Y. Tokura

Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double‐blind, placebo‐controlled, phase II study

Ustekinumab, a fully human monoclonal antibody against interleukin‐12/23, may potentially be effective for severe atopic dermatitis (AD) treatment.

Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas

Safety, tolerability, pharmacokinetics and efficacy of bexarotene, a novel retinoid X receptor (RXR)‐selective retinoid, were evaluated in Japanese patients with stage IIB–IVB and relapsed/refractory stage IB–IIA cutaneous T‐cell lymphomas (CTCL). This study was conducted as a multicenter, open‐label, historically controlled, single‐arm phase I/II study. Bexarotene was p.o. administrated once daily at a dose of 300 mg/m2 for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m2 in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m2 met the response criteria using the modified severity‐weighted assessment tool (mSWAT) at 24 weeks or discontinuation. Dose‐limiting toxic effects (DLT) were present in four of 13 patients (31%) at a dose of 300 mg/m2: two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m2 bexarotene. In the 13 patients at 300 mg/m2, common drug‐related adverse events (AE) included hypothyroidism (92%), hypercholesterolemia (77%), leukopenia or neutropenia (39%), nasopharyngitis or anemia (31%). The treatment‐related grade 3 AE included hypertriglyceridemia (4/16 patients, 25%), increased alanine aminotransferase, increased aspartate aminotransferase, dyslipidaemia, leukopenia and neutropenia (1/16 patients, 6%), and one of 16 patients experienced grade 4 hypertriglyceridemia. No patients discontinued bexarotene due to the AE during the study, but dose reduction or suspension was required. Bexarotene was shown to be well tolerated at 300 mg/m2 once daily and effective in Japanese patients with CTCL.

Chemical photoallergy: photobiochemical mechanisms, classification, and risk assessments

Chemical photosensitivity can be elicited by exposure of the skin to various pharmaceutical substances, foods, cosmetics and other environmental chemicals, followed by exposure to sunlight. There are at least three types of chemical photosensitivity, i.e., photoirritancy (narrowly defined as phototoxicity), photogenotoxicity and photoallergenicity, and their clinical characteristics and mechanisms are quite different. Concerns about chemical photoallergy is increasing, and various studies have been made to clarify the photobiochemical characteristics of photoallergens and the mechanisms involved. Various methodologies, including in silico prediction models, photochemical assay systems, and in vitro phototoxicity prediction tools, have been developed to predict the photoallergenic potential of chemicals over the past few years. The aim of this manuscript is to review the clinical characteristics, pathogenetic mechanisms and photobiochemical features of photoallergens, with special emphasis on the current status about development of screening systems for predicting photoallergenic potential of chemicals.

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment

BACKGROUND Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated. OBJECTIVE To investigate relationship between sensitive skin and AD-associated markers. METHODS Forty-two Japanese AD patients and 10 healthy subjects (HS) were enrolled. AD patients were divided into extrinsic (EAD; high IgE levels) and intrinsic (IAD; normal IgE levels) types. We conducted 1% LAST by assessing the four distinct sensations and calculated the frequencies of sensitive skin in EAD, IAD, and HS. We also performed clinical AD-related tests, including transepidermal water loss (TEWL), visual analogue scale (VAS) of pruritus, and quality of life, and measured laboratory markers, including blood levels of IgE, CCL17/TARC, lactate dehydrogenase (LDH) and eosinophil counts, and concentration levels of serum Th1/Th2 cytokines. Filaggrin (FLG) mutations were examined in 21 patients. These values were subjected to correlation analyses with each of the four sensation elements. RESULTS According to the standard criteria for LAST positivity, the frequencies of LAST-positive subjects were 54.8% and 10.0% in AD and HS, respectively (P=0.014). EAD patients showed a significantly (P=0.026) higher frequency of positive LAST (65.6%) than did IAD patients (20.0%). Among the four LAST sensation elements, the crawly feeling and pain scores positively correlated with VAS of pruritus, total serum IgE, mite-specific IgE, CCL17/TARC, and/or LDH. There was no association of the LAST scores with serum Th1/Th2 cytokine levels. Notably, neither TEWL nor FLG mutations correlated with LAST positivity or any sensation scores. CONCLUSIONS The frequency of sensitive skin is higher in EAD than in IAD. Sensitive skin is associated with AD severity, but not necessarily with barrier condition.

Complete type of pachydermoperiostosis with a novel mutation c.510G>A of the SLCO2A1 gene

women in Japanese (66.7% vs 31.3%; P < 0.05). Indeed, in this case, his sister had no skin lesions. No differences between sexes in the prevalence of pulmonary cysts and renal tumors were found (Table 1). Considering that renal cell carcinoma in general develops 2.5-times more frequently in men than women, a higher prevalence of renal tumors in women with BHDS may be considered. Thus, although Japanese patients, especially women, have less frequency of skin manifestations, dermatologists should consider BHDS when examining patients with an increasing number of multiple papules on their face. Early diagnosis would help in the early detection or prevention of further serious or life-threatening renal diseases.

Infiltration of mast cells in pachydermia of pachydermoperiostosis

Dear Editor, Pachydermoperiostosis (PDP; Online Mendelian Inheritance in Man #614441) is a rare hereditary disease characterized by distinctive digital clubbing, periostosis and pachydermia. Patients with PDP harbor homozygous mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) or the 15-hydroxyprostaglandin dehydrogenase gene (HPGD), resulting in elevated prostaglandin E2 (PGE2) levels.

