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Acyclovir, valacyclovir, and famciclovir are used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Helicase-primase inhibitors (HPIs) inhibit replication fork progression that separates double DNA strands into two single strands during DNA synthesis. The HPIs amenamevir and pritelivir have novel mechanisms of anti-herpetic action, and their once-daily administration has clinical efficacy for genital herpes. Among HPIs, amenamevir has anti-VZV activity. The concentrations of HSV-1 and VZV required for the 50% plaque reduction of amenamevir were 0.036 and 0.047 μM, respectively. We characterized the features of amenamevir regarding its mechanism, resistance, and synergism with acyclovir. Its antiviral activity was not influenced by the viral replication cycle, in contrast to acyclovir. A clinical trial of amenamevir for herpes zoster demonstrated its non-inferiority to valacyclovir. To date, amenamevir has been successfully used in over 1,240,000 patients with herpes zoster in Japan. Post-marketing surveillance of amenamevir in Japan reported side effects with significant potential risk identified by the Japanese Risk Management Plan, including thrombocytopenia, gingival bleeding, and palpitations, although none of these were serious. The clinical efficacy and safety profiles of amenamevir were established in patients with herpes zoster. Therefore, amenamevir as an HPI opens a new era of anti-herpes therapy.

Several traditional Japanese medicines including Keigairengyoto (KRT) are used to treat acne vulgaris, but there is no robust evidence of their effectiveness. In this study, we examined the effectiveness and safety of KRT in treating acne vulgaris. An open-label, randomized, parallel control group comparison was conducted with a conventional treatment group (adapalene and topical antibiotics; control group) and a KRT group (control treatment plus KRT). The test drugs were administered for 12 weeks to patients (15 to 64 years, outpatient) with inflammatory acne on their face, and the amount of acne at 2, 4, 8, and 12 weeks was measured. Sixty-four patients were enrolled; 29 patients in each group were included in the analysis. Twenty-eight patients in the control group and 24 patients in the KRT group were included in the efficacy analysis. The number of inflammatory skin rashes at 4 and 8 weeks in the KRT group was significantly decreased compared with the control group. There was no significant difference between the two groups in noninflammatory eruptions and general rashes. There were no serious adverse events in both groups. KRT may be a useful agent in patients with inflammatory acne in combination with conventional treatments. This trial is registered with UMIN 000014831.

The characteristic histopathological feature of mycosis fungoides (MF) and adult T-cell leukemia/lymphoma (ATLL) is epidermotropism. To identify the mechanism for epidermotropism of lymphoma cells, total RNAs were obtained from skin biopsies of epidermis and dermis of MF and ATLL patients by means of laser capture microdissection, and used for subsequent complementary DNA (cDNA) microarray experiments. This procedure has made it possible for us to observe and evaluate the regional environment of MF and ATLL. Hierarchical cluster analysis revealed that the cDNAs could be clearly differentiated into MF and ATLL. CCL27 was expressed in the dermis generated from keratinocytes, CCR4/CCR6/CCR7/CCR10/cutaneous lymphocyte-associated antigen (CLA) lymphoma cells in the dermis, and CCL21 in the extracellular matrix (stroma). Lymphotoxin (LT) β and CCL21 expression was significantly higher and that of CCR10 relatively for MF, while CCR4 and CLA expression was relatively higher for ATLL. In the epithelium, keratinocytes expressed CCL20/CCL27, and lymphoma cells CCR4/CCR6/CCR10, while CCR4, CCR6, CCL20 and CCL27 expression was relatively higher for ATLL than MF. The dermis of MF, but not that of ATLL, showed correlation between CCR7 and CCL21. These findings support the suggestion that chemokines and chemokine receptors are involved in the pathogenesis of MF and ATLL, indicate that cutaneous homing seems to be different for MF and ATLL, and point to the possibility that cutaneous T-cell lymphomas originate in regulatory T cells, especially in the case of ATLL.

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan-Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0 μg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster-associated pain including post-herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2-3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3-4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.

