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Neurofibromatosis 1 (NF1) is a genetic disorder characterized by various symptoms including dermatological, neurological, and osseous manifestations. These complications often cause cosmetic or functional disturbances, resulting in a significant impact on quality of life (QOL). However, there are limited data on QOL of individuals with NF1 in Japan. Therefore, we studied health-related QOL in patients with NF1 compared with that in general populations and the association with severity grade using EQ-5D. A cross-sectional study was conducted for 73 adult NF1 patients (26 males and 47 females; mean age, 44.16 years). The EQ-5D-5L values and visual analog scale (VAS) in patients with NF1 were 0.738 ± 0.137 and 69.93 ± 19.14, respectively. Both scores were significantly lower in patients with NF1 than in healthy volunteers (p 0.0001). The score for anxiety/depression was the highest among the five items of EQ-5D. Although we investigated differences in the index value and VAS between stage 2 or less and stage 3 or higher, there was no difference in the scores between groups related to certification criteria for the public medical expenses subsidy system. EQ-5D-5L is a valuable assessment tool for health-related QOL in patients with NF1, but it might not be sufficient for severity certification of NF1 in Japan. We would need the revision of the current certification based on the patients' demand in the future. Our findings might be useful for assessment of therapeutic effects and appropriate resource allocation in the care of patients with NF1.

Introduction Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients. Methods We conducted a multicenter, open-label, uncontrolled clinical trial in 94 Japanese patients with TSC. Patients applied the 0.2% sirolimus gel on their face or head twice daily for > 52 weeks (maximum 136 weeks for safety). The safety endpoints were the rate of adverse event (AE)-caused discontinuation (primary endpoint) and the incidence of AEs. The efficacy endpoint was the response rate of angiofibromas, cephalic plaques, and hypomelanotic macules. Results Among 94 enrolled patients (mean age, 21 years; range 3–53 years), the rate of AE-caused discontinuation was 2.1% (2/94 patients). Although application site irritation and dry skin occurred relatively frequently, none of the drug-related AEs were serious; most of the drug-related AEs resolved rapidly. The major drug-related AEs (≥ 5% in incidence) were application site irritation (30.9%), dry skin (27.7%), acne (20.2%), eye irritation (8.5%), pruritus (8.5%), erythema (7.4%), dermatitis acneiform (6.4%), and dermatitis contact (5.3%). The response rates of angiofibromas, cephalic plaques, and hypomelanotic macules were 78.2% [95% confidence interval (CI) 68.0–86.3%], 66.7% (95% CI 51.1–80.0%), and 72.2% (95% CI 46.5–90.3%), respectively. Conclusions The gel was well tolerated for a long time by patients with TSC involving facial skin lesions and continued to be effective. Trial Registration ClinicalTrials.gov identifier: NCT02634931.

Lichen nitidus and morphea are common diseases, but an associated localization of both lesions is rare. Here, we describe the first case of lesions distributed along Blaschko's lines. A 24-year-old Japanese woman was referred to our clinic for evaluation of band-like plaques of 18-months history on the right lateral side of her abdomen. In addition, multiple milky-white papules were seen within the plaques. Histopathological examination showed there was sclerosis in the lower half of the dermis and well-circumscribed, dense, papillary dermal lymphohistiocytic aggregations showing a so-called "claw clutching a ball." Immunohistochemical analysis revealed that the morphea and lichen nitidus had similar characteristics. We speculated that unique immunologic events led to the development of lichen nitidus and morphea in our patient.

Neurofibromatosis 1 (NF1) is a genetic disease characterized by cutaneous, neurological and osseous abnormalities. Approximately 20% of patients develop plexiform neurofibroma (PN), resulting in impaired quality of life. To evaluate distribution of diffuse PN on the body surface, a retrospective study was conducted for 354 patients with NF1 from 2007 to 2018 in Japan. We investigated a total of 40 patients with clinically apparent superficial diffuse PN. In the cases evaluated, 57.4% of the diffuse PN were located on the trunk, 19.2% the head and neck, 12.8% the lower limbs and 10.6% the upper limbs. Remarkably, 75.0% of the diffuse PN were located on the dorsal side. The frequency was significantly higher on the trunk than on the head and neck (P = 0.026). Our findings provide useful information for giving attention to the high possibility of diffuse PN on the dorsal side before progression in childhood and for future treatment in NF1.

