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Basal cell carcinoma (BCC) is the most common skin cancer. While Mohs micrographic surgery is commonly accepted for BCC treatment, surgical excision with free margins is widely considered the best treatment modality for BCCs in Japan. However, little is known about the predictors of the invasion levels of BCCs.To investigate the optimization of deep surgical margins by identifying factors significantly influencing the invasion levels of facial BCCs.The tumor invasion level was defined as the deepest part of a tumor. Tumor thickness was measured from the top of the granular layer to the deepest extension of the tumor or from the ulcer base overlying the deepest point of invasion in ulcerated lesions. Factors independently associated with tumor thickness and invasion level were identified by multivariate analysis. Six variables were tested: age, sex, anatomical region (nose, orbit, others), histologic pattern (aggressive, non-aggressive), presence of pigmentation, and diameter.We included 718 cases of facial BCCs involving 705 Japanese patients. The most frequent anatomical region and histologic pattern were the nose and nodular pattern, respectively. Only tumor diameter showed a correlation with tumor thickness (β = 0.377, P0.001). Tumor diameter (AOR = 71.189, 95 % CI: 11.420-430.931, P = 0.01) and the following anatomical regions showed correlations with the invasion level: nose/others: AOR=2.769, 95 % CI: 1.235-6.493, P = 0.01; orbit/others: AOR=6.369, 95 % CI: 2.728-15.429, P0.001; orbit/nose: AOR=2.300, 95 % CI: 1.056-4.984, P = 0.04.This study serves as a guide for optimizing deep surgical margins and planning surgery for facial BCCs considering independently associated factors.

In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.

Background The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. Objective The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. Methods The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan–Meier method was used to estimate disease-specific survival and relapse-free survival. Results In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. Conclusion The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.

Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Statement of contextA new grip part for the long cane used by visually impaired children was developed and the effect of this grip, using the muscle activity of the upper limbs, investigated.Critic...

Atypical lipomatous tumor (ALT) has been defined as a well-differentiated liposarcoma exhibiting a higher frequency of a local recurrence after surgical resection. ALT is mainly classified into deep type and superficial type. Compared with deep type ALT, superficial type ALT is rarely observed. One of the most important issues is that little has been known about superficial type ALT and it is not easy to predict the presence of superficial type ALT before surgical resection. To clarify the clinical manifestations of superficial type ALT, we examined 15 cases with superficial type ALT and 118 cases with benign lipoma, and analyzed their differences in clinical characteristics and the findings of MRI test. In clinical characteristics, the tumor size of superficial type ALT was significantly greater than that of benign lipoma, and superficial type ALT showed a significantly higher frequency of the tumor size of more than 4 cm. Superficial type ALT exhibited poor tumor mobility and hardness with elastic soft. In addition, a significantly higher frequency of tumor location of superficial type ALT was observed in extremities. Among tumor sites at the trunk, buttocks, and shoulder were high frequent location in superficial type ALT. In an MRI examination, superficial type ALT exhibited a significantly higher frequency of the septal structures compared with benign lipoma. The combinations of clinical characteristics, including physical examinations, MRI, and histological examinations, are helpful for the diagnosis of superficial type ALT.

Telaprevir used as a protease inhibitor against hepatitis C virus is frequently associated with cutaneous adverse reactions. To explore a histological biomarker of cutaneous adverse events induced by telaprevir, we systematically searched for genes that were dysregulated by telaprevir in normal human epidermal keratinocytes (NHEKs). Microarray analysis and real-time polymerase chain reaction (PCR) revealed the significant increase in the expression of S100 calcium-binding protein A2 (S100A2) gene following treatment of NHEKs with telaprevir. Immunohistochemical analysis demonstrated that the expression of S100A2 was dominant in the spinous layer of the epidermis in patients with telaprevir-mediated severe-type drug eruptions and limited to the basal layer of the epidermis in healthy subjects. Furthermore, S100A2 expression increased after treatment with trichloroethylene and other medications, and the degree of S100A2 expression correlated with the severity of cutaneous adverse events. S100A2 expression also significantly increased in the skin of patients with atopic dermatitis and psoriasis. Taken together, S100A2 is highly expressed in the epidermis under inflammatory conditions and drug eruptions and may serve as a marker for keratinocyte damage in response to any inflammatory or toxic condition.

The long cane has been the most widely used mobility aid for the visually impaired people in spite of many other aid systems. The purpose of this study was to investigate canes that are currently being used at the special needs education school for the visually impaired and to produce new long canes experimentally and evaluate it for visually impaired children. An 8-item-questionnaire was developed and distributed to 71 all the Japanese special needs education schools for the visually impaired. 83.1% subjects who received the questionnaire completed it properly. The new types of the long cane were assessed for their ability to transmit the vibration and their sensitivity to tactile information, flexibility, and durability. The materials that are used in new long cane shafts were carbon fiber, aluminum and composite material of carbon fiber and aluminum at three kinds of the most commonly used materials. The tips that are used in new long cane were standard (pencil), marshmallow, and teardrop at the types of three categories. According to questionnaire results, the visually impaired children tend to use a straight cane, and a rubber golf grip standard-type cane tip in the special needs education school for the visually impaired, even though there are many kinds of cane tips. In these experiments of the new long cane, it was found that the lightweight canes, the regulating mechanism of cane's lengths and the combination of tips and grip might be associated with a visually impaired children's performance.

Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical behavior. Nivolumab, a representative anti-programmed death 1 (PD-1) antibody, has recently been used for the treatment of metastatic malignant melanoma. However, there have been few appropriate biomarkers predicting the effect of nivolumab before the administration. Furthermore, the detailed characteristics of peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment remains unclear. In this study, we investigated fluctuations of PBMC profile during nivolumab treatment. PBMC analysis showed T-helper (Th)2-dominant conditions after a first course of nivolumab treatment. In a favorable case treated with nivolumab, a Th1/T-cytotoxic 1 shift was observed after nivolumab was administrated. These results suggest that flow cytometric analysis of PBMC may be helpful for the treatment of nivolumab.

Photoallergic drug eruptions are induced by various drugs, and sometimes coexist with other clinical manifestations, such as erythema multiforme [1]. Tocilizumab is a biological disease-modifying antirheumatic drug that targets IL-6 receptors and is used for the treatment of autoimmune diseases, such as rheumatoid arthritis [2]. Herein, we report the first case of photosensitivity due to tocilizumab presenting with erythema multiforme-like lesions.A 55-year-old female gradually developed arthralgia [...]

Background Calciphylaxis following acute renal failure is rare. Findings We report A 57-year-old male with an acute renal failure associated with necrotizing fasciitis. We also review the cases of calciphylaxis due to acute renal disorder further. Conclusions It should be kept in mind that calciphylaxis is observed in patient with not only chronic renal disease but also acute renal failure.

Erythema papulosa semicircularis recidivans (EPSR) is a new entity characterised by centrifugally expanding erythematous plaques that exacerbate after excessive sweating or during warm seasons [1, 2]. EPSR clinically resembles erythema annulare centrifugum of Darier, however, the edge of the annular ring is composed of papules rather than erythema and scales [1, 2]. Herein, we report the first case of EPSR associated with primary pancreas B-cell lymphoma.A 39-year-old woman was referred to our [...]

Smooth muscle tumor of uncertain malignant potential (STUMP) is a tumor that cannot be histologically diagnosed as unequivocally benign or malignant [1]. Uterine STUMP is histologically characterized by the existence of standard smooth muscle differentiation, low mitotic index and diffuse atypia. We describe a case of cutaneous skull metastasis from uterine STUMP. To our knowledge, this is the first case report in English of cutaneous metastasis of STUMP.A 68-year-old woman was referred to our department [...]

© 2016 The Authors. doi: 10.2340/00015555-2435 Journal Compilation © 2016 Acta Dermato-Venereologica. ISSN 0001-5555 Limaprost alfadex is a prostaglandin E1 (PGE1) deri­ vative, which is effective in the treatment of thrombo­ angitis obliterans through its pharmacological effect of improving peripheral blood circulation (1). Although some PGE1 analogue­related adverse events have been reported, e.g. liver dysfunction, to our knowledge, there have been only 2 case reports of cutaneous drug erup­ tion caused by PGE1 analogue published in English (2, 3). We report here a case of lichenoid drug erup­ tion caused by limaprost alfadex, as an unusual skin manifestation.

Background Malignant melanoma (MM) tends to be spontaneously regressed, however, complete regression of primary cutaneous MM is an extremely rare phenomenon. Our aim is to be aware that pathologists and/or dermatologists can readily misinterpret it as the other benign or malignant lesions. Case presentation A gradually growing and verrucous hypopigmented macule had been noticed in the right sole of a 65-year-old Japanese male since 2 years before, and it turned to be a solitary bluish to black patch with surrounding depigmentation and was recently decreased in size. In parallel, the patient had a rapidly growing black-pigmented mass lesion at the right inguen. The cutaneous specimen from the sole showed an aggregation of many melanophages predominantly in the middle to deep layer of dermis, associated with surrounding fibrosis, reactive vascular proliferation and CD8-positive T-lymphocytic infiltrate, covered by attenuated epidermis with absence of rete ridge. However, no remnant MM cells were completely seen in the step-serial sections. We first interpreted it as blue nevus. By contrast, the inguinal mass revealed a diffuse proliferation of highly atypical mono- to multi-nucleated large cells having abundant eosinophilic cytoplasm in the enlarged lymph node tissue. Immunohistochemical findings demonstrated that these atypical cells were specifically positive for HMB45 and Melan A. Therefore, we finally made a diagnosis of complete regression of primary cutaneous MM associated with distant lymph node metastasis of MM. Conclusion Careful, not only general/cutaneous but histopathological, examinations should be necessary and adjunctive aids for reaching the correct diagnosis of complete regression of cutaneous MM.

Background An anaphylactoid purpura affects small capillaries in the skin and other organs. Although two cases of anaphylactoid purpura exacerbated by cellulitis have been reported in Japanese literatures, its prognosis remains still unclear. Because cellulitis exacerbates various cutaneous inflammations, it has been speculated that cellulitis might also exacerbate cutaneous inflammation, such as vasculitis. Findings In this article, we report that 78-year-old woman exhibited anaphylactoid purpura, following cellulitis. We also reviewed the literature concerning about this subject. Conclusions This type of anaphylactoid purpura is thought to have a favorable prognosis dependent on the treatment for cellulitis.

Approximately 50% of patients with adult T-cell leukemia/lymphoma (ATLL) have skin involvement, and the smoldering, skin lesion-bearing cases are often treated with various skin-directed therapies, such as phototherapy and radiation therapy. Daily oral administration of etoposide plus prednisolone (EP) is also used for smoldering-type ATLL. However, it remains unclear whether these therapies improve patients' survival. We retrospectively analyzed the prognosis of patients with smoldering, skin lesion-bearing ATLL (n = 62), who were treated, as first therapy, with one skin-directed therapy (n = 29), oral EP alone (n = 14) or a combination of skin-directed therapy and oral EP (n = 19). Multivariate analysis revealed that the hazard ratios (HRs) for the overall survival (OS) and progression-free survival (PFS) with the combination therapy were significantly lower than those with the skin-directed therapy (HR 0.1, p = 0.001; HR 0.2, p = 0.002, respectively). These results suggest that the combination of skin-directed therapy and oral EP improves the clinical outcome of patients with smoldering, skin lesion-bearing ATLL.

There are increasing cases of wheat dependent exercise-induced anaphylaxis (WDEIA) with transcutaneous or transmucosal sensitization. Hydrolyzed wheat included in a certain brand of soap was identified as a cause of sensitization. The useful clues to detect this disorder consist of the patient's past usage of a soap containing hydrolyzed wheat, the appearance of cutaneous or mucosal symptoms after the intake of wheat or washing with this soap, and a high level of specific IgE for wheat gluten. Because hydrolyzed wheat is used as an additive in a wide variety of cosmetics, we should pay careful attention to the ingredients of cosmetics when observing WDEIA.

Doripenem is a carbapenem antibiotic drug with a strong bactericidal activity against many Gram-negative bacteria [1]. While doripenem is widely used for the treatment of various infectious diseases, only one report of drug eruption caused by doripenem has been reported, manifesting with Stevens-Johnson syndrome [2]. Herein, we report a case of doripenem-induced maculopapular drug eruption. We also review the reported cases of drug eruptions caused by carbapenem antibiotics.A 60-year-old man suffered [...]

The Th17 cell is a pro-inflammatory T helper cell subset defined by the production of IL-17, which plays an important role in various inflammatory diseases [1]. IL-17 exacerbates inflammatory responses through activation of various immune cells, such as neutrophils and keratinocytes. Therefore, the IL-17 axis is a key therapeutic target for the regulation of inflammatory diseases, such as psoriasis and rheumatoid arthritis [2]. Secukinumab is an IL-17 neutralizing antibody, and widely used for the [...]

