Where eosinophils come from and what they do in DRESS

Origin and Function of Eosinophilic Polynuclear During Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome

This project will see if eosinophils come from specific sources and how they behave in adults with DRESS compared with adults who have milder drug rashes.

Quick facts

• Study type: Observational
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Lille (other)
• Drugs / interventions: OMALIZUMAB, LIGELIZUMAB, MEPOLIZUMAB, BENRALIZUMAB, DUPILUMAB, TRALOKINUMAB
• Locations: 11 sites (Arras and 10 other locations)
• Trial ID: NCT04330118 on ClinicalTrials.gov

What this trial studies

This observational project enrolls adults with DRESS and two comparison groups of adults with drug-induced maculopapular exanthema (with and without blood eosinophilia). Investigators will collect blood and tissue samples to characterize eosinophil origin, surface activation markers, T-cell polarization, and potential involvement of type 2 innate lymphoid cells (ILC2). They will correlate tissue eosinophil infiltration and activation with organ involvement and clinical severity to identify distinct endotypes. Recruitment and sample collection take place at participating hospitals in France for laboratory and immunologic analyses.

Who should consider this trial

Good fit: Adults who meet the clinical DRESS criteria (rash after drug exposure, fever, organ involvement, and eosinophilia or RegiSCAR score ≥4) or adults with drug-induced maculopapular exanthema with or without blood eosinophilia are appropriate candidates.

Not a fit: People whose eosinophilia or rash is due to non-drug causes (for example cancer or preexisting hematologic disease) are unlikely to benefit from this project.

Why it matters

Potential benefit: If successful, the findings could identify patient subgroups where eosinophils drive organ damage and point to targeted treatments that reduce complications.

How similar studies have performed: This approach is largely novel—few prior studies have characterized eosinophil origin or the roles of T-cell polarization and ILC2s in DRESS, though preliminary data show increased activation markers on skin eosinophils.

Eligibility criteria

Inclusion Criteria:

Group 1 (DRESS): adult with a diagnosis of DRESS based on the following four criteria:

* Cutaneous rash occurring at least 24 hours and at most 2 months after continuous medication use
* Fever over 38 degre celcius
* At least one organ dysfunction among:
* Lymphadenopathy
* hepatitis
* Pulmonary involvement
* Cardiac involvement: myocarditis, pericarditis
* Renal impairment
* At least one of the following hematological anomalies:
* Eosinophilia ≥ 500 / mm3 .
* RegiSCAR Score ≥ 4

Groups 2 and 3 (Drug induced maculopapular exanthema without or with eosinophilia).

* Adult with drug-induced rash
* Without clinical criteria of severity defined by Djien among :
* An evolution of more than 21 days
* with organ damage as defined in group 1

Group 2 (MPE without eosinophilia): blood eosinophils \< 500 / mm3

Group 3 (MPE with eosinophilia): blood eosinophils ≥ 500 / mm3

Exclusion Criteria:

* Other cause of eosinophilia including cancer, blood disease before the introduction of suspected molecule(s).
* On going oral or local corticosteroid therapy, anti-leukotriene therapy (MONTELUKAST) by the month preceding the study;
* Anti-IgE therapy (OMALIZUMAB, LIGELIZUMAB), anti-IL-5 therapy (MEPOLIZUMAB, BENRALIZUMAB) or anti-IL4 and / or anti-IL13 therapy (DUPILUMAB, TRALOKINUMAB) in the 6 months preceding the study.
* Any pregnant or lactating woman.
* Contraindication related to the blood volume taken for the study.

Where this trial is running

Arras and 10 other locations

• CH d'Arras — Arras, France (RECRUITING)
• CH de Boulogne — Boulogne-sur-Mer, France (RECRUITING)
• Assistance Publique - Hôpitaux de Paris - HENRI MONDOR — Créteil, France (RECRUITING)
• CH de Douai — Douai, France (RECRUITING)
• CH de Dunkerque — Dunkirk, France (RECRUITING)
• CH LENS — Lens, France (RECRUITING)
• Hop Claude Huriez Chr Lille — Lille, France (RECRUITING)
• Groupe Hospitalier de l'Institut Catholique de Lille — Lille, France (RECRUITING)
• CH de Roubaix — Roubaix, France (RECRUITING)
• Hôpital FOCH — Suresnes, France (RECRUITING)
• CH de Valenciennes — Valenciennes, France (RECRUITING)

Study contacts

• Principal investigator: Delphine Staumont-Salle, MD,PhD — University Hospital, Lille
• Study coordinator: Delphine Staumont-Salle, MD,PhD

Conditions: Drug Hypersensitivity, DRESS Syndrome, DRESS syndrome, Drug hypersensitivity, eosinophils, allergy