Drug and Vaccine Allergies in Children

Educational Objectives

The goal of this program is to improve the management of drug and vaccine allergies in pediatric patients. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate between children with a true penicillin allergy and those who can safely take penicillin.
2. Reassure parents about potential reactions to influenza and COVID vaccines.

Summary

Introduction: a child experiencing a negative reaction while taking a medication could be due to the medication itself or just a coincidence; if the medication is the cause, the reaction may not always be immunologically mediated; if immunologically mediated, it does not necessarily involve immunoglobulin (Ig) E antibodies (ie, allergic reactions); ask when the reaction occurred, what medication was involved, how long they were taking the medication before the event, and the nature and timing of the symptoms, eg, rash; hypersensitivity refers to an overactive immune response, not the exposure itself; these reactions can include IgE-mediated allergic responses (eg, hives [urticaria], anaphylaxis) or non-IgE reactions, eg, type 4 (cell-mediated) immune responses (eg, many drug rashes)

IgE-mediated allergic reaction: requires prior exposure; sensitization and reactions are more likely with medications administered parenterally; a reaction repeating itself suggests an allergic response; family history is not a factor in drug allergies, as they do not run in families; IgE antibodies, once formed, cause mast-cell degranulation (MCD) on subsequent exposures; many medications (eg, penicillin [PCN]) are not proteins but rather act as haptens, binding to proteins (eg, albumin) to form the allergen; 6% of children are labeled as allergic to PCN, but only ≈5% of those are actually allergic (allergy may have been misdiagnosed or waned over time); such mislabeling can lead to suboptimal treatment, unnecessary adverse effects, increased expense, and antibiotic resistance

Candidates for delabeling PCN allergy: typically have a history of mild reactions, eg, hives or a benign rash; however, children with more serious reactions, eg, Stevens-Johnson syndrome (SJS) or drug reaction with eosinophilia and systemic symptoms (DRESS), should not be considered; true allergy will manifest ≤1 hr of the first dose of a new course of medication; a history of anaphylaxis should be investigated with skin testing; otherwise, proceed with an oral challenge of amoxicillin under supervision; if no reaction occurs, the allergy can be removed from the chart; PCN skin testing involves prick testing and intradermal injection; blood testing is not reliable

Desensitization: for children with a true allergy who need PCN, desensitization starts with 1/10,000 of a therapeutic dose, doubling every 15 min until a therapeutic dose is reached; however, this does not cure the allergy

Cephalosporins, carbapenems, and monobactams: carbapenems and monobactams are generally safe for children with a PCN allergy, as the allergy typically does not cross over; most children with a PCN allergy can tolerate cephalosporins, although there is a small overlap (likely due to shared side chains), especially if their previous reaction was mild and distant; however, if the child had a recent severe PCN reaction and is being given an intravenous cephalosporin, check whether the cephalosporin shares the same side chain as the PCN; “amoxicillin rash” is a common reaction, characterized by small, red, nonraised, nonitchy spots that typically appear a few days into a course of amoxicillin but does not indicate a PCN allergy

Rare and severe reactions: late-onset reactions include SJS (skin peeling and lesions of the mouth, eye, or nose) and DRESS (severe rash, high fever, and lymphadenopathy); more benign reactions include drug rashes or serum sickness (dermatitis, fever, arthralgia); SJS and drug rashes are immune-mediated but not IgE-mediated (testing is not useful); severe cutaneous adverse reactions (SJS, DRESS) require immediate cessation of the medication and systemic corticosteroids; these reactions are an absolute contraindication to future use of the drug; with drug rashes and serum sickness, the medication may be stopped but can continue if absolutely necessary, with treatment for the rash if needed

