Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Epidemiological survey of the psoriasis patients in the Japanese Society for Psoriasis Research from 2013 to 2018.

In Japan, the Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with psoriasis since 1982. The aim of this study was to conduct a recent epidemiological analysis of the psoriasis patients who were enrolled in the JSPR from 2013 to 2018. A total of 15 287 cases were enrolled from 132 medical institutions, out of which 65.3% (9989 cases) were male and 34.7% (5298 cases) were female. Approximately 50.0% of the cases had past history and comorbidities, such as hypertension (42.0%), dyslipidemia (30.0%), diabetes mellitus (23.7%), hyperuricemia (15.1%), cardiovascular disease (6.0%), and cerebral vascular disorders (6.0%). There was a yearly increase in the use of corticosteroid/vitamin D3 combinations and apremilast for treating psoriasis. In contrast, the use of phototherapy gradually decreased. From 2013 to 2018, approximately 18.6% of the cases were treated with biologics, such as infliximab (17.6%), adalimumab (23.3%), ustekinumab (21.4%), secukinumab (11.6%), ixekizumab (7.6%), brodalumab (6.3%), and guselkumab (4.3%). In the past decade, the biologics have changed the treatment and management of psoriasis. This survey includes significant information regarding the recent perspective of psoriasis in the Japanese Society, especially focusing on the treatment trends after the introduction of biologics.

P2X receptor agonist enhances tumor-specific CTL responses through CD70+ DC-mediated Th17 induction.

Extracellular ATP is known to promote Th17 cell differentiation in the intestinal lamina propria by stimulating CD70+CD11clow dendritic cells (DCs) via P2X receptors (P2XRs). Recent studies have also shown that Th17 cells enhance antitumor immunity by directly promoting proliferation of cytotoxic T lymphocytes (CTLs). These finding led us to test a P2XR agonist, αß-methylene ATP (αß-ATP), as a mucosal vaccine adjuvant to promote CTL responses through Th17 induction. We demonstrated that (i) CD70+CD11clow DCs were present in the nasal lamina propria and expressed P2X1R, P2X2R and P2X4R; (ii) CD70+CD11clow DCs isolated from the nasal lamina propria enhanced Th17 cell differentiation of cocultured splenic CD4+ T cells upon stimulation with αß-ATP; (iii) mice intranasally immunized with ovalbumin (OVA) and αß-ATP had increased OVA-specific Th17 cells and CTLs in the nasal lamina propria and regional lymph nodes; (iv) mice intranasally immunized with OVA and αß-ATP also had elevated resistance to E.G7-OVA tumor growth compared with those intranasally immunized with OVA alone; (v) suramin, a broad-range inhibitor of P2 receptors, suppressed the increases of OVA-specific Th17 cells and CTLs in mice intranasally immunized with OVA and αß-ATP; and (vi) suramin also abrogated the enhanced antitumor immunity of mice intranasally immunized with OVA and αß-ATP against E.G7-OVA. Collectively, αß-ATP may be a promising mucosal adjuvant that promotes antigen-specific CTL responses via CD70+CD11clow DC-mediated Th17 induction.

Ascorbic acid derivative DDH-1 ameliorates psoriasis-like skin lesions in mice by suppressing inflammatory cytokine expression.

Psoriasis is a chronic inflammatory skin disease in which inflammatory cytokines play a major role in its pathogenesis. Because DDH-1, a novel amphipathic ascorbic acid derivative, has been recently shown to reduce inflammatory cytokine expression in human keratinocytes in vitro, we investigated its effect on imiquimod-induced psoriasis-like skin lesions in C57BL/6 mice. We first found that IL-1ß and TNF-α mRNA expression was significantly decreased in the skin lesions treated with DDH-1. Furthermore, cutaneous administration of DDH-1 ameliorated psoriasis-like skin lesions. These results suggest that DDH-1 may be effective in the prevention and supplemental treatment of psoriasis.

A Highly Active Form of XCL1/Lymphotactin Functions as an Effective Adjuvant to Recruit Cross-Presenting Dendritic Cells for Induction of Effector and Memory CD8+ T Cells.

