金子 健彦

4歳男児,3歳男児.患者のペットであったモルモット,およびネコが感染源と思われる小児のkerion celsi2件を報告した.2例とも脱毛斑が拡大してから治療を開始しており,長期の内服治療を要した.小児では他覚的に症状がはっきりするまで病変に気づかないことも多く,小児の脱毛をみた場合には常に真菌感染症を念頭においた注意深い観察と,早期の適切な治療が必要であると再確認した

11歳女児.背部の環状紅斑を主訴とした.長野県軽井沢町で刺症し,20日後に拡大傾向を示す紅斑を生じた.抗Borrelia burgdorfei IgM抗体は経過とともに陰性から陽性に転じ,IgG抗体はより多数の陽性バンドを認めるようになった.虫刺痕部分の組織学的検索で虫体口器の残存を認め,標記と診断した.ドキシサイクリンハイドロクロタライド投与により皮疹は初診7日後に消失し,以後4週間の投薬を続けた.国内の報告は40〜60歳代が半数を超え,刺症部位は上肢が最も多かった.皮膚症状のみは32%で,関節痛,リンパ節腫脹などを43%に,何らかの神経症状を21%に認めた.脳神経炎では顔面神経麻痺を6例に認め,皮膚科臨床医にとって注目すべき症状と考えた

生後0日女児.出生時に右拇指基部橈側の小腫瘤を指摘された.生後3ヵ月半で,局所麻酔下に単純切除縫縮術を行った.組織学的に,腫瘤中央部に軟骨組織を認めたが,関節形成や骨分枝を認めず,中川らの分類によるfloating typeの拇指多指症と考えられた.術後1年2ヵ月が経過し,再発はない

Keratin K6 is known as an inflammatory and hyperproliferative keratin, and is induced by an inflammatory and hyperproliferative agent. In this study, we demonstrated that interferon-γ, an antiproliferative agent, also induces keratin K6. We used normal human ex vivo skin, normal human cultured keratinocytes, HaCaT keratinocytes, and DJM cells to examine the induction of K6 by interferon-γ, by immunohistochemical staining, Western blot analysis, promoter chloramphenicol acetyl transferase assay, and reverse transcriptase polymerase chain reaction of mRNA. We succeeded in demonstrating the induction of keratin K6 by interferon-γ in ex vivo human skin and HaCaT keratinocytes at the protein and message level, and in cultured normal human keratinocytes at the promoter level. The inhibition of the signal transducing activator of transcription 1 pathway by a dominant-negative transfer gene caused the inhibition of K6 induction by interferon-γ, and the blocking of nuclear factor κB using antisense oligonucleotides also inhibited the K6 induction. We also blocked the released interleukin-1α from keratinocytes after stimulation with interferon-γ by neutralizing antibodies, which showed a decrease in the K6 induction. Our results suggest that a small amount of interleukin-1α, which cannot induce K6 by itself, is secreted upon stimulation by interferon-γ, and that the induction of K6 occurs through the synergistic effect of the interferon-γ/signal transducing activator of transcription 1 and interleukin-1α/nuclear factor κB pathways. This is the first report to describe K6 induction in epidermal keratinocytes by interferon-γ and indicate a probable signal transduction pathway, and demonstrates that K6 is a possible partner of K17 in the inflammatory process.

76歳女.右第2指爪は全体に混濁肥厚し,末梢側の1/2が破壊され,爪周囲には発赤と落屑,軽度の腫脹を認めた.又,両側口角に亀裂と発赤,落屑を認めた.直接鏡検で菌糸と分芽胞子からなる菌要素を認め,分離培養よりCandida albicansを同定した.イトラコナゾール100mg/日の内服を開始し,爪甲混濁比は10/10から徐々に改善して6ヵ月後には0/10となった.その時点で若干爪甲表面の粗ぞうが残存したため治療を継続し,1ヵ月後の直接生検で真菌要素の陰性化を確認した.カンジダ性口角びらんは投与1週間後には亀裂,発赤が殆ど消失し,菌要素も認めなくなり,2週間後には完全に消失した

17歳男.就学以前よりアトピー性皮膚炎により加療中で,躯幹四肢のアトピー性皮膚炎に対して硫酸ゲンタマイシン含有吉草酸ベタメタゾンクリームを外用していたところ,皮疹が拡大増悪した.KOH法による直接検鏡では,胸部と下肢の鱗屑より多数の菌糸型真菌要素を認めた.培養検査でTrichophyton rubrumを同定した.ゼフナートクリーム外用を1日1回入浴後に開始したところ,1週間後には紅斑,落屑,掻痒感とも著明に減少し,2週間後にはさらなる改善を認めた.直接検鏡でも真菌要素の陰性化を認めた.元来のアトピー性皮膚炎症状と考えられる皮膚症状が残存した為,ゼフナートクリームに代えてジフルプレドナート軟膏を開始した.更に1週間後,ほぼ全ての皮疹が消失した

16歳女性.ほぼ全身に浮腫性紅斑や緊満性水疱がみられた.病理組織では表皮下水疱と真皮内の好酸球浸潤を認められ,さらに免疫蛍光法およびWestern blot法にて類天疱瘡と診断された.治療としてプレドニゾロン 60mg/dayの投与にて,症状は徐々に軽快し漸滅したが,本症は中高年に好発する後天性自己免疫性疾患であり,若年にて発症するのは比較的稀な例と思われた

症例1:79歳男.糖尿病はなく,10ヵ月前に両下腿に紅褐色斑が出現し,徐々に増数,拡大した.境界型耐糖能障害があり,necrobiotic typeの脂肪類壊死と診断した.フランカルボン酸モメタゾンの外用で浸潤と紅斑は消失し,淡褐色調の局面となっている.症例2:74歳女.糖尿病はなく,1ヵ月前より両下腿に褐色斑が出現し,徐々に増数,拡大した.耐糖能異常は見られず,granulomatous typeの脂肪類壊死と診断した.フランカルボン酸モメタゾンを外用しているが,特に変化は見られない

The "complete cure" of onychomycosis requires long-term treatment with a systemic antifungal agent. Therefore, to properly assess the effects of an antifungal agent on onychomycosis requires a long follow-up. We have conducted a retrospective analysis of the patients treated with griseofulvin (GRF) from 1962 to 1992 and a clinical study to compare the long-term effect of GRF with that of a new oral antifungal agent, itraconazole (ITCZ), for patients who received treatment from 1992 to 1995. For the retrospective study, 281 patients who were microscopically diagnosed as having onychomycosis at the Department of Dermatology, Faculty of Medicine, University of Tokyo, and received GRF administration in 1962, 1972, 1982, and 1992, were evaluated for cure rate and dropout rate. The total cure rate was 29.2%, but the cure rate was 68.8% for the patients who continued their medication for more than one year. For the comparative study, 139 patients who received the treatment at the same institution between 1992 and 1995 were evaluated. The cure rate and the dropout rate for GRF were found to be 23.8% (23/97) and 52.6% (51/97) respectively. The cure rate and the dropout rate for ITCZ were found to be 50.0% (21/42) and 38.1% (15/42). When the two treatment protocols were compared for their long-term effects, we found that most of the patients treated with ITCZ were cured within 3 years, and about 30% of the patients treated with GRF remained uncured even after long-term administration of the agent. Furthermore, from a multiple regression analysis, the GRF/ITCZ administration required to cure onychomycosis was estimated to be 3.92 + 0.161 [Age (years)] + 0.635 [Number of infected toenails] months. The results of this study suggest that the biggest problem associated with the treatment of onychomycosis with an oral antifungal agent is compliance in long-term therapy. Notably, the final cure rate of ITCZ therapy went over 90%, suggesting that the low dose continuous therapy, the standard treatment protocol in Japan, was a key contributing factor for the higher cure rate for ITCZ.

