What is the differential diagnosis and workup for a 17-year-old female presenting with jaundice (yellow eyes)?

Differential Diagnosis and Workup for Jaundice in a 17-Year-Old Female

Jaundice (yellow eyes) in a 17-year-old female requires prompt evaluation with abdominal ultrasound as the initial imaging test, followed by laboratory tests to differentiate between obstructive and non-obstructive causes. 1

Differential Diagnosis

Prehepatic Causes (Unconjugated Hyperbilirubinemia)

• Hemolysis (hemolytic anemias, sickle cell disease)
• Hematoma resorption
• Gilbert syndrome (common in adolescents)

Intrahepatic Causes

• Viral hepatitis (A, B, C)
• Drug-induced liver injury
• Autoimmune hepatitis (more common in young females)
• Wilson's disease (important consideration in adolescents)
• Non-alcoholic fatty liver disease (NAFLD)
• Alpha-1 antitrypsin deficiency

Posthepatic/Obstructive Causes (Conjugated Hyperbilirubinemia)

• Choledocholithiasis (gallstones)
• Biliary strictures
• Cholangitis
• Pancreatic disorders
• Malignancy (rare in this age group but possible)

Initial Workup Algorithm

Step 1: Laboratory Tests

• Complete blood count (CBC) - to evaluate for hemolysis or infection
• Liver function tests:
  • Total and fractionated bilirubin (direct/conjugated and indirect/unconjugated)
  • AST and ALT (liver cell damage)
  • Alkaline phosphatase and gamma-glutamyltransferase (cholestasis)
  • Albumin and prothrombin time/INR (synthetic function)
• Urine bilirubin - presence indicates conjugated hyperbilirubinemia 2

Step 2: First-Line Imaging

• Abdominal ultrasound - recommended by the American College of Gastroenterology as the initial imaging test 1
  • Evaluates liver parenchyma, biliary tree dilation, gallbladder, and pancreas
  • Sensitivity of 65-95% for detecting cirrhosis
  • Sensitivity of 32-100% and specificity of 71-97% for biliary obstruction

Step 3: Additional Tests Based on Initial Results

If Unconjugated Hyperbilirubinemia Predominates:

• Hemolysis workup: reticulocyte count, haptoglobin, LDH, peripheral blood smear
• Genetic testing for Gilbert syndrome if other tests normal

If Conjugated Hyperbilirubinemia Predominates:

• Viral hepatitis serologies (HAV, HBV, HCV)
• Autoimmune markers (ANA, ASMA, immunoglobulins)
• Ceruloplasmin and 24-hour urinary copper (Wilson's disease)
• Alpha-1 antitrypsin level

If Biliary Obstruction Suspected on Ultrasound:

• MRCP (Magnetic Resonance Cholangiopancreatography) - non-invasive evaluation of biliary system
  • More sensitive than CT or ultrasound for detecting ductal calculi
  • Sensitivity 77-88% for CBD stones 1
• CT abdomen with contrast - if malignancy suspected

Important Considerations

1. Age-specific concerns: In a 17-year-old female, consider:

   • Autoimmune hepatitis (more common in young females)
   • Wilson's disease (typically presents in adolescents/young adults)
   • Gilbert syndrome (common benign cause in adolescents)

2. Medication history: Assess for:

   • Prescription medications
   • Over-the-counter drugs
   • Herbal supplements
   • Oral contraceptives

3. Red flags requiring urgent evaluation:

   • Signs of liver failure (altered mental status, coagulopathy)
   • Fever with jaundice (suggests cholangitis)
   • Significant weight loss (concern for malignancy)

Common Pitfalls to Avoid

1. Missing Wilson's disease - critical diagnosis in adolescents that requires specific testing
2. Attributing jaundice to Gilbert syndrome without excluding other causes
3. Delaying imaging when obstructive jaundice is suspected
4. Overlooking drug-induced liver injury - thorough medication history is essential
5. Failing to consider autoimmune hepatitis in young females

The workup should be tailored based on the pattern of laboratory abnormalities and ultrasound findings. If initial testing is inconclusive, referral to a gastroenterologist or hepatologist is warranted for further evaluation, which may include liver biopsy in selected cases.