Psoriasis greatly impacts the health-related quality of life of patients, including any dermatological conditions that are listed in the dermatology life quality index (DLQI). We investigated the relationships between DLQI and the degree of patient satisfaction using questionnaires among psoriasis patients treated only with topical corticosteroids. Patients who were dissatisfied with topical corticosteroids alone and agreed to receive cyclosporin were given low-dose oral cyclosporin. We assessed changes of the DLQI and the psoriasis area and severity index (PASI) scores in patients dissatisfied with treatment during the period of cyclosporin addition. Of 32 enrolled patients, 17 reported dissatisfaction with the current treatment of topical corticosteroids alone. There was a significantly positive correlation between the degree of patient satisfaction questionnaires and the DLQI of these 32 patients. Among the 17 dissatisfied patients, 12 patients agreed to receive additional cyclosporin therapy and five did not. The 12 patients who started on cyclosporin had a significantly lower PASI after 12 weeks than they did at baseline. The DLQI improved significantly after 12 weeks in the cyclosporin-treated patients. The 12 patients who agreed to receive cyclosporin showed a significantly lower DLQI at 12 weeks compared to the five patients who declined the addition of cyclosporin to their treatment. Assessing the degree of patient satisfaction with therapy using a questionnaire could be useful for improving clinical interventions in psoriasis patients. Low-dose oral cyclosporin could be effective in patients who are dissatisfied with topical corticosteroid treatment alone.

16歳，女性。幼少時から四肢に褐色斑が散在しているのに気付いていた。その後次第に顔面，体幹，四肢の色素沈着と同部位の運動時の潮紅が目立つようになってきた。13歳時に皮膚科を受診しレーザー照射を行ったが明らかな効果はなく経過観察とされていた。2008年8月に当科を受診した。初診時，顔面・体幹・四肢に毛細血管拡張と色素沈着，疣状の褐色局面，色素脱失を伴う線状・斑状の萎縮性局面を認めた。上腕，下肢では一部Blaschko線に沿って線状に配列していた。左前腕の生検組織では，皮下脂肪組織が真皮上層まで突出，増生していた。特徴的な臨床像と病理組織像より，中外胚葉の先天性形成異常疾患とされるGoltz症候群（focal dermal hypoplasia）と診断した。

66歳，女性。2005年9月頃より，下肢を中心に浸潤を触れる紫斑を認めるようになり当科を受診した。下腿の紫斑より生検しleukocytoclastic vusculitisの診断であった。また，血液検査にて，クリオグロブリン弱陽性，RA 因子高値，補体低下(C4，C1q，CH50)HCV-Ab 陽性，HCV-RNA(ハイレンジ法)2700 IU/mlと高ウイルス量であった。以上より，慢性C型肝炎に伴うクリオグロブリン血症と診断した。保存的治療により，一旦皮膚症状は軽快したが，約2年半後に紫斑が再発し，同時に膜性増殖性糸球体腎炎の合併が判明した。本症では，速やかな診断と原疾患に対する治療が重要であり，加えて腎疾患の合併についても注意が必要と考えた。

Bullous pemphigoid (BP) usually responds well to conventional therapies, although some severe cases show less response to various therapies or develop side-effects due to long-term drug administration using high doses. Most BP patients are elderly and are thus prone to systemic deterioration or unfavorable outcome. In the present study, we investigated the efficacy of interferon-gamma on severe BP patients resistant to conventional therapies. Interferon-gamma was administered to 10 severe BP patients at a dose of 2 million Japan reference units (JRU) once a day for 7 consecutive days by i.v. infusion in addition to oral corticosteroids. The degree of improvement in the clinical symptoms, serum interleukin (IL)-4, IL-5, and plasma RANTES concentrations, as well as the results of indirect immunofluorescence and BP180 enzyme-linked immunosorbent assay index values, were compared before and after the 7-day drug administration. Among the nine patients whose clinical symptoms were evaluated, an improvement was observed in all patients. Except for one patient, the serum IL-4 concentrations decreased and similar results were observed for the serum IL-5 concentration. All five patients in whom the plasma RANTES concentration was measured showed decreased levels. The indirect immunofluorescence titers decreased in only four patients. However, in seven patients in whom index values of BP180 enzyme-linked immunosorbent assay were evaluated, all patients showed significant decrease of the index values. These results suggest that, in severe BP patients refractory to conventional therapies, interferon-gamma in addition to oral corticosteroids is effective and thus should be considered for further clinical use.

