What is the diagnosis and treatment for an 11-year-old female with fatigue, somnolence, bilious vomiting, and itching?

Diagnosis and Management of an 11-Year-Old Female with Fatigue, Somnolence, Bilious Vomiting, and Pruritus

Immediate Diagnostic Priority

This presentation requires urgent evaluation for cholestatic liver disease, with bilious vomiting necessitating simultaneous assessment for intestinal obstruction, though the combination of severe pruritus and systemic symptoms strongly suggests a hepatobiliary etiology.

The constellation of extreme fatigue, somnolence, generalized pruritus, and bilious vomiting in an 11-year-old female is highly concerning for cholestatic liver disease. While bilious vomiting typically raises concern for intestinal obstruction in younger children, the prominent systemic symptoms and pruritus point toward hepatic dysfunction 1.

Initial Diagnostic Workup

Laboratory Evaluation

Measure serum bile acids and liver transaminases (ALT, AST) immediately, along with gamma-glutamyl transferase (GGT), alkaline phosphatase, and bilirubin levels 2. These tests are essential to:

• Confirm cholestasis (elevated bile acids and alkaline phosphatase)
• Differentiate between low-GGT and high-GGT cholestatic disorders
• Assess severity of hepatic dysfunction 2

Additional initial labs should include:

• Complete blood count and coagulation studies (PT/INR) to assess synthetic liver function 2
• Comprehensive metabolic panel to evaluate for metabolic causes
• Vitamin K supplementation if prothrombin time is prolonged 2

Imaging Studies

Obtain abdominal ultrasound to evaluate liver parenchyma, bile ducts, and exclude structural abnormalities 2. This will help identify:

• Bile duct dilation or obstruction
• Liver texture abnormalities
• Gallbladder pathology 2

If bilious vomiting persists or abdominal examination suggests obstruction, obtain plain abdominal radiographs followed by upper GI series if indicated 2, 3. However, given the age and systemic symptoms, intestinal obstruction is less likely than in neonates 1.

Differential Diagnosis Based on Age and Presentation

Most Likely: Progressive Familial Intrahepatic Cholestasis (PFIC) or Related Disorder

The combination of severe pruritus, fatigue, and potential bilious vomiting (which may represent severe nausea from cholestasis rather than true obstruction) suggests:

PFIC Type 1 or 2 - characterized by:

• Low GGT levels
• Severe pruritus that can be debilitating
• Progressive cholestasis
• Potential extrahepatic manifestations including gastrointestinal symptoms 2

PFIC Type 3 - characterized by:

• Elevated GGT levels
• Later presentation (can occur in adolescence)
• Progressive cholestasis 2

Alternative Considerations

Benign Recurrent Intrahepatic Cholestasis (BRIC) - presents with:

• Acute episodes of cholestasis and severe pruritus
• Complete resolution between episodes
• Typically occurs in adolescence and adulthood 2

Alagille Syndrome - though typically diagnosed earlier, can present with:

• Chronic progressive cholestasis with severe pruritus
• Ductopenia on liver histology
• Multiorgan involvement 2

Drug-Induced Cholestatic Liver Disease - requires careful medication and herbal supplement history 2

Treatment Approach

Symptomatic Management of Pruritus

First-line: Cholestyramine 4g once or twice daily 2. This bile acid sequestrant:

• Binds bile acids in the gut, reducing reabsorption
• Has limited evidence base but is widely used as first-line therapy
• Common side effects include constipation, diarrhea, abdominal pain, nausea, and bloating 2

Second-line: Rifampicin starting at low dose (5-10 mg/kg/day) 2. This pregnane X receptor agonist:

• Has strong evidence for efficacy in cholestatic pruritus
• Requires monitoring for drug-induced hepatitis (occurs in up to 12% of cholestatic patients after 2-3 months)
• Start low and escalate dose with monitoring before each increase
• Causes discoloration of urine, tears, and body secretions 2

Third-line options include:

• Oral opiate antagonists (naltrexone), though opiate withdrawal-like reactions can occur on initiation 2
• Sertraline, with unclear mechanism but some evidence of benefit 2
• Antihistamines (diphenhydramine, hydroxyzine) have limited benefit but may help with sleep 2

Disease-Specific Therapy

Ursodeoxycholic acid (UDCA) 10-15 mg/kg/day divided into 2-3 doses may be beneficial if PFIC Type 3 is diagnosed, as it improves serum liver tests in some patients 2. However, UDCA has no proven benefit for PFIC Type 1 or 2 and may paradoxically worsen pruritus in some cholestatic conditions 2.

For PFIC Type 1 and 2, partial biliary diversion has shown beneficial clinical and biochemical effects 2. Rifampicin may alleviate pruritus in these patients 2.

Management of Bilious Vomiting

If bilious vomiting is confirmed and persistent:

• Nasogastric decompression may be needed 1
• Ondansetron 0.2 mg/kg oral (maximum 4 mg) for persistent vomiting 1
• However, if vomiting is secondary to cholestasis-induced nausea rather than obstruction, treating the underlying liver disease is paramount

Critical Next Steps

Refer urgently to pediatric hepatology for:

• Definitive diagnosis through genetic testing for PFIC variants
• Consideration of liver biopsy if diagnosis remains unclear
• Assessment for fat-soluble vitamin deficiency (common in advanced cholestasis) with empirical replacement 2
• Evaluation for liver transplantation if end-stage disease is present 2

Monitor for complications:

• Osteoporosis risk assessment (all patients with cholestatic liver disease require screening) 2
• Nutritional status and fat-soluble vitamin levels 2
• Progressive liver dysfunction requiring transplantation 2

Important Caveats

• The severity of pruritus in cholestatic liver disease can be debilitating and significantly impact quality of life, making aggressive symptomatic management essential 2
• Bilious vomiting in an 11-year-old is less likely to represent malrotation/volvulus compared to neonates, but cannot be completely excluded without imaging if symptoms persist 2, 1
• If symptoms persist 4-6 weeks after initiating therapy with persistently abnormal biochemical tests, specialist referral is mandatory 2
• Alternative causes of fatigue (anemia, hypothyroidism, sleep disorders) should be actively sought and treated 2