What are the causes of delayed hypersensitivity reaction to amoxicillin (amoxicillin) in children?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 28, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Delayed hypersensitivity reactions to amoxicillin in children are often caused by a benign interaction between the antibiotic and a virus, such as Epstein-Barr virus or other respiratory viruses, rather than a true allergic reaction. These reactions typically appear as a non-itchy, pink or red rash that develops 3-10 days after starting the medication, and are not related to specific IgE antibodies 1. The rash usually starts on the trunk and spreads to the extremities, lasting for several days to a week before resolving on its own. Some key points to consider include:

  • The reaction is not an indication of a true allergy and does not increase the risk of anaphylaxis with future amoxicillin use 1.
  • The presence of a concurrent viral infection or another underlying illness may contribute to the development of delayed-onset reactions 1.
  • Aminopenicillins, such as amoxicillin, are associated with a higher rate of delayed-onset reactions compared to penicillin VK 1.
  • The majority of delayed reactions are mild and can be managed by continuing the full course of antibiotics while monitoring the rash 1.
  • True allergic reactions, on the other hand, occur within minutes to hours of taking the medication and involve hives, swelling, or breathing difficulties requiring immediate medical attention 1. It's essential to document any reaction in the child's medical record, but it typically doesn't preclude future amoxicillin use 1. Recent studies suggest that single-day challenges are sufficient to detect delayed reactions, and multiple-day challenges are not recommended after negative single-day challenges 1. Additionally, resensitization after oral treatment with penicillins is rare, and routine repeat penicillin skin testing is not indicated in patients with a history of penicillin allergy who have tolerated one or more courses of oral penicillin 1.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS

  1. 1 Anaphylactic Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including amoxicillin. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

The causes of delayed hypersensitivity reaction to amoxicillin in children are not explicitly stated in the provided drug label. However, it can be inferred that a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens may increase the likelihood of hypersensitivity reactions, including delayed reactions.

  • Previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens may contribute to the development of hypersensitivity reactions. 2

From the Research

Causes of Delayed Hypersensitivity Reaction to Amoxicillin in Children

The causes of delayed hypersensitivity reactions to amoxicillin in children can be attributed to several factors, including:

  • The excipient in the amoxicillin solution, as suggested by a study published in 1989 3
  • Non-immediate reactions, which can occur in children presenting with symptoms such as urticaria, angioedema, arthritis, and arthralgia, as reported in a study published in 2022 4
  • Hypersensitivity reactions, which can be diagnosed using skin tests and drug provocation tests, as shown in a study published in 2022 5
  • Non-IgE-mediated reactions, which can occur in children with a history of non-immediate reactions to amoxicillin, as reported in a study published in 2015 6

Characteristics of Delayed Hypersensitivity Reactions

Delayed hypersensitivity reactions to amoxicillin in children can manifest with various symptoms, including:

  • Urticaria
  • Angioedema
  • Arthritis
  • Arthralgia
  • Serum sickness-like reactions
  • Maculopapular exanthem These symptoms can occur on days 7 to 10 of amoxicillin treatment, as reported in a study published in 2022 4

Diagnosis and Evaluation

The diagnosis of delayed hypersensitivity reactions to amoxicillin in children can be made using:

  • Skin tests, such as intradermal tests (IDTs) 5
  • Drug provocation tests (DPTs) 6, 5
  • Evaluation of medical history, including the type of reaction and the time of onset 7 It is essential to evaluate children with suspected delayed hypersensitivity reactions to amoxicillin to determine the appropriate course of treatment and to avoid unnecessary use of broad-spectrum antibiotics, as reported in a study published in 2019 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Severe delayed-onset hypersensitivity reactions to amoxicillin in children.

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 1989

Research

Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of nonimmediate reactions.

The journal of allergy and clinical immunology. In practice, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.