High migratory activity of dermal sheath cup cells associated with the clinical efficacy of autologous cell-based therapy for pattern hair loss.

BACKGROUND: Autologous cell-based therapy using dermal sheath cup (DSC) cells was reported as a new treatment for male and female pattern hair loss. However, the mechanisms underlying its action remain unclear. OBJECTIVE: We investigated the mechanisms underlying the efficacy of DSC cells in cell-based therapy. METHODS: We conducted multivariate analysis to categorize individuals based on treatment response as responders and non-responders. The differentially expressed genes in DSC cells from the two groups were evaluated using bulk transcriptome, quantitative polymerase chain reaction, and single-cell transcriptome analyses. We performed live cell imaging combined with immunostaining to characterize the DSC subpopulation associated with responders. RESULTS: We identified nine and three genes as high efficacy (HE) and low efficacy (LE) marker genes, respectively. The HE subpopulations were enriched for cell migration-related genes in single-cell analysis. In contrast, the LE subpopulation was enriched for basement membrane and vasculature-related genes. Moreover, DSC cells in culture were immunocytochemically and morphologically heterogeneous, expressing characteristic factors. Furthermore, live cell imaging showed that DSC cells expressing integrin subunit alpha 6 (ITGA6), an HE subpopulation gene, had markedly higher mobility than those expressing the LE subpopulation genes collagen type IV or CD36. CONCLUSIONS: ITGA6-positive DSC cells, with superior migratory activity, may contribute to cell-based therapy by promoting cell migration into nearby hair follicles.

Efficacy of autologous dermal sheath cup cell transplantation in male and female pattern hair loss: A Single-Arm, Multi-Center, phase III equivalent clinical study.

A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A phase III equivalent clinical study was conducted to further probe the therapeutic potential of this novel approach and verify its safety and efficacy in improving the appearance of PHL. Thirty-six participants with PHL were injected with dermal sheath cup cell harvested from non-affected occipital hair follicles twice in quarterly intervals. Global photographic assessment and phototrichogram were performed in a blinded manner. Patient-reported outcomes were assessed for 12 months. On global photographic assessment, 30% of the participants showed improvement. The analysis of phototricogram data detected the increases in the cumulative hair diameter, hair cross-sectional area, and mean hair diameter of 107.6 ± 152.6 µm/cm2 , 13069.1 ± 10960.7 µm2 /cm2 , and 0.9 ± 0.9 µm (ratios vs. baseline: +1.4%, +3.4%, and +2.2%), respectively. The female and high terminal hair ratio groups achieved better improvement. Of the total participants, 62.9% noted some degree of improvement. No serious adverse events were detected. This novel approach exhibited visible effects while ensuring safety and patient satisfaction. Therefore, it holds promise as a possible therapeutic option for treating PHL, especially in women.

Dosimetric Superiority of High-Dose-Rate (HDR) Brachytherapy Using a Surface Mold Applicator for Primary Cutaneous Angiosarcoma of the Scalp.

The aim of this study was to demonstrate the utility of the dose-volume parameters of the target lesions and the radiation dose to the organ at risk (OAR) in two patients with primary cutaneous angiosarcoma of the scalp (CAS) treated with high-dose-rate brachytherapy (HDR-BT) using a surface mold applicator. In 2020, two men, aged 80 years and 60 years, respectively, were treated with HDR-BT with paclitaxel for CAS with no distant metastases and no surgical indication at our institution. The total irradiated dose was 57 Gy administered in daily fractions of 3 Gy four days per week. The method of HDR-BT involved the construction of a helmet that fitted over the patient's head, with parallel catheters fixed to the outside at 2.0 cm intervals to transport the iridium-192 HDR-BT source. In conclusion, HDR-BT may be superior when the dose to the target lesion plays a more important role than the OAR dose in selecting radiotherapy modalities for CAS.

Low-Dose MST-16/VP-16 Combination Chemotherapy in 9 Patients with Tumor Stage Mycosis Fungoides.

BACKGROUND/AIM: MST-16 and VP-16, both of which are topoisomerase II inhibitors, are antitumor agents regularly used to treat malignant lymphoma and small cell lung carcinoma. New therapeutic agents for tumor stage mycosis fungoides (MF) have recently been developed, but their efficacy is limited. We herein retrospectively reported the use of MST-16/VP-16 combination therapy for tumor stage MF at multiple treatment centers and examined their antitumor effect. METHODS: Five male and four female patients with tumor stage MF were enrolled. Age at the start of therapy ranged from 33 to 80 years (average: 54.5 years), and the previous treatment consisted of R-CHOP, CAVOP-IFN, etc. The protocol for low-dose MST-16/VP-16 combination chemotherapy consisted of 800 mg MST-16 and 25 mg VP-16 administered 5 days per month. RESULTS: Three of the 9 patients died, but two of the three fatalities were unrelated to MF. A treatment effect was seen in three and 6 patients who showed a complete response and a partial response, respectively. The 5-year and 10-year overall survival rate was 85.7% and 57.1%, respectively. Adverse reactions consisted of 4 cases of nausea and 1 case of leukopenia. CONCLUSION: The present study demonstrated that the response rate to MST-16/VP-16 combination therapy was 100% and that the treatment effect was relatively long, suggesting that this therapy may be a viable option for treating tumor stage MF.

Treatment of intra-anal warts with imiquimod 5% cream: A single-center prospective open study.

Intra-anal warts are frequently recalcitrant to surgical removal, but imiquimod 5% cream is not formulated to use in clinical practice due to the risk of mucosal inflammation. In the present, prospective, open study examining the efficacy and safety of imiquimod 5% cream, the drug was applied to the entire inner surface of the anal canal with a cotton swab under anoscopy three times weekly for 16 weeks. If complete remission was not achieved, the treatment was continued until week 28. Electrocautery was applied once in a poorly responsive case. In total, 21 patients with intra-anal warts, of whom 16 were HIV-positive, were enrolled. Two patients withdrew before week 16, and nine more patients withdrew before week 28. The complete clearance rate was 36.8% (7/19) at week 16 and 70% (7/10) at week 28. Four patients achieved complete clearance at week 16 and maintained clearance at week 28 without further treatment. Three of four patients resistant to previous electrocautery achieved clearance with imiquimod 5% cream treatment. Adverse events occurred in 81% (17/21) of the patients mainly at the application site, but serious or previously unencountered adverse events were not observed. Imiquimod 5% cream applied to intra-anal warts was nearly as efficacious and safe as when applied to external anogenital warts. Since treatment modalities for intra-anal warts are very limited, application of imiquimod 5% cream alone with careful and frequent observation or in combination with electrocautery is a useful option for refractory cases of intra-anal wart.

Recent reductions in the size of facial pigmented basal cell carcinoma at diagnosis and the surgical margin: A retrospective and comparative study.

The present, retrospective, single-center study analyzed various factors associated with primary basal cell carcinoma (BCC) in the period before and after the introduction of dermoscopy (BD and AD, respectively). The demographic data of patients with primary BCC between 2001 and 2005 (BD: 84 patients, 90 cases) and 2011 and 2018 (AD: 297 patients, 320 cases) were analyzed. In the pigmented BCC-predominant cohort (94%), the proportion of smaller tumors as well as the total number of tumors significantly increased during AD (median tumor size, 10.0 mm in BD, 8.0 mm in AD; Mann-Whitney U-test, p = 0.011). BCC were excised with a significantly narrower margin during AD (median, 2.0 mm) than during BD (median, 3.0 mm; Mann-Whitney U-test, p < 0.001; odds ratio, 0.30; multivariate logistic regression analysis, p < 0.001); the incomplete excision rate was 1.9%, and the recurrence rate was 0%. The present study suggests that the introduction of dermoscopy might have aided in the early diagnosis of smaller BCC, especially in the face region, and determining the appropriate surgical margin. The smaller pigmented BCC can be excised with a narrower margin than stated in the guidelines (4 mm).

Histopathologic and dermoscopic features of 42 cases of folliculitis decalvans: A case series.

BACKGROUND: Folliculitis decalvans (FD) is a form of inflamed primary cicatricial alopecia (PCA). FD is classified as a neutrophilic PCA; however, only a few previous studies have described its histopathology, including the assessment of systematically evaluated and quantified follicular changes in horizontally sectioned biopsy specimens with clinical and dermoscopic findings of the early and advanced stages. OBJECTIVE: We aimed to clarify the histopathologic and dermoscopic features of early and advanced active stage FD. METHODS: We conducted a case series study of 42 patients with FD by dermoscopy and both horizontally and vertically sectioned biopsy specimens. RESULTS: The histopathologic findings of the early-stage lesions included loss of sebaceous glands; interfollicular acanthosis; and fibrosis with depressed, fused follicular infundibula showing thickened interfollicular keloid-like areas with tufted hairs on dermoscopy. Active lesions showed a greater number of hair clusters, clefting, and fused infundibula with dense inflammation predominantly in the upper follicles. Neutrophil-predominant infiltrates were observed in fewer than half of the patients, including those with early-stage lesions. LIMITATIONS: This was a retrospective study. CONCLUSION: FD has the features of mixed-cell PCA. The features of early-stage FD are thickened interfollicular keloid-like areas with tufted hairs and loss of sebaceous glands.

Wound, pressure ulcer and burn guidelines - 1: Guidelines for wounds in general, second edition.

The Japanese Dermatological Association prepared the clinical guidelines for the "Wound, pressure ulcer and burn guidelines", second edition, focusing on treatments. Among them, "Guidelines for wounds in general" is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added "Question 6: How should wound-related pain be considered, and what should be done to control it?" as a new section addressing wound pain, which was not included in the first edition.

Wound, pressure ulcer and burn guidelines - 6: Guidelines for the management of burns, second edition.

