Clinical trial NCT04330118: Origin and Function of Eosinophilic Polynuclear During DRESS Syndrome
Official title: Origin and Function of Eosinophilic Polynuclear During Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Drug Hypersensitivity
DRESS Syndrome
Keywords: DRESS syndrome
Drug hypersensitivity
eosinophils
allergy
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Société de Dermatologie Française
name: Société de Recherche en Dermatologie
First posted: 2020-04-01
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with drug induced rash (DRESS, maculopapular exanthema) and healthy patients.

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.


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.

Primary outcomes:
measure: Activation status of circulating eosinophils by flow cytometry
timeFrame: Baseline
Secondary outcomes:
measure: Mean fluorescence intensity of CCR3 and IL-5R markers
timeFrame: Baseline
measure: Percentage of Th2 polarized T cells
timeFrame: Baseline
measure: Percentage of ILC2
timeFrame: Baseline
measure: Serum levels (ELISA) of inflammatory markers
timeFrame: Baseline
measure: Correlation between the number of activated circulating eosinophils, area degranulation and severity of DRESS
timeFrame: Baseline
measure: Density of extracellular granules (degranulation area and number / mm2) on skin biopsies
timeFrame: Baseline
measure: NGS analysis of rearrangements of TCR (T cell receptor)
timeFrame: Baseline and 3 months
Other outcomes:
Locations:
city: Arras
country: France
facility: CH d'Arras
city: Boulogne-sur-Mer
country: France
facility: CH de Boulogne
city: Créteil
country: France
facility: Assistance Publique - Hôpitaux de Paris - HENRI MONDOR
city: Douai
country: France
facility: CH de Douai
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Lens
country: France
facility: CH LENS
city: Lille
country: France
facility: Hop Claude Huriez Chr Lille
city: Lille
country: France
facility: Groupe Hospitalier de l'Institut Catholique de Lille
city: Roubaix
country: France
facility: CH de Roubaix
city: Suresnes
country: France
facility: Hôpital FOCH
city: Valenciennes
country: France
facility: CH de Valenciennes
Study officials:
affiliation: University Hospital, Lille
name: Delphine Staumont-Salle, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: