Publications by authors named "Akimichi Morita"

202 Publications

Patient characteristics and burden of disease in Japanese patients with generalized pustular psoriasis: Results from the Medical Data Vision claims database.

J Dermatol 2021 Jul 1. Epub 2021 Jul 1.

Department of Dermatology, Tokyo Medical University Hospital, Tokyo, Japan.

Generalized pustular psoriasis (GPP) is a rare and severe systemic, neutrophilic skin disease. To date, accurate clinical profiling of patients with GPP remains poorly understood. In this study, we present the characteristics and estimate the burden of disease in patients with GPP compared with those with plaque psoriasis, in Japan. This retrospective study was conducted using the Medical Data Vision database between January 1, 2015, and December 31, 2019. Patients with at least one confirmed inpatient or outpatient diagnostic code for GPP (L40.1) or psoriasis vulgaris (L40.0) were included for analysis. The main outcome measures included comparisons of the prevalence of comorbidities, medication use, and healthcare resource utilization between patients with GPP, patients with plaque psoriasis, and a general population-matched cohort. In total, 718 patients with GPP and 27,773 patients with plaque psoriasis were identified. Patients with GPP were more likely to be female than those with plaque psoriasis (51.6% vs. 38.7%). During the 12-month follow-up period, patients with GPP were more likely to experience comorbidities than those with plaque psoriasis, including psoriatic arthritis, other forms of psoriasis, osteoporosis, interstitial pneumonia, and peptic ulcer disease. Medication use also differed between those with GPP and those with plaque psoriasis: patients with GPP were more likely to be prescribed antibiotics and psychiatric medication. Patients with GPP were also more likely to require more healthcare resource utilization with longer hospitalizations than those with plaque psoriasis. Overall, in Japan, patients with GPP have a higher burden of illness than those with plaque psoriasis.
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http://dx.doi.org/10.1111/1346-8138.16022DOI Listing
July 2021

Cultured epidermal autografts for treatment of stable vitiligo: Quantitative analysis of color matching with surrounding normally pigmented skin.

J Dermatol 2021 Jun 25. Epub 2021 Jun 25.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Cultured epidermal autografts (CEA) are surgical therapeutic alternatives for patients with stable vitiligo resistant to conventional medical treatments. In the present study, we assessed color matching before and at 12 months after CEA treatment. Eleven patients with 16 vitiligo lesions were included in this prospective study. The recipient sites were prepared by CO laser superficial ablation and subjected to CEA application. We clinically evaluated and categorized the color matching of the repigmented skin as well as the percentage of repigmentation. We also obtained three color values (L*a*b*) for the vitiligo lesions and surrounding normally pigmented skin. We then calculated the color differences between the two regions and compared them before and at 12 months after treatment. The mean percentage of repigmentation was 63.3% at 12 months. Six of the 16 lesions were categorized as "same as" and had color difference values of ≤5 at 12 months after treatment. Clinical evaluation of the color matching coincided well with the calculated color difference values. CEA application after CO laser superficial ablation was useful for treating vitiligo assessed by the percentage of repigmentation and color matching. Quantification of color differences may be a useful parameter for evaluating color matching in vitiligo.
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http://dx.doi.org/10.1111/1346-8138.16028DOI Listing
June 2021

Erratum to "Ultraviolet A1 phototherapy utilizing ultraviolet light-emitting diodes and a short wavelength cutoff filter" [J. Dermatol. Sci. 101 (2) (2021) 138-140].

J Dermatol Sci 2021 Jun 2. Epub 2021 Jun 2.

Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2021.05.007DOI Listing
June 2021

Tertiary lymphoid structures correlate with better prognosis in cutaneous angiosarcoma.

J Dermatol Sci 2021 May 25. Epub 2021 May 25.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Japan.

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http://dx.doi.org/10.1016/j.jdermsci.2021.05.006DOI Listing
May 2021

Daily photoprotection to prevent photoaging.

Photodermatol Photoimmunol Photomed 2021 Apr 25. Epub 2021 Apr 25.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Background: Extrinsic skin aging or photoaging was previously thought to be almost exclusively due to solar ultraviolet (UV) radiation. However, recent literature has described other contributing factors and clarification is thus required as to what extent and what type of daily photoprotection is needed to mitigate extrinsic skin aging.

Methods: We reviewed the existing scientific evidence on daily photoprotection, and specific requirements at the product level, to prevent extrinsic skin aging. We critically reviewed the existing evidence on potential ecological and toxicological risks which might be associated with daily photoprotection.

