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

University Hospital, Lille

Status

Enrolling

Conditions

DRESS Syndrome

Drug Hypersensitivity

Study type

Observational

Funder types

Other

Identifiers

NCT04330118

2019-A02026-51 (Other Identifier)

2019_01

Details and patient eligibility

About

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.

Enrollment

80 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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.