Pediatric case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm.

A 5-year-old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK-positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK-positive ALCL limited to the skin and reviews the medical published work.

Notch signaling may be involved in the abnormal differentiation of epidermal keratinocytes in psoriasis.

Localization of each keratin isoform differs among epidermal layers. Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells express keratin 10 (K10) in normal skin. Notch signaling is essential for keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2 in the basal cell layer and Notch3 in basal cell and spinous cell layers in normal epidermis. It has been poorly elucidated how localization and expression levels of Notch molecules are related to epidermal molecular markers K10 and K14 in psoriatic skin with abnormal differentiation of epidermal tissue. This study aimed to investigate the relationship between abnormal differentiation of epidermal cells in psoriatic skin and expression of Notch molecules. We investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal layer while it and K10 were co-expressed in some middle suprabasal layer cells. Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared with normal epidermis. These data suggest that decrements in these Notch molecules might cause aberrant expression of K10 and K14 leading to anomalous differentiation of the epidermis in psoriatic lesions.

A Case of Delayed Flare-up Allergic Dermatitis Caused by Jellyfish Sting.

A 7-year-old boy, taking lessons at a yacht school at Enoshima in Kanagawa prefecture in Japan, recognized a linear eruption on his left lower leg during practice in August 2012. As it gradually enlarged, he visited a local medical clinic. The eruption initially improved with topical treatment but exacerbated in October of the same year. Although topical treatment was started again, there was minimal improvement, so the patient visited our hospital in December. At his first visit, he had a hard linear nodule on his left lower leg, and papules with excoriation were scattered over the lower limbs. Considering eczema, topical steroid treatment and occlusive dressing technique were started but the nodule remained. Based on the clinical course, clinical features, and laboratory findings, the lesion was considered to be delayed flare-up allergic dermatitis caused by a jellyfish sting [1].

A case of foreign body granuloma induced by subcutaneous injection of leuprorelin acetate─clinical analysis for 335 cases in our hospital─.

We experienced a case of granuloma formation by subcutaneous injection of leuprorelin acetate for treatment of prostate cancer. This patient was an 80-year-old man visiting the clinic of gastroenterological surgery as an outpatient after gastric cancer surgery with a one-week's history of rash on the abdomen. Based on the history of gastric cancer and prostate cancer, though ultrasonography and CT were performed, the possibility of metastatic skin tumor could still not be ruled out. Finally, finding of a foreign-body granuloma in the subcutaneous adipose tissue was recognized histological. Then, an interview with the patient revealed that he had received subcutaneous injection of a 3-month depot formulation of leupurorelin acetate at the site of the lesion about two months earlier. Among urologists, as side effects for treatment, foreign body granuloma induced by subcutaneous injection of leuprorelin maybe well known. Therefore, it is tried to analyze as to clinical findings, especially granuloma formation for 335 cases that received leuprorelin acetate treatment at our hospital. In this report, we analyzed reported case and 335 cases that received leuprorelin acetate treatment at our hospital and summarized the cases that developed the granuloma formation by it.

HLA-C*12:02 is a susceptibility factor in late-onset type of psoriasis in Japanese.

Psoriasis is thought to be a multifactorial disease triggered by both genetic and environmental factors. The HLA-C locus on chromosome 6p21.33 remains the strongest susceptibility candidate locus in psoriasis. The strong association between psoriasis and the HLA-Cw6 allele has been well documented in various races. It is known that psoriatic patients with early onset are more likely to be familial and associated with HLA-Cw6. Familial occurrence of Japanese psoriasis is smaller than other populations. Furthermore, males are predominant over females in Japanese psoriasis. We investigated the relation between HLA-C alleles and age of onset, and in each gender for Japanese psoriasis, and discuss male predominance in the incidence of psoriasis in Japan. Four hundred forty six unrelated Japanese patients with psoriasis vulgaris and 557 sex- and age-matched unrelated Japanese healthy controls were investigated by genotyping. We confirmed the association between early-onset type of psoriasis with HLA-C*06:02 allele in Japanese. In addition, we detected the association between the late-onset type of psoriasis and the HLA-C*12:02 allele in Japanese. No significant differences in allele frequency were observed between females and males. Our results suggest that there is no genetic factor effect on male predominance in Japanese. In contract, the effect of environmental risk factors on the onset of Japanese psoriatic patients is stronger in males than in females. As a result, male predominant in psoriasis may occur in Japan.