Results: Evidence shows that broad protection against the entire solar range of UVB, UVA, UVA1, visible light, and short infrared (IRA) is required to prevent extrinsic aging. Other exposome factors, such as air pollution and smoking, also contribute to skin aging. Daily broad-spectrum sunscreen photoprotection should thus contain antioxidant ingredients for additional benefits against UV, IRA, and pollution-induced oxidative stress as well as anti-aging active ingredients to provide clinical benefits against skin aging signs, such as wrinkles and dark spots. Broad-spectrum sunscreen containing pigments, such as iron oxide, may be required for melasma prevention. There is no conclusive clinical evidence that daily sunscreen use is unsafe or that it compromises vitamin D synthesis.

Conclusion: Daily use of broad-spectrum sunscreen containing antioxidant and anti-aging active ingredients can effectively reduce extrinsic aging.
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http://dx.doi.org/10.1111/phpp.12688DOI Listing
April 2021

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results.

Dermatol Ther (Heidelb) 2021 Jun 22;11(3):943-960. Epub 2021 Apr 22.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

Introduction: Certolizumab pegol (CZP), an Fc-free, PEGylated anti-tumour necrosis factor biologic, dosed at 400 mg every 2 weeks (Q2W) and 200 mg Q2W over 16 weeks, resulted in improvements in Japanese patients with moderate to severe plaque psoriasis (PSO); no new safety signals were identified. We present 52-week efficacy and safety results.

Methods: Patients ≥ 20 years with PSO ≥ 6 months [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area ≥ 10%, Physician's Global Assessment (PGA) ≥ 3] were randomised 1:2:2 to placebo Q2W, CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks. Week 16 PASI 50 responders continued through week 52; CZP 200 mg Q2W-randomised patients were re-randomised 1:1 to CZP 200 mg Q2W or CZP 400 mg Q4W; patients initially randomised to other treatment groups continued in the same group. Outcomes included PASI 75/90/100, PGA 0/1, Dermatology Life Quality Index (DLQI) 0/1, Itch Numeric Rating Scale (INRS) 0, modified Nail Psoriasis Severity Index (mNAPSI), durability of response for week 16 PASI 75/90 responders, and safety.

Results: Of 26/53/48 patients randomised to placebo, CZP 400 mg Q2W and CZP 200 mg Q2W, 2/47/39 completed week 52, respectively. PASI 75/90 responses were generally maintained from weeks 16 to 52 for all CZP doses. Most week 16 PASI 75/90 achievers maintained their response through week 52. PASI 75/90/100 responses at week 52 in the CZP 400 mg Q2W and CZP 200 mg Q2W groups were 83.0/81.1/41.5% and 72.9/60.4/18.8%, respectively; DLQI/INRS remission rates were 64.2/50.9% in CZP 400 mg Q2W and 58.3/27.1% in CZP 200 mg Q2W-treated patients. Reductions in mNAPSI observed for CZP-treated groups were maintained through week 52. No new safety signals were identified.

Conclusion: CZP treatment resulted in improvements in signs and symptoms of PSO, which were maintained through week 52. The 400 mg Q2W dose could provide additional clinical benefit.

Trial Registration: NCT03051217.
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http://dx.doi.org/10.1007/s13555-021-00520-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163922PMC
June 2021

Analysis of biomonitoring data after full-thickness skin grafting.

J Dermatol 2021 Jul 2;48(7):1035-1043. Epub 2021 Apr 2.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Skin graft vascularization is investigated mainly by histological evaluation. Immunohistochemical analysis has been conducted only in mice. Transcutaneous oxygen tension (TcPO ), which is an index of blood flow, has not been evaluated in skin grafts and only a few studies have reported biologic monitoring data using color tone evaluation and surface temperature. In humans, these tests can be performed non-invasively. To evaluate human skin graft vascularization, we analyzed biomonitoring data after skin grafting. We evaluated 14 patients who underwent skin grafting surgery at Nagoya City University Hospital. The TcPO , color tone, surface temperature, and dermoscopic observations at recipient sites were measured at postoperative day (POD) 4, 6, and 11. Mean TcPO levels at POD4, 6, and 11 were 12.7, 15.2, and 33.5 mmHg, respectively, and significantly higher at POD11 than at POD4 (p = 0.003, Steel-Dwass test). Dermoscopic observation revealed gradually increasing redness and yellowness. Color tone evaluation measured by spectrophotometry supported the appearance. The a*(redness) value at POD4, 6, and 11 was 6.19, 9.20, and 11.27, respectively, and significantly higher at POD11 than at POD4 (p < 0.001, Steel-Dwass test). The b*(yellowness) value at POD4, 6, and 11 was 8.83, 9.24, and 13.02, respectively, and significantly higher at POD11 than at POD4 (p = 0.020, Steel-Dwass test). The surface temperature did not significantly differ between graft and control sites. These findings suggest that skin graft vascularization started by POD6 and stabilized by POD11. Because TcPO increases after POD4, skin grafts should remain undisturbed until at least POD11.
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http://dx.doi.org/10.1111/1346-8138.15873DOI Listing
July 2021

Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare.

BMJ Open 2021 03 30;11(3):e043666. Epub 2021 Mar 30.

Service de Dermatologie, Assistance Publique-Hôpitaux de Paris Hôpital Saint-Louis, Paris, France

Introduction: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare.

Methods And Analysis: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.

Ethics And Dissemination: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.

Trial Registration Details: ClinicalTrials.gov identifier: NCT03782792; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-043666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011793PMC
March 2021

Efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 64-week phase 3 study (reSURFACE 1).

J Dermatol 2021 Jun 25;48(6):853-863. Epub 2021 Feb 25.

Jichi Medical University, Tochigi, Japan.

Tildrakizumab is a high-affinity, humanized immunoglobulin G1κ, anti-interleukin-23p19 monoclonal antibody recently approved in Japan for treatment of plaque psoriasis. We report results from Japanese patients treated with tildrakizumab in the multinational, randomized, double-blind, placebo-controlled reSURFACE 1 study (clinicaltrials.gov NCT01722331). Adults with moderate to severe plaque psoriasis were randomized (2:2:1) to receive subcutaneous tildrakizumab 100 or 200 mg or placebo every 12 weeks. Placebo recipients were rerandomized to tildrakizumab 100 or 200 mg at week 12. The global study coprimary endpoints were the proportions of patients achieving 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) response (0/1 with ≥2 grade reduction from baseline) at week 12. Analyses included 158 Japanese patients randomized to tildrakizumab 100 (n = 64) or 200 mg (n = 62) or placebo (n = 32). Japanese patients had higher mean baseline body surface area involvement and PASI versus all reSURFACE 1 patients. At week 12, significantly more Japanese patients receiving tildrakizumab 100 and 200 mg versus placebo achieved PASI 75 (54.7% and 54.8% vs 6.3%, respectively, both nominal p < 0.001) and PGA 0/1 response (54.7% and 56.5% vs 9.4%, respectively, both nominal P < 0.001). Response rates increased over time with maximal efficacy after 22-28 weeks; >80% of patients achieving PASI 75 or PASI 90 at week 28 and continuing tildrakizumab treatment at the same dose maintained response at week 64. From baseline to week 28, absolute PASI decreased from >12 in all patients to ≤2 in >40% and ≤3 in >50% of patients receiving tildrakizumab. Tildrakizumab was generally well tolerated with an adverse event profile similar to that of placebo. Tildrakizumab treatment was associated with durable efficacy in Japanese patients with moderate to severe plaque psoriasis despite greater baseline disease severity versus the global reSURFACE 1 population.
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http://dx.doi.org/10.1111/1346-8138.15789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247960PMC
June 2021

Environmentally-Induced (Extrinsic) Skin Aging: Exposomal Factors and Underlying Mechanisms.

J Invest Dermatol 2021 Apr 1;141(4S):1096-1103. Epub 2021 Feb 1.

Department of Dermatology, University Hospital Regensburg, Regensburg, Germany.

As a barrier organ, the skin is an ideal model to study environmentally-induced (extrinsic) aging. In this review, we explain the development of extrinsic skin aging as a consequence of skin exposure to specific exposomal factors, their interaction with each other, and the modification of their effects on the skin by genetic factors. We also review the evidence that exposure to these exposomal factors causes extrinsic skin aging by mechanisms that critically involve the accumulation of macromolecular damage and the subsequent development of functionally altered and/or senescent fibroblasts in the dermal compartment of the skin.
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http://dx.doi.org/10.1016/j.jid.2020.12.011DOI Listing
April 2021

Long-term efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 5-year extension of a phase 3 study (reSURFACE 1).

