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Background Voiding dysfunction is a rare but important complication of lumbo-sacral herpes zoster. Although the symptoms are transient, the clinical impact on immunocompromised patients cannot be overlooked. Methods To clarify the time course of voiding dysfunction in herpes zoster, 13 herpes zoster patients with voiding dysfunction were retrospectively analyzed. Results Of 13 patients, 12 had background disease, and six of these were hematopoietic malignancies; four of these patients were hematopoietic stem cell transplant (HSCT) recipients. Ten patients had sacral lesions, two had lumbar, and one had thoracic lesions. Interestingly, patients with severe rash, or with hematopoietic malignancy had later onset of urinary retention than did patients with mild skin symptoms (Mann–Whitney U analysis, P = 0.053) or with other background disease (P = 0.0082). Patients with severe skin rash also had longer durations (P = 0.035). In one case, acute urinary retention occurred as late as 19 days after the onset of skin rash. Conclusions In immune compromised subjects, attention should be paid to patients with herpes zoster in the lumbo-sacral area for late onset of acute urinary retention even after the resolution of skin symptoms.

Background The entire minichromosome maintenance (MCM) family (MCM2–7) play roles in the initiation and elongation of DNA replication. Many studies have demonstrated that MCM proteins may be better indicators of a wide variety of proliferative or cancer cells in malignant tissues. Objectives To characterize the pattern and frequency of MCM5 expression in proliferative and malignant skin diseases in comparison with those of proliferating cell nuclear antigen (PCNA). Methods Twelve normal skin specimens, 12 specimens of psoriasis, 21 specimens of bowenoid papulosis (BP), 16 specimens of Bowen's disease (BD), 38 specimens of skin squamous cell carcinoma (SCC), and 11 specimens of basal cell carcinoma (BCC) were subjected to immunohistochemical staining for MCM5 and PCNA. Results MCM5 protein was expressed in the lower layers of epidermis in psoriasis, while MCM5 protein were present throughout the tumor cells in BP, BD, and moderately/poorly differentiated SCC. MCM5 protein was preferentially expressed in the periphery of well-differentiated SCC or bigger nests of BCC, although some small nests of BCC seemingly showed diffuse staining patterns. The percentages of MCM5-positive cells were 15.7% in normal skin, 21.8% in psoriasis, 75.9% in BP, 83.8% in BD, 63.5% in well-differentiated SCC, 77.5% in moderately differentiated SCC, 79.8% in poorly differentiated SCC, and 21.2% in BCC in average. Well-differentiated SCC showed a significantly lower percentage of positive cells than did moderately differentiated SCC or poorly differentiated SCC. MCM5 staining basically show a similar staining pattern to that of PCNA, but more cells tended to be stained with MCM5 than with PCNA. Conclusions Our results demonstrate pattern and frequency of MCM5 expression in various skin diseases and suggest that MCM5 may be a useful marker to detect cell proliferation in skin tissue sections.

We present a case of a 62-year-old woman with marked purpura, first appearing on both legs, then spreading over the whole body, including the face. At presentation, the patient was thought to have Henoch-Schonlein purpura. However, a skin biopsy from a purpuric lesion revealed prominent infiltrations of atypical lymphocytes into the papillary dermis and marked extravasation of erythrocytes through the epidermis and upper dermis. Antibody to human T-lymphotropic virus type 1 (HTLV-1) was present in the serum and samples from skin lesions revealed HTLV-1 proviral DNA integration, as well as a clonal T-cell receptor Cbeta1 gene rearrangement. We therefore diagnosed this case as adult T-cell leukemia/lymphoma (ATL), and the purpuric lesions as ATL-specific. Soon after the initiation of chemotherapy, these purpuric lesions began to resolve with pigmentation.

