A 69-year-old Japanese male had pustulosis palmaris et plantaris with precordial pain. Pustules had expanded over his whole body. His condition was satisfactory and he did not have a fever during his illness. Histologically, monolocular pustules were detected under the horny layer, while the epidermis around the pustules did not have any spongiosis and there was no presence of vasculitis. His blood test showed an increase of inflammatory findings. Therefore, we suspected that the patient had focal infection, and an antimicrobial agent was administered. The eruption improved immediately. However,when it recurred, we prescribed etretinate and administered an antimicrobial agent once more. A provocation test of his tonsil was positive and enucleation of the tonsil was performed. Differential diagnosis of pustulosis palmaris et plantaris with widespread distribution of the pustules is difficult. When a focal infection is suspected, we suggest that administration of an antimicrobial agent is one of the recommended therapies.

A 63-year-old woman presented with a hard and painful, subcutaneous plaque on the right upper arm. Excisional biopsy on the plaque revealed sclerotic changes and partially saponification in the adipose tissue. Histopathological examination showed multiple and irregular shaped cysts of variable sizes were characteristically lined by a thin amorphous eosinophilic layer. Accordingly, a diagnosis of membranous lipodystrophy was made. The walls of some cysts had anuclear and nuclear portions, and were therefore considered to be initial lesions. There were multiple vascular thrombi around the membranocystic changes. These pathologic observations suggest that membranous lipodystrophy may be a result of ischemic injury to the adipose tissue.

A 41-year-old Japanese woman presented with painful vulvar edema and ulcerations that had been ongoing for a year. She had been treated at several clinics, but her symptoms persisted. She had a past history of gastrointestinal Crohn's disease. A skin biopsy was performed from a painful ulcer. Histological examination showed ulceration and chronic inflammatory cell infiltration, as well as sarcoidal granulomas in the dermis with epithelioid histiocytes and multinucleated giant cells without caseation. Based on her cutaneous manifestations and histological findings, we diagnosed her with Crohn's disease of the vulva. She was first treated with adalimumab and her vulvar symptoms improved. However, she paradoxically developed psoriasiform cutaneous eruptions and had to discontinue adalimumab. We then treated her with oral metronidazole, and she achieved almost complete healing of the edema and ulcerations in the vulva. To date, nearly 100 cases with Crohn's disease of the vulva have been reported in the English literature. However, it is a rare and unrecognized entity in Japan, and diagnosis is difficult due to its rarity and non-specific clinical features. The present case suggests that we need to consider Crohn's disease of the vulva as a differential diagnosis for vulvar edema and ulcerations in female patients. This is the first case of Crohn's disease of the vulva successfully treated with oral metronidazole in Japan.

We describe a case of a 15-year-old man complaining of limb pain and hypohidrosis. He began experiencing the pain at 11 years old, and it gradually became stronger. Although he had no skin lesions typical of Fabry disease, we decided to perform a blind skin biopsy on his buttock for diagnostic purposes. The findings of light microscopy revealed the presence of some vacuoles in the secretory unit of the eccrine sweat glands in the deep dermis. Electron microscopy demonstrated the presence of some electron-dense lamellar inclusions in the cytoplasm of endothelial cells. His α-galactosidase A activity was below the normal range. Taken together, we diagnosed classic Fabry disease. His mother also had hypohidrosis, progressive sensorineural deafness, and abnormal findings on electrocardiography. Since both of them showed the same mutation of the α-galactosidase A gene (exon 7, C. 1212-1214 del AAG), they were diagnosed as Fabry disease. Here, we showed that electron microscopy of a blind biopsy is a useful tool for the diagnosis of Fabry disease. We should now examine which part of the skin is the most appropriate location for performing blind biopsy on patients with suspected Fabry disease.

An 8-day-old female baby visited our clinic with erythema, bullae formation, scale, and crust on the whole body, mainly on the extremities. She was born at full term by a natural birth. Histopathological examination of the dorsum of the right great toe revealed severe hyperkeratosis and acanthosis with epidermal edema. In the upper dermis there were heavy perivascular infiltrations of lymphocytes, including eosinophils. We applied only white soft paraffin onto her whole body. The erythema gradually disappeared and linear verrucous papules appeared on the extremities after 1 month. At 5 months,reticular and spiral pigmentation on the whole body became her main complaint. In addition, she had a vasa sanguinea retinae aberration in the left eye (vascular expansion and tortuosity with aberrant anastomosis) and retinal apoplexy. The vascular expansion and tortuosity were improved by photocoagulation. We thought that this was a typical case of Bloch-Sulzberger syndrome (also known as incontinentia pigmenti), in which we observed the eruptions from the inflammatory stage to the pigment stage.

