tract.6


Penicillamine (Cuprimine, Depen)

Forms soluble complexes with metals excreted in urine. DOC before newer regimens were available. Because of extensive toxicities, alternative agents are used. Must be administered with pyridoxine 25 mg PO qd.

Adult

Initial: 1.5-2 g PO qd
Maintenance: 750 mg to 1 g/d PO qid 30 min ac

Pediatric

25 mg/kg PO qd

Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; effects may decrease with coadministration of zinc salts, sucralfate, antacids, and iron; probenecid may increase adverse effects

Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia

Pregnancy

D - Unsafe in pregnancy

Precautions

Thrombocytopenia, agranulocytosis, and aplastic anemia may occur


Trientine (Syprine)

Effective oral chelator used to induce cupriuresis. Useful for patients who cannot tolerate penicillamine. Indicated in Wilson disease if initial presentation is hepatic. Should be administered with zinc.

Adult

250-500 mg PO tid ac

Pediatric

Not established

Effects decrease with iron or other mineral supplements

Documented hypersensitivity; biliary cirrhosis; rheumatoid arthritis; cystinuria

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Can cause bone marrow suppression and proteinuria; perform weekly CBC counts at initiation of therapy

Nutrients

Essential to normal growth and development. Play a role in many metabolic processes.


Zinc (Verazinc, Orazinc, Zincate)

Cofactor for >70 types of enzymes. Approved for patients initially treated with a chelating agent. Should be used for maintenance after initial therapy. DOC in presymptomatic, pregnant, and pediatric populations. Second DOC if initial presentation is neurologic.

Adult

150-300 mg PO qd

Pediatric

Not established

May reduce penicillamine and tetracycline effects

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in patients with renal impairment


Pyridoxine (Nestrex)

Involved in synthesis of GABA within the CNS.

Adult

25 mg PO qd

Pediatric

Not established

May decrease levodopa, phenytoin, and phenobarbital serum levels

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

>200 mg/d may precipitate withdrawal effects when medication is discontinued


Dimercaprol (BAL in Oil)

For refractory cases of Wilson disease not responding to first- or second-line treatment.

Adult

3-5 mg/kg IM q4h

Pediatric

Administer as in adults

Toxicity may increase when coadministered with selenium, uranium, iron, or cadmium

Documented hypersensitivity; G-6-PD deficiency; concurrent iron supplementation therapy

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May be nephrotoxic and may cause hypertension; caution when administering to patients with oliguria or G-6-PD deficiency; may induce hemolysis in patients with G-6-PD deficiency

More on Wilson Disease

Overview: Wilson Disease
Differential Diagnoses & Workup: Wilson Disease
Treatment & Medication: Wilson Disease
Follow-up: Wilson Disease
Multimedia: Wilson Disease
References
Further Reading
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References

  1. Schilsky ML. Wilson disease: Current status and the future. Biochimie. Jul 30 2009;[Medline].

  2. Bowcock AM, Farrer LA, Hebert JM, Agger M, Sternlieb I, Scheinberg IH, et al. Eight closely linked loci place the Wilson disease locus within 13q14-q21. Am J Hum Genet. Nov 1988;43(5):664-74. [Medline].

  3. Manolaki N, Nikolopoulou G, Daikos GL, Panagiotakaki E, Tzetis M, Roma E, et al. Wilson disease in children: analysis of 57 cases. J Pediatr Gastroenterol Nutr. Jan 2009;48(1):72-7. [Medline].

  4. Walshe JM. Copper: its role in the pathogenesis of liver disease. Semin Liver Dis. Aug 1984;4(3):252-63. [Medline].

  5. Dastych M, Prochazkova D, Pokorny A, Zdrazil L. Copper and zinc in the serum, urine, and hair of patients with Wilson's disease treated with penicillamine and zinc. Biol Trace Elem Res. Jun 27 2009;epub ahead of print. [Medline].

  6. Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, et al. Treatment of Wilson's disease with tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res. Aug 2009;154(2):70-7. [Medline].

  7. Brewer GJ. Recognition, diagnosis, and management of Wilson''s disease. Proc Soc Exp Biol Med. Jan 2000;223(1):39-46. [Medline].

  8. Cuthbert JA. Wilson''s disease. Update of a systemic disorder with protean manifestations. Gastroenterol Clin North Am. Sep 1998;27(3):655-81, vi-vii. [Medline].

  9. Gitlin N. Wilson''s disease: the scourge of copper. J Hepatol. Apr 1998;28(4):734-9. [Medline].

  10. Huster D, Kuhn HJ, Mossner J. Wilson disease. Internist (Berl). Jul 2005;46(7):731-2, 734-6, 738-40. [Medline].

  11. Perri RE, Hahn SH, Ferber MJ. Wilson Disease--keeping the bar for diagnosis raised. Hepatology. Oct 2005;42(4):974. [Medline].

  12. Pfeil SA, Lynn DJ. Wilson''s disease: copper unfettered. J Clin Gastroenterol. Jul 1999;29(1):22-31. [Medline].

  13. Schilsky ML. Wilson disease: new insights into pathogenesis, diagnosis, and future therapy. Curr Gastroenterol Rep. Feb 2005;7(1):26-31. [Medline].

  14. Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. Feb 1995;9(2):210-7. [Medline].

  15. Tarnacka B, Szeszkowski W, Golebiowski M, Czlonkowska A. Metabolic changes in 37 newly diagnosed Wilson's disease patients assessed by magnetic resonance spectroscopy. Parkinsonism Relat Disord. Sep 2009;15(8):582-6. [Medline].

  16. Soni D, Shukla G, Singh S, Goyal V, Behari M. Cardiovascular and sudomotor autonomic dysfunction in Wilson's disease-Limited correlation with clinical severity. Auton Neurosci. Aug 7 2009;epub ahead of print. [Medline].

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Further Reading

Related eMedicine Topics

National Guideline Clearinghouse

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Keywords

Wilson disease, Wilson's disease, hepatolenticular degeneration, copper metabolism, ATP7B, cirrhosis, fulminant hepatic failure, chronic liver disease, hepatitis, hepatic dysfunction, basal ganglia degeneration, Kayser-Fleischer ring, chelation therapy, transjugular intrahepatic shunting, TIPS, orthotopic liver transplantation

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Contributor Information and Disclosures

Author

Rahil Shah, MD, Consulting Staff, Department of Gastroenterology, University Medical Center
Rahil Shah, MD is a member of the following medical societies: American College of Gastroenterology and American Society for Gastrointestinal Endoscopy
Disclosure: Takeda Consulting fee Speaking and teaching; Santarus Consulting fee Speaking and teaching

Coauthor(s)

Michael H Piper, MD, FACG, FACP, Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates PLC
Michael H Piper, MD, FACG, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Robert J Fingerote, MD, MSc, BSc, FRCPC, Consultant, Clinical Evaluation Division, Biologic and Gene Therapies, Directorate Health Canada; Consulting Staff, Department of Medicine, Division of Gastroenterology, York Central Hospital, Richmond Hill, Ontario
Robert J Fingerote, MD, MSc, BSc, FRCPC is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Noel Williams, MD, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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