閉鎖陰圧療法は，創面を密封し持続的に陰圧をかけることにより，創傷の治癒を早める新しい潰瘍の治療法である。我々はこの方法を植皮術の際の植皮片の圧迫固定に用いることで良好な成績を得たので，その経験をここに報告する。植皮を行ったのは5症例9件の潰瘍で，いずれにおいても良好な生着が得られた。本方法は，吸引することによりポケット形成を抑制し，複雑な形の植皮床にも固定が可能で，持続的にドレナージすることで感染しにくく，簡単な手技で一定の効果が得られ，創の管理が容易であった。皮膚科領域の植皮の固定方法として適した方法と考えられた。

Adherence is defined as the extent to which a person's behavior corresponds with recommendations from health care providers. Adherence to treatment is an important factor for a good therapeutic outcome.This study aimed to examine the adherence of patients with tinea pedis and to clarify the factors related to it.We assessed medication adherence for oral and topical drugs using a translated version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with other background factors in 445 Japanese patients with tinea pedis, using a questionnaire in a web-based monitoring system.Overall, high, medium and low adherence rates as assessed by MMAS-8 were 8.7%, 31.7% and 59.6% for oral medication, and 8.6%, 17.4% and 74.0% for topical medication, respectively. The adherence level was significantly higher for oral medication than for topical medication. Subgroup analyses showed that the adherence level for topical medication was significantly higher when topical and oral medications were used in combination than when topical medication was used alone. A low adherence level was shown in employed patients, those for whom their oral medication had not been effective and those with topical medication who had visited their hospital less often than once every six months.Patient adherence to therapy can be effectively improved by selecting highly effective medication while considering the prescription of topical and oral antifungal medications concomitantly, by carefully selecting a therapy plan for employed patients and by encouraging patients to visit their doctor regularly.

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human-recombinant anti-interleukin-17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open-label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co-medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non-responders were up-titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as "worsened", "no change", "minimally improved", "much improved" or "very much improved". Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end-point) with CGI evaluated as "very much improved" (n = 9) and "much improved" (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52-week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP.

Neurofibromatosis type 1 (NF1) has many reported clinical characteristics. We previously found that NF1 patients (especially men) had lower body mass index (BMI) than controls, but the reason has not been elucidated. To address this issue, a retrospectively case-control study was conducted. Anthropometric and serum chemistry data that potentially relate to BMI were collected from medical records of NF1 patients and their age- and sex-matched controls. Enrollment of 98 adult patients who underwent skin surgery with NF1 (41 men, 57 women) and 173 without NF1 (74 men, 99 women) were investigated. The median BMI in male NF1 patients was significantly lower than that of the controls. Triglycerides in male NF1 patients were significantly lower than male controls, creatine kinase and lactate dehydrogenase in NF1 patients were also lower than controls, aspartate aminotransferase and alanine aminotransferase showed a lower tendency in NF1 patients, but were significantly lower in female patients. With correlation analysis, lactate dehydrogenase was moderately correlated with BMI in male NF1 patients. Creatine kinase and creatinine showed no statistical correlation with BMI in either group. Triglycerides and alanine aminotransferase showed a positive correlation with BMI in both male and female controls, but not in NF1 patients. In conclusion, only lactate dehydrogenase was moderately correlated with BMI in male NF1 patients, although results of some nutritional and metabolic parameters suggest a specific metabolism in NF1.

© 2015 Z. Background: Patients' high adherence to medication is indispensable for the management of skin diseases including atopic dermatitis. We previously showed poor medication adherence in Japanese dermatological patients. Objective: This study was conducted to determine the level of adherence to oral or topical medication in Japanese patients with atopic dermatitis, attempting to characterize the socioeconomic status of those patients with poor adherence. Methods: A web questionnaire survey on demographic data as well as adherence level was conducted on patients registered in the monitoring system. Adherence level was assessed with Morisky Medication Adherence Scale-8 (MMAS-8). Among a total of 3096 respondents with dermatological disorders, data of 1327 subjects with atopic dermatitis were extracted and analyzed. Results: More than 80% of subjects felt that both oral and topical medications were safe and efficacious, while less than 60% of them were satisfied with their treatment. Levels of adherence to oral and topical treatments were evaluated with MMAS-8, giving scores of 4.6 and 4.2, respectively. Demographic factors such as gender, marital status, state of employment, alcohol consumption, frequency of hospital visits, and experience of drug effectiveness had a significant impact on the degree of adherence to treatment. Conclusion: Medication adherence level in Japanese subjects with atopic dermatitis was relatively low compared with that of other chronic diseases. Our survey has characterized patients with poor adherence, who are good targets for interventions to maximize potentially limited healthcare resources.

