Origin and Function of Eosinophilic Polynuclear During DRESS Syndrome (DRESSEO)

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

Drug Hypersensitivity Syndrome or DRESS for "Drug Reaction with Eosinophilia and Systemic Symptoms" is a serious drug allergy which can be life-threatening for patients with serious organ damage. The pathophysiology of DRESS is still not fully understood. In particular, no study has focused on the characterization of eosinophils, while paradoxically eosinophilia is one of the diagnostic criteria. Likewise, there is no data about the origin of eosinophils and few data are available concerning immune polarization of T-cells or the involvement of innate lymphoid cells type 2 in the recruitment of eosinophils. Our preliminary data on increase activation markers membrane expression of cutaneous eosinophils suggest that this approach could allow the identification of endotypes in which eosinophils are involved and contribute to organ damages. The correlation between tissue infiltration of eosinophils and their degree of activation would then justify the development of targeted therapeutic strategies in DRESS syndrome (anti-IL-5 therapy?). The aim of the project is: 1) Evaluate the activation status of circulating and cutaneous eosinophils in patients with DRESS compared with drug induced maculopapular exanthema without or with eosinophilia (but do not fulfill DRESS criteria) and healthy subjects; 2) Understand the pathophysiological mechanisms at the origin of this eosinophilia.

Study Overview

• Status: Recruiting
• Conditions: Drug Hypersensitivity; DRESS Syndrome

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Delphine Staumont-Salle, MD,PhD; Phone Number: +33 0320444193; Email: delphine.salle@chru-lille.fr

Study Locations

• France
  • Arras, France
    • Recruiting
    • CH d'Arras
    • Principal Investigator: Céline DESVIGNES
  • Boulogne-sur-Mer, France
    • Recruiting
    • CH de Boulogne
    • Principal Investigator: Sophie DARRAS
  • Créteil, France
    • Recruiting
    • Assistance Publique - Hôpitaux de Paris - HENRI MONDOR
    • Principal Investigator: Olivier Chosidow
  • Douai, France
    • Recruiting
    • CH de DOUAI
    • Principal Investigator: Eve DESMEDT
  • Dunkirk, France
    • Recruiting
    • CH de Dunkerque
    • Principal Investigator: SOPHIE DUVERT-LEHEMBRE
  • Lens, France
    • Recruiting
    • CH LENS
  • Lille, France, 59000
    • Recruiting
    • Hop Claude Huriez Chr Lille
  • Lille, France
    • Recruiting
    • Groupe Hospitalier de l'Institut Catholique de Lille
    • Principal Investigator: PHILIPPE MODIANO
  • Roubaix, France
    • Recruiting
    • CH de Roubaix
    • Principal Investigator: Olivier CARPENTIER
  • Suresnes, France
    • Recruiting
    • Hopital Foch
    • Principal Investigator: Matthieu GROH
  • Valenciennes, France
    • Recruiting
    • Ch de Valenciennes
    • Principal Investigator: Marie WEINBORN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patient with drug induced rash (DRESS, maculopapular exanthema) and healthy patients.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
20 patients with DRESS syndrome
20 patients with drug induced MPE with eosinophilia; patients with drug induced maculopapular exanthema (MPE) with eosinophilia
20 patients with drug induced MPE without eosinophilia
20 Healthy subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Activation status of circulating eosinophils by flow cytometry	Baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean fluorescence intensity of CCR3 and IL-5R markers	Baseline
Percentage of Th2 polarized T cells	Baseline
Percentage of ILC2	Baseline
Serum levels (ELISA) of inflammatory markers	Baseline
Correlation between the number of activated circulating eosinophils, area degranulation and severity of DRESS	Baseline
Density of extracellular granules (degranulation area and number / mm2) on skin biopsies	Baseline
NGS analysis of rearrangements of TCR (T cell receptor)	Baseline and 3 months

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Société de Dermatologie Française; Société de Recherche en Dermatologie
• Investigators: Principal Investigator: Delphine Staumont-Salle, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: allergy; eosinophils; Drug hypersensitivity; DRESS syndrome
• Additional Relevant MeSH Terms: Immune System Diseases; Chemically-Induced Disorders; Skin Diseases; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity, Delayed; Dermatitis; Drug Eruptions; Skin and Connective Tissue Diseases; Hypersensitivity; Drug Hypersensitivity; Drug Hypersensitivity Syndrome
• Other Study ID Numbers: 2019_01; 2019-A02026-51 (Other Identifier: ID-RCB number,ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No