公立八女総合病院皮膚科にて過去2年間(2003年4月から2005年3月まで)にマムシ咬症21例を経験した。受診患者では男女差はみられず，月別では8月，9月に多く受診した。年齢別では60歳から70歳台が多くを占め，その理由としては八女地域の住民の高齢化と農作業中の受傷によるものが多いためと思われた。時刻別発生数では午前4時から深夜までに及んでいた。受傷の状況としては田畑や自宅庭での農作業中の受傷例が多く，受傷部位は手指，次いで足趾，足背の順に多かった。天候別発生数ではいずれの天候にもみられたが，曇りの日に多い傾向があった。マムシ咬傷による入院日数は臨床症状の程度が高度になるほど延長し，統計学的有意差が認められた。治療は局所治療としてマムシ毒の排除を目的に皮下切開を行い，全身療法としてセファランチン内服療法とマムシ抗毒素投与を行った。マムシ抗毒素の使用についてはいまだ確立された見解が得られておらず，各施設間での使用率が大きく異なっている。マムシ抗毒素投与後に起こる血清病発生の集計結果では血清病が生じた全例が軽症であったため，副作用としての血清病はさほど問題にならないと考えた。マムシ抗毒素の使用は投与基準に従い，重症例では原則としてマムシ抗毒素を投与する方が望ましいと考えた。

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.

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.

Summary Background: Epidermolysis bullosa simplex associated with muscular dystrophy is caused by plectin deficiency. Objective To report clinical, immunohistochemical, ultrastructural and molecular features of a 52-year-old Japanese patient affected with this disease, whose muscular disease had been followed-up for 27 years. Methods: We performed histopathological study, immunofluorescence, electron microscopic study and mutation detection analysis for plectin. Results: The patient developed blisters and erosions followed by nail deformity on the traumatized regions from birth. The skin lesions were continuously developed to date. The histopathological study showed subepidermal blister. Electron microscopic study showed blister formation inside the basal cells at the level just above the attachment plaque of hemidesmosome. Immunofluorescence showed complete loss of staining to plectin. The mutation analysis using protein truncation test and DNA sequencing revealed a C-to-T transition at nucleotide position 7006 of the plectin cDNA sequence, which lead a novel homozygous nonsense mutation (R2319X). Conclusion: From the above results, the diagnosis of epidermolysis bullosa simplex associated with muscular dystrophy was made. Slight muscular dystrophy was noticed at the age of 25 years. The muscular dystrophy gradually progressed and she could not walk at the age of 46 years. However, she can still breathe and swallow by herself. This is the patient of this disease with the longest follow-up, and may indicate the slow progress of muscular condition of this disease.

わが国では，乾癬に対するシクロスポリン療法が承認されて10年が経過した。その臨床的有用性は周知の事実となりつつあるが，より有効かつ安全に使用するために，2004年4月に『シクロスポリンMicroemulsion Preconcentrate (MEPC)による乾癬治療ガイドライン』が，可能な限りのエビデンスを基に改訂された。そういったなか，西部支部正会員に乾癬に対するシクロスポリン療法の現況と疑問点などについてアンケートを実施し，久留米市で開催された第56回日本皮膚科学会西部支部学術大会のセミナーにおいて討論を行った。アンケートの集計結果では，『シクロスポリンMEPCによる乾癬治療ガイドライン2004年度版』は，西部支部正会員の約8割に短期間で認知されていたが，実際に読んだと回答した医師は半数であった。また，シクロスポリンの適応基準の一つとして，患者QOL評価の考慮が認知されてきたが，PASIスコアや皮疹部位を基準とする回答は少なく，皮疹面積による基準は医師間で差が大きいことが判った。今後，シクロスポリンMEPCは，初発・再燃時の『早期寛解導入薬』として積極的に選択できる薬剤の一つとして有用であり，有効かつ安全に使用するには，さらなるガイドラインの普及と理解が重要と考えられた。

