Skin barrier damage after exposure to paraphenylenediamine

J Allergy Clin Immunol. 2020 Feb;145(2):619-631.e2. doi: 10.1016/j.jaci.2019.11.023. Epub 2019 Nov 26.

Abstract

Background: p-Phenylenediamine (PPD) is a strong contact allergen used in hair dye that is known to cause allergic contact dermatitis (ACD). Both private and occupational exposure to PPD is frequent, but the effect of PPD exposure in nonallergic occupationally exposed subjects is unknown.

Objective: We sought to investigate the effects of PPD exposure on the skin of occupationally exposed subjects with and without clinical symptoms.

Methods: Skin biopsy specimens were collected from 4 patients with mild and 5 patients with severe PPD-related ACD and 7 hairdressers without contact dermatitis on day 4 after patch testing with 1% PPD in petrolatum. RNA sequencing and transcriptomics analyses were performed and confirmed by using quantitative RT-PCR. Protein expression was analyzed in skin from 4 hairdressers and 1 patient with ACD by using immunofluorescence staining. Reconstructed human epidermis was used to test the effects of PPD in vitro.

Results: RNA sequencing demonstrated downregulation of tight junction and stratum corneum proteins in the skin of patients with severe ACD after PPD exposure. Claudin-1 (CLDN-1), CLDN8, CLDN11, CXADR-like membrane protein (CLMP), occludin (OCLN), membrane-associated guanylate kinase inverted 1 (MAGI1), and MAGI2 mRNA expression was downregulated in patients with severe ACD. CLDN1 and CLMP expression were downregulated in nonresponding hairdressers and patients with mild ACD. Filaggrin 1 (FLG1), FLG2, and loricrin (LOR) expression were downregulated in patients with ACD. Confocal microscopic images showed downregulation of CLDN-1, FLG-1, and FLG-2 expression. In contrast, 3-dimensional skin cultures showed upregulation of FLG-1 in response to PPD but downregulation of FLG-2.

Conclusion: PPD-exposed skin is associated with extensive transcriptomic changes, including downregulation of tight junction and stratum corneum proteins, even in the absence of clinical symptoms.

Keywords: Allergic contact dermatitis; RNA sequencing; hair dye contact hypersensitivity; p-Phenylenediamine; stratum corneum; tight junctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dermatitis, Allergic Contact / etiology
  • Dermatitis, Allergic Contact / pathology
  • Female
  • Filaggrin Proteins
  • Hair Dyes / adverse effects*
  • Humans
  • Occupational Exposure / adverse effects*
  • Phenylenediamines / adverse effects*
  • Skin / drug effects*
  • Skin / pathology
  • Tight Junction Proteins / drug effects

Substances

  • FLG protein, human
  • FLG2 protein, human
  • Filaggrin Proteins
  • Hair Dyes
  • Phenylenediamines
  • Tight Junction Proteins
  • 4-phenylenediamine