Transcriptomic Landscape of T Lymphocytes of Atopic Dermatitis, Atopic Prurigo Nodularis (of Besnier) and Non-atopic Prurigo Nodularis (of Hyde) Using Single Cell RNA-sequencing (PRURISEQ)

Prurigo nodularis (PN) is a skin condition characterized by symmetrically distributed widespread, pruritic nodules that occurs in patients with chronic pruritus. There are 2 subtypes of PN depending on the association with an atopic dermatitis (AD) : atopic PN (Besnier) and non-atopic PN (Hyde). There are no approved therapies, and treatment options currently used have limited efficacy and their long-term use carries the risk of potential severe toxic effects.

The mechanisms triggering PN are still unknown. However, recent findings suggest a major role for the Th2 inflammatory pathway.

Beyond advancing the basic understanding of PN pathophysiology, our study might also pave the way for developing novel Th2-targeted therapeutic strategies for PN and AD. The primary objective of this study is to characterize the transcriptional profile of the T lymphocytes isolated from skin samples from patients with PN. This study will allow a gain a deeper understanding of the pathophysiologic mechanism of PN, a better classification of its subtypes, as well as their physiopathologic link with AD. Moreover, it will help shape new effective and safe therapeutic approaches in these diseases which are important for optimal therapeutic management.

Study Overview

• Status: Unknown
• Conditions: Atopic Dermatitis; Prurigo Nodularis
• Intervention / Treatment: Other: Skin biopsy; Other: Plastic surgery remnants

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with confirmed diagnosis of atopic dermatitis (n=5), atopic prurigo nodularis (of Besnier) (n=5) and non-atopic prurigo nodularis (of Hyde) (n=5) or from surgical residues of normal skin (n=5).

Description

Inclusion Criteria:

• More than 18 years of age
• Signature of the written contentment
• Clinical diagnostic of PN defined by the following: a minimum of 20 PN lesions, in total on both legs, and/or both arms; an average worst itch score of ≥7. Atopic PN will be defined as PN associating clinical sings or history of AD according to Hanifin et Rajka criteria. Non-Atopic PN will be defined as PN non-associated with clinical sings or history of AD according to Hanifin et Rajka criteria.
• or confirmed diagnosis of AD according to Hanifin et Rajka criteria without associated PN.
• Washout period for topical treatments (> 1 week) ans systemic treatments (> 1 month).
• Indication and absence of contraindication to performing a skin biopsy as part of the treatment

Inclusion criteria for healthy controls:

• more than 18 years of age
• Signature of the written contentment
• Hospitalised in the plastic surgery department of Saint-Louis Hospital.
• No associated inflammatory or tumoral skin condition
• No contraindication for biopsy

Exclusion criteria :

• Presence of inflammatory or tumoral skin morbidities other than PN and atopic dermatitis
• Treatment induced pruritus
• Pruritus secondary to other medical conditions such as bullous dermatosis, renal insufficiency, infectious diseases, …)
• AD under biologic therapy
• Patient under guardianship or conservatorship
• No health insurance coverage
• Patient under State Medical Assistance (AME)
• Pregnancy or breastfeeding
• Persons deprived of their liberty by a judicial or administrative decision
• People undergoing psychiatric care making their consent impossible
• Adults who are the subject of a legal protection measure or unable to express their consent
• Patients unable to read and write

Exclusion criteria for healthy controls:

• Inflammatory or tumoral medical condition
• Biological therapy for any other medical condition
• Associated inflammatory or tumoral skin condition
• Pregnancy or breastfeeding
• Persons deprived of their liberty by a judicial or administrative decision
• People undergoing psychiatric care making their consent impossible
• Adults who are the subject of a legal protection measure or unable to express their consent
• Patients unable to read and write

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with atopic Prurigo nodularis , non-atopic Prurigo nodularis or atopic dermatitis	Other: Skin biopsy; a skin sample will be taken using a 4 mm punch biopsy in lesional skin
Patients with plastic surgery interventions	Other: Plastic surgery remnants; healthy skin from plastic surgery interventions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Transcriptional profile of the T lymphocytes	at inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Inflammatory pathways	at inclusion
Molecular differences	at inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): July 15, 2021
• Study Completion (Anticipated): July 15, 2021

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 6, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Prurigo; Neurodermatitis
• Other Study ID Numbers: APHP200325

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No