Topical calcipotriol is a widely used treatment for plaque-type psoriasis worldwide, and has been shown to improve psoriatic plaques as well as very potent corticosteroids. However, there remains the practical question of whether calcipotriol application should continue on healed pigmentation/depigmentation associated with psoriatic plaques. Therefore, we conducted a pilot clinical study to answer this question. Plaque-type psoriatic patients not receiving systemic treatment were enrolled and treated with calcipotriol for 8 weeks (stage I) to achieve maximum effect. The patients were then divided into two groups: group A continued to apply calcipotriol to the entirety of the previous lesion (including pigmentation/depigmentation) regardless of whether skin was healed or not, while group B applied calcipotriol to the remaining lesion only. Patients were followed for 12 weeks (stage II) and dates of plaque recurrence were recorded. A total of 29 patients (13 men, 16 women) were enrolled. During stage I, reductions in scores for redness, induration and scale occurred in 40%, 47% and 55% of patients, respectively. After stage II was completed, group A (n = 19) showed a significantly better Kaplan-Meier curve of non-recurrence than group B (n = 8, P < 0.01). The mean non-recurrence duration was 76.8 ± 11.8 in group A and 35.0 ± 12.0 in group B. Our study showed that applying topical calcipotriol on seemingly healed psoriatic plaque lesions suppresses recurrence better than applying it only on remaining plaques. This finding may be important for instructing psoriatic patients on topical calcipotriol treatment.

© 2015 Japanese Dermatological Association. Previously we assessed the medication adherence for oral and topical remedies by a translated Japanese version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with socioeconomic backgrounds in 3096 Japanese dermatological patients, and found the medication adherence, especially to topical drugs, was poor in these patients. In order to elucidate the disease-specific sociomedical factors, we further sub-analyzed the medication adherence in 237 psoriasis patients and compared it with that in other dermatological diseases such as atopic dermatitis, urticaria or tinea. This study was conducted among patients registered in monitoring system and 3096 eligible patients were enrolled. Our web-based questionnaire included the following items such as age, sex, annual income, main health-care institution, experience of effectiveness by oral or topical medication, overall satisfaction with treatment, and MMAS-8 for oral or topical medication. Mean adherence score by MMAS-8 was 5.2 for oral and 4.3 for topical medication. More patients with psoriasis used a university hospital and fewer used a private clinic compared with those with the other skin disease patients. Experience of drug effectiveness by oral medication and overall satisfaction with treatment was lower in psoriasis patients than in other patients. In oral medication, significantly better adherence was observed in those of higher age and with higher annual income. The adherence to medication, especially to topical drugs, was poor in 237 psoriasis patients. We speculated that some severe psoriasis patients were not sufficiently treated systemically and were resistant to topical therapy, leading to poor adherence.

Background Herpes zoster (HZ), a reactivation of varicella zoster virus manifested by skin blisters and neuralgia, can lead to postherpetic neuralgia in 10–20% of affected subjects. Method In this study, a cohort of 764 patients with HZ was treated with 1500 mg/day of famciclovir for 7 days, and zoster-associated pain (ZAP) was monitored monthly thereafter for up to 12 months until pain resolution was achieved. Patients were questioned monthly by telephone, and pain was recorded using a numerical rating scale (NRS, 0–10). Key results A total of 751 of 764 (98.3%) patients completed follow-up. The percentage of patients with ZAP was 12.4% at day 90, 7.1% at 6 months and 4.0% at 1 year. After the third month, the NRS were 3 or less in most of the remaining patients with ZAP. Stratified analysis revealed significant persistence of ZAP in patients aged ≥50 years and in those aged ≥65 years, and in patients with either moderate-to-severe skin symptoms or severe pain at the initial consultation. Stratified analyses unexpectedly showed patients who commenced famciclovir at 0–2 days after onset of the eruption had a higher prevalence of ZAP at day 90 than those treated at 3–5 days or ≥6 days after rash onset (P = 0.0164, log-rank test). On further analysis, a higher proportion of patients (45.4%) treated at 0–2 days had moderate to severe symptoms compared with those treated at 3–5 days (40.5%) or ≥6 days (37.0%) (P = 0.0987, Cochran-Armitage test). Conclusion & Inference This study, with an exceptionally high follow-up rate, revealed several new findings, including the influence of disease severity on the delay between the onset of symptoms and seeking medical attention. Six adverse drug reactions were reported in five of 721 patients in the safety analysis, including two severe cases of vomiting and convulsions.