Epidermal keratinocytes respond to injury by becoming activated, i.e. hyperproliferative, migratory, and proinflammatory. These processes are regulated by growth factors and cytokines. One of the markers of activated keratinocytes is keratin K6. We used a novel organ culture system to show that tumor necrosis factor a (TNFα) induces the expression of K6 protein and mRNA in human skin. Multiple isoforms of K6 are encoded by distinct genes and have distinct patterns of expression. By having shown previously that proliferative signals, such as epidermal growth factor (EGF), induce expression of the cytoskeletal protein keratin K6b, we here demonstrate that the same isoform, K6b, is also induced by TNFα, a proinflammatory cytokine. Specifically, TNFα induces the transcription of the K6b gene promoter. By using co-transfection, specific inhibitors, and antisense oligonucleotides, we have identified NFκB and C/EBPβ as the transcription factors that convey the TNFα signal. Both transcription factors are necessary for the induction of K6b by TNFα and act as a complex, although only C/EBPβ binds the K6b promoter DNA. By using transfection, site-directed mutagenesis, and footprinting, we have mapped the site that responds to TNFα, NFκB, and C/EBPβ. This site is separate from the one responsive to EGF and AP1. Our results show that the proinflammatory (TNFα) and the proliferative (EGF) signals in epidermis separately and independently regulate the expression of the same K6b keratin isoform. Thus, the cytoskeletal responses in epidermal cells can be precisely tuned by separate proliferative and inflammatory signals to fit the nature of the injuries that caused them.

皮膚科領域感染症に対し,1回100〜200mg 1日2回投与で有用な薬剤となり得ることが期待できた

32歳女.約4年前より左膝蓋部に虫刺様の小皮疹が出現,掻痒と熱感を伴いながら拡大したが,約6週間で自然消退した.3年後にも同様の丘疹が出現,約6週間で自然消退した.その1ヵ月後,同部位に紅色丘疹が出現,周囲に紅斑も拡大した.WBC:7,200/μl,eosino:6.0%,CRP<0.3mg/dl,便虫卵陰性,抗ライム病抗体陰性.組織学的に膠原線維内への好酸球の浸潤といわゆるflame figureを認めた.生検後2週間で皮疹は自然消退した.その後約1年半再燃を認めない

70歳女,約5年前から,全身のび漫性紅斑を繰り返し生じるため受診.約10回パモ酸ヒドロキシジン(アタラックス-P)カプセルの投与歴あり.初診時,ほぼ全身に掻痒感を伴うび漫性紅斑を認め,一部に粃糠様落屑,四肢には強い浮腫を伴っていた.前胸部の生検組織像では,角層下微小膿瘍を認めた.パモ酸ヒドロキシジンの貼布試験,リンパ球幼若化試験は陰性であったが,内服試験にて紅斑の再現をみた.誘発された紅斑の組織では,表皮内リンパ球と真皮上層の好中球浸潤を軽度認めた.パモ酸ヒドロキシジンによる膿疱型薬疹は比較的まれであり,文献的考察を加えて報告する

71歳女.数年前より感冒に伴い後頭部痛が出現.8ヵ月前より新たに側頭部痛も出現,投薬により一時軽快したが,頭痛の再発と共に強い耳鳴を生じ,側頭動脈の怒張と拍動消失を認めた為,入院.検査所見では白血球7,000/μl, CRP 0.5mg/dl,血沈86mm/h.側頭動脈生検組織像は血管壁内巨細胞,内弾性板の断裂,リンパ球を主体とする炎症細胞浸潤等の典型像を呈した.プレドニゾロン 30mg/dayの内服を開始したところ,血沈値は2週間後に正常化した.経過中,血沈値は病勢を反映して下降しており,治療効果の指標となった.現在,プレドニゾロンを10mg/dayまで減量し経過観察中であるが,特に再燃傾向はない

1)30年前から現在迄の患者背景の変化, 2)GRFの爪白癬に対する有効性について検討した.患者背景は,患者は高年齢化していた.griseofulvin(GRF)の有効性に関しては,1962年のみ治療期間が有意に短かったが,年齢別では,40〜60歳の1962年のみ有意差があり,他の年齢層では有意な変化はなかった.全体の治癒率は91/281, 4ヵ月以上継続して治療した者については91/172であった.治癒に至った患者の平均内服期間は415日であった.副作用発現率は,24/281で重篤なものはなかった.4ヵ月以上継続して治療した患者について考えると,その半数以上が治癒に至っていることから,GRFは継続して内服するとかなり有効性の高い,安全な薬剤と考えられた

61歳男,初診時,顔面を除くほぼ全身に浸潤を触れる紅斑が多発し一部で腫瘤を形成していた.組織学的に表皮,真皮の広範囲に異型リンパ球の浸潤を認めた.抗ATLA抗体陰性であった.菌状息肉症の腫瘍期と診断してinterferon-γ全身投与,電子線全身照射療法を行うが,頭部から下肢まで次々と手拳大にも及ぶ腫瘤が出現し潰瘍を形成し感染を繰り返した.初診半年後には痙攣発作を生じ脳CTにて脳転移が疑われた.その2ヵ月後,敗血症のため死亡.剖検にてリンパ節,肺などと共に脳内にも転移巣が認められた

The true nature of nevocellular nevus is still unknown and it has been ambiguously classified as a neoplasm or a hamartoma. We studied the clonality of nevocellular nevus and melanoma (malignant melanoma), using an expression- based clonality analysis at the X-linked genes by means of polymerase chain reaction. DNA was extracted from cryostat sections of 20 nevocellular nevi (10 compound and 10 intradermal type) and five melanomas from female patients. A polymorphic portion of the inactivated X-linked gene was amplified after selective digestion of the active X-chromosome with a methylation-sensitive restriction enzyme, Hpa II. Paternal- and maternal- derived fragments were resolved with electrophoresis using the polymorphic restriction endonuclease (BstX I) site for the phosphoglycerate kinase assay, and using the difference of CAG repeats for the human androgen-receptor gene assay. Both assays revealed that all informative nevocellular nevi were polyclonal in origin and all melanomas were monoclonal. Results of the clonality were independent of either the histologic type of nevocellular nevus or whether the nevocellular nevus was of congenital or acquired origin. Thus, nevocellular nevus, congenital or acquired, may be a hamartomatous rather than a neoplastic lesion. The analysis of clonality could be applied to the differential diagnosis of benign melanocytic disease and melanomas.

54歳男.1990年,背部の徐々に隆起,増大する黒褐色斑を主訴に受診.悪性黒色腫の臨床診断で,腫瘍切除植皮術ならびに両側腋窩リンパ節郭清,化学療法(DAV)を施行.組織学的には,表在拡大型悪性黒色腫でクラーク分類level IV, tumor thicknessは最大2.8mm.1991〜1992年,右腋窩皮膚に頻回に出現した転移巣を切除.同時期に上背部に径5mm大の,軽度に浸潤を触れる紅斑が出現.これには,真皮内に中等度の異型を有するリンパ球の帯状浸潤を認め,細胞表面マーカーはUCHL-1に約70%の細胞が陽性,L26では,約30%に陽性,CD30(Ki-1)は陰性.その後,胸部,背部にも同様の局面が数個出現.いずれもlymphomatoid papulosis(LP)と診断した

29歳男.初診の1年前より左肩甲上部に自覚症状のない小腫瘤出現,その後急速に増大し,数ヵ月で現在の大きさに達するも,その後増大傾向なし.左頸部に15×13×15mmの有茎性腫瘤を認める.腫瘤の被覆皮膚は著変なく,その下に可動性のあるやや凹凸のある弾性硬の結節を触れる.頸部,腋窩リンパ節腫脹なし.組織所見では,薄い被膜を有する腫瘍塊は異型性の強い線維芽細胞様細胞と泡沫状の組織球様細胞からなり,storiform patternがみられ,核分裂像,多核巨細胞も散見する.炎症性細胞浸潤はなく,一部に粘液腫様変化を認めた

A case of crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma is presented. Unlike previous cases, this patient presented with signs and symptoms suggestive of Weber-Christian disease. Biopsy of subcutaneous nodules showed numerous deposits of crystal-storing histiocytes with lymphoplasmacytic cells, the latter exhibiting fight chain restriction (λ-chain) with a predominance of immunoglobulin (Ig)G heavy chain. Polymerase chain reaction (PCR) analysis of CDR-III region of the immunoglobulin heavy chain locus confirmed monoclonality of the lymphoplasmacytic cells in the nodule. Electron microscopy showed polygonal- shaped amorphous crystals, characteristic of immunoglobulin in the histiocytic cells. Crystal-storing histiocytosis should be examined by immunohistochemical and DNA analysis to confirm or exclude the possibility of lymphoplasmacytic lymphoma.

臨床的及び組織学的に扁平苔癬と診断された48例の臨床的特徴を検討した.著明な性差は認められず,年齢的には男女とも50歳前後にピークがあり,部位としては四肢の特に末梢に最も高い発症頻度が示された.特殊なものとしては線状型が3例,環状型が2例,水疱型が1例あった.合併症としては高血圧と肝疾患が比較的高頻度に認められた

Azithromycin (AZM), a 15-membered new macrolide, was compared with cefaclor (CCL) in a multicenter, double-blind, double-placebo trial in the treatment of skin and skin structure infections. Patients, more than 16 years of age, with hair follicle- and nailassociated deep infections (furuncle, furunculosis, carbuncle, sycosis barbae, and acute suppurative paronychia: group II a), diffuse deep infections (lymphangitis, erysipelas, and cellulitis: group II b), and cutaneous and subcutaneous abscesses (infected atheroma, suppurative hidradenitis, and miscellaneous abscesses: group III) were enrolled after informed consent had been obtained. Patients assigned to the AZM group received two 250 mg tablets once a day for three days and one CCL placebo capsule three times a day for seven days. Patients assigned to the CCL group received two AZM placebo tablets once a day for three days and one CCL 250 mg capsule three times a day for seven days. © 1995, Japanese Society of Chemotherapy. All rights reserved. © 1995, Japanese Society of Chemotherapy. All rights reserved.

background. Recently, liposuction surgery has been widely accepted for body contouring or other noncosmetic applications, including lipoma and angiolipomatosis. objective. We treated a case of multiple angiolipomas at 49 years of age to confirm the Utility of liposuction. methods. Liposuction under general anesthesia was performed for angiolipomas distributed over the trunk. results. The patient has been followed for 2 years without recurrence. conclusion. We believe that liposuction is a safe and easy method of removing multiple angiolipomas. 1994 American Society for Dermatologic Surgery, Inc.

A multicenter, double-blind, double-placebo trial was conducted to compare the efficacy and safety of SY 5555, a new oral penem, with cefaclor (CCL) in the management of skin and skin structure infections. Patients, aged more than 15 years, with deep-seated hair structure infections (furuncle, furunculosis, carbuncle), impetigo, deep-seated diffuse infections (erysipelas, cellulitis, lymphangitis, lymphadenitis). and chronic pyodermas (infectious atheroma, hidradenitis suppurativa, miscellaneous abscesses) were enrolled after informed consent had been obtained. Patients assigned to the SY 5555 group received one 200 mg tablet of SY 5555 and one CCL placebo capsule three times a day after meals, and patients assigned to the CCL group received one SY 5555 placebo tablet and one CCL 250 mg capsule three times a day after meals. Patients were treated for 7 days except for those with chronic pyoderma, who were treated for 10 days. Patients were evaluated in terms of clinical efficacy, safety and bacteriologic response. Three hundred twenty-three patients (SY 5555 group, 161 patients; CCL group, 162 patients) were enrolled. The clinical efficacy rates were 89.0% (129/145) for the SY 5555 group and 90.7% (136/150) for the CCL group. Overall general improvement rates on day 5 were 85.9% (110/128) for the SY 5555 group and 81.6% (111/136) for the CCL group. The safety rates were 87.2% (130/149) for the SY 5555 group and 93.5% (143/153) for the CCL group. Adverse reactions were almost all of gastrointestinal origin and were minor in both groups. Abnormal laboratory findings were also all minor in both groups. Bacteriologic response rates were 93.5% (87/93) for the SY 5555 group and 89.8% (79/88) for the CCL group. These differences were not statistically significant. These data suggest that SY 5555 is as effective and safe as CCL in the management of skin and skin structure infections. © 1994, Japanese Society of Chemotherapy. All rights reserved.

A combination therapy of mycosis fungoides (MF) with interferon-α (INF-α) and etretinate was reported. A 53-year-old patient suffering from MF was treated with intramuscular administration of INF-α at a dosage of 9 x 106 IU daily; skin lesions poorly responded to the treatment. After oral etretinate with a dosage of 50 mg daily was combined with INF-α, marked clinical improvement was seen in skin lesions with minor side effects. INF-α in combination with etretinate can have beneficial effects in the treatment of MF.

