Masaru Arima

Psychosomatic analysis of atopic dermatitis using a psychological test.

In patients with atopic dermatitis (AD), psychosomatic factors are important elements in treating the condition. In this study, we surveyed 51 outpatients with AD who consulted the Department of Dermatology of Fujita Health University Hospital using a questionnaire involving present illness/treatment history regarding AD to analyze psychosomatic factors. The severity of AD was evaluated using the severity classification described by Yoshiike et al. Four psychological tests were used to examine depression, anxiety, personality, and upbringing experiences during childhood. Beck Depression Inventory (BDI) was used as a scale for depression, Self‐rating Anxiety Scale (SAS) as a scale for anxiety, the Temperament and Character Inventory (TCI) as a scale for the personality tendency, and the Parental Bonding Instrument (PBI) as a scale for upbringing experiences during childhood. The BDI and SAS scores were high in the severe AD group. Among patients with the same grade of AD, the BDI and SAS scores were higher in the low IgE RIST group. In the patients with AD, the BDI scores were significantly higher than those in the healthy controls (P<0.05). In clinical practice, the treatment of AD should include psychosomatic approaches.

Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae.

It has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB‐induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR‐1× HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear β‐catenin‐positive McSCs were increased as compared to non‐irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of β‐catenin, was significantly upregulated in McSCs of UVB‐irradiated mice. The Wnt1 expression and the number of nuclear β‐catenin‐positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte‐related genes including Dct in early‐passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.

Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines

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.

Epithelial–mesenchymal transition of the eccrine glands is involved in skin fibrosis in morphea

Morphea is a type of localized scleroderma. It is a skin disease involving the development of fibrosis in the dermis and subcutaneous fat tissue beneath without a visceral lesion, and the cause is still unclear. An involvement of epithelial–mesenchymal transition (EMT) has been reported as a cause of tissue fibrosis, but this was mostly observed in pulmonary and hepatic fibrosis, and the involvement of EMT in a skin disease, morphea, has not been studied . Thus, we analyzed the involvement of EMT in skin fibrosis in morphea patients using pathological techniques. Skin lesions of six morphea patients were analyzed (five female and one male patient). As a control, non‐light‐exposed skin lesions of 11 healthy females were analyzed. Concretely, tissue samples were prepared from these subjects and subjected to immunostaining of transforming growth factor (TGF)‐β1, α‐smooth muscle actin (α‐SMA) and fibronectin, which have been reported to be associated with fibrosis, and Snail1 and E‐cadherin, which are considered to be involved in EMT, and expressions of these were analyzed. In morphea patients, dermal expression of TGF‐β1, α‐SMA and fibronectin, which are involved in fibrosis, was enhanced, and, at the same time, enhanced expression of Snail1 and reduced expression of E‐cadherin, which are involved in EMT, were observed in the dermal eccrine glands. These findings suggested the progression of EMT in the dermal eccrine glands in morphea.

Occupational food allergy due to parvalbumin and phaseolin induced by epicutaneous sensitization

Sensitization in food allergy is traditionally thought to occur via the intestinal tract. In recent years, it has been proposed that the primary mechanism for the development of food allergies is epicutaneous sensitization.1,2 In Japan, numerous cases of wheat allergy that developed from epicutaneous sensitization to hydrolyzed wheat protein (Glupearl 19S) in soap (sold by Yuuka Co., Ltd., Fukuoka, Japan) have been reported; this finding suggests that food allergies may be caused by epicutaneous sensitization.3 A 25-year-old man with atopic dermatitis (LDH: 321 U/L, TARC level: 2208 pg/ml, SCORAD index: 24) and pollinosis visited our hospital for investigation of food allergy and hand eczema. He had worked as a sushi chef and handled raw fish with his bare hands. After one year, he experienced itchiness in his hands after touching multiple types of fish, and intraoral itchiness, respiratory difficulty, diarrhea and abdominal pain occurred after consuming them. Consequently, he changed his job and become a Japanese sweets maker. He touches white bean paste (white kidney beans) with his bare hands for making Japanese sweets in daily work. After 6 months in this job, he felled itchy on his hands after touching white bean paste, and the hand eczema had worsened. When he consumed white bean paste, he began to experience the same symptoms as consuming fish. He had no history of food allergy before working in the aforementioned occupations. We considered the possibility that his food allergies were induced by epicutaneous sensitization. The total IgE level was 841 IU/mL. The levels of specific IgE antibodies by ImmunoCAP (Phadia Inc., Tokyo, Japan) were: class 2 for codfish, flatfish, salmon, mackerel, sardine and horse mackerel, class 3 for soybeans and class 4 for kidney beans. On the other hand, specific IgE antibodies for wheat, gluten, u-5 gliadin, latex and anisakis were not detected. In skin prick test, he showed positive reactions for several kinds of fish (raw, as is) such as young yellowtail, horse mackerel, salmon roe, flatfish, sardine and white kidney bean.4 The tests for prawns, octopus, spiral shellfish, anisakis and black bean paste with azuki beans were negative. The positive control (1% of histamine dihydrochloride, Wako Pure Chemical Industries, Ltd., Osaka, Japan) exhibited a reaction of 3 3 mm. The negative control (physiological saline) exhibited no reaction. The skin prick test reaction was considered positive if a wheal 3 mm diameter appeared after 15e20 min of application. The fluorescence intensities of specific IgE antibodies to