Summary Background The insulin-like growth factor-1 (IGF-1) receptor (R)-induced phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD). Objectives To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to evaluate the relationships among them. Methods Thirty-six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF-1R, p-AKT and p-ERK1/2. Results Of thirty-six EMPD tissue samples, 34, 34 and 28 were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2 expression. Taken together, these results indicate that IGF-1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD. Conclusions Our study shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system might be a potential therapeutic target in EMPD.

Human synovial mast cells (MC) can be immunolabelled with antihuman CXCR3 antibody (Ab) (clone 49801). We have investigated whether cutaneous and mucosal MC are stained with anti-CXCR3 Ab in paraffin-embedded sections. Immunohistochemical staining and immunofluorescence double staining assays were performed with anti-CXCR3, anti-tryptase, and anti-chymase Ab using normal skin, psoriatic skin lesions, and normal colon. When compared with tryptase and chymase staining, 100% of the cutaneous and 98% of the mucosal MC were positive for CXCR3. Anti-CXCR3 staining is a useful marker for human cutaneous and mucosal MC in paraffin-embedded sections.

蕁麻疹患者25例を対象として，ベシル酸ベポタスチン錠(タリオン®錠)の即効性と有用性に関するアンケート調査を行なった。即効性(内服後痒みの抑制効果を自覚した時間)に関しては回答を得た20例で，全例が内服後90分以内に痒みの抑制効果を自覚していた(内服後30分以内が50％，内服後60分以内が89％)。また92％以上が何らかの有効性を自覚していた。効果の持続時間に関しては，回答を得た19例で，4時間が16％，8時間32％，12時間が47％という結果であった。眠気の副作用は33％に認められたが，84％の患者は再処方を希望したことから，本剤の高い有用性が示された。

Summary Background Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin D1 protein has not been investigated in extramammary Paget disease (EMPD). Objectives To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D1 protein in EMPD and to evaluate the relationships among them. Methods Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL. Results Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1 expression and between p-Stat3 and Bcl-xL expression. Conclusions Our study shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.

68歳の男性。数年前より右頬部に結節を自覚するも放置していた。徐々に隆起してきたため，2004年6月当科受診。初診時，右頬部に一部にびらんを伴った1.5×1cmの境界明瞭な隆起性結節を認めた。脂腺腺腫などを疑い同年7月切除術施行した。病理組織像では，境界明瞭で左右ほぼ対称的な広基性の腫瘤を認め，底部は一部凹凸不整を呈していた。腫瘍の構成細胞は好塩基性に染まる小型の暗調細胞と，泡沫状の細胞質を有する脂腺細胞類似の細胞で，異型が強く核分裂像も多く認めた。免疫組織化学的染色では，低分子ケラチン，EMA，MIB 1が陽性で，S-100蛋白は陰性であった。以上の結果より自験例をsebaceous carcinomaと診断した。脂腺腫瘍の分類はいまだ確立されたとは言い難いが，自験例はその組織学的所見から，2002年に提唱されたlow grade sebaceous carcinomaに相当するものと考えられた。

Yusho was a mass food poisoning event due to the ingestion of rice oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. At its outbreak in 1968, Yusho patients suffered severe skin symptoms. Although the blood concentrations of PCBs and dioxins, especially highly toxic 2,3,4,7,8-pentachlorinated dibenzofuran (2,3,4,7,8-PeCDF) remain high in these patients, extensive analysis has not been performed on their current skin symptoms. We categorized and evaluated the specific skin symptoms in Yusho in 2012 by grading their severity using an arbitrary scoring system, and analyzed their correlations with the blood concentrations of 2,3,4,7,8-PeCDF and PCBs. A total of 352 Yusho patients underwent annual dermatological check-ups, in which five skin symptoms: black comedones, acneiform eruptions, scar formation, pigmentation and nail deformity, were evaluated for their distribution and severity. Approximately one-third of Yusho patients still presented with black comedones, acneiform eruptions and scar formation; the distributions of these symptoms were similar to those at the time of the Yusho outbreak. The mean blood concentrations of 2,3,4,7,8-PeCDF and total PCBs in Yusho patients were still higher than those in controls. The prevalence and severity of black comedones were correlated with age. Severity scores of black comedones and scar formation were positively correlated with 2,3,4,7,8-PeCDF blood level, and those of black comedones, scar formation, and pigmentation were positively correlated with total PCBs blood level. This study suggests that 2,3,4,7,8-PeCDF and PCBs remaining in Yusho patients still play crucial roles in the development of skin symptoms in Yusho.

