Pediatric Non-Steroidal Anti-Inflammatory Drugs (NSAID) Allergy Study

Hypersensitivity reactions (HSR) to NSAID in children, although similar to those in adults, present unique challenges in terms of diagnosis and management. While international classification systems are useful, real-world clinical scenarios often fall outside established criteria. Examples include:

• Multiple NSAID HSR involving both cutaneous and respiratory symptoms.
• NSAID-induced anaphylaxis dependent on food intake.
• Immediate selective reactions to more than one NSAID. These scenarios are frequently observed in pediatric patients, highlighting the need for a regional study to evaluate and properly address them.

This is a single-center, ambispective observational study.

Primary Objective:

To describe the clinical characteristics of children with NSAID hypersensitivity.

Secondary Objectives:

• To describe the different clinical phenotypes and assess age-related differences.
• To assess tolerance to alternative NSAIDs in patients with confirmed hypersensitivity.
• To evaluate the usefulness of in vivo and in vitro tests in the diagnostic process.
• To disseminate study findings.

The study design is based on 2 components:

• Retrospective Component: include participants diagnosed with NSAID HSR, who underwent DPT in the Pediatric Allergy Department at Hospital Sant Joan de Déu between January 2014 and December 2021. Data will be pseudonymized. A waiver of informed consent will be requested due to the long study period, the absence of risk, and the fact that many patients are no longer under follow-up.
• Prospective Component: participants with suspected NSAID HSR were included. Participants will be assessed during outpatient visits, where the following steps will occur:
• In vivo testing, where appropriate, using validated prick and intradermal techniques for paracetamol and metamizole. Controls will include saline (negative) and histamine (positive).
• A DPT will be performed with the suspected medication and/or suitable alternatives, in accordance with standard clinical practice.
• Nasal DPT using a rhinomanometer for patients suspected of NSAID-exacerbated respiratory disease (NERD).
• Families will be informed about the procedures, and informed consent will be obtained.

On the day of the DPT, a blood test (including total IgE, IgG, IgA, IgM, tryptase, IL-6) and urine sample (uLTE4 levels) will be collected.

If the DPT is positive, a second round of blood and urine samples will be collected.

The NSAID to be used in testing are commonly prescribed in pediatric practice and grouped by chemical structure:

Salicylic acid derivatives: Aspirin Para-aminophenol derivatives: Paracetamol (acetaminophen) Propionic acid derivatives: Ibuprofen, naproxen Acetic acid derivatives: Diclofenac Enolic acid derivatives: Pyrazolones, oxicams Fenamates (fenamic acid derivatives) COX-2 inhibitors: Celecoxib

Inclusion criteria

• Children aged 0-17 years
• Completed DPT with the suspected and/or alternative NSAID

Exclusion criteria

• Patients who did not undergo or complete the DPT