Outbreak of immediate-type hydrolyzed wheat protein allergy due to a facial soap in Japan
Authors: Akiko Yagami, Michiko Aihara, Zenro Ikezawa, Michihiro Hide, Reiko Kishikawa, Eishin Morita, Yuko Chinuki, Yuma Fukutomi, Atsuo Urisu, Atsuki Fukushima, Yasuharu Itagaki, Shin-ichi Sugiura, Hiroyuki Tanaka, Reiko Teshima, Zenichiro Kato, Emiko Noguchi, Masashi Nakamura, Hirohisa Saito, Kayoko Matsunaga
Journal: Journal of Allergy and Clinical Immunology (2017)

Wheat proteins in hydrolyzed form have been widely used in cosmetic products. The number of patients allergic to hydrolyzed wheat protein (HWP) in cosmetic products seems to be small in Western countries (see Table E1 and this article's Online Repository at www.jacionline.org). However, in Japan, Fukutomi et al1Fukutomi Y. Taniguchi M. Takino S. Tanimoto H. Sekiya K. Saito M. et al.Jpn J Allergol. 2009; 58: 1325Google Scholar first reported 5 Japanese patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) after using the facial soap containing 0.3% of a specific type of HWP, Glupearl 19S, in 2009, and thousands of subjects showed allergic contact urticaria, anaphylaxis, and/or WDEIA after using the soap. Here, we provide an overview of the outbreak of immediate-type wheat allergy caused by a specific HWP (HWP-IWA) by facial soaps in Japan. A nationwide survey for HWP-IWA was conducted to collect the information on Glupearl 19S–containing soaps. A flowchart of the patient registration and the diagnostic criteria are shown in Fig E1 and Table E2, respectively, and details are also described in this article's Online Repository at www.jacionline.org. On the basis of the diagnostic criteria listed in Table E2, the number of patients who satisfied the diagnostic criteria was 2111 (2025 females, 86 males; age, 1-93 years; average age, 45.8 ± 14.5 years). The age group with the largest share consisted of those in their 40s (see Fig E2 in this article's Online Repository at www.jacionline.org). Because sales of the soap containing Glupearl 19S were discontinued in May 2011, the number of reported patients has gradually decreased, and the nationwide survey for HWP-IWA ended in October 2014 (Fig 1). The symptoms typically appeared 1 year after starting use of the soap. Most patients used the soap only for their faces, but some used it on other body parts as well. Symptoms observed in patients are listed in Table I. No patients had shown apparent wheat allergy before using this soap. Twenty-five percent of patients experienced anaphylactic shock, 43% experienced dyspnea, and 11% experienced vomiting. Most of the patients with food ingestion–related symptoms reacted to traditional wheat products such as bread and pasta. This was in contrast to non-Japanese patients allergic to HWP in cosmetic products, who tolerated traditional wheat products but showed the symptoms of allergic reaction after eating processed food such as ham and pâté (see Table E1 and Online Repository). Initial symptoms of anaphylaxis in the patients were facial symptoms, including swelling of the eyelids, urticaria/itchiness of the face, and runny nose, which were distinct from conventional WDEIA with initial symptoms of systemic reaction of itching and urticaria.Table ISymptoms observed in immediate-type wheat allergy caused by Glupearl 19S (n = 899)Skin symptoms during or after using soap, n (%) Skin symptoms640 (71) Swelling of eyelids360 (40) Urticaria, itching, and rubefaction280 (31) Skin symptoms negative246 (27) Unknown13 (2)Symptoms after eating wheat products, n (%) Swelling of eyelids694 (77) Urticaria537 (60) Dyspnea385 (43) Erythema344 (38) Itching278 (31) Anaphylactic shock227 (25) Diarrhea148 (16) Nausea122 (14) Nasal discharge117 (13) Vomiting103 (11) Nasal congestion95 (11) Open table in a new tab In contrast to conventional wheat allergies that react mainly with gliadin and high molecular weight glutenin in wheat protein,2Morita E. Matsuo H. Chinuki Y. Takahashi H. Dahlstrom J. Tanaka A. Food-dependent exercise-induced anaphylaxis—importance of omega-5 gliadin and HMW-glutenin as causative antigens for wheat-dependent exercise-induced anaphylaxis.Allergol Int. 2009; 58: 493-498Abstract Full Text PDF PubMed Scopus (150) Google Scholar immunoblot analysis and ELISA revealed that sera from patients allergic to the HWP-containing soap showed a pattern distinct from that of conventional wheat allergy.1Fukutomi Y. Taniguchi M. Takino S. Tanimoto H. Sekiya K. Saito M. et al.Jpn J Allergol. 