J Dermatol 2021 Jun 1;48(6):844-852. Epub 2021 Feb 1.

Jichi Medical University, Tochigi, Japan.

The three part, double-blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long-term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long-term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment. The primary efficacy outcomes were the proportions of patients who maintained PASI 75 and Physician Global Assessment (PGA) clear or minimal with ≥2-grade reduction from baseline (PGA 0/1) from base study week 64 to extension week 192. Secondary outcomes were the proportion of patients who maintained PASI 90/100 from base study week 64 to extension week 192. Adverse events (AEs) were monitored throughout the study and for up to 20 weeks after the last study visit. Of the 120 Japanese patients who entered the reSURFACE 1 extension study, 43 (79.6%) patients receiving tildrakizumab 100 mg and 58 (87.9%) patients receiving tildrakizumab 200 mg completed the extension study. Of all Japanese patients with PASI 75/90/100 and PGA 0/1 at week 64, 85%/88% receiving TIL100/TIL200 maintained PASI 75, 70%/96% maintained PASI 90, 63%/67% maintained PASI 100, and 68%/72% maintained PGA 0/1 at extension week 192. AEs led to discontinuation in 1.7 patients per 100 patient-years (P100PY) receiving tildrakizumab 100 mg and 0.8 P100PY receiving tildrakizumab 200 mg. Incidences of severe infections, malignancies, confirmed major adverse cardiac events, and hypersensitivity reactions were low in both treatment groups. Through 5 years of treatment, tildrakizumab maintained efficacy and was well tolerated with low rates of AEs of special interest.
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http://dx.doi.org/10.1111/1346-8138.15763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248015PMC
June 2021

Resignation as JSID President.

Authors:
Akimichi Morita

J Dermatol Sci 2021 Jan 3;101(1):2-3. Epub 2020 Dec 3.

Professor and Chairman, Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2020.12.001DOI Listing
January 2021

Increase in primary cilia in the epidermis of patients with atopic dermatitis and psoriasis.

Exp Dermatol 2021 Jun 12;30(6):792-803. Epub 2021 Feb 12.

Laboratory of Mock up Vaccine, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.

Primary cilia influence cell activity, and thus have a unique role in maintaining cell proliferation and differentiation. In atopic dermatitis (AD) and psoriasis, areas of skin inflammation exhibit dysregulated keratinocyte homeostasis. The role of primary cilia in these conditions remains unclear. The objectives of this study is to elucidate the incidence of primary cilia in skin inflammation and the potential mechanism underlying the dysregulation of keratinocytes. Primary cilia were observed using immunofluorescence staining. Normal skin samples were compared with skin samples from patients with AD or psoriasis in terms of cilia numbers and length. The effect of cytokine stimulation on ciliogenesis in keratinocytes was analysed using a primary keratinocyte culture. IFT88, an important ciliary intraflagellar protein, was blocked in Th2 and Th17 cytokines-stimulated keratinocytes. These effects were analysed with quantitative polymerase chain reaction and Western blot. Significant increases in ciliated cells were observed in AD and psoriasis skin samples compared with normal skin samples. The stimulation of keratinocytes using Th2 and Th17 cytokines modulated the formation of primary cilia. The amount of IFT88 in the primary cilia associated with the phosphorylation of JNK, but not p38, in keratinocytes stimulated with interleukin-13, 17A and 22. An increase of ciliated cells in the epidermis may impair keratinocyte differentiation under stress conditions caused by inflammation in both AD and psoriasis patients.
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http://dx.doi.org/10.1111/exd.14285DOI Listing
June 2021

Effect of adalimumab on axial manifestations in Japanese patients with psoriatic arthritis: a 24 week prospective, observational study.

Rheumatology (Oxford) 2021 Jan 4. Epub 2021 Jan 4.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya.

Objectives: PsA is characterized by enthesitis, synovitis and osseous involvement in the peripheral and axial joints. Few studies have examined axial involvement in PsA using imaging techniques. Here we examined axial involvement in PsA patients using MRI. In addition, we determined the efficacy of 24 week adalimumab treatment in improving the MRI findings of spondylitis and sacroiliitis.

Methods: This was a prospective, open-label, single-arm study in patients with PsA. Adalimumab was administered to patients for a total of 24 weeks. MRI examinations were conducted at baseline and at week 24 of adalimumab treatment.