Cutaneous involvement is seen in ∼ 50% of adult T-cell leukemia/lymphoma (ATLL) patients. We investigated the association between skin eruption type and prognosis in 119 ATLL patients. ATLL eruptions were categorized into patch (6.7%), plaque (26.9%), multipapular (19.3%), nodulotumoral (38.7%), erythrodermic (4.2%), and purpuric (4.2%) types. When the T stage of the tumor-node-metastasis-blood (TNMB) classification of mycosis fungoides/Sézary syndrome was applied to ATLL staging, 16.0% were T1, 17.7% T2, 38.7% T3, and 4.2% T4, and the remaining 23.5% were of the multipapular and purpuric types. For the patch type, the mean survival time (median survival time could not be estimated) was 188.4 months. The median survival times (in months) for the remaining types were as follows: plaque, 114.9; multipapular, 17.3; nodulotumoral, 17.3; erythrodermic, 3.0; and purpuric, 4.4. Kaplan-Meier curves of overall survival showed that the erythrodermic type had the poorest prognosis, followed by the nodulotumoral and multipapular types. The patch and plaque types were associated with better survival rates. Multivariate analysis demonstrated that the hazard ratios of the erythrodermic and nodulotumoral types were significantly higher than that of the patch type, and that the eruption type is an independent prognostic factor for ATLL. The overall survival was worse as the T stage became more advanced: the multipapular type and T2 were comparable, and the purpuric type had a significantly poorer prognosis than T1.

© 2016 The Authors. doi: 10.2340/00015555-2225 Journal Compilation © 2016 Acta Dermato-Venereologica. ISSN 0001-5555 Faropenem is an oral beta-lactam antibiotic, which is structurally different from carbapenems and other available beta-lactams (1). Its administration is effective for upper respiratory tract infection (pharyngitis or tonsillitis), acute bronchitis, and other infectious disease (2). Although diarrhoea and vomiting occur occasionally as adverse effects of faropenem, cutaneous side-effects have not been reported in the English literature. Furthermore, beta-lactam antibiotics, such as meropenem (4), are a common cause of acute generalized exanthematous pustulosis (AGEP) (3); however, there has been no previous report of AGEP associated with administration of faropenem. We report here a first case of AGEP caused by faropenem.

Urocanic acid (UCA) is an epidermal chromophore that undergoes trans to cis isomerization after UVB irradiation. cis-UCA is a potent inhibitor of cutaneous acquired immunity. The aim of this study was to explore the genes, which are upregulated by cis-UCA in normal human epidermal keratinocytes (NHEK) and investigated its role in vitro using human T-lymphocyte cell line, Jurkat cells. DNA microarray analysis and real-time PCR investigation revealed that cis-UCA, not trans-UCA, increased the expression of a gene encoding a β-galactoside-binding lectin, galectin-7, LGALS7B. Immunohistochemical study demonstrated that galectin-7 was highly expressed in the epidermis in the patients with actinic keratosis. Galectin-7 administration upregulated apoptosis and inhibited the expression of interleukin-2 (IL2) and interferon-γ (IFNG) mRNA in Jurkat cells. Taken together, galectin-7 may play important roles in downregulating the functions of T lymphocytes after UVB irradiation and can be developed into novel immunosuppressive therapies for inflammatory skin diseases.

A prodrug strategy is based on the temporary derivatization of a functional drug in order to improve its pharmaceutical utility [1], such that the physiological chemical conditions that are required for the release of a drug through various enzymatic activations are exploited. Fosphenytoin is a water-soluble prodrug of phenytoin and is converted to the active compound by non-specific phosphatases in the blood [2]. Owing to its prodrug form, fosphenytoin exhibits greater tolerability than phenytoin [...]

Febuxostat is a newly-developed non-purine selective inhibitor of xanthine oxidase that decreases uric acid production, and is used for the treatment of hyperuricaemia in patients with gout [1]. Although its adverse events have been reported to be mild-to-moderate [1], several cases of febuxostat-related drug eruptions have been described in the English literature [2-4]. We report here the first case of fixed drug eruption-like macules caused by febuxostat and review the previously reported cases [...]

Parkinson's disease is derived from a degeneration of the dopaminergic neurons in the substantia nigra pars compacta, which leads to a marked loss of striatal dopamine concentration. Among the treatment for Parkinson's disease, the number of patients taking dopamine D2 receptor agonist is on the rise. Ropinirole, a selective dopamine D2 receptor agonist, shows a strong inhibitory effect on the pathogenesis of Parkinson's disease. 1 Although several adverse events of ropinirole are well-known, such as sleep disturbance, a drug eruption due to ropinirole has not been reported in English so far. Herein, we describe here an unusual case of a patient with Parkinson's disease who developed multiple fixed drug eruption after ropinirole treatment. We also reviewed the past literature on drug eruption caused by other dopamine D2 receptor agonists further. A 60-year-old female with Parkinson's disease was referred to our department for evaluation of an eruption of 2 days' duration. An erythematous eruption on the extremities had developed three hours after 7th daily administration of ropinirole for her Parkinson's disease. The erythematous lesions gradually became pigmented. On physical examination, well-defined pigmentations