Case of generalized pustular psoriasis with end-stage renal disease successfully treated with granulocyte monocyte apheresis in combination with hemodialysis.

Granulocyte monocyte apheresis (GMA) is an extracorporeal apheresis instrument that removes activated neutrophils and monocytes. Generalized pustular psoriasis (GPP) is characterized by neutrophil infiltration into the epidermis that causes Kogoj's spongiotic pustule. Thus, GMA is one of the useful therapies for GPP, and it was approved for the treatment in 2012 in Japan. Herein, we report a case of GPP with end-stage renal disease (ESRD) successfully treated with GMA in combination with hemodialysis (HD). A 54-year-old Japanese female visited our outpatient clinic because of erythema with pustules on her trunk and extremities over the past 4 months. Histopathological examination showed an intraepidermal pustule filled with numerous neutrophils and spongiosis. These findings led to the diagnosis of GPP. She had ESRD and had been treated with HD twice a week for approximately 4 years. During maintenance HD twice a week, weekly GMA was started at Tokai University Hospital. The skin symptoms disappeared after five administrations of GMA. We suggest that GMA is an effective therapy for GPP patients with ESRD who are treated with HD.

A novel small compound accelerates dermal wound healing by modifying infiltration, proliferation and migration of distinct cellular components in mice.

BACKGROUND: Impaired wound healing in skin ulcer is one of the major medical issues in the aged society. Wound healing is a complex process orchestrated by a number of humoral factors and cellular components. TGF-ß is known to stimulate collagen production in dermal fibroblasts while inhibiting proliferation of epidermal keratinocyte. A screening of small compounds that suppress type I collagen production in fibroblasts has identified HSc025 that antagonizes the TGF-ß/Smad signal. OBJECTIVE: We examined the effects of HSc025 on dermal wound healing and elucidated the underlying mechanisms. METHODS: Effects of HSc025 on the wound closure process were evaluated in a murine full-thickness excisional wound healing model. Cell proliferation and migration were estimated using primary cultures of human keratinocytes and fibroblasts. Comprehensive analyses of gene expression profiles were performed using untreated and HSc025-treated fibroblasts. RESULTS: Oral HSc025 administration suppressed macrophage infiltration and accelerated wound closure as early as at day 2 after the dermal excision. Treatment of cultured keratinocytes with HSc025 counteracted the inhibitory effects of TGF-ß on cell proliferation and migration. On the other hand, HSc025 stimulated migration, but not proliferation, of dermal fibroblasts independently of TGF-ß. Experiments using an artificial dermis graft revealed that HSc025 stimulated migration of collagen-producing cells into the graft tissue. A cDNA microarray analysis of untreated and HSc025-treated fibroblasts identified pirin as a critical mediator accelerating fibroblast migration. CONCLUSION: HSc025 accelerates wound healing by modifying infiltration, proliferation and migration of distinct cellular components, which provides a novel insight into the therapy for intractable skin ulcer.

Case of exogenous insulin-derived acanthosis nigricans caused by insulin injections.

A 73-year-old male with diabetes mellitus had been treated with insulin for six years. He developed a solid mass on his left lateral of the abdomen at the insulin injection site. A firm subcutaneous mass with dark-red erythema was overlaid by dark-brown keratinized plaques. On histological examination of the mass, keratin proliferation and epidermal papilloma were observed. There were four previously reported cases of acanthosis nigricans that were considered to be caused by continuous injections of insulin. Using immunohistochemistry, in our case the findings were positive in the basal epithelial and prickle cell layers when the patient's lesion was dyed with insulin-like growth factor (IGF)-1 antibody. The coexistence of dermal IGF-1 receptor and acanthosis nigricans found in our patient has not been reported previously, to our knowledge.

Case of disseminated vesicles of herpes zoster developing one day before the onset of local eruption in a hospitalized immunocompromised patient.

Disseminated herpes zoster is not rare in immunocompromised patient. It is defined as at least 20 lesions in multiple dermatomes that occur within a week of the onset of local eruption. Herein, we report that a case of disseminated vesicles of herpes zoster (HZ) that developed one day before the onset of local eruption in an immunocompromised patient. A 44 year-old Japanese male, who had been in the hospital with acute myelocytic leukemia, developed disseminated hemorrhagic vesicles of 5 to 10 mm in diameter. The next day, grouped vesicles, including hemorrhagic vesicles erupted on the right side of the second to third cervical (C2-C3) dermatomes. At this point, the diagnosis was made as disseminated herpes zoster. The activation of varicella-zoster virus (VZV) is believed to be due to waning of VZV-specific memory T cell responses. In our case, the memory immunity to VZV which had been increased by last episode of HZ might affect on the appearance of skin eruptions.