Stasis ulcers of the upper limbs are rare, and only 30 cases have been reported, all of which were due to rheological abnormalities. A 59-year-old woman sustained an injury to her right upper limb, resulting in incomplete transections of the brachial artery and the brachial vein. Emergent reconstruction of the brachial artery was performed. Raynaud's phenomenon was observed postoperatively, followed by extreme edema, eczematization and the development of ulcers on the forearm. She was referred to our hospital for treatment. 3-D computed tomography (CT) revealed end-to-end anastomosis of the brachial artery and the brachial vein. An additional brachial-radial artery bypass and closure of the anastomosis dramatically improved her skin symptoms. Vascular anomalies including surgery should be suspected when patients present with stasis dermatitis of the upper limbs.

症例は62歳の男性。生後よりカフェ・オ・レ斑，20歳ごろより全身の皮膚に多発性の神経線維腫が認められるようになり神経線維腫症1型の診断であった。初診の1年前より後頭部右側に皮下腫瘤が出現し増大してきた。腫瘍部の病理組織検査では腫瘍内に複数の胚中心様構造を呈した中型～大型の腫瘍細胞の密な増殖が認められ，免疫組織化学染色では，CD20陽性，CD10陽性，Bcl-2陽性，Bcl-6陽性，CD3陰性，MUM-1陰性で濾胞性リンパ腫Grade3a(WHOの分類)と診断した。全身精査で，脾臓に腫瘍の浸潤像が認められた。R-CHOP療法8クールが行われ，後頭部腫瘍は平坦化，脾臓病変は縮小した。神経線維腫症とB細胞性リンパ腫の合併の報告は少なく偶発的合併と考えられた。

Aim The use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the usefulness of and indication criteria for SNB for cutaneous SCC. Materials and methods Twenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method. Results Of the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis ( p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively ( p = 0.016). Conclusions SNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.

Background Bowen’s disease (BD) is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. However, little is known about its immunohistology. Objectives To evaluate the relationship between the cytological properties of the tumour cells in BD and the host immune response. Methods We examined the expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 antigen, and the number of mitotic cells, together with the number of intratumoral and dermal infiltrating CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen (CLA)+ cells in 18 cases of genital BD. Results When compared with normal genital skin (n = 10), there was a significantly higher number of mitotic cells as well as higher expression of p53+, PCNA+ and Ki67+ cells in BD. There was significant mutual correlation between CD3+, CD4+ and CD68+ cells in the tumoral epidermis. The number of CD1a+ Langerhans cells significantly decreased in BD epidermis; however, dermal CD1a+ cells were increased. Interestingly, numbers of dermal CD1a+ cells significantly correlated with those of intratumoral CD3+, CD4+ and CD68+ cells. In situ hybridization for human papillomavirus (HPV) demonstrated that HPV-infected BD had significantly less infiltration of intratumoral CD3+ cells and CLA+ cells. Conclusions The present data suggest that dermal CD1a+ cells may participate in the immune surveillance and that HPV infection may interfere with the intratumoral infiltration of CLA+ cells in BD.