A 41-year-old female presented with red papules on her right cheek, which had appeared in her childhood. A biopsy specimen of one lesion revealed an increased amount of dilated small blood vessels and fibrosis around the hair follicles and sebaceous glands, which are characteristic features of angiofibroma. She also had a shagreen patch on the right lowen leg,and two renal angiomyolipomas in the right kidney were found by a computed tomography scan. Therefore, she was diagnosed with tuberous sclerosis (TSC). Nineteen cases of unilateral angiofibromas of the face were reported from 1987 to 2016. In 5 of those cases, other manifestations of TSC were found, and 2 of the 5 cases fulfilled the diagnostic criteria for TSC. Important manifestations of TSC such as angiomyolipoma and lymphangiomyomatosis develop during adulthood, but angiofibromas appear during childhood. Therefore, long term follow up is needed when angiofibromas are observed, even if they are distributed unilaterally.

A 36-year-old woman presented to us with a red, soft, and mobile skin mass on the back measuring 2.3×3 cm in size. Histopathologically, the mass was well-demarcated and contained nests of various sizes comprised of follicular germinative cells, as well as some nests comprised of matrical cells, shadow cells, and inner root sheath cells with trichohyalin granules. In addition, enlargement of the infundibulum and isthmus of the hair follicle was observed. Based on these findings, the patient was diagnosed as having panfolliculoma. This case has a relatively rare condition, showing a nodular type histopathologically and arising from the trunk, which is an unusual site for this disease.

We report two cases of umbilical tumor. Case 1 : A 46-year-old woman noticed a growing nodule in her navel that grew larger over the course of more than one year and started to bleed occasionally. On her first visit, she presented with a 25×20 mm light red-brown solid nodule in the umbilical fossa. It was not clear whether the tumordirectly communicated with the abdominal cavity on computed tomography imaging. Skin biopsy confirmed the diagnosis of cutaneous endometriosis, and so we surgically resected the lesion. Case 2 : A 73-year-old man had an umbilical tumor that often festered. On his first visit, he presented with a 15×15 mm dark violet solid nodule in the umbilical fossa. The tumor was resected, and histopathological examination showed a cystic lesion surrounded by scar tissue composed of fibroblasts and collagen fibers. He underwent laparoscopic cholecystectomy, and we concluded that the scar became hypertrophic with fistula formation. These findings confirmed the diagnosis of an epidermoid cyst covered with scar tissue. Before planning the surgical resection of an umbilical tumor, careful preoperative examination is necessary to evaluate the extent of tumor invasion, especially its communication with the abdominal cavity.

A 63-year-old Japanese woman was referred to our hospital for the treatment of a pigmented macule on the chest, which was histopathologically diagnosed as basal cell carcinoma (BCC) at another clinic. The patient noted the macule 14 years ago,and it had gradually increased in size. Physical examination revealed multiple brown macules (nine in total) distributed on the head and trunk ; all of them were later confirmed as BCC after excision. There are several conditions that can predispose patients to BCC, such as nevoid basal cell carcinoma syndrome, xeroderma pigmentosum, and multiple sebaceous nevus ;however, in this case, the patient did not suffer from any such known predisposing condition.

Actinic keratosis (AK) lesions have been reported to regress when they are protected from chronic exposure to sunlight. To determine the effect of sunscreen cream on AK lesions, we had three patients, each of whom had an histopathologically diagnosed AK lesion, use sunscreen cream 3 times/day for 83 to 109 days, and we compared the lesions clinically,histopathologically, and immunohistochemically before and afterwards. After the sunscreen use, the AK lesions were improved clinically and histopathologically. In addition, immunostaining showed that the proportions of p53- and Ki67- positive cells among all epidermal cells in the three AK cases decreased after the sunscreen cream use. Ultraviolet light (UV)irradiation acts as a tumor initiator and promoter, and the p53 gene is the most frequent target of genetic alterations in UV-induced carcinogenesis. We speculated that the tumor-promoting action of UV was prevented by the use of a sunscreen cream, leading to the suppression of both the proliferation of AK cells and the expression of p53 protein, and then the AK cells differentiated to normal squamous cells. Taken together, our results showed that AK lesions were improved clinically,histopathologically, and immunohistochiemically by several months of sunscreen use.

A 78-year-old woman presented with a 3-month history of febrile erythroderma. Physical examination revealed diffuse erythema with scale over her whole body including the scalp and face. She also showed swelling of the axillary lymph nodes. Serum anti-HTLV-1-antibody was present. Histological examination of a biopsy specimen showed an infiltration of CD25- positive atypical lymphocytes in the epidermis, including numerous CD8-positive lymphocytes. Furthermore, there were vacuolar changes in the basal epidermis and scattered apoptotic keratinocytes, resembling a graft versus host disease (GVHD) reaction. A PCR analysis of the skin biopsy specimen revealed a monoclonal HTLV-1 proviral load, although a Southern blot analysis failed to prove the monoclonality. Adult T cell leukemia/lymphoma (ATLL) cells in the peripheral blood were never observed during the clinical course. It is considered that an intense response of the patient's cytotoxic T lymphocytes to the ATLL cells inhibited their proliferation and led to a GVHD-like reaction, resulting in erythroderma without a preceding ATLL specific skin eruptions.

