What is the diagnosis and management for an 11-year-old child presenting with jaundice, dark urine (cola-colored), hepatomegaly, anemia, and a low-grade fever?

Diagnosis: Giant Cell Hepatitis with Autoimmune Hemolytic Anemia

This 11-year-old child most likely has giant cell hepatitis (GCH) with autoimmune hemolytic anemia, a rare but life-threatening condition that requires immediate corticosteroid therapy and urgent pediatric hepatology consultation. 1, 2

Clinical Presentation Matches GCH with Autoimmune Hemolytic Anemia

The constellation of fever, jaundice, cola-colored urine (indicating hemoglobinuria from hemolysis), hepatomegaly, and anemia in a child is highly characteristic of this syndrome 1, 2. This presentation differs from typical neonatal cholestasis because:

• Fever is a prominent feature in GCH with autoimmune hemolytic anemia, whereas it is uncommon in biliary atresia or alpha-1 antitrypsin deficiency 1, 2
• The combination of hemolytic anemia with liver disease points specifically to this autoimmune process rather than primary hepatobiliary disorders 1, 2
• Dark urine reflects both conjugated hyperbilirubinemia AND hemoglobinuria, distinguishing this from isolated cholestatic conditions 1, 2

Immediate Diagnostic Workup Required

Order these tests urgently:

• Direct Coombs test (DAT) - expect positive results of mixed type (IgG + C3d), which is pathognomonic for this condition 1, 2
• Complete blood count with peripheral smear - will show hemolytic anemia with spherocytes, elevated reticulocyte count, and possibly thrombocytopenia (Evans syndrome) 1, 2
• Fractionated bilirubin - expect elevated conjugated bilirubin from liver disease plus unconjugated from hemolysis 1, 2
• Liver function tests including PT/INR - transaminases will be markedly elevated, and prolonged prothrombin time indicates poor prognosis 1, 2
• LDH, haptoglobin, indirect bilirubin - confirms hemolysis 3
• Serum gamma globulins - typically elevated in this condition 1

Exclude other causes:

• Alpha-1 antitrypsin phenotyping - mandatory in any child with conjugated hyperbilirubinemia and hepatomegaly 3, 4
• Viral serologies (hepatitis A, B, C, EBV, CMV, HSV) - to exclude infectious hepatitis 2
• Autoantibodies (ANA, anti-smooth muscle, LKM-1) - typically negative in GCH, which helps distinguish it from autoimmune hepatitis 2

Critical Management Algorithm

Immediate interventions:

1. Start high-dose corticosteroids immediately - methylprednisolone 2 mg/kg/day or prednisone 1-2 mg/kg/day, as this is the only treatment shown to improve survival 1, 2
2. Administer vitamin K for coagulopathy if PT/INR is prolonged 5
3. Transfuse packed RBCs cautiously only if symptomatic anemia (do not transfuse more than minimum necessary due to ongoing hemolysis) 3
4. Urgent pediatric hepatology and hematology consultation 4

Liver biopsy confirmation:

• Percutaneous or transjugular liver biopsy should be performed once coagulopathy is corrected to confirm giant cell transformation and marked lobular fibrosis 1, 2
• This histologic pattern is diagnostic when combined with positive Coombs test 1, 2

Escalation if steroid-refractory:

• Add azathioprine as steroid-sparing immunosuppression 2
• Consider IVIG for severe hemolysis 3
• Urgent liver transplant evaluation if progressive liver failure develops, as three of four patients in the original case series died from liver failure despite treatment 1

Prognosis and Pitfalls

This condition carries extremely high mortality - 75% mortality in the original case series, with death from progressive liver failure 1. However, one patient showed clear benefit from corticosteroids, emphasizing the critical importance of early aggressive treatment 1.

Common pitfalls to avoid:

• Do not delay corticosteroids while waiting for liver biopsy confirmation - the clinical presentation with positive Coombs test is sufficient to start treatment 1, 2
• Do not miss Evans syndrome (concurrent thrombocytopenia with hemolytic anemia), which occurs in some cases and requires platelet monitoring 2
• Do not attribute jaundice solely to hemolysis - the conjugated hyperbilirubinemia indicates severe hepatocellular injury requiring specific treatment 1, 2
• Monitor for sepsis as a complication of immunosuppression, which was the terminal event in one reported case 2

Alternative Diagnoses to Consider

While GCH with autoimmune hemolytic anemia is most likely, briefly consider:

• Severe falciparum malaria can present identically with fever, jaundice, hepatomegaly, and hemolytic anemia, but requires travel history to endemic areas 6
• Gaucher disease type 2 can cause neonatal hepatitis with splenomegaly, but typically presents earlier in infancy 7
• Tyrosinemia type 1 presents with hepatomegaly and conjugated hyperbilirubinemia, but hemolytic anemia is not a feature 4, 8