Mast cell degranulation: certain medications can cause MCD with histamine release without involving IgE antibodies; opiates (eg, codeine) can directly trigger MCD, causing hives; skin testing is not useful for these reactions; opiates may still be used cautiously, typically under observation; children with aspirin-exacerbated respiratory disease (a type of asthma) experience asthma exacerbation with nonsteroidal anti-inflammatory drugs (NSAIDs) and need to avoid these drugs; children who are prone to hives may experience urticaria with NSAID use, but anaphylaxis is rare; when parents report their child is allergic to local anesthetics (eg, lidocaine, novacaine), the reaction is often vasovagal; if there is concern, skin testing can confirm the child is not allergic; a more serious concern is reactions to radiocontrast media, wherein high osmolarity causes MCD; these reactions do not involve IgE, can occur on the first exposure, and are not related to iodine; similarly, shellfish allergies are not caused by iodine; to prevent future reactions in children with a history of contrast-related reactions, use iso-osmolar contrast rather than premedicating with antihistamines and corticosteroids (shown to be ineffective at preventing reactions)

Reaction to vaccines: influenza vaccines — grown in eggs and containing trace amounts of egg protein (ovalbumin); safe for children with egg allergies, including those with severe anaphylactic reactions; studies involving thousands of egg-allergic children have shown that they tolerate injectable and intranasal flu vaccines without issues, as the amount of egg protein in the vaccine is too small to trigger a reaction; the American Academy of Pediatrics has stated that egg allergy is not a contraindication for the influenza vaccine, and there is no need to ask about egg allergy on screening forms before administering the vaccine; COVID vaccines — some children and adolescents have experienced reactions resembling anaphylaxis after receiving their first COVID vaccine dose, despite the fact that prior exposure is needed for an allergic reaction and mRNA vaccines do not contain proteins to trigger IgE production; anaphylaxis typically involves urticaria and respiratory or cardiovascular symptoms; vasovagal reactions are distinguished by pallor and bradycardia (vs flushing and tachycardia with anaphylaxis); vocal cord spasms or panic attacks can mimic anaphylaxis but are actually immunization stress-related responses with symptoms that typically do not have objective physical findings; some initially thought polyethylene glycol (PEG) in the vaccines might be causing issues, but studies showed that people with true PEG allergies do not react to the COVID vaccine

Second dose of the COVID-19 vaccine: only 0.16% of people who experienced a possible allergic reaction after the first dose had a similar reaction to the second dose; if a child had a mild reaction to the first dose, the benefits of vaccination outweigh the very low risk for a repeat reaction; if there is concern about a severe reaction, refer to an allergy clinic

Readings

Greenhawt M, Turner PJ, Kelso JM. Administration of influenza vaccines to egg allergic recipients. Ann Allergy Asthma Immunol. 2018;120:49-52; Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: A 2022 practice parameter update. Journal of Allergy and Clinical Immunology. 2022; 150:1333-93; Luxi N, Giovanazzi A, Capuano A, et al. COVID-19 Vaccination in Pregnancy, Paediatrics, Immunocompromised Patients, and Persons with History of Allergy or Prior SARS-CoV-2 Infection: Overview of Current Recommendations and Pre- and Post-Marketing Evidence for Vaccine Efficacy and Safety. Drug Saf. 2021;44(12):1247-1269. doi:10.1007/s40264-021-01131-6; Nilsson L, Brockow K, Alm J, et al. Vaccination and allergy: EAACI position paper, practical aspects. Pediatr Allergy Immunol. 2017;28(7):628-640. doi:10.1111/pai.12762; Podlecka D, Jerzyńska J, Brzozowska A. Don’t we overestimate drug allergies in children?. Int J Occup Med Environ Health. 2023;36(5):632-642. doi:10.13075/ijomeh.1896.02227.

Disclosures

For this program, members of the faculty and the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Kelso was recorded at Pediatrics in the Islands: Clinical Pearls 2024, held October 28, 2024, in Waikoloa, HI, and presented by Children’s Hospital Los Angeles Medical Group. For information about upcoming CME activities from this presenter, please visit https://www.chla.org/chla-medical-group/cme-conferences. Audio Digest thanks Dr. Kelso and Children’s Hospital Los Angeles Medical Group for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

PD710402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.