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Background: Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population. Objective: The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU. Methods: This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12-75 years) who were symptomatic despite H1AH treatment. Eligible participants (N = 218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300 mg, 150 mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs). Results: Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes -10.22, -8.80, and -6.51 for omalizumab 300 mg, 150 mg and placebo; p < 0.001 and p = 0.006 vs placebo, respectively). Overall AE incidence was similar across treatment groups (54.8%, 57.7%, and 55.4% in omalizumab 300 mg, 150 mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms. Conclusion: The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU.

ファイル公開：2019-02-01

Backgroud : More effective treatment strategies are needed for the chronic skin ulcers. Recently, it has been reported that clinical application of stem cells improve wound healing. Objective We aimed to determine the dynamic time-course movement of epidermal stem cell markers especially p75 neurotrophin receptor (p75NTR) and Integrin beta-1 in wound healing process. Furthermore, we also investigated the presence of these markers in human. Methods Epidermal Integrin beta-1 + and p75NTR + cells were counted in wound healing process in mice. Both cells were also counted in human skin specimen obtained from chronic skin ulcers and healthy controls. Growth factor gene expression levels by purified mouse epidermal p75NTR + cells were also analyzed using real-time RT-PCR. Results Integrin beta-1 + and p75NTR + cells were proliferated from 3 days after wounding. Reepithelization was completed 7 days after wounding, and the numbers of cells were returned to the baseline levels by 14 days after wounding. Integrin beta-1 + cells were proliferated in the basal layer, and p75NTR + cells were proliferated in the upper layer of epidermis. In human skin, Integrin beta-1 + and p75NTR + cells were 81% ± 12% and 36% ± 15% of the basal cells, respectively. In patients with chronic skin ulcers, the percentage of Integrin beta-1 + cells in the epidermis was identical to healthy controls. Surprisingly, p75NTR + cells were significantly decreased in chronic skin ulcer patients (1.2% ± 2.6%; p + cells expressed higher transforming growth factor-beta2 and vascular endothelial growth factor-alpha transcripts and lower epidermal growth factor transcripts than p75NTR − cells. Conclusion These results suggest that Integrin beta-1 + and p75NTR + cells play an important role in wound healing process, and that p75NTR may be a key molecule and a candidate for new therapeutic target besides preexisting molecules for chronic skin ulcer patients.

Background Solar lentigines (SLs) are characterized by hyperpigmented macules, commonly seen on sun-exposed areas of the skin. Although it has been reported that an increase in the number of melanocytes and epidermal melanin content was observed in the lesions, the following questions remain to be answered: (1) Is acceleration of melanogenesis in the epidermis caused by an increased number of melanocytes or the high melanogenic potential of each melanocyte? (2) Why does the number of melanocytes increase? Objective To elucidate the pathogenic mechanism of SLs by investigating the number, melanogenic potential and proliferation status of the melanocyte lineage in healthy skin and SL lesions. Methods Immunostaining for melanocyte lineage markers (tyrosinase, MART-1, MITF, and Frizzled-4) and a proliferation marker, Ki67, was performed on skin sections, and the obtained images were analyzed by image analysis software. Results The expression level of tyrosinase to MART-1 of each melanocyte was significantly higher in SL lesions than healthy skin. The numbers of melanocytes in the epidermis, melanoblasts in the hair follicular infundibulum and melanocyte stem cells in the bulge region were increased in SL; however, no significant difference was observed in the Ki67-positive rate of these cells. Conclusion The melanogenic potential of each melanocyte was elevated in SL lesions. It was suggested that the increased number of melanocytes in the SL epidermis might be attributed to the abnormal increase of melanocyte stem cells in the bulge.

Background In recent years, it has been reported that stem cells exist in the mesenchymal tissues of the bone marrow and adipose. These stem cells are thought to express specific cell surface markers such as CD44, CD54, CD105, CD90, and CD271 and have been confirmed to be pluripotent. Furthermore, although it has been reported that stem cells are also present in the dermis, their cell surface markers and characteristics are not fully understood. Objective To confirm the presence of stem cells in the dermis and their ability, employing the mesenchymal stem cell markers which have previously been reported as an indication. Methods We analyzed the percentages of CD44 (+), CD54 (+), CD90 (+), CD105 (+), and CD271 (+) cells in the dermis of neonatal mice (HR-1 mouse) by performing immunostaining and FACS. Secondly, we isolated each type of marker-positive and -negative cells from dermal tissues and evaluated their proliferation potential and their ability to differentiate into adipocytes, osteoblasts, and chondrocytes. Results According to the immunostaining and FACS results, we confirmed that stem cells that express CD44, CD54, CD90, CD105, and CD271 are present in the dermal tissues of neonatal mice. In addition, when we measured the proliferation and differentiation potentials of each type of marker-positive cells, it was revealed that cells expressing CD54 or CD271 have a high proliferation potential and are able to differentiate into adipocytes, osteoblasts, and chondrocytes. Conclusions These results indicated that dermal tissues contain stem cells that express CD44, CD54, CD90, CD105, and CD271 which are stem cell markers. More precisely, it was suggested that both CD54 (+) and CD271 (+) stem cells have high proliferation and differentiation potentials.