The chemokine receptor XCR1 is known to be selectively expressed by cross-presenting dendritic cells (DCs), while its ligand XCL1/lymphotactin is mainly produced by activated CD8+ T cells and natural killer cells. Recent studies have shown that XCL1-antigen fusion proteins efficiently induce CD8+ T cell responses by preferentially delivering antigens to XCR1+ DCs. However, XCL1 per se was found to be a poor adjuvant for induction of CD8+ T cell responses. XCL1 is unique because of its lack of one of the two disulfide bonds commonly conserved in all other chemokines and thus has an unstable structure with a relatively weak chemokine activity. In the present study, we generated a variant form of murine XCL1 termed mXCL1-V21C/A59C that contained a second disulfide bond to stabilize its chemokine structure. We confirmed that mXCL1-V21C/A59C had much more potent chemotactic and calcium mobilization activities than the wild type XCL1 (mXCL1-WT). Intradermal injection of mXCL1-V21C/A59C, but not that of mXCL1-WT, significantly increased the accumulation of XCR1+CD103+ DCs in the injection site, and most of the accumulated XCR1+CD103+ DCs were found to take up co-injected ovalbumin (OVA). Furthermore, recruited XCR1+CD103+ DCs efficiently migrated to the draining lymph nodes and stayed for a prolonged period of time. Consequently, mXCL1-V21C/A59C strongly induced OVA-specific CD8+ T cells. The combination of OVA and mXCL1-V21C/A59C well protected mice from E.G7-OVA tumor growth in both prophylactic and therapeutic protocols. Finally, memory CTL responses were efficiently induced in mice immunized with OVA and mXCL1-V21C/A59C. Although intradermal injection of OVA and polyinosinic-polycytidylic acid (poly(I:C)) as an adjuvant also induced CD8+ T cell responses to OVA, poly (I:C) poorly recruited XCR1+CD103+ DCs in the injection site and failed to induce significant memory CTL responses to OVA. Collectively, our findings demonstrate that a highly active form of XCL1 is a promising vaccine adjuvant for cross-presenting DCs to induce antigen-specific effector and memory CD8+ T cells.

Enhanced sterilization and healing of cutaneous pseudomonas infection using 5-aminolevulinic acid as a photosensitizer with 410-nm LED light.

BACKGROUND: Pseudomonas aeruginosa (PA) frequently develops antibiotic-resistant characteristics, which is clinically problematic. The main reason behind the rise of antibiotic-resistant PA is the extensive use of antibiotics. Therefore, a novel technique is needed to treat PA infections. Photodynamic therapy (PDT) is thought to have the potential to be a non-antibiotic treatment for infections. 5-Aminolevulinic acid (ALA), which works as a photosensitizer after being metabolized into protoporphyrin IX (PpIX) in the heme synthetic pathway, is used for PDT. Thus far, the in vivo effectiveness of PDT using ALA against PA is unknown. OBJECTIVE: In this study, we investigated PDT using ALA both in vitro and in vivo. METHODS AND RESULTS: Although PDT with ALA alone did not show a bactericidal effect on PA, PDT with both ALA and EDTA-2Na had a bactericidal effect in vitro. In in vivo experiments, wounds healed faster in PA-infected mice treated with PDT using both EDTA-2Na and ALA compared to non-PDT. CONCLUSION: These results suggest that PDT with EDTA-2Na and ALA is a potential novel treatment option for PA-infected wounds.

Epidemiological survey of patients with psoriasis in Matsumoto city, Nagano Prefecture, Japan.

A local epidemiological survey of psoriasis was conducted from 19 February to 30 June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and psoriatic erythroderma (0.3%). The topical therapeutic agents included corticosteroids (84.0%), vitamin D3 analogs (61.5%), and a combination of calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant phototherapy in which narrow band ultraviolet B therapy accounted for the majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the recent evolution of psoriasis treatment, the use of biologics has been increasing. This study demonstrates the changes of treatment trends of psoriasis in a non-metropolitan regional area.

Adjuvant alternative treatment with chemical peeling and subsequent iontophoresis for postinflammatory hyperpigmentation, erosion with inflamed red papules and non-inflamed atrophic scars in acne vulgaris.

The standard management of acne vulgaris in Japan includes a combination of topical treatment with benzoyl peroxide (BPO) and BPO/clindamycin (CLDM), topical adapalene and systemic antimicrobials. However, the treatment of therapy-resistant complications such as postinflammatory hyperpigmentation (PIH), erosions with inflamed red papules and atrophic scars has not been established. We performed chemical peeling with glycolic acid and iontophoresis with ascorbyl 2-phosphate 6-palmitate and DL-α-tocopherol phosphate for the treatment of PIH, erosions with inflamed red papules and non-inflamed atrophic scars in 31 patients with acne vulgaris (mild to severe severity), and evaluated the efficacy and safety of these interventions. In most of cases, there was remarkable improvement in PIH and erosions with inflamed red papules after treatment. There was also some improvement in non-inflamed atrophic scars without erythema. Mild redness and irritation was observed in four cases as adverse reactions. Early initial treatment of PIH and erosions with red papules by chemical peeling and iontophoresis is an effective and safe method to prevent the formation of atrophic scars in patients with acne vulgaris.