Diagnostic usefulness of findings in Doppler sonography for amelanotic melanoma.

To evaluate the diagnostic usefulness of Doppler sonography for amelanotic melanoma (AM), the correspondence between the findings of dermoscopy and Doppler sonography was investigated in AM in comparison with other hypopigmented tumors. Seven cases with AM and 11 cases with squamous cell carcinoma (SCC), 10 cases with non- or hypopigmented basal cell carcinoma (NP-BCC) and six cases with eccrine poroma (EP) as hypopigmented tumors were investigated. EP is readily recognized by differences from AM and SCC based on a single vertical and non-torvtuous vessels. NP-BCC is distinguished from AM based on tortuosity running in a vertical direction. Though findings of tortuosity in vessels and heterogeneity of vessel size are recognized both in AM and SCC: (i) abundant blood flow was recognized more clearly in AM; (ii) total blood flow was more than 40% in most cases of AM (average, 60.9%); and (iii) more vessels which flow into a tumor are found in AM (85.7%). There is no relationship between dermoscopic findings of vessel types and Doppler sonography findings of vessels. In this study, the diagnostic usefulness of the above-mentioned specific findings in examination may suggest using Doppler sonography for AM as one non-invasive method.

Long-term efficacy of psoriasis vulgaris treatments: analysis of treatment with topical corticosteroid and/or vitamin D3 analog, oral cyclosporin, etretinate and phototherapy over a 35-year period, 1975-2010.

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.

Random skin biopsy of intravascular large B-cell lymphoma: a case report.

A 72-year-old woman visited our clinic with fever of unknown origin above 38°C and arthralgia from 7 months before. Her symptoms recurred as oral steroid was reduced. Random skin biopsy was carried out from five points. One of the five specimens taken from abdomen revealed large atypical lymphoid cells in the vascular space of subcutaneous fat. Immunohistochemical analysis showed that these cells were positive for CD20, CD79a, bcl-2, bcl-6 and MUM-1. From these findings, a diagnosis of intravascular large B cell lymphoma was made.

Psoriasis affects patient's quality of life more seriously in female than in male in Japan.

OBJECTIVE: The aim of this study was to assess the quality of life (QOL) of patients with psoriasis in Japan using Dermatology Life Quality Index (DLQI). Furthermore, we had evaluated the correlation between DLQI and clinical severity of psoriasis. METHODS: The Japanese version of DLQI was used to assess the QOL of patients. Psoriasis area and severity index (PASI) and Itch visual analogue scale (VAS) were used to assess clinical severity of psoriasis. RESULTS: The subjects were 102 Japanese patients with mild to severe psoriasis (77 males, 25 females, mean age 55.2 ± 14.2). There were no statistically significant differences in age, PASI, and itch VAS between male and female. The mean DLQI scores in total were 3.6 ± 3.2 in male and 7.2 ± 1.2 in female. The mean total DLQI scores in female were higher than that in male (p = 0.0016). Significant correlation was observed between DLQI scores and PASI score (p < 0.001) or itch VAS score (p < 0.001). CONCLUSIONS: The mean total DLQI scores in female were significantly higher than that in male. Also, we confirmed the correlation between DLQI and clinical severity of psoriasis. These findings suggest that QOL assessment plays a greater role in females than in the males, when assessing the severity of psoriasis.

A case of chromomycosis treated by surgical therapy combined with preceded oral administration of terbinafine to reduce the size of the lesion.

Chromomycosis is a chronic fungal disease of the skin and subcutaneous tissues caused by a group of dematiaceous black fungi. Small lesions can be removed with excision, but other cases are difficult to treat. We report a case of chromomycosis caused by Fonsecaea pedrosoi (F. pedrosoi). The case involved a 74-year-old man, who had noted a lesion on the back of the right thigh, that was gradually enlarging and reaching up to 30 cm in diameter, in 20-years. From microscopic examination, sclerotic cells were seen. We diagnosed this case as chromomycosis caused by F. pedrosoi on mycological examination. The patient was initially treated with oral terbinafine (250 mg/day) as the lesion was very large. After the 18 months treatment, the size of the lesion reduced to 1 cm, then the remaining lesion was excised.

A novel splicing variant of CADM2 as a protective transcript of psoriasis.

