Origin and Function of Eosinophilic Polynuclear During DRESS Syndrome

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

Sponsors

Lead Sponsor: University Hospital, Lille

Collaborator: Société de Dermatologie Française
Société de Recherche en Dermatologie

Source 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.

Overall Status Recruiting
Start Date 2020-07-15
Completion Date 2022-12-01
Primary Completion Date 2022-12-01
Study Type Observational
Primary Outcome
Measure Time Frame
Activation status of circulating eosinophils by flow cytometry Baseline
Secondary 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
Enrollment 80
Condition
Eligibility

Sampling Method:

Non-Probability Sample

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 or ≥ 10% of absolute value - Lymphocytosis > 5000 / mm3 - Presence of atypical blood lymphocytes. - 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 - Associated visceral involvement. - Do not fulfill DRESS criteria 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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Delphine Staumont-Salle, MD,PhD Principal Investigator University Hospital, Lille
Overall Contact

Last Name: Delphine Staumont-Salle, MD,PhD

Phone: 0320444193

Phone Ext.: +33

Email: [email protected]

Location
Facility: Status:
CH LENS | Lens, France Recruiting
Hop Claude Huriez Chr Lille | Lille, 59000, France Recruiting
Location Countries

France

Verification Date

2020-03-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: 20 patients with DRESS syndrome

Label: 20 patients with drug induced MPE with eosinophilia

Description: patients with drug induced maculopapular exanthema (MPE) with eosinophilia

Label: 20 patients with drug induced MPE without eosinophilia

Label: 20 Healthy subjects

Acronym DRESSEO
Study Design Info

Observational Model: Case-Control

Time Perspective: Prospective

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