Background Rhododendrol (rhododenol), an inhibitor of tyrosinase activity, is used as a skin-whitening component. Many cases of leukoderma after the application have been reported, termed rhododenol-induced leukoderma (RIL). The aim of this study was to clarify the pathogenesis of RIL morphologically through comparison with vitiligo. Methods We examined 14 cases of RIL and 15 cases of vitiligo using routine histopathology and immunohistochemistry. Thirteen cases of RIL, six cases of vitiligo and specimens of the RIL mouse model were evaluated by electron microscopy. Results There were common findings in RIL and vitiligo at the light-microscopic level: (a) vacuolar changes in the dermo-epidermal junction, (b) melanophages in the papillary dermis, (c) perifollicular lymphocyte infiltration, (d) loss or decrease of basal melanin pigment and (e) decrease of melanocytes in the lesions. The ultrastructural observations showed specific findings of RIL: (a) remaining melanocytes in depigmented lesions, (b) inhomogeneous melanization in melanocytes and (c) degenerated melanosomes in melanocytes. Some of the findings were observed in a RIL mouse model. Furthermore, it is notable that cell organelles of melanocytes were intact in our RIL cases. Conclusion Morphological changes of RIL targeting melanosomes in melanocytes without degeneration of organelles reflect the reversible clinical course of most cases.

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Neurofibromatosis 1 has various complications. To elucidate the frequency of neurofibromatosis 1-related major complications requiring medical intervention, a nationwide retrospective study was conducted of 3,530 patients with neurofibromatosis 1 registered from 2001 to 2014 in Japan. The ratio of certified patients requiring medical intervention (>stage 3) was 82%. Patients classified in the most severe grade experienced dermatological complications (71.8% of patients), neurological complications (38.1%) and bone complications (33.3%). In patients with dermatological manifestations, medical treatment was needed for cutaneous neurofibromas (58%), diffuse plexiform neurofibromas (31%) and malignant peripheral nerve sheath tumours (10%). Patients with neurological manifestations needed medical treatment mainly for brain tumours (53%) and intellectual disability (26%). Patients with bone manifestations needed medical treatment for pseudoarthrosis (9%), scoliosis (55%) and bone defects (16%). It is necessary for physicians to be aware of neurofibromatosis 1-related complications requiring medical intervention in order to provide appropriate care for patients with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a genetic disease characterized by cutaneous, neurological and osseous complications. Although clinical manifestations of NF1 are variable, there has been no report on evaluation of severity in patients with NF1. To elucidate the grade of severity of NF1, a retrospective study was conducted in 124 NF1 patients at the Department of Dermatology of Tottori University Hospital in 2007-2016. The DNB classification (dermatological, neurological and bone manifestations) in Japan was used for assessment. Based on our current epidemiological data, there were 55 patients (44.3%) in stage 1, 23 (18.6%) in stage 2, three (2.4%) in stage 3, one (0.8%) in stage 4 and 42 (33.9%) in stage 5. The grade of severity in patients with NF1 tended to be higher with aging. Remarkably, 61.8% of the patients in stage 5 had diffuse plexiform neurofibromas with functional disability. We should pay attention to diffuse plexiform neurofibromas that greatly affect quality of life in patients with NF1.

Skin grafting is a simple method for reconstruction of a large defect on the foot. Although skin grafting on the foot sometimes fails, it is not clear what factors influence the success rate of skin grafting. We analyzed data for 71 patients with skin cancer of the foot who underwent reconstruction of defects with skin grafting. The factors we evaluated were success rate of skin grafting, weight-bearing or non-weight-bearing area, immediate or delayed reconstruction, and whether a tie-over bolster was used or not. The success rates were higher in patients with lesions in non-weight-bearing areas than in patients with lesions in weight-bearing areas and in patients who underwent delayed reconstruction than in patients who received immediate reconstruction. On the other hand, the use of a tie-over bolster did not improve the success rate. In conclusion, delayed reconstruction is desirable if the lesion is located in a weight-bearing area.

Nagashima-type palmoplantar keratosis (PPK) is characterised by transgressive PPK with an autosomal recessive trait [1]. We describe a case of melanoma in a patient with Nagashima-type PPK.A 63-year-old Japanese woman presented with erythematous hyperkeratotic lesions on her palms and soles that had persisted since infancy. The lesions extended to the dorsal surfaces of the hands and feet and the Achilles tendon area, showing a whitish appearance after bathing. There was no family member with similar [...]

