Origin and Function of Eosinophilic Polynuclear During DRESS Syndrome

Recruiting

• Conditions: Drug Hypersensitivity; DRESS Syndrome

• Registration Number: NCT04330118
• Lead Sponsor: University Hospital, Lille

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-03-30
• Study First Submitted QC: 2020-03-30
• Study First Posted: 2020-04-01
• Study Start: 2020-07-15
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-20
• Last Update Posted: 2022-09-21
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Activation status of circulating eosinophils by flow cytometry	Baseline

Secondary Outcome Measures

Name	Time	Method
Correlation between the number of activated circulating eosinophils, area degranulation and severity of DRESS	Baseline
Percentage of Th2 polarized T cells	Baseline
Percentage of ILC2	Baseline
Mean fluorescence intensity of CCR3 and IL-5R markers	Baseline
Serum levels (ELISA) of inflammatory markers	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

Trial Locations

Locations (11)

CH d'Arras; 🇫🇷 Arras, France

CH de Boulogne; 🇫🇷 Boulogne-sur-Mer, France

Assistance Publique - Hôpitaux de Paris - HENRI MONDOR; 🇫🇷 Créteil, France

CH de Douai; 🇫🇷 Douai, France

Hôpital FOCH; 🇫🇷 Suresnes, France

CH de Dunkerque; 🇫🇷 Dunkerque, France

CH LENS; 🇫🇷 Lens, France

Hop Claude Huriez Chr Lille; 🇫🇷 Lille, France

Groupe Hospitalier de l'Institut Catholique de Lille; 🇫🇷 Lille, France

CH de Valenciennes; 🇫🇷 Valenciennes, France

CH de Roubaix; 🇫🇷 Roubaix, France