What is the risk of anaphylaxis in a child who develops an urticarial (hives) rash after taking Penicillin (antibiotic)?

From the Guidelines

If a child gets an urticarial rash on penicillin, the chance of anaphylaxis is extremely low, and a direct penicillin challenge without preceding skin tests is recommended in pediatric patients with a history of benign cutaneous reaction, such as urticaria, according to the 2022 practice parameter update 1. The risk of anaphylaxis in children with penicillin-induced urticarial rash is not explicitly stated in the provided evidence, but it can be inferred that the risk is low, as the studies mentioned in the evidence did not include patients reporting respiratory symptoms, cardiovascular symptoms, anaphylaxis, and vesicular or exfoliative eruptions 1.

• The evidence suggests that aminopenicillins are associated with development of delayed-onset maculopapular exanthem (MDE) in < 7% of patients, compared to about 2% for penicillin VK, and these reactions are not related to specific IgE antibodies 1.
• The rate of reactions observed in rechallenging testing ranged from about 5% to 10% and were generally no more severe than the historical reactions, with no reports of anaphylaxis 1.
• The 2022 practice parameter update recommends against penicillin skin testing prior to direct amoxicillin challenge in pediatric patients with a history of benign cutaneous reaction, such as urticaria, with a strong strength of recommendation and moderate certainty of evidence 1. Therefore, the approach to a child with a history of urticarial rash on penicillin should be to discontinue the medication and consider a direct penicillin challenge without preceding skin tests, while monitoring for signs of anaphylaxis, as the risk of anaphylaxis is extremely low 1.

From the FDA Drug Label

Although the incidence of reactions to oral penicillins has been reported with much less frequency than following parenteral therapy, it should be remembered that all degrees of hypersensitivity, including fatal anaphylaxis, have been reported with oral penicillin The hypersensitivity reactions reported are skin eruptions (maculopapular to exfoliative dermatitis), urticaria and other serum sickness-like reactions, laryngeal edema and anaphylaxis.

The chance of anaphylaxis in a child who gets an urticarial rash on penicillin cannot be quantified from the provided information, as the FDA drug label does not provide a specific probability or incidence rate of anaphylaxis in this scenario 2, 2.

• Anaphylaxis is a possible reaction to penicillin, but the label does not provide enough information to determine the likelihood of anaphylaxis in a child with an urticarial rash.
• Urticarial rash is listed as a hypersensitivity reaction to penicillin, and anaphylaxis is also listed as a possible reaction, but there is no direct link between the two in terms of probability or risk.

From the Research

Urticarial Rash and Anaphylaxis

• A child who develops an urticarial rash after taking penicillin may be at risk of anaphylaxis, although the exact chance is not specified in the provided studies.
• According to 3, of patients who test negative for penicillin allergy with skin testing, 1% to 4% will have non-life-threatening urticarial reactions.
• A study published in 4 categorizes patients with urticaria or other pruritic rashes as having a moderate-risk history for developing an allergic reaction to penicillin.
• The same study 4 notes that patients with a moderate-risk history can be evaluated with penicillin skin testing, which has a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge.

Penicillin Allergy and Anaphylaxis

• Penicillin and its derivatives are a common cause of drug-induced anaphylaxis, accounting for some 500 deaths per year in the United States, as reported in 3.
• However, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon, affecting less than 5% of the population, according to 4.
• A study published in 5 notes that treatments for penicillin allergy include epinephrine, antihistamines, and/or glucocorticoids, depending on the type of reaction.

Evaluation and Management of Penicillin Allergy

• Evaluation of penicillin allergy is an important tool for antimicrobial stewardship, as reported in 4.
• Penicillin skin testing is a useful method for evaluating patients with a vague or inconsistent history of penicillin allergy, as noted in 3.
• Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories, according to 4.