"Wound, pressure ulcer and burn guidelines - 6: Guidelines for the management of burns, second edition" is revised from the first edition which was published in the Japanese Journal of Dermatology in 2016. The guidelines were drafted by the Wound, Pressure Ulcer and Burn Guidelines Drafting Committee delegated by the Japanese Dermatological Association, and intend to facilitate physicians' clinical decisions in preventing, diagnosing and treating burn injury. All sections are updated by collecting documents published since the publication of the first edition. Especially, the recommendation levels of dressing materials newly covered by the Japanese national health insurance are mentioned. In addition, the clinical questions (CQ) regarding the initial treatment of electrical (CQ15) and chemical burns (CQ16), and also the use of escharotomy (CQ22), are newly created.

Autologous cell-based therapy for male and female pattern hair loss using dermal sheath cup cells: A randomized placebo-controlled double-blinded dose-finding clinical study.

BACKGROUND: Few effective treatments are available for male pattern hair loss (MPHL) or, especially, for female pattern hair loss (FPHL). Recently, cell-based therapies using autologous or allogeneic cells have been used clinically. OBJECTIVE: We examined the safety and efficacy of autologous cell-based therapy using dermal sheath cup (DSC) cells to treat MPHL and FPHL. METHODS: DSCs dissected from occipital hair follicles were cultured to manufacture DSC cells. Participants with MPHL or FPHL received single injections of 7.5 × 106, 1.5 × 106, or 3.0 × 105 DSC cells or a placebo in 4 randomized separate regions on the scalp, and hair densities and diameters were measured for 3, 6, 9, and 12 months. RESULTS: Fifty men and 15 women aged 33 to 64 years were injected with DSC cells. Total hair density and cumulative hair diameter at the 3.0 × 105 DSC cells injection site was significantly increased compared with the placebo after 6 and 9 months. Men and women showed similar improvements, and there were no serious adverse events. LIMITATIONS: No lower cell numbers were tested, and the positive effect was temporary until 9 months. CONCLUSION: The results suggest that cell therapy with autologous DSC cells may be useful as a new therapeutic method for treating MPHL and FPHL.

Wound, pressure ulcer and burn guidelines - 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers.

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

IL-17-positive mast cell infiltration in the lesional skin of lichen planopilaris: Possible role of mast cells in inducing inflammation and dermal fibrosis in cicatricial alopecia.

Lichen planopilaris (LPP) is a primary cicatricial alopecia characterized by the infiltration of lymphocytes in the upper portion of hair follicles. Inflammation around the bulge region of hair follicles induces destruction of hair follicle stem cells and tissue fibrosis, resulting in permanent hair loss. Treatment is still challenging, and the precise pathophysiology of this disorder is unknown. To clarify the pathogenesis of LPP, we performed histological and immunohistochemical analysis on specimens obtained from LPP patients. Formalin-fixed and paraffin-embedded samples were evaluated by staining with haematoxylin and eosin (HE), toluidine blue stain, immunohistochemistry and immunofluorescence. The immunohistochemical analysis demonstrated that CD4-positive T cells preferentially infiltrated into the follicular infundibulum in the LPP lesions. Toluidine blue stain detected a large number of mast cells in the inflammatory lesions of LPP. Interestingly, immunohistochemical analysis demonstrated that the mast cells harboured IL-17A- and IL-23-producing activity and expressed the IL-23 receptor. The number of IL-17A-positive mast cells was significantly higher in the LPP lesions than in normal scalp. Moreover, the IL-17 receptor was expressed exclusively in the follicular epithelial cells in the LPP lesions. These results suggested that mast cells infiltrating hair follicles might play a role in the pathogenesis of LPP via the IL-23/IL-17 axis.

Clinical outcome and dose volume evaluation in patients who undergo brachytherapy for angiosarcoma of the scalp and face.

The present study was conducted to retrospectively evaluate survival and local control with definitive brachytherapy in patients with cutaneous angiosarcoma of the scalp and/or face, and to determine the optimal radiation dose and irradiated volume. Between November, 2009 and January, 2015, 9 consecutive patients with histologically proven angiosarcoma of the scalp and/or face who received image-guided brachytherapy were retrospectively evaluated. The median age of the patients was 83.4 years (range, 67.7-91.9 years). Of the 9 patients, 8 had no lymph node metastasis and 1 patient had cervical lymph node metastasis. The patients were irradiated with a dose of 3 Gy three times per week for varying lengths of time; 4 patients received a total dose of 60 Gy, 1 received 48 Gy and the 4 remaining patients received 45 Gy. The patient who received 48 Gy also underwent additional electron therapy of 16 Gy in 8 fractions. The overall survival, progression-free survival and local progression-free rates at 3 years were 50.8% [95% confidence interval (CI): 15.6-78.1%], 37.0% (95% CI: 6.8-69.3%) and 77.8% (95% CI: 36.5-93.9%), respectively. The local progression-free rate in the 4 patients who received a total of ≥60 Gy was statistically significantly better compared with that in the 5 patients who received a dose of <60 Gy (P=0.027). A total of 7 patients had grade 2 radiation dermatitis, whereas the remaining 2 patients had grade 3 dermatitis. All the patients had grade 2 alopecia. Local disease control achieved by radiotherapy resulted in higher survival. Therefore, prescribing ≥60 Gy in 20 fractions for the gross tumor volume is recommended for angiosarcoma of the scalp and face.