Results: Thirty-seven patients with PsA were included in this study. Spondylitis was observed in at least one site of the positive scan in 91% (n = 31) of patients with PsA. The number of arthritic sites in the cervical, thoracic and lumbar regions of the spine was 48, 67 and 53, respectively. All patients had MRI-determined sacroiliitis of grade ≥1 severity while 28 patients (82%) had grade ≥2 sacroiliitis in at least one sacroiliac region. Sacroiliac arthritis was statistically more severe on the right side than on the left side (P < 0.05). In 34 patients with PsA, the thoracic spine was the most common site of spondylitis. In addition, 24 week adalimumab treatment led to an improvement in the mean number of spondylitis sites and the mean grade of sacroiliitis.

Conclusion: Treatment with adalimumab for 24 weeks resulted in improvement in spondylitis and sacroiliitis.
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http://dx.doi.org/10.1093/rheumatology/keaa829DOI Listing
January 2021

Japanese experiment of a complete and objective automatic grading system of facial signs from selfie pictures: Validation with dermatologists and characterization of changes due to age and sun exposures.

Skin Res Technol 2020 Dec 27. Epub 2020 Dec 27.

L'Oréal Research and Innovation, Clichy, France.

Objective: To evaluate the capacity of the automatic detection system to accurately grade, from smartphones' selfie pictures, the severity of ten facial signs in Japanese women and their changes due to age and sun exposures.

Methods: A three-step approach was conducted, based on self-taken selfie images. At first, to check on 310 Japanese women (18-69 years) enrolled in the northerner Hokkaido area (latitude 43.2°N), how, on ten facial signs, the A.I-based automatic grading system may correlate with dermatological assessments, taken as reference. Second, to assess and compare age changes in 310 Japanese and 112 Korean women. Third, as these Japanese panelists were recruited according to their usual behavior toward sun exposure, that is, non-sun-phobic (NSP, N = 114) and sun-phobic (SP, N = 196), and through their regular and early use of a photo-protective product, to characterize the facial photo-damages.

Results: (a) On the ten facial signs, detected automatically, nine were found significantly (P < .0001) highly correlated with the evaluations made by three Japanese dermatologists (Wrinkles: r = .75; Sagging: r = .80; Pigmentation: r = .75). (b) The automatic scores showed significant changes with age, by decade, of Wrinkles/Texture, Pigmentation, and Ptosis/Sagging (P < .05). (c) After 45 years, a significantly increased severity of Wrinkles/Texture and Pigmentation was observed in NSP vs. SP women (P < .05). A trend of an increased Ptosis/Sagging (P = .09) was observed.

Conclusion: This work illustrates, for the first time through investigations conducted at home, some impacts of aging and sun exposures on facial signs of Japanese women. Results significantly confirm the importance of sun avoidance coupled with photo-protective measures. In epidemiological studies, the AI-based system offers a fast, affordable, and confidential approach in detection and quantification of facial signs and their dependence with ages, environments and lifestyles.
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http://dx.doi.org/10.1111/srt.12982DOI Listing
December 2020

Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma.

J Immunother Cancer 2020 12;8(2)

Departments of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Background: Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes. We performed RNA sequencing to evaluate the immune response and comprehensively estimate prognostic values of immunogenic factors in patients with MCC.

Methods: We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC at 10 facilities. The mRNA was extracted from formalin-fixed paraffin-embedded tissues. Next-generation sequencing, immunohistochemical staining and blood serum tests were performed.

Results: Next-generation sequencing results classified MCC samples into two types: the 'immune active type' was associated with better clinical outcomes than the 'cell division type'. Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene was highly significantly upregulated in the 'cell division type'. Among 395 genes, G6PD expression correlated with the presence of lymph node or distant metastases during the disease course and significantly negatively correlated with PD-L1 expression. Immunohistochemical staining of G6PD also correlated with disease-specific survival and exhibited less heterogeneity compared with PD-L1 expression. G6PD activity could be measured by a blood serum test. The detection values significantly increased as the cancer stage progressed and significantly decreased after treatment.

Conclusions: G6PD expression was an immunohistochemically and serum-detectable prognostic marker that negatively correlated with immune activity and PD-L1 levels, and could be used to predict the immunotherapy response.
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http://dx.doi.org/10.1136/jitc-2020-001679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759960PMC
December 2020

Ultraviolet A1 phototherapy utilizing ultraviolet light-emitting diodes and a short wavelength cutoff filter.

