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's Global Assessment (IGA), clinical polarized photography (CPP), colorimetry and Skindex, we experimentally determined an optimum TCA concentration and assessed our model's 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.

Assessment of inter-rater reliability of clinical hidradenitis suppurativa outcome measures using ultrasonography.

BACKGROUND: Hidradenitis suppurativa (HS) staging and severity is typically based upon physical examination findings, which can result in misclassification of severity based on subclinical disease activity and significant variation between healthcare providers. Ultrasonography (US) is an objective tool to help evaluate subclinical disease and to more accurately classify disease severity. AIM: To evaluate inter-rater reliability in HS disease severity assessment using clinical and US techniques. METHODS: In total, 20 subjects underwent clinical evaluation of HS, independently by two physicians, using clinical outcome measures, including Hurley, Sartorius, HS Physician Global Assessment (HS-PGA) and Hidradenitis Suppurativa Clinical Response (HiSCR). US was subsequently performed, and clinical assessments were repeated. Intraclass correlation coefficients (ICC) were obtained to evaluate inter-rater agreement of each outcome measure before and after US. RESULTS: Pre-US to post-US improvement in ICC was seen with the Sartorius, HiSCR nodule and abscess count, and the HiSCR draining fistula count. The scores went from having 'good' rater agreement for Sartorius and HiSCR nodule and abscess count, to 'poor' rater agreement for HiSCR draining fistula count, to 'excellent' rater agreement among these scores. CONCLUSION: US improved inter-rater agreement and should be used in conjunction with physical examination findings to evaluate disease severity to ensure uniform staging of HS.

Identifying key components and therapeutic targets of the immune system in hidradenitis suppurativa with an emphasis on neutrophils.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent and debilitating skin disease of the hair follicle unit that typically develops after puberty. The disorder is characterized by comedones, painful inflammatory nodules, abscesses, dermal tunnels and scarring, with a predilection for intertriginous areas of the body (axillae, inguinal and anogenital regions). Recruitment of neutrophils to HS lesion sites may play an essential role in the development of the painful inflammatory nodules and abscesses that characterize the disease. This is a review of the major mediators involved in the recruitment of neutrophils to sites of active inflammation, including bacterial components (endotoxins, exotoxins, capsule fragments, etc.), the complement pathway anaphylatoxins C3a and C5a, tumour necrosis factor-alpha, interleukin (IL)-17, IL-8 (CXCL8), IL-36, IL-1, lipocalin-2, leukotriene B4, platelet-activating factor, kallikreins, matrix metalloproteinases, and myeloperoxidase inhibitors. Pharmacological manipulation of the various pathways involved in the process of neutrophil recruitment and activation could allow for successful control and stabilization of HS lesions and the remission of active, severe flares.

Synergistic effects of long-wavelength ultraviolet A1 and visible light on pigmentation and erythema.

BACKGROUND: Visible light (VL) induces multiple cutaneous effects. Sunscreen testing protocols recommended by regulatory bodies throughout the world require the use of solar simulators with spectral output in the ultraviolet (UV) domain only. However, sunlight contains VL and infrared radiation also. OBJECTIVES: This study aimed to evaluate the contributions of VL and UVA on pigmentation and erythema, and optimize parameters for in vivo testing. METHODS: Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. Subjects were irradiated on their back with VL using two light sources: one containing pure VL and one containing VL with less than 0·5% UVA1 (VL+UVA1). Four different irradiances were administered to investigate reciprocity behaviour. Assessments, including photography, Investigator's Global Assessment, colorimetry and spectroscopy, were performed immediately, 24 h, 7 days and 14 days post-irradiation. RESULTS: Pigmentation was observed with both light sources; however, pigment intensity was greater with VL+UVA1 than with pure VL. Reciprocity was observed in pure VL sites, but not VL+UVA1. Variation in spectral output had greater impact on pigment intensity than irradiance. Clinical erythema was observed on the VL+UVA1 side, but not on the pure VL side. A protocol for testing photoprotection product efficacy against VL-induced effects has been proposed. CONCLUSIONS: The findings suggest a synergistic relationship between VL and UVA1 and emphasize the need for developing means of photoprotection against VL.

An in vivo model for postinflammatory hyperpigmentation: an analysis of histological, spectroscopic, colorimetric and clinical traits.

BACKGROUND: Acne vulgaris is a common condition that occurs in all skin types. Postinflammatory hyperpigmentation (PIH) is often associated with acne in patients of darker skin types, making it a common complaint in dermatology offices. Despite this, there is limited understanding of and effective treatment options for PIH. OBJECTIVES: The study objective was to validate an in vivo model for PIH and to compare the clinical, histological and spectroscopic characteristics of artificially induced PIH and acne-induced PIH. METHODS: A nonblinded, nonrandomized pilot study was performed. Thirty subjects served as their own control in which four sites treated with 35% trichloroacetic acid (TCA) solution and four truncal acne pustules were followed for 8 weeks and were evaluated clinically and histologically, and by colorimetry and spectroscopy. RESULTS: The initial phases of inflammation between TCA- and acne-induced PIH differ. However, clinical evaluations were similar on and after day 14. Acne- and TCA-induced lesions were clinically, histologically and spectroscopically indistinguishable at day 28. CONCLUSIONS: Clinical, spectroscopic and histological similarities of acne-induced and TCA-induced PIH at day 28 suggest that TCA-induced PIH can be a reproducible model for the study of acne-induced PIH.

An update on new and emerging options for the treatment of vitiligo.

Vitiligo is an acquired leukoderma that results from the loss of epidermal melanocytes, and is characterized by macules and patches of depigmented skin. With a relatively high rate of prevalence, vitiligo occurs in localized, generalized, or segmental patterns; it can run a rapidly progressive course or remain stationary. The pathogenesis of vitiligo is not yet fully understood, but the autoimmune hypothesis is the most commonly accepted one, based on which, many treatment modalities have been described. Although many therapeutic options exist and new modalities are still emerging, treatment challenges persist, as not all patients respond to available therapies. Variables that affect the choice of treatment include the extent, distribution, and progression rate of the lesions. Another challenge is the lack of a standardized scoring system, which hampers the production of level 1a evidence studies for the treatment of this condition.