What is the diagnosis of an older adult patient presenting with cataract, hepatomegaly, and cholestasis?

Diagnosis: Wilson Disease

The most likely diagnosis in a patient presenting with cataract, hepatomegaly, and cholestasis is Wilson disease, particularly when sunflower cataracts are identified on slit-lamp examination alongside evidence of chronic liver disease. 1

Key Diagnostic Features

Ophthalmologic Findings

• Sunflower cataracts represent copper deposits in the lens and are pathognomonic for Wilson disease when found in the context of liver disease 1
• These cataracts typically do not obstruct vision and require slit-lamp examination for detection 1
• Kayser-Fleischer rings (copper deposition in Descemet's membrane) are present in only 50-62% of patients with primarily hepatic presentations, so their absence does not exclude Wilson disease 1
• In children presenting with liver disease, Kayser-Fleischer rings are usually absent 1

Hepatic Manifestations

Wilson disease presents with diverse hepatic patterns including: 1

• Asymptomatic hepatomegaly (as in this case)
• Persistently elevated aminotransferases
• Acute hepatitis
• Cirrhosis (compensated or decompensated)
• Cholestasis
• Fulminant hepatic failure

Age Considerations

• Wilson disease should be considered in any individual between ages 3 and 45 years with liver abnormalities of uncertain cause 1
• The majority present between ages 5 and 35, though cases have been diagnosed as young as 3 years and as old as the eighth decade 1
• When neurologic, psychiatric symptoms, or specific histologic/biochemical findings suggest Wilson disease, evaluation should proceed even in older individuals beyond age 40 1

Diagnostic Workup Algorithm

Initial Laboratory Testing

1. Serum ceruloplasmin level - typically <20 mg/dL in Wilson disease 2
2. 24-hour urinary copper excretion - elevated in Wilson disease
3. Serum aminotransferases - generally abnormal except at very early age 1

Confirmatory Testing

If ceruloplasmin is low (<20 mg/dL), confirm diagnosis with either: 2

• Quantitative liver copper concentration >250 mcg/g dry weight on liver biopsy, OR
• Presence of Kayser-Fleischer rings on slit-lamp examination

Ophthalmologic Examination

• Mandatory slit-lamp examination by experienced observer to identify both Kayser-Fleischer rings and sunflower cataracts 1
• The absence of Kayser-Fleischer rings does not exclude Wilson disease, even in patients with predominantly neurologic disease 1

Differential Diagnosis Considerations

Other Causes of Cholestasis with Hepatomegaly

While the combination of cataracts with cholestasis strongly suggests Wilson disease, other rare considerations include:

• AL amyloidosis can present with severe intrahepatic cholestasis and hepatomegaly, but does not cause cataracts 3, 4, 5
• Primary sclerosing cholangitis presents with cholestasis and hepatomegaly but lacks cataract association 1
• Intrahepatic cholangiocarcinoma may present with hepatomegaly and cholestasis but occurs in older adults without cataracts 1

Important Caveat

Kayser-Fleischer rings can rarely occur in chronic cholestatic diseases (primary biliary cirrhosis, primary sclerosing cholangitis) and neonatal cholestasis, but these can usually be distinguished from Wilson disease on clinical grounds and lack sunflower cataracts 1

Treatment Implications

Dietary Copper Restriction

• Daily diet should contain no more than 1-2 mg copper 2
• Exclude chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and copper-enriched cereals 2
• Use distilled or demineralized water if drinking water contains >0.1 mg/L copper 2

Chelation Therapy

• Penicillamine is the standard copper chelating agent for Wilson disease 2
• Treatment usually produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction 2
• Both Kayser-Fleischer rings and sunflower cataracts gradually disappear with effective medical treatment or following liver transplantation 1
• Noticeable improvement may not occur for 1-3 months 2

Critical Warning

Neurologic symptoms occasionally worsen during initiation of penicillamine therapy, but the drug should not be withdrawn as temporary interruption increases risk of sensitivity reactions upon resumption 2

Prognosis

• Clinical experience suggests life is prolonged with appropriate copper restriction and chelation therapy 2
• Asymptomatic patients treated continuously with penicillamine have had symptoms and signs prevented indefinitely for over 30 years 2
• The reappearance of ophthalmologic findings in a treated patient suggests medication noncompliance 1