矢上 晶子

BACKGROUND: Immediate allergy caused by natto, a popular Japanese food prepared by fermenting soybeans with Bacillus subtilis var. natto, has been reported. Polygamma glutamic acid (PGA) in the sticky substance around natto beans has been reported to be a causative allergen of natto allergy. However, some of our patients with natto allergy were negative for PGA in the skin prick test (SPT). The sticky substance of natto beans contains a subtilisin family serine protease, nattokinase, along with PGA. In this study, we aimed to examine the antigenicity of nattokinase in natto allergy. METHODS: Eight patients, who developed symptoms after ingesting natto and positively reacted to natto (seven to the sticky substance in natto and one to the whole natto product) in their SPT, were enrolled in this study. To analyze IgE reactivity, we performed immunoblotting, ELISA, and SPT for natto (bean and sticky substance), and/or PGA, and/or nattokinase and/or cultured B. subtilis var. natto extract. RESULTS: In the SPT, four cases each were PGA-positive and PGA-negative. Immunoblotting of the sera from PGA-negative patients showed a protein band at 30 kDa, which was identified as nattokinase. Three PGA-negative cases, but not three PGA-positive cases, showed a positive reaction to nattokinase in the SPT and had a history of atopic dermatitis. The ELISA for nattokinase revealed a positive reaction of PGA-negative cases and negative reaction of PGA-positive cases in the SPT. CONCLUSIONS: We identified a subtilisin family serine protease, nattokinase, as a novel allergen in natto allergy patients unsensitized to PGA.

＜文献概要＞16歳,女性。モモ,イチジク摂取後にアナフィラキシー症状を発症した。複数の果物類摂取後にアレルギー症状を繰り返したとの臨床経過からgibberellin-regulated protein(GRP)抗原の関与を疑い,諸検査を施行した。その結果,プリックテストではイチジク(4+),モモ自体・モモGRPともに(3+)陽性であり,モモGRPの特異的IgEも陽性で,かつこの抗原はイチジク粗抗原で阻害されたため,自験例をGRPアレルギーと診断した。GRPは熱安定性および消化酵素抵抗性を有しているため当初はクラス1アレルゲンであると考えられていたが,近年はヒノキ花粉やスギ花粉中のGRP抗原との交差反応性に注目されており,今後同様の症例の発現に留意する必要がある。

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a life-threatening food allergy triggered by wheat in combination with the second factor such as exercise. The identification of potential genetic risk factors for this allergy might help high-risk individuals before consuming wheat-containing food. We aimed to identify genetic variants associated with WDEIA. A genome-wide association study was conducted in a discovery set of 77 individuals with WDEIA and 924 control subjects via three genetic models. The associations were confirmed in a replication set of 91 affected individuals and 435 control individuals. Summary statistics from the combined set were analyzed by meta-analysis with a random-effect model. In the discovery set, a locus on chromosome 6, rs9277630, was associated with WDEIA in the dominant model (OR = 3.95 [95% CI, 2.31-6.73], p = 7.87 × 10-8). The HLA-DPB1∗02:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 [95% CI, 2.66-7.63], p = 2.28 × 10-9), as determined via HLA imputation following targeted sequencing. The association of the allele with WDEIA was confirmed in replication samples (OR = 3.82 [95% CI, 2.33-6.26], p = 3.03 × 10-8). A meta-analysis performed in the combined set revealed that the HLA-DPB1∗02:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 [95% CI, 2.89-5.93], p = 1.06 × 10-14). Individuals carrying the HLA-DPB1∗02:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed.

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.

BACKGROUND: There is controversy over late and long-lasting reactions to gold sodium thiosulfate (GST). OBJECTIVES: To study the GST patch-test reaction by observing the application site after 1 month, and to clarify the relevance of GST sensitization by piercings and dental metals. PATIENTS: A retrospective analysis was performed on 746 patients (143 male; 603 female) who were patch tested using GST of the TRUE Test. We conducted a questionnaire on the presence of piercings or dental metals in these patients. RESULTS: The GST positive rate was 27.9% at day (D)3 and/or D7 and 40.3% up to the 1-month reading. The positive rate was significantly higher in female patients and increased with age. Sixty-two percent of cases with a positive reaction at D7 continued to show a positive reaction after 1 month. Eleven percent of cases with a negative reaction at D3 and D7 showed a late reaction. Both piercings and dental metals were related to gold sensitization. CONCLUSIONS: The GST of the TRUE Test had a high positive and low false-negative rate. The 1-month reading after the patch test was important for identifying late reactions. Piercing history and dental metal were associated with gold sensitization.

