Regulation of immune response genes in the skin of allergic and clinically tolerant individuals exposed to p-phenylenediamine.

BACKGROUND: p-Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non-responders to PPD or whether they mount a response to PPD without showing any symptoms. METHODS: Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. RESULTS: T cell activation, inflammation and apoptosis pathways were up-regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up-regulated both pro- and anti-inflammatory cytokines genes. Interestingly, PPD treatment induced significant up-regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non-responders and allergic individuals. CONCLUSION: This study demonstrates that there are no true non-responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy.

Skin barrier damage after exposure to paraphenylenediamine.

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.

Carriers of filaggrin gene (FLG) mutations avoid professional exposure to irritants in adulthood.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) are associated with xerosis, atopic dermatitis, and early onset of hand eczema. Irritant exposure is a risk factor for occupational hand eczema, and FLG mutations increase the risk of occupational irritant contact dermatitis on the hands in hospital cohorts. It is unknown whether FLG mutations affect the level of irritant exposure. OBJECTIVES: To evaluate whether exposure to occupational irritants was dependent on FLG mutations, atopic dermatitis, and age at hand eczema onset. METHODS: Randomly chosen Danish adults completed a questionnaire on general health and occupational exposures. Genotyping for FLG mutations (R501X, 2282del4, and R2447X) and patch testing were performed. RESULTS: Overall, 38.7% of subjects reported present or previous occupational exposure to irritants. Among individuals who reported hand eczema onset before entering their work life, 50.6% (45/89) of FLG non-mutation carriers became exposed to irritants, as compared with 28.6% (4/14) of heterozygous and 0% (0/6) of homozygous mutation carriers (p = 0.006). Avoidance was conspicuous among mutation carriers reporting childhood hand eczema and atopic dermatitis (odds ratio 0.08, 95% confidence interval 0.01-0.65). CONCLUSIONS: Carriers of FLG mutations who have had hand eczema onset in childhood avoid occupational exposure to irritants; the association is most marked with homozygous mutation status combined with atopic dermatitis.

[Atypical presentation of penile blue naevus].

Blue naevus is a rare lesion on genital mucosa and may cause confusion in differential diagnosis with other pigmented lesions. In this case report, a 39-year-old man presented with a sudden onset in adulthood of blue naevus on the glans penis. A biopsy confirmed the diagnosis. Due to the unusual presentation, the onset and the risk of turning invasive, a careful examination was performed in order to minimise any risk of misclassification with melanoma. Afterwards, the patient was followed in a dermatologic department every six months. To our knowledge, only few similar cases have been described in literature.

Skin pH, atopic dermatitis, and filaggrin mutations.

BACKGROUND: The acidic pH of the skin plays a role in antimicrobial defense by regulating the bacterial skin flora and aspects of barrier. Filaggrin is a co-factor in maintaining a low skin pH because of its degradation into acidic amino acids. Accordingly, lack of filaggrin due to filaggrin mutations may influence skin pH. OBJECTIVE: We aimed to determine the epidermal pH in different groups stratified by filaggrin mutations and atopic dermatitis. Further, we investigated the changes in pH according to severity of mutational status among patients with dermatitis, irrespective of skin condition. METHODS: pH was measured with a multiprobe system pH probe (PH 905), and the study population was composed of 67 individuals, who had all been genotyped for 3 filaggrin mutations (R501X, 2282del4, R2447X). RESULTS: We found no clear pattern in relation to filaggrin mutation carrier status. Individuals with wild-type filaggrin displayed both the most acidic and most alkaline values independent of concomitant skin disease; however, no statistical differences between the groups were found. CONCLUSIONS: The lack of significant diversity in skin pH in relation to filaggrin mutation carrier status suggests that the effect of filaggrin mutations on skin pH is not pronounced.