大型犬による飼い主以外の犬咬傷の3例を経験した。症例は高齢者2例と小児であり，いずれも上肢を受傷していた。高齢者の2例では広範囲の皮膚欠損により植皮術を要し，8歳男児例では受傷後早期に閉鎖された創の縫合不全がみられた。犬咬傷では創汚染がほとんど必発であり，初期治療としては創の閉鎖を急がずにとりあえず開放創とすべきであると考えた。感染予防対策としては予防的抗生剤の投与を行い，場合によっては破傷風トキソイドと抗破傷風免疫グロブリンの投与を考える必要がある。近年のペットブームにより，今後比較的大きな皮膚欠損を認める犬咬傷を診療する機会が増えるものと考えられ，本疾患に対するプライマリケアの知識は重要と考えた。

久留米大学病院皮膚科でアトピー性皮膚炎に対しタクロリムス軟膏(プロトピック®軟膏)を使用した症例で経過を評価しえた101症例について,効果と副作用を集計するとともに,特に皮疹軽快後の維持療法,中止後の経過について調査検討した。その結果,顔面に使用した例では全体でやや有効以上が93%で,副作用の認められた41%のうち局所刺激感が30%と最も多く,重篤な副作用は少なかったが,注意を要するものとしてカポジ水痘様発疹症が5例(5%)に出現した。症状消失後は,軽症例では皮疹再燃時に使用を再開するよう指導した上で外用中止した5例全例が経過良好であった。中等症ないし重症例では,症状が消失した後も外用中止すると2ないし3日後に再燃の見られた例が多く,2ないし3日に1回の外用に減量してほぼ皮疹のコントロール可能で,症状の増悪した時に適宜外用回数を戻す方式で対応できた。しかし,1日1回外用への減量から様子をみながら数週間ないし数ヵ月に一度外用間隔をみなおして徐々に減らしていく方法をとった群が,14例全例に再燃がなく維持ないしさらに減量可能であり,患者のコンプライアンスの低下しない選択肢であると思われた。

Th17 cells play crucial roles in the pathogenesis of autoimmune diseases. We previously reported that Th17 cells are recruited to the lesional skin in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The aim of this study was to evaluate lesional Th17 cells and Treg cells in bullous pemphigoid (BP). Correlations between these cells and disease severity of BP were also evaluated. Immunohistochemical studies showed that both IL-17+ and Foxp3+ cells were present in higher numbers in BP lesions, compared with control skin. IL-17/CD4 ratio in BP was significantly higher than that in PF. Foxp3/CD4 ratio in BP was significantly less than that in either PV or PF. There were no obvious correlations between these cells and disease severity of BP. This study suggests that, compared with pemphigus, BP shows more Th17 cell-related inflammation and less Treg-related regulation.

39歳，女性。既往歴にアレルギー性鼻炎。初診の6日前より上気道炎症状があり，その後，左膝部，踵部のしびれ，右下肢の腫脹・紫斑が出現したため当科受診。両下腿の腫脹と右下腿に限局した地図状の浸潤を触れない紫斑を認め，両下肢の振動覚，表在覚の低下を伴っていた。白血球数17300/μl（好酸球81％），IgE 1380 IU/ml，RAPA 1280倍，ANCAは陰性であった。病理組織学的に，真皮上層から脂肪織にかけて血管周囲を中心とした高度な好酸球浸潤を認めたが，肉芽腫の形成は認められなかった。以上の所見からChurg-Strauss症候群と診断した。プレドニゾロン30mg/日内服を開始し，末梢血好酸球数は低下し皮疹は速やかに軽快した。プレドニゾロン2.5mg/日まで漸減し経過をみていたが，初診から9ヵ月後，夜間に喘鳴を伴う気管支喘息発作が出現した。

Several studies have suggested that autoantibodies directed against multiple epitopes occur via epitope spreading in autoimmune bullous skin diseases. However, the precise sequence of events in epitope spreading has not been elucidated for any of the epidermal autoantigens. In this issue, using a transgenic mouse model, Di Zenzo et al. report that intramolecular epitope spreading does occur for human BPAG2.

