【I】In the foregoing discussion, it was shown that Bowen's disease may regress spontaneously. As an application, we describe the effectiveness of local hyperthermia treatment inducing apoptosis for Bowen's disease. 【II】The frequency of Bowen's disease for invasive cancerization was discussed. As with conventional counting, invasive carcinogenesis rate was higher in multiple Bowen disease than in single Bowen disease. It was also shown that this occurs more frequently than the probability distribution of a binomial distribution. 【III】Of nine cases dying from Bowen's disease, seven had mutiple lesions, and in 2 cases, coexistence of immunosuppressed state was observed. 【IV】In patients with multiple Bowen's disease, arsenic intake is an important risk factor. Some points how to get information about the expose to arsenic were considered. In particular, information on river bottom arsenic concentration by region is useful.Skin Research, 16: 298-305, 2017

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Case 1. A 38-year-old male visited the after-hours outpatient clinic of our hospital with chief complaints of fever, and swelling and pain in the dorsum of the right hand over the forearm. We made a diagnosis of cellulitis and performed a drip infusion of antibiotics, then sent the patient home with an oral drug prescription. Upon visitation to the outpatient service of our department the following day, marked swelling with redness, pain, and blisters were observed. The patient appeared to have facial pain and pallor, and exhibited cold sweating. He was immediately sent to the intensive care unit, and test results revealed a qSOFA score of 2 points, white blood cell count of 11,200/μl, CRP level of 30.11mg/dl, and LRINEC score of 6 points. An incision made on the dorsum of the right hand for treatment resulted in a large drainage volume. Case 2. A 68-year-old female visited the night-time service of our department with chief complaints of redness and swelling of the left lower leg. We made a diagnosis of cellulitis and sent her home with an oral antibiotic prescription. After 2 days, the patient returned to the outpatient service of our department, and test results revealed a white blood cell count of 13,900/μl. CRP level of 32.67mg/dl, and LRINEC score of 6 points. A test incision in the left lower leg resulted in a large drainage volume. We report here two patients with necrotizing soft tissue infection. In the first case, qSOFA, a screening test that utilizes a new definition of sepsis, was considered useful. For the second case, the test incision was helpful to understand the depth of the infection. For patients with necrotizing soft tissue infection, early diagnosis and surgical treatment highly influence prognosis. Prompt examinations, including qSOFA, LRINEC, and a test incision, were useful in the present cases.Skin Research, 16: 306-309, 2017

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A 46-year-old female was referred to our hospital for scaly erythema in the occipital region of the head 7 months after starting abatacept for rheumatoid arthritis (RA). A skin biopsy from the lesion demonstrated psoriasiform epidermal hyperplasia with parakeratosis and a perivascular lymphoeosinophilic inflammatory infiltrate in the upper dermis. As the skin rash developed after administration of abatacept and improved after its discontinuation, we diagnosed this case as possible abatacept-induced psoriasiform eruption. Abatacept, a selective T-cell co-stimulation modulator, is recently used for RA. It is well known that paradoxical reactions, including the induction of severe psoriasiform eruption, sometimes occur after the administration of anti-TNF-α agents. Although abatacept is not a direct TNF-α antagonist, it may induce psoriasiform eruption by modulating T cell-associated antigens, resulting in indirect TNF-α inhibition. The possibility of psoriasiform eruption due to abatacept in RA patients should be kept in mind.Skin Research, 16: 310-314, 2017

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Case 1 is a 35-year-old female who noticed a small nodule on a proximal nail fold of the first right toe after trauma 10 years before her first visit to our hospital. As the tumor had enlarged gradually, she had repeatedly cut parts of it by herself and finally, a double-headed tubular nodule developed. Case 2 is a 37-year-old female who noticed a small nodule on the first right toe 5 years before her first visit to our hospital. Resection was performed, but the tumor redeveloped, and she came to our hospital. A papillary nodule was noted on the first right toe nail. Histopathologically, the epidermis was thickened due to proliferating papillary hyperkeratosis in both cases. In addition, collagen fiber bundles were swollen from hyperplasia of the capillary vessels in the dermis. Based on these findings, we diagnosed these two cases as acquired periungual fibrokeratoma (APF), a type of acquired fibrokeratoma (AF). Both cases had unique clinical features, and we considered a strong or repeated mechanical stimulation to have induced the peculiar APF lesions.Skin Research, 16: 315-321, 2017