Enhancement of individual differences in proliferation and differentiation potentials of aged human adipose-derived stem cells

Background Adipose-derived stem cells (ASCs) are a robust, multipotent cell source. They are easily obtained and hold promise in many regenerative applications. It is generally considered that the function of somatic stem cells declines with age. Although several studies have examined the effects of donor age on proliferation potential and pluripotency of ASCs, the results of these studies were not consistent. Objective This study tested whether the donor age affects the yield of ASCs from adipose tissue, as well as the proliferation and differentiation potentials of ASCs. Methods This study used ASCs obtained from adipose tissues of 260 donors (ages 5–97 years). ASCs were examined for individual differences in proliferation, and adipogenic, osteogenic and chondrogenic differentiation potentials in vitro. Characteristics of ASCs from each donor were evaluated by the principal component analysis (PCA) using their potential parameters. Results Analyses on ASCs demonstrated that adipogenic potentials declined with age, but proliferation, osteogenic and chondrogenic potentials were not correlated with age. Interestingly, in all ASC potentials, including adipogenesis, individual differences were observed. Principal component analysis (PCA) revealed that individual differences became evident in the elderly, and those variations were more prominent in females than in males. Conclusions This study demonstrated age-related changes in the potentials of ASCs and revealed that the individual differences of ASCs become significant in people over 60 years of age (for females over 60, and for males over 80). We believe that it is important to carefully observe ASC potentials in order to achieve effective regenerative medicine treatments using ASCs.

Case report of multiple pustules of the bilateral lower limbs caused by a granulocyte colony-stimulating factor-producing solid pseudopapillary tumour of the pancreas.

Here we report a rare case of neutrophilic dermatoses related to a granulocyte colony‐stimulating factor (G‐CSF)‐producing solid pseudopapillary tumour (SPT). The patient was a 39‐year‐old woman presenting with scattered pustules and crusts of the palms, heels and thighs and plaques of the bilateral lower legs. The skin biopsy revealed dense neutrophil infiltration in the epidermis to the dermis. A pancreatic head tumour was detected using computed tomography. A pathological examination of the resected specimen suggested an SPT. As the skin eruption promptly disappeared after SPT resection, we hypothesized that SPT secretes growth factors including epidermal growth factor (EGF) and G‐CSF. The SPT cells stained positive for both EGF and G‐CSF tumour cells. The serum levels of interleukin (IL)‐6 and IL‐10 and tumour necrosis factor‐α were within normal limits before and after the SPT resection. In contrast, the serum IL‐8, EGF and G‐CSF levels decreased after the SPT resection. This is a rare case of neutrophilic dermatoses related to a G‐CSF‐producing SPT. The present case suggests that physicians should be aware that a G‐CSF‐producing tumour is a differential diagnosis to consider in patients with unusual aseptic pustulosis.

A Patient with Giant Rippled-Pattern Sebaceoma in the Occipital Region

A 72-year-old male visited a nearby hospital with a large tumor in his occipital region, which had existed since 20 years. Since malignant tumor was suspected, he was referred to our department. At the initial consultation, an elastic-hard, yellow-brown, sessile tumor, measuring 8 × 7 × 5 cm and with a flat surface, was observed in the occipital region. The tumor was resected and covered with artificial dermis. Histopathologically, the lesion was composed of basal-cell-like cells with nest formation in the dermis. A rippled pattern, or the single-line arrangement of tumor cells involving the stroma, was present. In addition, some tumor clusters revealed the differentiation to sebaceous glands, and these cells were positive for cytokeratin (AE1/AE3) and epithelial membrane antigen, which is consistent with the staining of sebaceous glands. On the contrary, tumor cells were negative for epithelial antigen (Ber-EP4), and Ki67 (MIB1) index was 5% or lower. Therefore, we diagnosed the tumor as rippled-pattern sebaceoma and not as basal cell carcinoma. Although this case was quite unique in its large size, immunostaining was useful for the definite diagnosis.

Case of malignant melanoma developing from the dermal component of a small intradermal nevus

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The novel GJB3 mutation p.Thr202Asn in the M4 transmembrane domain underlies erythrokeratodermia variabilis

T . HAMADA K. TEY E T . HASH IMOTO Y. HATANO S . FU J IWARA Ueo Dermatology Clinic, Saiki, Oita 876-0831, Japan Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan Department of Dermatology, Faculty of Medicine, Oita University, Hasama, Yufu, Oita 879-5593, Japan Correspondence: Sakuhei Fujiwara. E-mail: fujiwara@oita-u.ac.jp