鈴木 加余子

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.

BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.

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.

Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.

BACKGROUND: The proportion of positive test results with gold sodium thiosulfate included in a patch test panel (P-GST) had been found to be greater than that with gold sodium thiosulfate 0.5% pet. by allergEAZE (A-GST). OBJECTIVES: To compare positive reactions to P-GST and A-GST, and to evaluate late reactions after the day (D) 7 reading. METHODS: A retrospective analysis was performed of 588 patients at participating departments (119 males; 469 females) who were patch tested with P-GST and A-GST in May 2015 to March 2016. RESULTS: Positive test reactions to P-GST and A-GST were observed in 15% and 6% of patients, respectively. Three patients reported a positive reaction occurring after the D7 reading. CONCLUSIONS: Gold sodium thiosulfate often gives a positive reaction after 2 to 3 weeks, and, in such cases, the positive reaction may be sustained, so it is recommended to assess the reaction for up to 1 month after application.

Background: Cochineal dye is used worldwide as a red coloring in foods, drinks, cosmetics, quasi-drugs, and drugs. The main component of the red color is carminic acid (CA). Carmine is an aluminum- or calcium-chelated product of CA. CA and carmine usually contain contaminating proteins, including a 38-kDa protein thought to be the primary allergen. Severe allergic reactions manifest as anaphylaxis. The aim of this study was to review all Japanese reported cases and propose useful diagnostic chart. Methods: All reported Japanese cases of cochineal dye-induced immediate allergy were reviewed, and newly registered cases were examined by skin prick test (SPT) with cochineal extract (CE) and measurement of CE and carmine-specific serum IgE test. Two-dimensional (2D) western blotting using patient serum was conducted to identify the antigen. Results: Twenty-two Japanese cases have been reported. SPT and the level of specific IgE test indicated that six cases should be newly registered as cochineal dye allergy. All cases were adult females, and all cases except three involved anaphylaxis 13 cases involved past history of local symptoms associated with cosmetics use. Japanese strawberry juice and fish-meat sausage, and European processed foods (especially macarons made in France) and drinks were recent major sources of allergen. 2D western blotting showed that patient IgE reacted to the 38-kDa protein and other proteins. Serum from healthy controls also weakly reacted with these proteins. Conclusions: SPT with CE and determination of the level of CE and carmine-specific IgE test are useful methods for the diagnosis of cochineal dye allergy.

A 72-year-old male visited a nearby hospital with a large tumor in his occipital region, which had existed since 20 years. Since malignant tumor was suspected, he was referred to our department. At the initial consultation, an elastic-hard, yellow-brown, sessile tumor, measuring 8 × 7 × 5 cm and with a flat surface, was observed in the occipital region. The tumor was resected and covered with artificial dermis. Histopathologically, the lesion was composed of basal-cell-like cells with nest formation in the dermis. A rippled pattern, or the single-line arrangement of tumor cells involving the stroma, was present. In addition, some tumor clusters revealed the differentiation to sebaceous glands, and these cells were positive for cytokeratin (AE1/AE3) and epithelial membrane antigen, which is consistent with the staining of sebaceous glands. On the contrary, tumor cells were negative for epithelial antigen (Ber-EP4), and Ki67 (MIB1) index was 5% or lower. Therefore, we diagnosed the tumor as rippled-pattern sebaceoma and not as basal cell carcinoma. Although this case was quite unique in its large size, immunostaining was useful for the definite diagnosis.

症例1は32歳女で、アトピー性皮膚炎の治療で通院していた。臨床症状と皮膚テスト結果よりラテックス・フルーツ症候群と診断した。歯列矯正ゴムの使用の中止を指示し、今後はラテックス含有製品を使用しないように注意を促した。皮膚テスト陽性であった果物は摂取しないように指導した。症例2は25歳女で、臨床実習の頃からラテックス手袋を装着すると手首まで蕁麻疹が出ることがあった。臨床症状と皮膚テスト結果よりLAと診断した。仕事で用いる手袋はラテックスフリーのものにするよう指導し、その他のラテックス含有製品の使用を禁止した。症例3は38歳女で、就業中にラテックスゴム手袋を装着したところ腹痛、全身の蕁麻疹が出現した。臨床症状と皮膚テスト結果よりLAと診断した。仕事中はラテックスを含まない手袋を使用するように指導した。また、その他のラテックス含有製品の使用を禁止した。