J Dermatol Sci 2021 Feb 6;101(2):138-140. Epub 2020 Nov 6.

Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2020.11.004DOI Listing
February 2021

Celebrating 100 volumes of JDS: A huge achievement together with expansion of the JSID.

Authors:
Akimichi Morita

J Dermatol Sci 2020 Oct 9;100(1):10-12. Epub 2020 Oct 9.

President of Japanese Society of Investigative Dermatology (JSID) Professor and Chairman, Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546676PMC
October 2020

Safety and effectiveness of secukinumab in psoriasis vulgaris and psoriatic arthritis: Real-world evidence in Japan.

J Dermatol 2021 Feb 25;48(2):175-183. Epub 2020 Oct 25.

Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan.

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, has been available for the treatment of moderate to severe psoriasis and psoriatic arthritis since February 2015 in Japan. Because there was a time gap after the previous approval of biologics for psoriatic disease indication, it was suggested that patients to be treated with secukinumab at its launch might have refractory disease symptoms. In order to assess the safety and effectiveness of secukinumab in those patients, a 52-week, open-label, multicenter, observational cohort study was conducted. In total, 306 and 250 patients were included in the safety and effectiveness analysis sets, respectively. Over half of patients had previously received biologics (56.9%). Adverse events, serious adverse events and adverse reactions were reported in 41.2%, 7.2% and 24.2% of patients, respectively. The most commonly reported adverse reactions were oral candidiasis (2.9%), consistent with those reported in clinical studies. In addition, none of the patient characteristics assessed for the effect on safety of secukinumab increased the occurrence of adverse reactions. Psoriasis Area and Severity Index score (mean ± standard deviation) improved from baseline (14.7 ± 12.3) to week 12 (1.78 ± 3.3), which was maintained up to week 24 (1.59 ± 3.0). The proportion of patients with a Dermatology Life Quality Index score of 0/1 improved from baseline (2.2%) to week 12 (64.7%) and sustained up to week 24 (71.4%). In addition to the skin symptoms, improvement was observed in all psoriatic arthritis disease-related assessments. The current study reaffirmed the safety and effectiveness of secukinumab with broader patients than those in the clinical studies.
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http://dx.doi.org/10.1111/1346-8138.15655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894540PMC
February 2021

Dupilumab probably reduces transepidermal water loss but does not increase stratum corneum hydration in atopic dermatitis.

J Dermatol 2021 Feb 9;48(2):e74-e75. Epub 2020 Oct 9.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

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http://dx.doi.org/10.1111/1346-8138.15638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891664PMC
February 2021

Long-term analysis of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa: Open-label phase 3 results.

J Dermatol 2021 Jan 7;48(1):3-13. Epub 2020 Oct 7.

Nihon University School of Medicine, Tokyo, Japan.

This phase 3, multicenter, open-label single-arm study evaluated adalimumab (ADA) in Japanese patients with moderate to severe hidradenitis suppurativa (HS). Fifteen patients received ADA 160 mg s.c. at week 0, 80 mg at week 2 and 40 mg at week 4 and every week thereafter. At any time after week 52, patients were given the option to receive 80 mg ADA every other week or remain on 40 mg every week. The primary end-point (achievement of HS Clinical Response [HiSCR] at week 24) and results up to week 24 were published previously. Secondary end-points included total abscess and inflammatory nodule (AN) count, 30% or more and 1 unit or more reduction in Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS30), modified Sartorius score and quality of life (QoL). After 12 weeks of ADA treatment, the achievement rate in HiSCR was 86.7%; HiSCR achievement rate was sustained through week 52 at 66.7%. Improvements at week 12 were also seen in the proportion of patients achieving an AN count of 0-2; NRS30 response rate among the nine patients with a baseline NRS of 3 or more; mean decrease in modified Sartorius score (61.4); and QoL as assessed by Dermatology Life Quality Index and Treatment Satisfaction Questionnaire; these improvements were maintained through 52 weeks. Similar efficacy was observed when patients switched dosing from ADA 40 mg every week to ADA 80 mg every other week. There were no new safety findings with ADA 40 mg weekly dosing during the study, and no differences in safety were found between patients who switched to 80 mg ADA every other week and patients who remained on 40 mg every week. The results of this study indicate that long-term ADA treatment is effective and well tolerated in Japanese patients with moderate to severe HS.
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http://dx.doi.org/10.1111/1346-8138.15605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821142PMC
January 2021

Combination immunosuppressant therapy for rapidly progressive pyoderma gangrenosum in a child.