Efficacy and safety of a low-energy double-pass 1450-nm diode laser for the treatment of acne scars.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a 1450-nm diode laser on acne scars in Asian patients. BACKGROUND DATA: Acne and acne scars affect individuals during puberty and adolescence, and decrease their quality of life. METHODS: An open study was performed on 24 Japanese patients (17 female and 7 male, aged 15-44 years) with acne scars on the face treated with five sessions of low-energy double-pass 1450-nm diode laser at 4-week intervals. The mean duration of the acne scars prior to receiving laser therapy was 4.8 years (range 1-9). Clinical evaluation by physicians and with photographs was conducted at baseline, 1 month after the final treatment, and at a 3-month follow-up visit. Topical therapies for acne vulgaris were permitted during the follow-up period. RESULTS: All patients completed the five treatment sessions. Seventy-five percent of the subjects showed at least 30% improvement of acne scars. At the 3-month follow-up evaluation, 92.9% of the subjects with >30% improvement maintained the effectiveness. Vesicle formation and transient hyperpigmentation also occurred in one case. CONCLUSIONS: The 1450-nm diode laser therapy was effective and well-tolerated in patients with acne scars, suggesting that this may be an appropriate modality for treating facial acne scars.

Clinical effectiveness of intense pulsed light therapy for solar lentigines of the hands.

Intense pulsed light (IPL) treatment, as a nonablative phototherapy, is known to improve various signs of facial photoaging skin, e.g., solar lentigines, fine wrinkles, and telangiectasias. The purpose of the present study was to investigate the efficacy and tolerability of IPL with a 515-nm filter in patients with solar lentigines on the back of hands. An open study was performed in 31 patients who were treated with a 1-month interval up to five times. Sixty-two percent of patients had more than 50% improvement and 23% had more than 75% improvement. No patients discontinued due to adverse effects, and no patients showed hyperpigmentation or scarring after the treatments. Phototherapy using this IPL source was effective and well tolerated in the patients, suggesting that this phototherapy may be an appropriate modality for the treatment of solar lentigines of the hands.

Allergic contact dermatitis caused by sesame oil in a topical Chinese medicine, shi-un-ko.

Topical Chinese medicines are used for skin disorders as traditional medicine in Japan. We describe a case of allergic contact dermatitis from a topical Chinese medicine, shi-un-ko.

Clinical effectiveness of a novel intense pulsed light source on facial pigmentary lesions.

Intense pulsed light (IPL) therapy improves various clinical symptoms of photoaging skin. In this study we have investigated clinical effects of a novel IPL, Lumenis One (LUMENIS, Tokyo) on facial pigmentary lesions in 18 Japanese female patients. Measurement was performed after 3-5 treatments. IPL showed marked and slight improvements in 28 and 39%, respectively. The data of melanin index demonstrated the improvement after IPL therapy. These results indicated that IPL therapy using Lumenis One may be useful to treat solar lentigines and ephelides on the face.

An evaluation of whitening effect of an intense pulsed light source using computer analysis of the video-captured digital image.

Recently, we reported an evaluation method with computer analysis of the video-captured digital image for whitening effects of cosmetics. In this study we have developed a new evaluation method of change of skin color using Robo Skin Analyzer that analyzes digital-camera-captured image. We have also investigated whitening effects of an intense pulsed light (IPL), NatuLight (LUMENIS, Tokyo), on skin color of the face in 27 Japanese female patients. Measurement was performed after three to five treatments. Whitening effects were evaluated in pigmentary and normal areas. IPL showed improvement in Value data (lightness) of the pigmentary and normal areas. In 16 (59%) of 27 patients IPL had whitening effects on the pigmentary lesions. In 18 (66%) of 27 patients IPL also demonstrated whitening effects on normal skin. Fourteen patients (52%) showed whitening effects both on pigmentary and normal areas. These results indicated that IPL therapy may have a whitening effect both on pigmentary and normal areas of the face. This novel method may be useful to evaluate the whitening effect of phototherapy and color change of cutaneous disorders.

New approach to the evaluation of skin color of pigmentary lesions using Skin Tone Color Scale.

Objective methods of measuring skin color are needed to evaluate pigmentary lesions quantitatively. We have developed a new method of measuring skin color using a plastic bar system called the Skin Tone Color Scale based on Munsell's color space system. We have also evaluated the effectiveness of various therapies using this measurement system. Our system was designed to measure skin color in normal skin, pigmentary lesions of solar lentigo, chloasma and ephelides, and postinflammatory pigmentation. Moreover, effectiveness of various therapies for these pigmentary lesions was evaluated. The evaluations made with this system were closely related to physician assessment. This method may be useful in measuring of skin color and evaluating the effectiveness of therapies for pigmentary diseases.

Acne phototherapy with a 1450-nm diode laser: an open study.

The purpose of this study was to investigate the efficacy of phototherapy with a newly-developed 1450-nm diode laser in patients with mild to moderate acne. An open study was performed in acne patients who were treated up to five times with a two week interval. Acne lesions were reduced by 63%. Only one patient discontinued treatment due to vesicle formation as an adverse effect. Phototherapy using this diode laser source was effective and well tolerated in acne patients, suggesting that this phototherapy may be a new modality for the treatment of acne.