Protocols for drug allergy desensitization in children

ABSTRACT

Introduction: When a drug hypersensitivity reaction is proven, desensitization protocols allow the reintroduction of the molecule in patients for whom such therapy is essential. Through drug desensitization (DDS), a temporary immune tolerance is maintained for the single course of a specific therapy. In pediatrics, indications for such a procedure include children with chronic diseases, severe infectious diseases and/or malignancies, who have a proven drug hypersensitivity.

Areas covered: We ran a search on PubMed and Web of Science for papers on DDS and on DDS in children. Most protocols and recommendations on DDS focus on adults and have been adapted for children. The best candidates for desensitization are children with a history of immediate, IgE-mediated drug allergy, but this therapy may be applied also in nonallergic hypersensitivities and in non-immediate reactions. Most protocols in literature focus on antibiotics, especially beta-lactams, on chemotherapeutic agents, and on monoclonal antibodies.

Expert opinion: Pediatric allergists should cooperate with specialists in infectious diseases and onco-hematology to provide DDS to children in need. Standardized protocols and international guidelines are still needed to optimize such treatment and to implement it in clinical daily practice.

KEYWORDS:

• Antibiotics
• chemotherapeutic agents
• children
• drug allergy
• drug desensitization
• monoclonal antibodies
• pediatrics
• protocols

Article highlights

• When a DHR is confirmed, a DDS protocol may be proposed to provide a temporary tolerance to the drug.

• DDS is indicated, after a positive risk/benefit analysis, when possible alternatives are not available, or the alternative drug is less effective and/or noxious.

• Most protocols and recommendations on DDS focus on adults and have been transported and adapted for children.

• The exact mechanisms and molecular targets of DDS have not been fully clarified yet; nevertheless, they may be applied both in patients reporting IgE- and non-IgE-mediated reactions.

• Several protocols to perform desensitization have been described in the scientific literature for different antibiotics, proving to be safe and effective procedures.

• The traditional desensitization protocol for immediate hypersensitivity drug reactions to BLs starts with an initial drug concentration ranging from a 10⁻² to 10⁻⁶ dilution of the full therapeutic dose, depending on the child’s clinical history.

• One of the more experienced desensitization protocols is the penicillin one, in which the concentration is traditionally doubled every 15–20 min, until reaching the target therapeutic dose in few hours.

• In pediatrics, carboplatin and l-asparaginase are the two main chemotherapeutic agents associated to DHR; several different protocols are available to desensitized children to these drugs.

• As for mAbs, the most commonly used protocol has 12 steps but is associated to an increased risk of reaction during the last dose administration; a different 13-step protocol seems safe and equally effective.

• In pediatrics, there is still lack of standardized protocols and specific international guidelines on DDS are required.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.