Bowen's disease is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. In order to evaluate the relationship between the cytological properties of the tumor cells and the host immune response, we have examined the expression of p53 and proliferating cell nuclear antigen (PCNA), and the number of mitotic cells, clumping cells, koilocytes, Langerhans cells (LCs) and dermal lymphoid cell infiltration in 18 cases of anogenital Bowen's disease. When compared with normal anogenital skins (n = 10), a statistically significant number of p53-positive cells, PCNA-positive cells, mitotic cells, clumping cells, koilocytes and dermal lymphoid cells was observed in the cases of Bowen's disease. Importantly, there existed a very strong correlation between the number of PCNA-positive tumor cells and the number of infiltrated dermal lymphoid cells. Moreover, the number of mitotic cells significantly correlated with the number of intratumoral LCs. The in situ hybridization technique for human papilloma virus (HPV) demonstrated that the HPV-infected Bowen's disease showed a similar histological and immunohistological pattern as the HPV-non-infected counterparts, except for increased koilocyte formation and decreased p53 positivity. The present data suggest that the proliferative activity of Bowen's disease significantly correlates with the host immune reaction, and that the host immune system may differentially recognize the different cytological properties of tumor cells in the Bowen's disease.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma that causes immunological disorders such as immunosuppression, autoimmune disease-like symptoms and allergy. We report a case of a 67-year-old man with AITL who had a serious varicella zoster virus (VZV) reinfection that appeared clinically to be varicella. Forty percent of cases of AITL are associated with skin rash. A variety of cutaneous manifestations have been reported; however, the majority are macropapular eruptions that are often diagnosed as drug associated. Our study emphasizes the need to correctly diagnose opportunistic infections, such as the varicella that is documented in our patient, at early stages in AITL.

A common form of erythema multiforme, herpes-associated erythema multiforme (HAEM), occurs following infection with herpes simplex virus (HSV). Here we report that HSV gene expression and the qualitative nature of the virus-specific T-cell responses are related to HAEM lesion development. Skin from HAEM lesions and 1-3 months healed HAEM lesional skin were positive for the viral DNA polymerase gene (Pol) by polymerase chain reaction. However, gene expression as determined by immunohistochemistry with Pol-specific antibody was seen only in HAEM lesions, suggesting that lesion development is associated with Pol gene expression. Similar HSV-specific T-cell lymphoproliferative responses were seen in peripheral blood mononuclear cells (PBMCs) from patients with acute or healed HAEM lesions or HSV lesions and from HSV-seropositive patients with unrelated inflammatory diseases. However, the T-cell receptor variable (V beta) chain repertoire of HSV-stimulated PBMCs obtained from HAEM lesions was altered; the prevalence of some families of variable chain (namely V beta 16 and V beta 19) was reduced, whereas the prevalence of others was increased (namely V beta 2 and V beta 7). V beta 2 cells were found in HAEM lesional skin positive for Pol antigen, suggesting that these cells home to viral antigen-positive skin.

症例は40歳の男性。両下眼瞼の黒色小結節を主訴に佐賀県立病院好生館皮膚科を受診した。四肢·躯幹には扁平疣贅様皮疹, 癜風様皮疹が混在していた。臨床的, 病理組織学的所見から疣贅状表皮発育異常症(epidermodysplasia verruciformis)と診断した。下眼瞼の結節は脂漏性角化症と考え, 液体窒素凍結療法を施行した。他部位に悪性を思わせる皮疹は認められず, 臨床検査成績においても免疫異常を示唆する所見は得られなかった。

Psoriasis is a chronic inflammatory disease mainly involving the skin and joints, mediated by pro-inflammatory cytokine tumor necrosis factor (TNF)-α. In hepatitis C, continuous inflammation mediated by TNF-α leads to liver cirrhosis and diabetes mellitus. Hence, psoriasis and hepatitis C have pathophysiological factors in common. An epidemiological association between the two conditions has been reported, but no detailed research has yet been performed. Frequency of hepatitis C virus (HCV) infection was assessed in 717 patients with psoriasis and 38 057 with all other dermatological diseases who visited Fukuoka University Hospital in 1998-2011. HCV⁺ and HCV⁻ psoriatic patients were further compared. Frequency of HCV infection was significantly higher in psoriasis (7.5%) than in controls (3.3%) in overall ages. When stratified by age at the first visit, the frequency was significantly higher in patients with psoriasis than in controls aged in their 60s (11.8% vs 6.6%, respectively, P = 0.0215) and 70s (19.5% vs 7.3%, P < 0.0001). HCV⁺ psoriatic patients were significantly older at onset than HCV⁻ ones (median, 54 vs 39 years), stronger male predominance (male/female ratio, 4.4:1), similar family history of psoriasis, higher association of diabetes mellitus and hypertension, and significantly lower body mass index (22.4 ± 2.73 vs 24.2 ± 4.61), in age-stratified (≥ 40 years) analysis. HCV⁺ psoriatic patients were less obese, but still had a higher frequency of diabetes mellitus and hypertension, possibly due to chronic inflammation in the liver and other organs. HCV infection may trigger psoriasis, especially late-onset psoriasis, possibly via overproduction of TNF-α, a common mediator of the two conditions.

