Ryoichi Kamide

DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen

Mutations in the human DDB2 gene give rise to xeroderma pigmentosum group E, a disease characterized by increased skin tumorigenesis in response to UV-irradiation. Cell strains derived from xeroderma pigmentosum group E individuals also have enhanced resistance to UV-irradiation due to decreased p53-mediated apoptosis. To further address the precise function(s) of DDB2 and the consequence of non-naturally occurring DDB2 mutations, we generated mice with a disruption of the gene. The mice exhibited significantly enhanced skin carcinogenesis in response to UV-irradiation, and cells from the DDB2–/– mice were abnormally resistant to killing by the radiation and had diminished UV-induced, p53-mediated apoptosis. Notably, the cancer-prone phenotype and the resistance to cellular killing were not observed after exposure to the chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), to which mice carrying defective nucleotide excision repair genes respond with enhanced tumors and cell killing. Although cells from heterozygous DDB2+/– mice appeared normal, these mice had enhanced skin carcinogenesis after UV-irradiation, so that XP-E heterozygotes might be at risk for carcinogenesis. In sum, these results demonstrate that DDB2 is well conserved between humans and mice and functions as a tumor suppressor, at least in part, by controlling p53-mediated apoptosis after UV-irradiation.

Use of a wrist activity monitor for the measurement of nocturnal scratching in patients with atopic dermatitis.

Background The amount of nocturnal scratching can be an indirect correlate of itch in pruritic dermatoses. We have previously used an infrared video camera to measure nocturnal scratching in atopic dermatitis (AD). Although this is a reliable method of measuring nocturnal scratching, it is not suitable for routine monitoring in clinical use.

A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

Summary We report a case of febrile ulceronecrotic Mucha–Habermann disease (FUMHD) in a 21‐year‐old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.

Sensitive skin evaluation in the Japanese population

Sensitive skin syndrome was first described in 1977; however, no robust study has been carried out to evaluate its prevalence in Japan. A national representative sample of the Japanese population over the age of 18 years was taken. Individuals were questioned by telephone and selected according to the quota method. When asked “Do you have a sensitive skin?”, 52.84% of men and 55.98% of women answered “rather sensitive” or “very sensitive”. There was no significant difference (P = 0.22) between the two sexes. The non‐response rate among respondents was zero, suggesting that the term “sensitive skin” held a meaning for the majority of the population. Concerning questions about the onset of a rash, tingling or irritation in the presence of various factors, such as emotional issues, cold, heat, sun, dry air, air‐conditioning, water, air pollution and temperature variations, respondents with rather sensitive or very sensitive skin responded “yes” more often than others: approximately three‐times more often for water (18.97%/6.15%), air pollution (39.29%/12.45%) and warm climatic conditions (29.74%/9.8%). To our knowledge, this epidemiological study is the first to focus on sensitive skin among Japanese people of this century. It is of particular interest for two reasons: (i) it was conducted on a representative sample of the Japanese population; and (ii) the methodology used was identical to that used for sensitive skin assessment studies conducted in Europe and the USA, making it possible to draw certain comparisons.

Sweet's syndrome with neurologic manifestation: case report and literature review

Background Sweets syndrome with involvement of the central nervous system (CNS) is rarely reported.

Five cases of photocontact dermatitis due to topical ketoprofen:photopatch testing and cross‐reaction study

Background: In parallel with the popular usage of topical ketoprofen, the number of reported cases of ketoprofen‐induced photoallergic contact dermatitis has been increasing. It is clinically important to know the cross‐reactivity of ketoprofen in order to avoid cross‐sensitization caused by several structurally similar non‐steroidal anti‐inflammatory drugs (NSAID) on the market.