CADM2, a candidate gene for psoriasis, was identified by a genome-wide association study using microsatellites in the Japanese population (561 cases and 561 controls). Moreover, haplotype analysis included an additional 68 SNPs and indicated that a 110-kb haplotype block was detected for the protective risk haplotype of psoriasis. We also identified an initial exon of novel splicing variants in this haplotype block. A functional analysis by qRT-PCR using RNAs from the blood of 56 cases and 64 controls significantly demonstrated an inverse correlation between expression frequencies in a novel splicing variant and the number of alleles associated with psoriasis. To confirm these results, we must perform replication studies using other ethnic groups and more functional analysis particularly for skin tissues.

A novel case of nocardiosis with skin lesion due to Nocardia araoensis.

Nocardiosis is caused by gram-positive aerobic actinomycetes that live in soil and are known to be responsible for opportunistic infections. The condition mostly affects the lung, brain or skin. Here, we present a 24-year-old Japanese woman who had had systemic lupus erythematosus since the age of 20 years, and lupus nephritis since the age of 23 years. She developed cutaneous lymph duct-type nocardiosis due to Nocardia araoensis while on immunosuppressant therapy. The patient had cutaneous findings from the right inguinal region to the right lower thigh and did not have lesions on the rest of the body. Minocycline and co-trimoxazole were co-administrated, and her condition improved. To our knowledge, this is the first case in which N. araoensis was detected by analysis on rRNA base sequence in skin lesions.

Multiple Bowen's disease in a patient with a history of possible arsenic exposure: a case report.

A 81-year-old man with a patch of scaly erythema on his scrotum visited Hiratsuka Kyosai Hospital in June 2006. Reddish, scaly plaques, which were untreated, were present on his back and lower legs since 1999. Pathological examination of the lesions on the scrotum revealed Bowen's disease; therefore he was referred to our clinic for further treatment. During his visit Tokai University Hospital, irregularly bordered scaly erythematous patches were observed on his back, left arm, right knee, and right foot, sizing from 2 to 4 cm in diameter. He was treated with phenol and liquid nitrogen cryotherapy; however, he dropped out of clinic after receiving treatment for a year. At this point, most lesions were cured and only scars remained. In June 2009, he revisited Tokai University Hospital, and this time, multiple scaly erythematous patches were noted on his back and both the arms and legs. The results of the biopsies of 4 lesions obtained from the back, right arm, right knee, and the right foot led to the diagnosis of multiple Bowens' disease. During the inquiry, we learned that since birth, he has resided in Hiratsuka City and had often used water from wells. We researched the possibilities of water and soil contaminations in the Hiratsuka area.

Protein oxidative damage and heme oxygenase in sunlight-exposed human skin: roles of MAPK responses to oxidative stress.

Oxidative stress derived from ultraviolet (UV) light in sunlight induces different hazardous effects in the skin, including sunburn, photo-aging and DNA mutagenesis. In this study, the protein-bound lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8OHdG) were investigated in chronically sun-exposed and sun-protected human skins using immunohistochemistry. The levels of antioxidative enzymes, such as heme oxygenase 1 and 2, Cu/Zn-SOD, Mn-SOD and catalase, were also examined. Oxidative stress is also implicated in the activation of signal transduction pathways, such as mitogen-activated protein kinase (MAPK). Therefore, the expression and distribution of phosphorylated p38 MAPK, phosphorylated Jun N-terminal kinase (JNK) and phosphorylated extracellular signal-regulated kinase (ERK) were observed. Skin specimens were obtained from the surgical margins. Chronically sunlight-exposed skin samples were taken from the ante-auricular (n = 10) and sunlight-protected skin samples were taken from the post-auricular (n = 10). HNE was increased in the chronically sunlight-exposed skin but not in the sunlight-protected skin. The expression of heme oxygenase-2 was markedly increased in the sunlight-exposed skin compared with the sun-protected skin. In contrast, the intensity of immunostaining of Cu/Zn-SOD, Mn-SOD and catalase was not different between the two areas. Phosphorylated p38 MAPK and phosphorylated JNK accumulated in the ante-auricular dermis and epidermis, respectively. These data show that particular anti-oxidative enzymes function as protective factors in chronically sunlight-exposed human skin. Taken together, our results suggest (1) antioxidative effects of heme oxygenase-2 in chronically sunlight-exposed human skin, and that (2) activation of p38 MAPK may be responsible for oxidative stress.