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.

63歳の女性。不明熱の原因検索の過程で骨髄異形成症候群(MDS)が疑われ, 佐賀県立病院好生館内科へ検査·治療目的で入院した。慢性骨髄単球性白血病(CMMoL)の慢性期と診断された。その後急性転化時に両大腿に紫斑型の白血病細胞浸潤(特異疹)が認められた。

We treated 12, 15 and 13 Japanese actinic keratosis (AK) lesions with 5-aminolevulinic acid photodynamic therapy (PDT), 5% imiquimod cream and combination of both therapies, respectively, and compared the effects. Patients underwent the second course, when AK lesions remained after the first course. Efficacy was evaluated 1 month after each treatment. Combination therapy cleared all AK lesions only after the first course, while PDT and imiquimod therapy cleared 41.7% and 66.7% of AK lesions after the first course, respectively. All residual AK lesions after the first course were cleared by the second courses of PDT or imiquimod therapy. During the course, erosion and crust developed significantly more frequently in combination therapy (P

Psoriasis greatly impacts the health-related quality of life of patients, including any dermatological conditions that are listed in the dermatology life quality index (DLQI). We investigated the relationships between DLQI and the degree of patient satisfaction using questionnaires among psoriasis patients treated only with topical corticosteroids. Patients who were dissatisfied with topical corticosteroids alone and agreed to receive cyclosporin were given low-dose oral cyclosporin. We assessed changes of the DLQI and the psoriasis area and severity index (PASI) scores in patients dissatisfied with treatment during the period of cyclosporin addition. Of 32 enrolled patients, 17 reported dissatisfaction with the current treatment of topical corticosteroids alone. There was a significantly positive correlation between the degree of patient satisfaction questionnaires and the DLQI of these 32 patients. Among the 17 dissatisfied patients, 12 patients agreed to receive additional cyclosporin therapy and five did not. The 12 patients who started on cyclosporin had a significantly lower PASI after 12 weeks than they did at baseline. The DLQI improved significantly after 12 weeks in the cyclosporin-treated patients. The 12 patients who agreed to receive cyclosporin showed a significantly lower DLQI at 12 weeks compared to the five patients who declined the addition of cyclosporin to their treatment. Assessing the degree of patient satisfaction with therapy using a questionnaire could be useful for improving clinical interventions in psoriasis patients. Low-dose oral cyclosporin could be effective in patients who are dissatisfied with topical corticosteroid treatment alone.

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster-associated pain including post-herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2-3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3-4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.

Th17 cells play crucial roles in the pathogenesis of autoimmune diseases. We previously reported that Th17 cells are recruited to the lesional skin in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The aim of this study was to evaluate lesional Th17 cells and Treg cells in bullous pemphigoid (BP). Correlations between these cells and disease severity of BP were also evaluated. Immunohistochemical studies showed that both IL-17+ and Foxp3+ cells were present in higher numbers in BP lesions, compared with control skin. IL-17/CD4 ratio in BP was significantly higher than that in PF. Foxp3/CD4 ratio in BP was significantly less than that in either PV or PF. There were no obvious correlations between these cells and disease severity of BP. This study suggests that, compared with pemphigus, BP shows more Th17 cell-related inflammation and less Treg-related regulation.

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.