Three-microneedle device as an effective option for intralesional corticosteroid administration for the treatment of alopecia areata

Dear Editor, Intralesional injection of corticosteroids is reportedly a favorable therapy for patchy alopecia areata (AA) by guidelines published in Japan and the UK. However, the procedure is associated with several issues, such as pain and inaccurate depth of injection, that is dependent on the skill of the physician. Recently, we studied the three-microneedle device (TMD), Paskin (Nanbu Plastics, Shizuoka, Japan) for intralesional injection of corticosteroids for AA treatment (Fig. 1a). The tip of

Idiopathic segmental anhidrosis associated with varicella.

1 Kubota Y, Koga K, Nakayama J. Polyarteritis nodosa cutanea with a varied course. Nishinihon J Dermatol 2007; 69: 505–510. [In Japanese]. 2 Wakabayashi N, Ishiguro N, Hayama M et al. Antiphospholipid antibodies in patients with cutaneous polyarteritis nodosa and livedo vasculopathy: an additional report. J Tokyo Wom Med Univ 2013; 83: 417–418. 3 Kawakami T, Yamazaki M, Mizoguchi M et al. High titer of antiphosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum 2007; 57: 1507–1513. 4 Wakabayashi N, Ishiguro N, Hayama M et al. Antiphospholipid antibodies in patients with cutaneous polyarteritis nodosa and livedo vasculopathy. J Tokyo Wom Med Univ 2013; 83: 86–94.

Extrinsic and Intrinsic Atopic Dermatitis

Atopic dermatitis (AD) can be categorized into extrinsic and intrinsic types. The serum levels of IgE are high in extrinsic AD and normal in intrinsic AD. This dichotomy also corresponds to the following terminology: mixed AD vs pure AD, allergic AD vs non-allergic AD, and classical AD vs atopiform dermatitis. While extrinsic AD is the common type with high prevalence, intrinsic AD is approximately 20% in incidence and shows apparent female predominance. Extrinsic AD is closely associated with barrier perturbation and Th2-skewing immunological condition, but the causes and mechanisms of intrinsic AD remain elusive. In extrinsic AD, antigens can penetrate through disrupted barrier, and epidermal Langerhans cells serve as antigen-presenting cells to Th2 cells. In intrinsic AD, nonprotein antigens, such as metals and haptens, and Th1/Th17 cells participate as well as Th2 cells. Notably, intrinsic AD shows significantly higher percentages of positive patch test to nickel and cobalt than extrinsic AD, indicating high frequency of metal allergy in intrinsic AD.

Transverse nasal crease with milia and comedones: Dermoscopic observation

Dear Editor, Transverse nasal crease (TNC) is a rare asymptomatic skin disease with a fold or a line located at the junction of the middle and lower third of the nose. This crease is caused by anatomically linear attachment of the triangular and alar cartilages at this junction, producing a potential embryonic fault line. There are the variants of TNC, which exhibit a groove, a row of milia or comedones, or a faint erythematous line at the same location. In particular, the simultaneous occurrence of milia and/or comedones represents a characteristic manifestation of TNC and has been documented in only a few cases. Here, we report a case of TNC with milia and comedones investigated with dermoscopy. A 7-year-old Japanese girl was referred to us because of a 2-year-history of an asymptomatic whitish belt on the nose. It tended to be conspicuous in summer. She had no habit of rubbing her nose. Her own and familial medical history was unremarkable. On examination, the patient had a depigmented linear lesion extending transversely on the nose (Fig. 1a). The lesion was up to 2 mm in width and accompanied by a row of small papules. Dermoscopic examination revealed that the papules consisted of two types (Fig. 1b,c): several white rounds, 0.5–1 mm in diameter, indicating milia (black arrows), and many white to brown clear spots, up to 0.5 mm in diameter, representing comedones (red arrows). In addition to the visible comedones, numerous microcomedones were observed as small white spots localized within the belt (black arrowheads). An aggregate of small white comedones seemed to gradually merge into the white lesion. Although the crease was not visible in our case, it was observed dermoscopically as intermittent transverse white thin streaks (red arrowheads), which were 0.1 mm in width and were located in the center of the white belt. It is possible that the thin streaks reflect fibrosis adhesive to the cartilage. Both the white belt and the crease were prominent at the center of the nose (Fig. 1b) and disappeared at the peripheries (Fig. 1c). Transverse nasal crease should be distinguished from the “allergic nasal crease”, a similarly appearing line seen in allergic rhinitis or atopic patients with a habit of repetitive upward rubbing of the nose. In the vast majority of reports, including epidemiological studies, TNC was not fully discriminated from allergic nasal crease, as represented by an allergic crease case showing cornified papules with seborrheic keratosis-like hyperplasia and horn cysts. It is thought that TNC with prominent milia and/or comedones seen in our case is very rare, and to our knowledge, this is the first Asian case. Our dermoscopic examination demonstrated that nasal crease can be observed as intermittent transverse white thin streaks, and many invisible microcomedones are present within the white belt. This finding provides a great help in the diagnosis of TNC even without visible crease, milia or comedones. Because this is the first reported case of TNC investigated with dermoscopy, further studies are necessary to determine the typical dermoscopic features.