Basal cell carcinoma (BCC), the most frequent skin cancer, has been increasing in incidence. However, the characteristics of multiple BCC have not been clarified in Japan. Therefore, we conducted a retrospective study to elucidate the features of multiple BCC compared with solitary BCC. The study population consisted of 327 patients with histopathologically proven BCC who were referred to the Department of Dermatology in Tottori University Hospital between November 2006 and April 2016. Of the 327 patients, 304 (93.0%) had solitary BCC and 23 (7.0%) had multiple BCC. The mean age of the patients with solitary BCC was 74.7 years (range, 31-102) and that of patients with multiple BCC was 79.3 years (range, 63-91). There was a significant difference in mean age between the two groups (P = 0.01). Approximately four-fifths of the BCC were located on the head or neck in the total study population. In the group of patients with multiple BCC, the incidence of lesions on the head and neck was lower and that on the trunk was higher than those in patients with solitary BCC. There was a significant difference in the tumor site between the two groups (P < 0.0001). With respect to tumor histopathology, the ratio of superficial BCC was significantly higher in the group of patients with multiple BCC than in the group of patients with solitary BCC (P < 0.0001). In conclusion, we demonstrated that older age, truncal location and superficial histopathological type of tumor are features of multiple BCC in Japanese subjects.

Cutaneous adverse events are relatively common in patients being treated with molecular-targeted drugs. Paronychia is one of the cutaneous adverse events that influences the patient's quality of life because of pain, and it often affects anticancer treatments in severe cases. However, there are few effective treatments, especially for severe paronychia. Here, we present our experiences of treatment for paronychia due to oncology pharmacotherapy. Although we treated paronychia with various methods, only corticosteroid ointment and phenol chemical matricectomy significantly improved the paronychia. Dermatologists must perform appropriate and effective treatments for paronychia in order to enable patients to continue anticancer drug treatment without impairing their quality of life.

Background Mechanic's hands are a well-known symptom often associated with dermatomyositis and are similar to hand eczema clinically. Histopathology of them usually shows hyperkeratosis, focal parakeratosis, psoriasiform acanthosis, basal vacuolar changes and necrotic keratinocytes in the epidermis and upper dermal mucin deposition. However, there have been few comparative histopathologic evaluations of mechanic's hands and palmoplantar eczema. Methods We evaluated the histopathology of mechanic's hands in 6 patients with dermatomyositis who visited our hospital between 2006 and 2014 comparing with histopathology of 27 patients with palmoplantar eczema, retrospectively. Results As previously reported, hyperkeratosis, basal vacuolar change and necrotic keratinocytes were seen in all cases of mechanic's hands. Basal vacuolar change was not observed in any cases of palmoplantar eczema. Three cases of mechanic's hands demonstrated a characteristic finding, a pseudocheckerboard pattern, in the hyperkeratotic horny layer; there were areas of alternating parakeratosis and orthokeratosis in a vertical arrangement and these areas alternated with the completely orthokeratotic areas in a horizontal arrangement. This pattern has not been focused in mechanic's hands so far. Same pattern was also observed in four patients with palmoplantar eczema. Conclusion ‘Pseudocheckerboard pattern’ was not specific but may be a possible diagnostic clue for mechanic's hands.

A cutaneous metastatic tumor is relatively rare, and patients with such a tumor usually have a poor prognosis. Even if the metastases can be treated, the treatment cannot improve the prognosis. However, neglecting metastatic lesions sometimes results in a great deterioration of quality of life. Cutaneous metastatic foci are generally treated with chemotherapy and/or radiotherapy. On the other hand, surgical treatment is sometimes chosen for cutaneous metastases. In this study, we analyzed data for 40 patients with cutaneous metastatic tumors who received surgical treatment at Shizuoka Cancer Center between January 2009 and August 2014. Among these cases, lung cancer was the most common primary cancer and the craniocervical region was the most frequent metastatic site. Among the patients who died, the average duration to death after the operation was 186 days. We consider that resection of cutaneous metastatic tumors as palliative therapy is an appropriate therapeutic option if the patient's condition permits resection. Such treatment can improve quality of life for both the patients and their families.