64歳男.約35年前に右脛骨結核性骨髄炎で骨移植術の既往がある.15年前より,右膝に紅色皮疹が出現し,徐々に拡大した.5年前外傷を受けてからは常に中心部から出血を認めていた.初診時,右膝蓋部に潰瘍を伴い周囲に赤色疣状丘疹が集簇する局面を認めた.組織学的にラングハンス型巨細胞を伴う類上皮細胞肉芽腫で,膿および組織片よりMycobacterium tuberculosis培養陽性,INAH, RFP, EBの三者併用療法で軽快した.最近9年間の尋常性狼瘡本邦報告例64例に自験例を加えて考察を加えた

49歳男,6ヵ月来,躯幹及び四肢に自覚症状のない紅色丘疹・紅斑が出没し,一部は落屑・び爛を伴っていた.組織学的には真皮乳頭層から中層に密な細胞浸潤を認め,一部は表皮内に侵入していた.浸潤細胞はリンパ球と組織球からなり,その中に脳回転様核を有する異型細胞と大型で核小体が明瞭な異型細胞を認めた.これらの異型細胞はhelper/inducer T cellで,大型異型細胞はCD 25, CD 30陽性であった.以上より,Lymphomatoid papulosisと診断.PUVA療法を行い,皮疹は消退した

新セフェム系抗生物質cefepimeを8例の浅在性化膿性疾患の患者に1回0.5または1 gを1日2回,4〜26日間投与し,その臨床効果および安全性について検討した.各疾患に対する臨床効果は,二次感染6例では著効3例,有効1例,やや有効2例,伝染性膿痂疹および膿皮症各1例はともに著効であった.副作用に関しては自他覚的なものはなく,臨床検査値異常変動は1例にGOT上昇を認めた

新セフェム系抗生物質cefepimeを8例の浅在性化膿性疾患の患者に1回0.5または1gを1日2回, 4～26日間投与し, その臨床効果および安全性について検討した。その結果, 各疾患に対する臨床効果は, 二次感染6例では著効3例, 有効1例, やや有効2例, 伝染性膿痂疹および膿皮症各1例はともに著効であった。副作用に関しては自他覚的なものはなく, 臨床検査値異常変動は1例にGOT上昇を認めた。

Cryptococcus neoformansの静注によって作成したラットの肝肉芽腫についてFNの関与を検討するため,肉芽腫構成細胞と,別に腹腔より採取したMφを材料とし,FNの局在を電顕酵素抗体法を用いて検索した.1)肝肉芽腫の構成細胞の相互接着面に一致してFNの陽性像が得られた.2)一部の培養ラット腹腔Mφの相互接着部分にも,FNの陽性像を認めた.3)Mφがクリプトコックス感染巣において肉芽腫の様な強固な相互接着を必要とする場合には,FNが重要かつ不可欠な役割を果している

大学第2病理学教室の全剖検例(1975〜1984年)を対象として集計した.全剖検例714例中,真菌症は93例(13.0%)に存在した.各真菌症の内訳は,カンジダ症が50.5%で一番多く,ついでアスペルギルス症22.6%,クリプトコックス症5.4%,ムーコル症3.2%の順であった.続発性真菌症の基礎疾患では,白血病が最も多く33.3%を占め,ついで白血病および悪性リンパ腫以外の悪性腫瘍(悪性腫瘍),悪性リンパ腫,白血病以外の血液疾患の順であった.また主な基礎疾患別にみた真菌症の発生頻度は,悪性リンパ腫瘍で最も高く(80.0%),ついで白血病,白血病以外の血液疾患,悪性腫瘍の順であった.各真菌症における組織病変では,カンジダ症,アスペルギルス症で壊死性病変が過半数を占め,宿主の免疫不全状態をよく反映していた.一方,クリプトコックス症とムーコル症では,それら原因菌に対応した組織病変を示した.各種組織病変と白血球数の関係では,好中球数についてみると,白血病例の83.3%にあたる15例で,2,500/mm3を下回っており,宿主の免疫不全状態とよく呼応していると考えられた.リンパ球数についてみると,好中球数が2,500/mm3を下回っている場合には,それと相関したリンパ球数の減少傾向を認めた