Because some users develop depigmentation after the use of melanogenesis-inhibiting products containing the quasi-drug ingredient Rhododenol, Japanese Dermatological Association (JDA) established a Special Committee on the Safety of Cosmetics Containing Rhododenol on July 17, 2013 and management guide for dermatologists has been updated on the website in order to delineate the diagnostic criteria for Rhododenol-induced leukoderma and provides a broad guide for standard treatment based on current knowledge. This guide is produced on the basis of the guide (version 7) updated on June 20, 2014 in the website. Rhododenol-induced leukoderma refers to depigmentation of varying severity that develops after the use of cosmetics containing Rhododenol, mainly at the site of use. In most cases, repigmentation of part or all the affected area is evident after discontinuation. Histopathologically cellular infiltration around the hair follicles and melanophages are present in most cases. The number of melanocytes in the lesion is declined but not totally absent in most cases. Rhododenol itself is a good substrate for tyrosinase, resulting in the formation of Rhododenol metabolites (e.g., Rhododenol quinone). Melanocytes are damaged by Rhododenol metabolites during the subsequent metabolic process. The continued use of cosmetics containing Rhododenol thus induces tyrosinase activity-dependent cytotoxicity in melanocytes in the epidermis at application sites, resulting in decreasing the amount of melanin produced by melanocytes; the addition of some other factor to this process is believed to subsequently cause the decrease or disappearance of melanocytes themselves from the epidermis.

A 13-year-old girl who had had pollinosis since the age of eight began to experience itching of the ears and vomiting after eating fresh fruits such as peach, apple and watermelon. This occurred at 10 years of age. The girl displayed positive reactions to six kinds of pollens, eleven kinds of fruits, numerous vegetables and to recombinant: rBet v2 present in specific IgE antibodies. She also reacted positively to several pollens, fruits and rBet v2 in the skin prick test. In the component-resolved diagnosis (CRD) using microarray technology, she also tested positive for profilin, a pan-allergen among plants. It is reported that profilin cross-reacts between pollen, fruits, vegetables and latex. From these results, we concluded that the allergic reactions to multiple kinds of foodstuff and pollens observed in this subject were due to cross-reactivity induced by profilin. Our results demonstrate that CRD by microarray is a reliable test in the diagnosis of PFAS.

BACKGROUND: Natural rubber latex (NRL) allergy is a common occupational disease in health care workers (HCW). However, few reports have compared the major allergen of HCWs to those in gloves that are routinely used in the hospital. The aim of this study was to evaluate the major NRL allergens in gloves used by HCWs. METHODS: We studied 20 HCWs who were suspected to have latex allergy (LA). We performed a skin prick test (SPT) using NRL allergens. Serological testing was performed using the ImmunoCAPTM. The total amount of protein and the antigenic protein concentrations extracted from NRL gloves were measured. Four different types of FITkitTM were used to measure the concentrations of Hev b 1, 3, 5, and 6.02 in the gloves. RESULTS: A SPT using NRL extract identified 14 cases with positive reactions. The sensitivity and specificity of the SPT scores to the NRL glove extract were 100%. The sensitivity of latex specific IgE was 100% but the specificity was 14.2%. The sensitivity and specificity of rHev b 6.02 specific IgE were 100% in the LA group. The total amounts of protein from the medical gloves for surgery and examination were 265 microg/g and 95 microg/g, respectively. The antigenic protein concentrations in the gloves were 24.9 microg/g and 1.0 microg/g, respectively. The total amounts of the specific four allergens in the NRL gloves were 2.18 microg/g and 0.45 microg/g, respectively. CONCLUSIONS: We concluded that the main allergen of HCWs who have been sensitized occupationally by NRL gloves was Hev b 6.02.

We report a 22-year-old woman with urticaria, dyspnea and bronchial asthma-like attacks after eating curried rice. We found the symptoms to be due to an immediate-type allergy caused by spice antigens contained in curry spices by detailed questioning, skin test and measurement of specific immunoglobulin (Ig)E antibodies. This case was complicated with pollen-food allergy syndrome (PFAS) from melon and latex allergy (LA) to natural rubber latex (NRL) antigen and she had also had atopic dermatitis, allergic rhinitis and pollinosis. Serum specific IgE antibodies to birch profilin (Bet v 2), latex profilin (Hev b 8), and timothy profilin (Phl p 12) were detected. She also showed positive reactions to several Apiaceae families, fruits and latex antigens in skin prick test. Based on these findings, we considered her symptoms to be involved with spice allergy, PFAS and latex-fruit syndrome.

Oral allergy syndrome to soy milk is classified as a phenotype of pollen-food allergy syndrome (PFAS). As causative antigens, Gly m 4 (Bet v 1 homolog, 17 kD) and oleosin (23 kD), have been reported. In this study, we report two cases of PFAS to soy milk. Both cases showed positive reactions to soy milk in skin prick tests (SPT) and to Gly m 4 in specific serum immunoglobulin (Ig)E antibody. When we measured specific serum IgE antibody of soy-related proteins using a new laboratory testing method, microarray analysis, both cases showed a positive reaction for Bet v 1. One case was weakly positive for a soybean protein, beta-conglycinin. Other results for reactivity to soy, peanut, cross-reactive carbohydrate determinants and profilin were negative. Based on these results, we diagnosed the two cases as PFAS to Gly m 4. We also performed protein microarray analysis and found it useful as a screening test for immediate allergy, such as PFAS.

