What is the management for a patient with an amoxicillin (amoxicillin) rash, leukocytosis (elevated white blood cells), elevated liver enzymes, and hyperbilirubinemia (elevated bilirubin)?

Management of Amoxicillin-Induced Hepatic Reaction with Rash, Leukocytosis, and Hyperbilirubinemia

Immediate discontinuation of amoxicillin is essential in patients presenting with rash, elevated white blood cells, liver enzymes, and bilirubin, as this constellation of symptoms indicates a potentially serious drug-induced liver injury that requires prompt intervention. 1

Clinical Assessment and Diagnosis

Initial Evaluation

• Assess severity of symptoms:
  • Skin: Extent of rash, presence of blisters, mucosal involvement
  • Liver: Jaundice, right upper quadrant tenderness
  • Systemic: Fever, malaise, lymphadenopathy

Laboratory Testing

• Complete liver panel:
  • AST/ALT (hepatocellular damage)
  • Alkaline phosphatase/GGT (cholestatic pattern)
  • Total and direct bilirubin
  • Complete blood count with differential
  • Coagulation studies (PT/INR)

Pattern Recognition

This presentation likely represents one of two clinical entities:

1. Drug-induced liver injury (DILI) with hypersensitivity features
2. Infectious mononucleosis with amoxicillin-induced rash and secondary liver involvement 2

Management Algorithm

Step 1: Immediate Actions

• Discontinue amoxicillin immediately 1
• Assess for signs of severe cutaneous adverse reactions (SCAR) such as:
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)

Step 2: Severity Assessment

• If ALT/AST >5× upper limit of normal: Urgent hepatology consultation 3
• If total bilirubin ≥2× upper limit of normal with elevated transaminases: Consider hospitalization 3
• If signs of hepatic encephalopathy or coagulopathy: Immediate hospitalization

Step 3: Specific Management

• For mild-moderate reactions (ALT/AST <5× ULN, normal bilirubin):

  • Supportive care
  • Monitor liver enzymes every 3-5 days until improving
  • Antihistamines for pruritus

• For severe reactions (ALT/AST >5× ULN or bilirubin >2× ULN):

  • Hospitalization for close monitoring
  • Consider systemic corticosteroids if evidence of immune-mediated injury 4
  • Cholestyramine may help with pruritus in cholestatic cases 5

• For life-threatening reactions (encephalopathy, coagulopathy):

  • ICU admission
  • Consult hepatology for potential liver transplant evaluation 6

Special Considerations

Infectious Mononucleosis

• High percentage of patients with mononucleosis develop erythematous rash when given amoxicillin 1
• Check for Epstein-Barr virus serology if suspected
• Management focuses on supportive care and avoiding hepatotoxic medications

Monitoring and Follow-up

• Monitor liver enzymes every 3-5 days initially, then weekly until normalizing
• Follow-up liver function tests at 2 weeks, 1 month, and 3 months after resolution
• Document amoxicillin allergy in medical record and alert patient

Future Antibiotic Use

• Avoid all penicillin-class antibiotics
• Cross-reactivity with cephalosporins is possible but not absolute
• Consider allergy consultation for skin testing after complete resolution if future beta-lactam therapy may be needed

Prognosis

Most cases of amoxicillin-induced liver injury are self-limited and resolve with drug discontinuation 7. However, severe cases can progress to fulminant hepatic failure, especially when associated with systemic hypersensitivity reactions 6. The presence of both rash and liver injury indicates an immune-mediated reaction that requires close monitoring.

Pitfalls to Avoid

• Continuing amoxicillin despite early signs of reaction
• Failing to consider infectious mononucleosis in young adults
• Missing progression to Stevens-Johnson syndrome or DRESS syndrome
• Inadequate monitoring of liver function during recovery phase
• Reintroducing penicillin-class antibiotics without proper evaluation