Skin Microbiome and Polymorphic Light Eruption (PLE_microbio)

The Significance of the Skin Microbiome in the Pathophysiology of Polymorphic Light Eruption

Polymorphic light eruption (PLE) is the most common form among UV-inducible disorders with a prevalence of approximately 11-21% worldwide and a clear predisposition of women. Usually, within several hours after an intense UV exposure, most likely in spring or early summer, the formation of itchy skin lesions particularly at the upper arms and V-neck and neck is distinctive for PLE. It has been suggested that the development of a potential photo-induced antigen may initiate a delayed-type hypersensitivity reaction in PLE (causing the skin rash) and the microbiota of the skin may be involved. We thus hypothesized that eliminating the microbiota of the skin by disinfection may affect the formation of PLE. The concept of this study covers a combined interindividual and intraindividual half-body comparison of the skin reactions of disinfected and contralateral non-disinfected areas upon UV exposure in PLE patients and healthy subjects.

Study Overview

• Status: Recruiting
• Conditions: Polymorphic Light Eruption
• Intervention / Treatment: Other: Octeniderm (octenidine dihydrochloride, 1-propanol, 2- propanol)

Detailed Description

UV-induced erythema and pigmentation is quantified by visual scoring and reflectance spectroscopy to determine the minimum erythema dose (MED) exploring the fields of an UV test ladder on the dorsal skin of the study subjects.

Investigations after determining the MED and consecutive photo provocations on 4 subsequent days (PLE group only) using solar simulated UV radiation with slight dose increments include a half-body site comparison of test areas located on the back of the subjects in a randomized, double blinded manner. The microbiota of a respective test area is removed by the disinfection with Octeniderm (octenidine dihydrochloride, 1-propanol, 2- propanol) whereas a control site remains non-disinfected (sham-treated with physiologic sodium chloride solution).

The PLE related symptoms are evaluated by a validated PLE score, which is composed as follows:

Affected skin area (AA) [range, 0-4] + skin infiltration (SI) [range, 0-4] + 0.4 pruritus (P) [range, 0-10]; ([total range 0-12].

As additional procedures, tape strips and skin swabs are taken immediately after UV exposures. The material is used for shotgun metagenomic sequencing of microbes and further analysis such as quantitative measures of antimicrobial peptides and urocanic acid levels. Furthermore, suction blisters are produced after MED testing and the last day of photo provocation [Time Frame: At day 3 and 6] to profile the inflammatory milieu of the skin by transcriptomics. The epidermal blister roof is used together with optional skin biopsies (PLE patients only) for various investigations, including H/E and immunohistochemical stainings and messenger ribonucleic acid (mRNA) analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Wolf, MD; Phone Number: 80315 0043 316 385; Email: peter.wolf@medunigraz.at
• Study Contact Backup: Name: Maximilian Zarfl; Phone Number: 00 43 660 6682953‬; Email: maximilian.zarfl@stud.medunigraz.at

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Recruiting
      • Department of Dermatology, Medical University of Graz
      • Contact: Maximilian Zarfl; Phone Number: 00 43 660 6682953‬; Email: maximilian.zarfl@stud.medunigraz.at
      • Contact: Peter Wolf; Phone Number: 031638580315; Email: peter.wolf@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of PLE by typical patient history, typical histology of skin lesions and/or positive photo provocation test
• Healthy subjects

Exclusion Criteria:

• Presence or history of malignant skin tumors; dysplastic melanocytic nevus syndrome
• Photosensitive diseases such as porphyria, chronic actinic dermatitis, xeroderma
• pigmentosum, basal cell nevus syndrome
• Autoimmune disorders such as lupus erythematosus or dermatomyositis
• Antinuclear antibodies titer over 1:160 within 12 months prior study
• Systemic treatment of steroids and/or immunosuppressive drugs within 4 weeks prior the study start
• Systemic treatment of antibiotics within the last 6 weeks prior study
• Local treatment of anti-microbial treatment in the test field area within the last 6 weeks prior the study
• Systemic treatment of medications/drugs/ that could affect inflammatory responses within 2 weeks prior study
• Allergy on tape strips and/or adhesive material
• Psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polymorphic light eruption patients; PLE patients subjected to MED testing and photoprovocation	Other: Octeniderm (octenidine dihydrochloride, 1-propanol, 2- propanol); Administering Octeniderm (octenidine dihydrochloride, 1-propanol, 2- propanol) or 0,9% sodium chloride (as control agent) to the skin
Other: Healthy subjects; Normal healthy subjects	Other: Octeniderm (octenidine dihydrochloride, 1-propanol, 2- propanol); Administering Octeniderm (octenidine dihydrochloride, 1-propanol, 2- propanol) or 0,9% sodium chloride (as control agent) to the skin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of PLE	determined by PLE score (range, 0-12) of photo provocation results (0 best, 12 worst)	1 week
Quantification of erythema score (range, 0-4)	determined by visual and spectroscopic erythema score	1 week
Quantification of pigmentation (range, 0-4)	determined by visual and spectroscopic erythema score	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of multiple cytokines (panel of 96 cytokines)	determined by transcriptomics	1 week
Assessment of multiple microbiomes of the skin (quantity and variety)	determined by metagenomics	1 week
Measurement of quantity and quality of multiple Antimicrobial peptides (AMP)	determined by proteomics	1 week
Measurement of concentration of cis/trans-urocanic acid	determined by high pressure liquid chromotography (HPLC)	1 week
Quantification of cellular skin infiltration (T cells, granulocytes and macrophages)	determined by hematoxylin and eosin (H/E) and immunohistochemical stainings	1 week

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Peter Wolf, MD, Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Dermatitis; Skin Diseases, Eczematous; Exanthema; Dermatitis, Contact; Anti-Infective Agents, Local; Anti-Infective Agents; Octenidine
• Other Study ID Numbers: 33-196 ex 20/21

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