633 Comparison of soluble proteins from skin sections of acne and TCA induced postinflammatory hyperpigmentation and erythema

Postinflammatory hyperpigmentation (PIH) is an acquired hypermelanosis occurring after cutaneous inflammation or injury that can arise in all skin types, but more frequently affects skin-of-color. The differences in the ethology of PIH and Postinflammatory erythema (PIE) in skin of color were evaluated from soluble protein extracts collected from skin section samples, using Somascan protein kit1.3 k (n=5). The skin samples were collected from selected gluteal TCA-induced lesions and truncal acne pustules, of either PIH or PIE, at day 28 post initial evaluation. Differences between proteins (FDR\u3c0.05) from PIH and PIE were analyzed with STRING version 11.5 and analysis points toward involvement of JAK/STAT signaling pathway and enhanced IL17 signaling in PIH compared to PIE lesions (OSM, CSF3, IL10RA, IL12RB2, IL10RB, IL3, CSF2, IL17D, IL17F, IFNA2, IFNA10, CRLF2, IL5RA, TYK2, IL12RB1, PRLR, GHR). The involvement of JAK/STAT signaling pathway has been described for some chronic cutaneous inflammatory conditions and acne. A higher occurrence of dermal remodeling proteases and inhibitors were found in PIE (MMP1, MMP2, MMP7, TIMP2) indicating a dermal remodeling phase at the time of excision. Concurrently, elevated levels of IL-1β, and TGF-β (critical for triggering and continuing differentiation programs of naïve CD4+ T cells to IL-17 secreting Th17 cells) in PIH samples suggests continuing promotion of macrophage infiltration and sustained inflammation. In addition to MMP13 and MMP16, the protein Keap1 was found to be increased in the PIH samples. Keap1, a repressor of master cellular defense against oxidative and electrophilic stresses, has been reported to be involved in the imbalance of proteolysis that can lead towards premature aging and in a senescent phenotype of endothelial cells. The sustained inflammation with excess of Keap1 protein might contribute to an altered proteostasis and ethology of PIH

An in vivo model for post-inflammatory hyperpigmentation.

Background: Post-inflammatory hyperpigmentation (PIH) is an acquired hypermelanosis occurring after cutaneous inflammation. A validated, in vivo model of acne-induced PIH was previously established using 35% trichloracetic acid (TCA). We aim to determine the minimum TCA concentration that induces PIH that results in validated measurements that are most similar to acne-induced PIH. Methods: Thirty subjects (skin types I-VI) were enrolled; 20 had a history of PIH, and 10 had a history of post-inflammatory erythema with acne resolution. Study procedures have been completed by 25/30 subjects. At day 0, two acne papules were identified on the back and 35%, 30%, 25%, and 20% TCA was applied to the buttocks. At day 28, clinical photography, Investigator Global Assessment (IGA) of hyperpigmentation and erythema, and colorimetry were performed for all lesions and adjacent uninvolved sites.Results: For 25 subjects, IGA and colorimeter data for day 28 were analyzed with one way repeated measures ANOVA. There were no significant differences of IGA scores of hyperpigmentation between acne and 25% and 30% TCA-induced lesions. Colorimetry L* (lightness) found no significant difference between acne and 30% and 35% TCA-induced lesions. Colorimeter parameter a* (erythema) demonstrated similarities between acne and 35% TCA-induced lesions.Conclusion: Our results show that 25% TCA has the potential to induce PIH similar to acne without necrosis. A higher concentration TCA (35%) resulted in the erythema similar to acne. We suggest that TCA-induced changes could serve as a model for the study of PIH

An in vivo model of postinflammatory hyperpigmentation and erythema: clinical, colorimetric and molecular characteristics

BACKGROUND: Postinflammatory hyperpigmentation (PIH) is a common, acquired pigmentary disorder of the skin associated with significant quality-of-life impairment, especially in individuals with skin of colour. Current treatment for PIH is limited, largely due to a poor understanding of disease pathogenesis and the lack of a representative disease model. OBJECTIVES: This study is intended to further develop, update and validate our previously designed in vivo model of acne-induced PIH/postinflammatory erythema (PIE) using different concentrations of trichloroacetic acid (TCA), a medium-depth chemical peel. METHODS: Twenty-nine patients with skin types II-VI and clinician-confirmed presence of two or more truncal acne pustules and PIH/PIE were included. On the basis of Investigator\u27s Global Assessment (IGA), clinical polarized photography (CPP), colorimetry and Skindex, we experimentally determined an optimum TCA concentration and assessed our model\u27s ability to exhibit a dose-response relationship between degree of inciting insult and severity of resulting pigmentation. We also performed differential microRNA profiling and pathway analysis to explore the potential of microRNAs as molecular adjuncts to our model. RESULTS: Application of TCA 30% produced lesions indistinguishable from acne-induced PIH and PIE lesions on the basis of colorimetry data without causing epidermal necrosis. Application of progressively increasing TCA doses from 20% to 30% resulted in concentration-dependent increases in CPP, IGA and colorimetry scores at all timepoints during the study. miRNA-31 and miRNA-23b may play a role in PIH pathogenesis, although further validation is required. CONCLUSIONS: Our TCA-based in vivo model, using TCA concentrations between 20% and 30% with an optimum of 30%, enables the quantitative assessment of the pigmentary response to varying degrees of cutaneous inflammation in a fashion that mirrors natural acne-induced PIH and PIE