BACKGROUND: Human herpesvirus 6 (HHV-6) reactivation has been suggested to modify the clinical features of drug induced hypersensitivity syndrome (DIHS). However, mechanisms for viral reactivation and modification of the clinical features remain unclear. OBJECTIVE: To determine whether cytokines play an important role in viral reactivation and modification of the clinical features. STUDY DESIGN: We examined the kinetics of serum cytokines and viral load in HHV-6 infections of six patients with DIHS. RESULTS: HHV-6 infection occurred three to four weeks after the onset of disease. Elevated TNF-alpha and IL-6 levels were observed to precede HHV-6 infection in four of the six patients. Although high levels of IL-6 were observed in samples collected prior to HHV-6 infection, the amounts of this cytokine significantly decreased to undetectable levels during viral infection in five of the six patients. Subsequently, serum IL-6 levels were increased after viral infection in five patients. IL-1beta levels were also increased at the time of viral infection in three of the six patients. Neither IL-4 nor IFN-gamma could be detected in any of the samples. CONCLUSION: These results demonstrate that cytokines play an important role in HHV-6 reactivation in patients with DIHS.

BACKGROUND: While many cases of latex allergy have been reported in Japanese health care workers (HCWs) since 1992, there have been no follow-up studies after removing latex from the workplace. We had previously replaced all working environment latex gloves and latex products with low-allergen or non-latex products. The purpose of the investigation was to evaluate the benefits of the latex allergy countermeasures that were taken in our hospital, and the effects of life guidance education. METHODS: We investigated 16 latex-allergic HCWs in our hospital. We gave them a detailed questionnaire and tested them by a skin prick test (SPT) with latex extract and specific IgE antibodies against latex using the Pharmacia CAP RAST system, RAST FEIA. We compared these results with earlier results from the time of diagnosis. RESULTS: According to the questionnaire, none of the HCWs had changed their work habits, though all were avoiding the use of latex products as much as possible. Of the 16 patients, 81.2% were eating foods for which cross reactivity with latex has been reported. However, the foods had not induced severe allergic symptoms. In the SPT, 62.5% of scores decreased and 81.2% of patients had decreases in specific IgE antibody levels. CONCLUSIONS: After avoiding latex products and following our educational suggestions, the patients' allergy symptoms had generally improved. This indicates that our countermeasures against latex allergy were largely successful.

For the first time in Japan, a large-scale survey to investigate awareness of latex allergy was carried out, targeting all health care workers at Fujita Health University School of Medicine (total 1512 people). At first, we used questionnaires to collect information regarding the level of awareness of latex allergy as well as the incidence of clinical symptoms when using natural rubber products. The results of the survey revealed that approximately 85% of respondents were aware of latex allergy. Among all respondents, approximately 19% had actual experience with clinical symptoms. As a result of skin tests conducted on respondents who had acknowledged clinical symptoms, 44 people (total 3.3%) were diagnosed with latex allergy. In addition, the results revealed that people who were diagnosed with latex allergy tended to suffer atopic dermatitis and hand eczema. Furthermore, it became evident that health care workers whose work environment involved frequent exposure to natural rubber products showed a higher incidence of latex allergy. We demonstrated that a specific IgE assay was not sufficiently sensitive for diagnosing latex allergy. However, skin tests such as prick and use tests were confirmed to be effective diagnostic measures for latex allergy.

The subject was a 34-year-old female with asthma and atopic dermatitis who had previously undergone a Cesarean section. In December 1995, the patient had an acute abdominal pain, so she underwent a barium enema examination. During the procedure, severe anaphylactic shock developed, and the examination was stopped. The patient responded well to appropriate emergency therapy, and her symptoms were resolved. However, the woman visited our outpatient clinic because the symptoms of her atopic dermatitis got worse. She indicated that she felt itchy when using rubber gloves. Also, at the age of thirty, she had urticaria and dyspnea after drinking a glass of fruit juice. Subsequently radioallergosorbent testing demonstrated the presence of specific IgEs against latex, banana, kiwi, grapefruit, and avocado. Skin prick tests were positive for banana, grapefruit, avocado, and latex extract at a dilution of 1:1000. A scratch test was positive to an extract of a balloon catheter which included 0.3 microg/g latex proteins by the LEAP method. In conclusion, the patient was diagnosed with an anaphylaxis to the latex contained in a balloon catheter used for the barium enema.

We report a case of electric shock injury in a 42-year old man who was electrocuted with a current of 200. V voltage while performing civil engineering work. Electric current spots were observed on both his right and left forearms and the back of his right hand, suggesting that the electric current entered through the back of the hand, exiting from the forearm on the right side, and through the switch to the palm, and then exiting from the forearm on the left side. We performed an MRI, which provided confirmation of the degree and range of local muscular tissue damage. A relaxation incision, debridement and the attachment of an artificial dermis preceded full-thickness grafting. Following post-surgical rehabilitation, a mild contracture of finger joints was observed, but the motor functions were observed to have significantly improved.