Background Blastic plasmacytoid dendritic cell neoplasm (BPDC) is a rare hematologic neoplasm, which almost always involves the skin and shows poor prognosis. Objective The aim of our study was to enhance BPDC diagnosis and indications for prognosis. Methods This study involved 26 patients with BPDC. To investigate the histogenesis of BPDC, we reviewed the clinical features and stained markers of various hematopoietic lineages, chemokines, and their receptors. Results Bone-marrow infiltration was detected in 13 of the 19 cases examined and leukemic changes in 18. Complete remission was achieved in 14 cases, but more than half of the patients showed recurrence within a short time, and 14 patients died of the disease after 1 to 25 months (mean 8.5 months). Positivity for CD123 was detected in 18 of 24 cases and for T-cell leukemia 1 in 18 of 22 cases. Of the chemokines and their receptors, 8 of 15 skin biopsy specimens proved to be positive for CXCL12. Leukemic change subsequent to skin lesions occurred in 7 of 8 CXCL12-positive cases (87.5%) and in 3 of 6 CXCL12-negative cases (50%). Seven of the 8 CXCL12-positive patients (87.5%) and two of the 6 CXCL12-negative patients (33.3%) have died, whereas one of 8 CXCL12-positive patients (12.5%) and 4 of 6 CXCL12-negative patients (66.7%) remain alive. Limitations The number of patients was limited. Conclusions We speculate that the presence of CXCL12-positive cells in the skin may be associated with leukemic change and a poor prognosis.

Anti-laminin gamma1 pemphigoid is an autoimmune subepidermal bullous disease first described in 1996, and has been distinct from previously known subepidermal blistering diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita. Circulating autoantibodies of the patients do not react to any known autoantigen of the skin, but react to a 200-kDa molecule (p200) from dermal extracts. The identity of p200 was unmasked as laminin gamma1, an extracellular matrix glycoprotein composing several forms of laminin heterotrimers. We renamed this disease from the previously used anti-p200 pemphigoid to anti-laminin gamma1 pemphigoid, a new entity of an autoimmune bullous disease. In this decade, we have experienced over 70 cases of this disease. Although the number of the cases of anti-laminin gamma1 pemphigoid is half as many as the number of definitely diagnosed cases of epidermolysis bullosa acquisita in the same duration, a considerable number of the cases could be clinically misdiagnosed as epidermolysis bullosa acquisita. Unveiling the pathogenicity and development of a useful diagnostic method is necessary for appropriate management of this new disease.

Type VII collagen is an adhesion molecule of the extracellular matrix in epithelial basement membranes, and the main constituent of anchoring fibrils at the dermal-epidermal junction (DEJ). Autoimmunity against this protein is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). EBA is a rare acquired, heterogeneous, chronic blistering disease of skin disease of skin and mucous membranes characterized by subepidermal blisters and tissue-bound as well as circulating autoantibodies to the DEJ. EBA has several distinct clinical presentations with other subepidermal bullous diseases, such as mainly dystrophic epidermolysis bullosa or bullous pemphigoid. The circulating immunoglobulin G autoantibodies for EBA react with a 290-kDa dermal protein, type VII collagen, as detected by immunoblot analysis using dermal extracts. The pathogenicity of these autoantibodies has been demonstrated by experimental animal models, in which anti-type VII collagen antibodies injected into a mouse produced an EBA-like blistering disease in the animal. EBA cases often require high doses of systemic corticosteroids and a variety of immunosuppressants. Although treatment for EBA is frequently difficult and unsatisfactory, some therapeutic success has been reported with colchicine, dapsone, infliximab and i.v. immunoglobulin. In this review, we will focus on recent progress in our understanding of the clinical manifestations, the etiopathogenesis as well as the management of EBA.

Mycophenolate mofetil has been used as an immunosuppressive agent to prevent acute rejection in kidney transplantation since the early 1990s. There are several reports that mycophenolate mofetil is effective in autoimmune bullous diseases including pemphigus vulgaris in combination with high doses of systemic corticosteroids or as a monotherapy. In Japan, however, there are few reports of pemphigus vulgaris treated with mycophenolate mofetil. The present study showed that mycophenolate mofetil treatment combined with systemic corticosteroid was successful in four Japanese patients with pemphigus vulgaris who were refractory to therapies including systemic corticosteroids, plasmapheresis, and oral immunosuppressives. For Japanese and European patients, mycophenolate mofetil may be an excellent therapy in a combination with systemic corticosteroid for refractory patients with pemphigus vulgaris.