Mod Rheumatol Case Rep 2021 01 5;5(1):137-140. Epub 2020 Oct 5.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.

An 8-year-old girl was presented to our clinic with fever, arthritis in her left knee, a necrotic right fifth toe, and multiple large deep-seated ulcerations. She was diagnosed with pyoderma gangrenosum. Treatment with corticosteroids alone was ineffective for her skin lesions, and therefore combination immunosuppressant therapy was administered. Her skin lesions rapidly improved, enabling discontinuation of the corticosteroid therapy and avoiding systemic infection through the ulcers. Combination immunosuppressant therapy may be a treatment option for patients with severe, rapidly progressive pyoderma gangrenosum.
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http://dx.doi.org/10.1080/24725625.2020.1749359DOI Listing
January 2021

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol.

Medicine (Baltimore) 2020 Sep;99(38):e22043

Department of Dermatology, Osaka Habikino Medical Center, Habikino City, Osaka.

Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab.

Methods: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment."

Discussion: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.
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http://dx.doi.org/10.1097/MD.0000000000022043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505282PMC
September 2020

Tumor lysis syndrome associated with nivolumab plus ipilimumab combination therapy in a melanoma patient.

J Dermatol 2020 Nov 27;47(11):e411-e412. Epub 2020 Aug 27.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

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http://dx.doi.org/10.1111/1346-8138.15547DOI Listing
November 2020

Proenkephalin regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function.

Proc Natl Acad Sci U S A 2020 08 7;117(34):20696-20705. Epub 2020 Aug 7.

Department of Immunology, Nagoya City University Graduate School of Medical Sciences, 467-8601 Nagoya, Japan;

Regulatory T (Treg) cells, expressing CD25 (interleukin-2 receptor α chain) and Foxp3 transcription factor, maintain immunological self-tolerance and suppress various immune responses. Here we report a feature of skin Treg cells expanded by ultraviolet B (UVB) exposure. We found that skin Treg cells possessing a healing function are expanded by UVB exposure with the expression of an endogenous opioid precursor, proenkephalin (PENK). Upon UVB exposure, skin Treg cells were expanded with a unique TCR repertoire. Also, they highly expressed a distinctive set of genes enriched in "wound healing involved in inflammatory responses" and the "neuropeptide signaling pathway," as indicated by the high expression of We found that not only was PENK expression at the protein level detected in the UVB-expanded skin Treg (UVB-skin Treg) cells, but that a PENK-derived neuropeptide, methionine enkephalin (Met-ENK), from Treg cells promoted the outgrowth of epidermal keratinocytes in an ex vivo skin explant assay. Notably, UVB-skin Treg cells also promoted wound healing in an in vivo wound closure assay. In addition, UVB-skin Treg cells produced amphiregulin (AREG), which plays a key role in Treg-mediated tissue repair. Identification of a unique function of PENK UVB-skin Treg cells provides a mechanism for maintaining skin homeostasis.
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http://dx.doi.org/10.1073/pnas.2000372117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456133PMC
August 2020

Effectiveness of combined low-dose radiotherapy and pazopanib for controlling the local manifestations of taxane-resistant recurrent angiosarcoma of the head.

JAAD Case Rep 2020 Aug 10;6(8):713-715. Epub 2020 Jun 10.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

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http://dx.doi.org/10.1016/j.jdcr.2020.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369525PMC
August 2020

Specific single nucleotide polymorphism genotypes and association of an IL-12B polymorphism with secondary failure of infliximab therapy in Japanese psoriasis patients.

J Dermatol Sci 2020 Aug 31;99(2):135-136. Epub 2020 May 31.

Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2020.05.011DOI Listing
August 2020

Surgical invasion resulted in increased programmed death ligand 1 expression in a case of multicentric Merkel cell carcinoma with six primary lesions.

J Dermatol 2020 Aug 17;47(8):e305-e307. Epub 2020 Jun 17.

Department of Geriatric and Environmental Dermatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

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http://dx.doi.org/10.1111/1346-8138.15429DOI Listing
August 2020

Successful treatment of dyshidrotic palmoplantar eczema with ultraviolet A1 light-emitting diodes.

J Dermatol 2020 Aug 22;47(8):922-923. Epub 2020 May 22.

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

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http://dx.doi.org/10.1111/1346-8138.15402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497185PMC
August 2020