We report a rare case of streptococcal necrotizing soft tissue infection in the lower leg caused by Group G Streptococcus infection. A 61-year-old female had idiopathic lymph edema of the left leg. She complained of swelling and burning of the leg after pharyngitis and flulike symptoms with high fever. Laboratory examinations showed elevated white blood cells (11110/μl), creatine phosphokinase (1781 U/l), and C-reactive protein (CRP ; 25.86 mg/dl). Magnetic resonance imaging (MRI) T1-weighted imaging showed a high-intensity area in the muscle, suggesting muscle necrosis with hemorrhage. MRI T2-weighted imaging also showed the presence of a high-intensity area in subcutaneous tissue and superficial fascia. Over a few hours, redness and purpura of the left leg progressed rapidly. We performed a fasciectomy and debridement 7 hours after admission. At the fasciectomy, the subcutaneous tissue, superficial fascia and muscle appeared necrotic with a large amount of translucent fluid. Considering the findings that (1) group G Streptococcus was isolated from blood cultures, (2) a blood coagulation test suggested disseminated intravascular coagulation, and (3) deep soft tissue infection or necrotizing fasciitis was observed, we diagnosed a toxic shock-like syndrome. She was treated with penicillin, clindamycin, and meropenem antibiotics in combination with intravenous immunoglobulin administration. Because this treatment was insufficient to improve the elevated CRP, we again performed MRI analysis to evaluate whether other areas of necrotic tissue remained in the leg. MRI T1-weighted imaging still showed the presence of a high-intensity area in the gastrocnemius, suggesting that the streptococcal infection had resulted in necrosis of the muscle. We performed debridement of the necrotic gastrocnemius and tibialis anterior muscles, which successfully improved her general condition and laboratory data. Subsequently, she underwent split-skin grafting and was discharged.

We report here a case of dermal cutaneous alternariosis in a 65-year-old man, who was taking systemic steroids and cyclosporin for pemphigus vulgaris. The patient also had steroid-induced diabetes mellitus. A reddish-brown nodule 2 cm in diameter developed on the left thigh. Diagnosis was based on histopathological examination, periodic acid-Schiff staining, and positive results of fungal culture. Treatment with oral itraconazole and reduction of immunosuppressive drugs were effective. We review the literature of dermal cutaneous alternariosis reported in Japan from 2000 to 2015. Including our case, only 13 cases have been reported. Cutaneous alternariosis should be considered in the initial diagnosis of skin lesions,such as small nodules or granulomatous lesions, particularly in immunocompromised patients.

Pruritus is a frequently observed symptom in chronic cholestatic liver diseases. However, only a few reports have been published regarding the incidence and intensity of liver disease-associated pruritus. We assessed itching sensation by a questionnaire survey of 71 patients with chronic liver diseases including primary biliary cirrhosis, chronic hepatitis B, and chronic hepatitis C. In this study, half of the patients (36/71) suffered from itching sensation. Itching was frequently observed in the patients with primary biliary cirrhosis or liver cirrhosis due to hepatitis B or C. In patients with hepatitis C,pruritus was more frequently detected in the patients with liver cirrhosis than in those without it. The mean value of visual analogue scale measurements of pruritus was 19.2±3.4 during the daytime and 25.9±4.1 during the night in all of the patients who had pruritus (n = 36). Seventeen of the 36 patients (47.2％) with itching were treated with anti-histamines and topical ointments. Although 82.4％ (14/17) of these patients experienced some limited alleviation of their itching sensation, complete suppression of pruritus was achieved in none of them. The clinical use of a κ-opioid receptor agonist that became available in 2015 in Japan may be a promising approach for treating liver disease-associated pruritus.

A new preparation of a cream containing ellagic acid at 0.5％, ascorbic acid 2-glucosid at 2％ and liquiritin at 0.1％ (AAGE cream) was applied twice a day on the skin lesion of melasma, pigmented cosmetic dermatitis (PCD), the dirty neck of a patient with atopic dermatitis, solar lentigo (SL), etc. The effect was observed for 3 to 6 months through macroscopical observation and photographs from the same angles. AAGE cream proved to be effective on melasma in 63 out of 68 cases (92.6％). It was effective 22 out of 62 cases (35.5％) on SL, in all 4 cases (100％) on PCD and 18 out of 19 cases (94.7％) on post inflamatory pigmentation. No side effects were seen in all cases, i.e., no sensitization, no irritant dermatitis and no leukoderma. It was concluded that AAGE cream is effective enough and quite safe.