Development and validation of the psychosomatic scale for atopic dermatitis in adults

Psychosocial factors play an important role in the course of adult atopic dermatitis (AD). Nevertheless, AD patients are rarely treated for their psychosomatic concerns. The purpose of the present study was to develop and validate a brief self‐rating scale for adult AD in order to aid dermatologists in evaluating psychosocial factors during the course of AD. A preliminary scale assessing stress‐induced exacerbation, the secondary psychosocial burden, and attitude toward treatment was developed and administered to 187 AD patients (82 male, 105 female, aged 28.4 ± 7.8, 13–61). Severity of skin lesions and improvement with standard dermatological treatment were assessed by both the dermatologist and the participant. Measures of anxiety and depression were also determined. In addition, psychosomatic evaluations were made according to the Psychosomatic Diagnostic Criteria for AD. Factor analysis resulted in the development of a 12‐item scale (The Psychosomatic Scale for Atopic Dermatitis; PSS‐AD) consisting of three factors: (i) exacerbation triggered by stress; (ii) disturbances due to AD; and (iii) ineffective control. Internal consistency indicated by Cronbachs alpha coefficient was 0.86 for the entire measure, 0.82 for (i), 0.81 for (ii), and 0.77 for (iii), verifying the acceptable reliability of PSS‐AD. Patients with psychosomatic problems had higher PSS‐AD scores than those without. PSS‐AD scores were positively associated with the severity of the skin lesions, anxiety and depression. The scores were negatively associated with improvement during dermatological treatments. In conclusion, PSS‐AD is a simple and reliable measure of the psychosomatic pathology of adult AD patients. It may be useful in dermatological practice for screening patients who would benefit from psychological or psychiatric interventions.

Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutation in the NF1 tumor‐suppressor gene, and may sometimes manifest in a mosaic form. “Segmental NF1” is generally assumed to be the result of somatic mosaicism for a NF1 mutation, and patients with mosaic NF1 have typical features of NF1 limited to specific body segments. The clinical features of 58 patients (42 females and 16 males; aged 1–69 years; mean age, 23.4 years) with mosaic NF1 seen at the Jikei University Hospital during 2004–2007 and at the Jikei University Daisan Hospital during 2007–2011, were retrospectively studied. Somatic or gonosomal mosaicism was not investigated. Patients were classified into four groups: (i) pigmentary changes (café‐au‐lait spots and freckling) only (n = 32); (ii) neurofibromas only (n = 5); (iii) neurofibromas and pigmentary changes (n = 13); and (iv) solitary plexiform neurofibromas (n = 8). The area of involvement was variable. The majority of patients were asymptomatic, except patients with plexiform neurofibromas who presented most commonly with pain or tenderness. Lisch nodules were rarely seen. Only four of our 58 patients (6.9%) had specific NF1 complications, including language delay (n = 1) and bone deformity (n = 3). Two patients were ascertained through their children with generalized NF1. Patients with mosaic NF1 are at low risk of developing disease‐associated complications, except patients with plexiform neurofibromas. However, they need to be aware of the small risk of having a child with generalized NF1.

A Case of Pemphigus Vulgaris Successfully Treated with Single Filtration Plasmapheresis: A Correlation of Clinical Disease Activity with Serum Antibody Levels

We report a patient with pemphigus vulgaris (PV) successfully treated with single filtration plasmapheresis. A 40‐year‐old man with PV was started on therapy with prednisolone (PSL). Although the dosage of PSL was doubled, and both cyclosporin A (CyA) and pulse therapy were added, the disease was not controlled. After single filtration plasmapheresis began, most of the eroded lesions on the trunk reepithelialized. A switch to double filtration was followed by recurrence. Finally, additional treatments with single filtration plasmapheresis were required to obtain remission. To evaluate the efficacy of the treatment, circulating antibodies were measured by immunofluorescence (IIF) and enzyme‐linked immunosorbent assays (ELISAs) using recombinant desmoglein (Dsg) 3. IIF titer and the ELISA scores correlated with the clinical disease activity. It is suggested that ELISA was more sensitive than IIF.

A variety of skin responses to ultraviolet irradiation in patients with atopic dermatitis

Skin responses to ultraviolet irradiation in patients with atopic dermatitis were studied to evaluate the role of sunlight in the exacerbation of atopic dermatitis. A total of 15 patients, seven males and eight females, with atopic dermatitis who complained of exacerbation of their dermatitis after sun exposure were examined by photo testing with UVB and UVA irradiation and photopatch tests. Nine out of 15 patients showed abnormal skin reactions. Lowered minimal erythema doses (MEDs) to a single exposure of UVB, papular or erythematous responses after single or repeated exposures to UVB or UVA and positive photopatch test reactions to sunscreen ingredients and fragrances were found. There are apparently multiple mechanisms of photoexacerbation in patients with atopic dermatitis.