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A 66-year-old man with a history of cirrhosis due to chronic hepatitis C infection and hepatocellular carcinoma presented with a skin nodule on his left foot that had gradually increased in size over the previous two months. He recalled no traumatic injury that could account for the lesion. Upon examination, a semispherical skin nodule with tenderness, 20×16mm in size, was observed on the dorsum of his left foot. The nodule, excised under local anesthesia, exhibited a capsulated cystic structure containing pus in the dermis and subcutis. Direct microscopic examination of the pus revealed hyphal fungal elements. Histopathological examination demonstrated hyphal fungal elements in granulomatous tissue lining the cystic lesion and in the cavity. Fungal cultures from the pus identified Phaeoacremonium parasiticum as the causative agent. The skin nodule was successfully removed; however, he died of liver failure three weeks after the excision. This case was suggested to be an opportunistic infection due to immunodeficiency associated with liver failure.Skin Research, 16: 322-327, 2017

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A 75-year-old man (case 1) and his 46-year-old son (case 2) presented with multiple diffuse subcutaneous tumors. Finger and toe leukonychia and koilonychia were observed in both on the first presentation to our hospital. In case 1, we excised 6 subcutaneous tumors from the head, trunk, and thigh. Based on histopathological findings, 2 were diagnosed as trichilemmal cysts (TCs) and 4 as proliferating trichilemmal cysts (PTC). In case 2, 2 subcutaneous tumors were excised from the back and right forearm, and both were diagnosed as TCs. The occurrence of familial multiple TCs with leukonychia and koilonychia is a rare autosomal dominant condition, and has been reported in 8 families. The molecular basis and candidate gene in this disorder remain unknown. Herein, we report a 4-generation family history of leukonychia and koilonychia associated with multiple TCs, appearing as an autosomal dominant trait.Skin Research, 16: 328-336, 2017

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We have treated 5 cases of necrobiosis lipoidica (NL) at our department between April 2010 and June 2015. Case 1 was a 67-year-old female with brownish macules that appeared on her legs during treatment with a topical steroid for vitiligo vulgaris. The macules improved after 10 months of steroid occlusive therapy. Case 2 was a 50-year-old female who had skin lesions on her legs for 10 years. They disappeared after 6-month application of a high-strength topical steroid. Case 3 was a 73-year-old female with skin lesions that appeared on her legs approximately 6 months prior. They were unchanged by application of high-strength topical steroids, but they improved after 9 months of additional narrow band-ultraviolet B (NB-UVB) therapy. There was no relapse of the skin lesions after the cessation of topical steroids and UV therapy. Case 4 was a 76-year-old female who had a 15-year history of NL. Neither topical steroid therapy nor additional NB-UVB therapy was effective. Topical psoralen and ultraviolet A (PUVA) therapy was and continues to be effective. Case 5 was a 67-year-old female who had received topical steroid therapy, and was referred to us because of the appearance of small skin ulcers and no improvement of skin lesions. A high-strength topical steroid was effective for the skin lesions and ulcers. Trauma and subsequent inappropriate self-therapy induced the skin ulcers again, which improved with bed rest, compression bandages, and oral antibiotics. Only one case accompanied diabetes mellitus. There were no other NL-associated complications. Treatment for NL is not usually effective, and should be started at an early stage. A combination of topical steroid therapy with UV therapy and strategies for improvement of circulation were considered to improve the outcome of NL.Skin Research, 16: 337-342, 2017

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Sarcoidosis is a multisystem granulomatous disorder with varying initial symptoms. We herein report a case of sarcoidosis with fever, which was diagnosed based on skin biopsy. A 51-year-old female had fever for more than one month before visiting our hospital's internal medicine department. The differential diagnosis included infection and connective tissue disease. Malignant lymphoma was also suspected because of high serum levels of soluble IL-2 receptor and swollen lymph nodes. Four months later, she was referred to us for random skin biopsies to discriminate intravascular lymphoma. Pruritic, miliary red papules were seen on her back and thighs. As the skin biopsy demonstrated noncaseating epithelioid granulomas, the diagnosis was sarcoidosis. Treatment with 20mg/day of oral prednisolone improved her fever, general fatigue, and skin lesions, and reduced serum levels of soluble IL-2 receptor. Although sarcoidosis with fever is rare, it should be considered as a cause of fever of unknown origin and any skin lesions should be carefully evaluated.Skin Research, 16: 343-346, 2017

