What is the first line treatment for a child presenting with jaundice, arthritis, rash, hyperbilirubinemia, and positive Immunoglobulin G (IgG) and autoantibodies?

First-Line Treatment for Pediatric Autoimmune Hepatitis

The first-line treatment is prednisone (1-2 mg/kg/day, maximum 60 mg/day) plus azathioprine (1-2 mg/kg/day) - option (b) - which achieves remission in 75-90% of children within 6-12 months while minimizing growth-impairing effects of prolonged high-dose corticosteroids alone. 1, 2

Clinical Presentation Analysis

This child presents with the classic triad of autoimmune hepatitis (AIH):

• Hepatic manifestations: Jaundice and hyperbilirubinemia indicating active liver inflammation 1
• Systemic autoimmune features: Arthritis and rash suggesting multi-system involvement 3
• Serologic markers: Positive IgG and autoantibodies confirming autoimmune etiology 1, 2

Why Combination Therapy is Superior

Prednisone plus azathioprine is the established standard because:

• Achieves biochemical remission in 75-90% of pediatric patients within 6-9 months 2
• Allows lower corticosteroid doses, minimizing growth impairment and cushingoid features 2, 4
• More than 50% of children present with established cirrhosis, requiring aggressive initial treatment 2, 5
• Pediatric AIH appears more aggressive than adult disease, making prompt combination therapy essential 2, 5

Specific Dosing Regimen

Initial phase (weeks 1-8):

• Start prednisone at 1-2 mg/kg/day (maximum 60 mg/day) 2, 6
• Add azathioprine at 1-2 mg/kg/day simultaneously or after 2 weeks if bilirubin >6 mg/dL 1, 2
• Taper prednisone over 6-8 weeks to maintenance dose of 0.1-0.2 mg/kg/day or 5 mg/day, whichever is higher 2, 6

Expected response:

• Almost all children show improvement in liver enzymes within 2-4 weeks 2, 5
• Complete remission achieved in 6-12 months in most cases 2, 4

Why Other Options Are Incorrect

Plasma exchange (option a) is not indicated because:

• No role in standard AIH management 1
• Reserved only for acute liver failure unresponsive to medical therapy as bridge to transplantation 1
• This patient has jaundice but no evidence of fulminant hepatic failure requiring emergency intervention 1

NSAIDs (option c) are contraindicated because:

• Provide no immunosuppression for autoimmune disease 1
• May worsen liver injury in setting of hepatitis 1
• The arthritis is a manifestation of systemic autoimmune disease requiring immunosuppression, not symptomatic treatment 3

Monitoring and Response Assessment

Essential monitoring parameters:

• Check AST, ALT, bilirubin, and IgG levels at 4-6 week intervals 2, 5
• Expect normalization of transaminases within 2-4 weeks as first sign of response 2
• Monitor for azathioprine-related cytopenia with regular blood counts 2, 6
• Consider TPMT testing before starting azathioprine to identify patients at risk for severe myelosuppression 1, 6

Critical Pitfalls to Avoid

Do not delay azathioprine initiation:

• Can start simultaneously with prednisone if bilirubin <6 mg/dL (100 μmol/L) 1
• Delaying azathioprine prolongs high-dose corticosteroid exposure and increases growth impairment 2

Do not use prednisone monotherapy unless specific contraindications exist:

• Monotherapy appropriate only for severe pre-treatment cytopenia, TPMT deficiency, active malignancy, or pregnancy 2, 6
• This patient has none of these contraindications 2

Do not consider cyclosporine as first-line:

• A 2020 randomized trial showed similar effectiveness to prednisone-azathioprine but remission achieved later (13.6 vs 8.6 weeks) 4
• Associated with gingival hypertrophy and lacks the established track record of combination therapy 4

Long-Term Considerations

Counsel family about high relapse risk:

• Relapse occurs in 60-80% of children after treatment withdrawal, substantially higher than adult rates 2, 5
• Most children require lifelong maintenance therapy with azathioprine 2, 5
• Treatment should continue for at least 2-3 years with normal liver tests and IgG for at least 1 year before considering withdrawal 2

Provide supportive care:

• All children on long-term corticosteroids require calcium and vitamin D supplementation 2, 5, 6
• Monitor bone mineral density at 1-2 year intervals 5, 6
• Vaccinate against hepatitis A and B early in treatment 2, 6