2015年に化粧品による接触皮膚炎を疑った69例(男性2例、女性67例、平均年齢44.6歳)を対象に、背部または上腕外側に48時間閉鎖貼付によるパッチテスト(PT)を施行した。試料は患者が持参した化粧品とJapanese standard allergens 2008または2015および化粧品関連アレルゲンとした。判定は72時間または1週間後にInternational Contact Dermatitis Research Group基準で+以上を陽性とした。化粧品または関連アレルゲンのPTが陽性で臨床的に関連性があると考えられた症例は14例で、原因製品は9製品であった。最も多い原因製品はヘアカラー剤であった。例年と比較して特に増加傾向の陽性製品や新規のアレルゲンは認めなかった。

Here, we report 3 cases of necrotizing fasciitis that were successfully treated by minimal surgical debridement. Case 1: a 73-year-old woman had bruised her right hand, and redness rapidly spread to the right upper arm. Initial debridement was performed on her right hand, and administration of an antibiotic was started. The redness and fever diminished in 10 days. Case 2: a 39-year-old man was admitted to our hospital because of purpura and necrosis accompanied by tenderness over a wide area from the right knee to the thigh. Since he also had severe diabetes, we limited initial debridement by incision only to the markedly necrotic site. The inflammatory response was improved after the administration of an antibiotic and strict general care for a few days. Case 3: a 73-year-old man was aware of a swelling of the dorsal side of the right hand since his first visit 2 days before. The swelling and redness rapidly expanded to the entire right upper arm, and he suffered from septic shock. In addition to an incision to his right hand, intensive care including the intravenous administration of antibiotics and endotoxin adsorption therapy were performed. He recovered from septic shock and was fully recovered within a month after admission. In conclusion, proper debridement is required for the treatment of necrotizing fasciitis.

7歳女児，シェーグレン症候群を伴った小児皮膚筋炎(juvenile dermatomyositis;JDM)の1例を報告する。1歳時，下肢に皮疹が出現し，よく転ぶ，力が入らない，動作が止まるなどの筋力低下の症状が出現した。2歳時，他院で皮膚病理所見，筋原性酵素の上昇からJDMと診断され，ステロイド剤内服を開始した。3歳時に当科を紹介され受診した際には筋力低下，ヘリオトロープ疹，Gottron徴候を認めた。4歳時にシェーグレン症候群を併発した。4歳時以後，筋炎症状は消失し，7歳時にステロイド剤を中止した。一時耳下腺腫脹を認めたが，筋炎の再燃は認めなかった。

50歳，女性。飼い猫のけんかを止めようとして，右前腕部を爪で引っ掻かれた。その翌日から同部位に腫脹，疼痛，膿瘍を生じ当科を受診した。膿の細菌培養の結果，原因菌をPasteurella multocidaと同定した。ミノマイシン200mg/日投与で治療し，症状は軽快したが，病巣部に違和感が1ヵ月残存した。本疾患は基礎疾患を有する患者が罹患すると重症化するおそれがあるため，初期の適切な診断，検査，治療が重要である。

We aimed to develop an animal model for atopic dermatitis. HR-1 hairless mice fed a diet with reduced magnesium and zinc levels were compared with mice fed a standard diet. Skin dryness and wrinklelike changes, scratching behaviour, decreased skin water content, increased transepidermal water loss and raised blood immunoglobulin E levels were seen in the group receiving the reduced magnesium and zinc diet compared with control mice. There were no significant differences in body weight or the weight of the major organs between the two groups. Haematological examination in both groups was normal apart from increased immunoglobulin E levels in mice fed a reduced magnesium and zinc diet. These mice may be useful models of atopic dermatitis; preparation of the animals is not particularly time consuming, the reproducibility is 100%, and atopic dermatitis symptoms occur even in a specific pathogen-free environment.

小児アトピー性皮膚炎(AD)患者は皮膚バリア機能が弱く，外来性刺激物質によって接触皮膚炎を起こしやすい。その結果として障害された皮膚からスキンケア製品や外用薬など日常頻繁に接触する単純化学物質が吸収され，感作された結果アレルギー性接触皮膚炎を起こす。また，ラテックスなどの蛋白抗原による接触蕁麻疹も発症しやすい。小児ADにおける刺激性接触皮膚炎の原因は洗浄用スキンケア製品と消毒薬があげられる。アレルギー性接触皮膚炎の原因は外用薬，スキンケア製品，金属などがあげられる。これらの診断にはパッチテストやプリックテストを行ない，合併する接触皮膚炎を早期に治療し，代替品の選択を行なうことが肝要である。

敏感肌用化粧品dプログラム^®シリーズの新しいメーキャップ化粧品(リキッド/パウダリーファンデーション，アイカラー，チークカラー，口紅，リップクリーム)について，接触皮膚炎の既往を有する患者(CD)と軽症から中等症のアトピー性皮膚炎患者(AD)を対象として4週間の使用試験を行い，安全に使用できるか否かを検討した。副作用により試験試料の使用を中止した例は，口紅についてはやや高く5.2%であったが，リキッドファンデーションでは中止例はなく，その他の試料では2～3%であった。副作用の程度も軽微～軽度であり，本メーキャップ化粧品シリーズは，敏感肌に対して安全に使用できるものと考えられた。