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Background: Coffee polyphenols (CPPs), including chlorogenic acids, have many physiological effects such as anti-tumor, anti-oxidant, blood-pressure normalizing and body fat reducing effects. Recently, the improvement of skin xerosis and increased cutaneous moisture retention capacity by oral ingestion of CPPs has been reported. Purpose: We investigated the effects of ingesting CPPs for 8 weeks on cutaneous moisture retention capacity and barrier function of facial and lower thigh skin, and on stress symptoms. Method: This was a randomized double-blind study of 108 healthy female subjects who were divided into two groups. Half of the subjects were given a 100mL drink containing 300mg of CPPs daily for 8 weeks, and the other group received the same drink without CPPs for 8 weeks. At weeks 0, 4 and 8, cutaneous conditions, microcirculatory functions and stress symptoms were evaluated. Results: After ingesting CPPs for 8 weeks, the moisture retention capacity increased in the measured areas of the body. In addition, the increase in transepidermal water loss levels after tape-stripping was suppressed. Furthermore, an improvement of subjective stress symptoms was observed. Conclusion: The present study suggests that the ingestion of drinks containing CPPs is beneficial for skin dryness and subjective stress symptoms.Skin Research, 16: 347-355, 2017

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Objective: To evaluate the efficacy and safety of a heparinoid foam (hereinafter, the foam) in patients with asteatosis, a heparinoid soft ointment (Hirudoid Soft Ointment 0.3%, hereinafter, the soft ointment) was switched to the foam, and the subjective impressions of both preparations were surveyed. Method: In a multi-center, uncontrolled, open-label study, the soft ointment was applied to patients with asteatosis for 2 weeks. Thereafter, the foam was applied for 2 weeks. Whether the efficacy of the soft ointment was maintained after switching to the foam was examined by investigators, and the skin symptom score was assessed Safety was confirmed based on adverse events and laboratory test values. Patients' impressions of the study drug were surveyed with a patient questionnaire. Results: Sixty patients were enrolled in the study. The study drug was administered to all patients, and they all completed the study without discontinuation. The effects of the two-week application of the soft ointment were maintained after switching to the foam for all patients, excluding one patient with missing data. The skin symptom score improved over time. Switching to the foam neither increased the incidence of adverse events nor affected the laboratory test values. The results of the patient questionnaire indicated that the foam was superior in that it spread easily and was not sticky. Conclusion: The efficacy of the foam was confirmed as the effects of the soft ointment were maintained after switching to the foam. There were no safety issues associated with the foam. The results of the patient questionnaire also suggested the foam to be a new option for patients who prefer a moisturizer that spreads easily and is not sticky.Skin Research, 16: 356-365, 2017

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Objective: To evaluate the safety of heparinoid foam on the skin of healthy adult subjects using a 48-hour closed patch test and photo-patch test. Method: An empty skin test chamber and chambers containing either heparinoid foam or placebo were randomly applied to the bare skin on the upper back of each subject. Skin safety was evaluated by a 48-hour closed patch test and photo-patch tests. Physical safety was also assessed based on adverse events, laboratory test values, and vital signs. Results: Thirty subjects were enrolled in the study, and all subjects completed the study. The skin irritation index of both the heparinoid foam and the placebo was 3.3, indicating a safe product. In the photo patch test, one subject exhibited a photo-contact urticarial reaction at the application sites of both the heparinoid foam and the placebo, but these were not considered to be clinically problematic. Six subjects demonstrated a slight skin reaction to UV irradiation after 48 hours at the heparinoid foam application site, and 5 of these subjects also had an equivalent reaction with the placebo. Mild photo-sensitivity of the base component was observed, but lack of a causal relationship with the study drug was confirmed for all adverse events observed. The study drug was also found to have no effect on clinical test values or vital signs. Conclusion: Heparinoid foam causes tolerable skin irritation, and absence of clinically problematic skin reactions to UV irradiation was confirmed. Therefore, heparinoid foam was considered to not have any particular skin safety problems. However, photo-sensitivity must be monitored in practical clinical use.Skin Research, 16: 366-371, 2017

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