The serum vitamin D₃ levels in patients with neurofibromatosis 1 has been reported to be significantly lower than that in control subjects, and the level of vitamin D₃ reversely correlates with the severity of neurofibroma formation. We found that narrowband ultraviolet B (NB-UVB) irradiation increased the serum level of 1,25(OH)₂ vitamin D₃ in patients with neurofibromatosis 1. The difference in the 1,25(OH)₂ vitamin D₃ levels between patients who had received irradiation for more than 18 months and those who had no irradiation was highly significant. Time-course analyses of the serum vitamin D₃ levels in the patients who were enrolled after informed consent revealed that the levels became higher significantly after 6 months of irradiation. It is suggested that NB-UVB irradiation is effective for increasing the serum level of vitamin D₃ in patients with neurofibromatosis 1, which may be of benefit for skin symptoms such as pigmented macules or neurofibromas.

The serum vitamin D₃ levels in patients with neurofibromatosis 1 has been reported to be significantly lower than that in control subjects, and the level of vitamin D₃ reversely correlates with the severity of neurofibroma formation. We found that narrowband ultraviolet B (NB-UVB) irradiation increased the serum level of 1,25(OH)₂ vitamin D₃ in patients with neurofibromatosis 1. The difference in the 1,25(OH)₂ vitamin D₃ levels between patients who had received irradiation for more than 18 months and those who had no irradiation was highly significant. Time-course analyses of the serum vitamin D₃ levels in the patients who were enrolled after informed consent revealed that the levels became higher significantly after 6 months of irradiation. It is suggested that NB-UVB irradiation is effective for increasing the serum level of vitamin D₃ in patients with neurofibromatosis 1, which may be of benefit for skin symptoms such as pigmented macules or neurofibromas.

Cyclosporin A (CsA) has various adverse effects including neurotoxicity. We report the case of a 49-year-old Japanese woman with dermatomyositis who showed CsA-induced cortical blindness. The patient demonstrated cortical blindness despite having a normal blood concentration of CsA. The risk factors of CsA-induced cortical blindness include the use of corticosteroids and vascular injury, which are frequently observed in patients with systemic autoimmune diseases. Clinicians should consider CsA neurotoxicity when using CsA for patients with systemic autoimmune diseases.

74歳男性。1999年4月に肺扁平上皮癌を指摘され,放射線療法,化学療法併用により部分寛解となった。その経過中に吐血し,内視鏡にて胃癌を指摘され,1999年8月胃全摘術を施行された。2000年3月当科初診時は,ほぼ腹壁全体に紅色調の板状硬結が認められた。組織学的には真皮から皮下脂肪組織にわたりびまん性に,印環細胞を混ずる腫瘍細胞の浸潤が認められた。リンパ管の拡張,及びリンパ管内腫瘍塞栓像は認めなかった。腹部CTでは肝転移およびリンパ節転移の所見は認められなかったが,広い範囲に癌性腹膜炎の所見が認められた。転移の経路として血行性,リンパ行性の経路よりも広範囲な癌性腹膜炎からの直接浸潤が推察された。

Stasis ulcers of the upper limbs are rare, and only 30 cases have been reported, all of which were due to rheological abnormalities. A 59-year-old woman sustained an injury to her right upper limb, resulting in incomplete transections of the brachial artery and the brachial vein. Emergent reconstruction of the brachial artery was performed. Raynaud's phenomenon was observed postoperatively, followed by extreme edema, eczematization and the development of ulcers on the forearm. She was referred to our hospital for treatment. 3-D computed tomography (CT) revealed end-to-end anastomosis of the brachial artery and the brachial vein. An additional brachial-radial artery bypass and closure of the anastomosis dramatically improved her skin symptoms. Vascular anomalies including surgery should be suspected when patients present with stasis dermatitis of the upper limbs.