What should I tell a patient with infectious mononucleosis (caused by Epstein-Barr virus) about developing a rash while taking amoxicillin (amoxicillin)?

Amoxicillin Rash in Infectious Mononucleosis: Patient Education

Patients with infectious mononucleosis who receive amoxicillin have a 30-100% chance of developing a non-pruritic morbilliform rash, which is not a true allergy but rather a unique interaction between the virus and medication. 1

What is Infectious Mononucleosis?

• Infectious mononucleosis (IM) is a self-limiting illness caused by the Epstein-Barr virus (EBV) 2
• Common symptoms include sore throat, fever, fatigue, swollen lymph nodes (particularly in the neck), and sometimes an enlarged spleen 2
• The illness typically resolves on its own within 2-4 weeks, though fatigue may persist longer 2
• It is commonly spread through saliva, earning it the nickname "kissing disease" 2

About Amoxicillin Rash in Mononucleosis

• When patients with EBV infection take amoxicillin or ampicillin, approximately 30-100% develop a characteristic rash 1

• This rash is typically:

  • Non-pruritic (non-itchy) 1
  • Morbilliform (measles-like) with widespread red spots or patches 2
  • Appears after starting the antibiotic 3
  • Not a true allergic reaction to the antibiotic 1

• The rash occurs due to a unique interaction between the EBV infection and the aminopenicillin, not due to a true drug allergy 1, 4

• The mechanism is thought to be either virus-mediated immunomodulation or altered drug metabolism during the infection 5

Important Information for Patients

• This rash is generally self-limiting and resolves within days of discontinuing the antibiotic 6
• The occurrence of this rash does NOT mean the patient has a true penicillin allergy 1
• Patients should NOT be permanently labeled as "penicillin allergic" based solely on developing a rash during mononucleosis 1
• Amoxicillin and other aminopenicillins should be avoided during active EBV infection to prevent this reaction 7
• The FDA specifically warns: "A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin should not be administered to patients with mononucleosis." 7

Management of the Rash

• Discontinue the amoxicillin if a rash develops 7
• The rash typically resolves on its own without specific treatment 6
• Supportive care may include:
  • Maintaining hydration 2
  • Using acetaminophen or ibuprofen for fever or discomfort (avoid aspirin in children due to risk of Reye syndrome) 8
  • Rest until symptoms improve 2

Future Antibiotic Use

• Patients who develop this rash during mononucleosis can typically take penicillins safely after the EBV infection resolves 1
• No penicillin skin testing is required for these patients in the future 1
• This reaction is specific to the combination of EBV infection and aminopenicillins 1
• If there is uncertainty about whether the rash was due to mononucleosis or represents a true allergy, consultation with an allergist may be helpful 1

When to Seek Medical Attention

• Patients should seek immediate medical attention if they develop:
  • Difficulty breathing or swallowing 7
  • Severe blistering or peeling of skin 7
  • Swelling of face, lips, tongue, or throat 7
  • Signs of severe allergic reaction (anaphylaxis) 7

Prevention

• Avoid prescribing amoxicillin or ampicillin to patients with suspected or confirmed infectious mononucleosis 7
• Consider EBV infection in patients with sore throat and lymphadenopathy before prescribing antibiotics 2
• If antibiotics are needed for a confirmed bacterial infection in a patient with mononucleosis, non-aminopenicillin antibiotics may be safer choices 8