Origin and Function of Eosinophilic Polynuclear During DRESS Syndrome

Drug Hypersensitivity Clinical Trial

— DRESSEO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04330118
• Other study ID #: 2019_01
• Secondary ID: 2019-A02026-51
• Status: Recruiting
• Start date: July 15, 2020
• Est. completion date: December 2023

Study information

• Verified date: September 2022
• Source: University Hospital, Lille
• Contact: Delphine Staumont-Salle, MD,PhD
• Phone: 0320444193
• Email: delphine.salle[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• DRESS Syndrome
• Drug Hypersensitivity
• Drug Hypersensitivity Syndrome
• Hypersensitivity
• Syndrome

Locations

Country	Name	City	State
France	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	CH de Dunkerque	Dunkerque
France	CH LENS	Lens
France	Groupe Hospitalier de l'Institut Catholique de Lille	Lille
France	Hop Claude Huriez Chr Lille	Lille
France	CH de Roubaix	Roubaix
France	Hôpital FOCH	Suresnes
France	CH de Valenciennes	Valenciennes

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Lille	Société de Dermatologie Française, Société de Recherche en Dermatologie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Activation status of circulating eosinophils by flow cytometry		Baseline
Secondary	Mean fluorescence intensity of CCR3 and IL-5R markers		Baseline
Secondary	Percentage of Th2 polarized T cells		Baseline
Secondary	Percentage of ILC2		Baseline
Secondary	Serum levels (ELISA) of inflammatory markers		Baseline
Secondary	Correlation between the number of activated circulating eosinophils, area degranulation and severity of DRESS		Baseline
Secondary	Density of extracellular granules (degranulation area and number / mm2) on skin biopsies		Baseline
Secondary	NGS analysis of rearrangements of TCR (T cell receptor)		Baseline and 3 months