2009; 58: 1325Google Scholar Glupearl 19S that was produced by acid treatment of gluten (pH, 0.5-1.2) at 95°C for 40 minutes is the HWP responsible for the allergenicity of the soap. The SDS-PAGE analysis of Glupearl 19S showed a smear staining pattern from the low to high molecular weight range in contrast to the staining pattern of gluten. Fig E3 in this article's Online Repository at www.jacionline.org shows the SDS-PAGE of Glupearl 19S and IgE reactivity against Glupearl 19S by ELISA3Nakamura M. Yagami A. Hara K. Sano A. Kobayashi T. Aihara M. et al.A new reliable method for detecting specific IgE antibodies in the patients with immediate type wheat allergy due to hydrolyzed wheat protein: correlation of its titer and clinical severity.Allergol Int. 2014; 63: 243-249Abstract Full Text PDF PubMed Scopus (14) Google Scholar (see this article's Methods section in the Online Repository at www.jacionline.org) using sera obtained from conventional patients with WDEIA, patients with HWP-IWA who satisfied the diagnostic criteria, subjects who had used soaps containing Glupearl 19S but did not meet the diagnostic criteria, and healthy controls. As shown in Fig E3, strong IgE reactions were observed only in those patients who satisfied the diagnostic criteria, and none of the sera obtained from patients with conventional WDEIA reacted with Glupearl 19S. Because patients used the soap repeatedly on the face, it is likely that allergen exposure occurred through the eyelids and noses, leading to the strong allergic reactions with their eyelids that were not commonly observed in patients with conventional wheat allergy. Airaksinen et al4Airaksinen L. Pallasaho P. Voutilainen R. Pesonen M. Occupational rhinitis, asthma, and contact urticaria caused by hydrolyzed wheat protein in hairdressers.Ann Allergy Asthma Immunol. 2013; 111: 577-579Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar reported 2 patients of occupational rhinitis, asthma, and contact urticaria due to a sprayable hair conditioner containing HWP, and both of them showed exercise-induced eyelid edema and other symptoms after eating wheat-containing food. Glupearl 19S was produced by acid treatment of gluten (pH, 0.5-1.2) at 95°C for 40 minutes. It has been reported that gluten treated with 0.1 N hydrochloric acid for 30 minutes at 100°C markedly increased IgE-binding capacity of patients' sera, indicating that neoepitopes on the gluten might be generated after the treatment.5Nakamura R. Adachi R. Itagaki Y. Fukutomi Y. Teshima R. Evaluation of allergenicity of acid-hydrolyzed wheat protein using an in vitro elicitation test.Int Arch Allergy Immunol. 2013; 160: 259-264Crossref PubMed Scopus (13) Google Scholar The acid treatments at high temperature for a short time produce random degradation of gluten, and mixed short and long peptides, leading to smear pattern by electrophoresis (Fig E3). Because most food products do not contain HWP, it was speculated that gastrointestinal enzyme reaction after ingestion of wheat protein might be responsible for acquiring allergenicity. Glupearl 19S itself is not deamidated by transglutaminase in the body, but deamidated peptides were produced during the process of acid and heat treatment of gluten,6Nakamura R. Sakai S. Haishima Y. Fukui C. Suzuki T. Nakamura R. et al.Comprehensive analyses of hydrolyzed wheat protein using shotgun proteomics.Bull Natl Inst Health Sci. 2013; 131: 50-57Google Scholar and then specific IgE antibodies against Glupearl 19S were produced when patients used the soap repeatedly (Fig E3). Nakamura et al7Nakamura R. Sakai S. Adachi R. Hachisuka A. Urisu A. Fukutomi Y. et al.Tissue transglutaminase generates deamidated epitopes on gluten, increasing reactivity with hydrolyzed wheat protein-sensitized IgE.J Allergy Clin Immunol. 2013; 132: 1436-1438Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar showed that tissue transglutaminase treatment of gluten dramatically increased reactivity against IgE from the patients' sera by cell-based assay (EXiLE). Yokooji et al8Yokooji T. Kurihara S. Murakami T. Chinuki Y. Takahashi H. Morita E. et al.Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap.Allergol Int. 2013; 62: 435-445Abstract Full Text PDF PubMed Scopus (60) Google Scholar reported that IgE-binding epitope QPQQPFPQ in γ-gliadin reacted more strongly with IgE of the patients in its deamidated form, PEEPFP.8Yokooji T. Kurihara S. Murakami T. Chinuki Y. Takahashi H. Morita E. et al.Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap.Allergol Int. 2013; 62: 435-445Abstract Full Text PDF PubMed Scopus (60) Google Scholar Ingested wheat food product such as bread and/or pasta might be deamidated by transglutaminase in the body, and specific IgE antibodies against Glupearl 19S could cross-react with deamidated peptide derived from food gluten, which may lead to anaphylactic/allergic reaction in the patients. The detailed analysis of allergenicity of HWP and predisposition to type I allergy against HWP will lead to the safe use of cosmetic products containing wheat protein. Hiragun et al9Hiragun M. Ishii K. Yanase Y. Hiragun T. Hide M. Remission rate of patients with wheat allergy sensitized to hydrolyzed wheat protein in facial soap.Allergol Int. 2016; 65: 109-111Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar reported the status of remission of 110 patients with IWA-HWP who were part of the 2111 patients mentioned above, and the remission rate of 110 patients was still 56.1% at 60 months after stopping usage of HWP-containing soap. Therefore, it is necessary to find effective treatment for the long-lasting and refractory cases. Discovering the molecular mechanisms underlying the HWP-IWA, in comparison with conventional WDEIA and wheat intolerance such as celiac diseases, may lead to better understanding of the molecular basis of wheat protein–related diseases. We used PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) to search the National Library of Medicine and MEDLINE to collect information about patients allergic to HWP. For the electronic searches, we used a combination of keywords related to "hydrolyzed wheat protein" and "allergy/anaphylaxis," then manually excluded patients allergic to HWP in food. We included articles published in English or those with English translations available. We also used the information published in Scientific Committee on Consumer Safety in 2014.E1European Union. Opinion of the Scientific Committee on Consumer Safety on Hydrolysed Wheat Proteins. Available at: http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_160.pdf. Accessed May 12, 2017.Google Scholar The soap, Yuuka-no-sekken, commonly known as Cha-no-shizuku soap (Yuuka, Fukuoka, Japan) containing Glupearl 19S (Katayama Chemical Industries, Osaka, Japan), was sold only by mail order between March 2004 and December 2010. Glupearl 19S was derived from wheat gluten, and had not been exported to other domestic/foreign companies. The soap was very popular, especially among women, due to the advertised effects of beautifying and whitening the skin. The number of registered customers at Yuuka, the company selling the soap, was 4,667,000, and the total number of soaps sold to the customers was 46,508,000.E2Japanese Society of Allergology. Available at: http://www.fa.kyorin.co.jp/jsa/jsa_0528_06.pdf. Accessed May 12, 2017.Google Scholar On the basis of the number of adult Japanese women, 54,444,000,E3Statistics Bureau, Ministry of Internal Affairs and Communications. Statistics Japan. Available at: http://www.e-stat.go.jp/SG1/estat/List.do?lid=000001118081. Accessed May 12, 2017.Google Scholar it was estimated that approximately 1 in 12 Japanese adult women used the soap. The Special Committee for the Safety of Protein Hydrolysates in Cosmetics was formed by the Japanese Society of Allergology, and the diagnostic criteria were established in October 2011, with patient registration beginning in April 2012. Among hospitals/clinics eligible for proper diagnosis, 270 clinics/hospitals reported confirmed cases of HWP-IWA by the facial soaps to the Special Committee. Fig E1 shows the flowchart of patient registration. Subjects who experienced any symptoms after using the soap and/or ingestion of wheat products contacted the company that sold the soaps (Yuuka), the Ministry of Health, Labour, and Welfare of Japan, the Consumer Affairs Agency of Japan, or the Japanese Society of Allergology. They provided information regarding which clinics/hospitals provided proper diagnosis for HWP-IWA and which could perform skin prick tests using Glupearl 19S and/or specific IgE antibody detection tests for Glupearl 19S. The Glupearl 19S specific IgE antibody detection test was provided in the laboratory organized by the Special Committee. Some consumers visited clinics/hospitals directly, and some of them were referred to allergy/dermatology specialists for proper diagnosis. Because the information regarding allergic symptoms and usage of the soaps was provided from many resources, including the company (Yuuka), the Consumer Affairs Agency of Japan, the Japanese Society of Allergology, and the Ministry of Health, Labour, and Welfare of Japan, and the incident was also covered in the mass media, it is considered that we covered most of the cases of the incident. SDS-PAGE was performed using Novex NuPAGE 4% to 12% gels and MOPS buffer (Thermo Fisher Scientific, Waltham, Mass) according to the manufacturer's instructions. Separated proteins of Glupearl 19S and gluten were stained with SimplyBlue SafeStain (Thermo Fisher Scientific). Sera were obtained from patients with conventional WDEIA who reacted to ω-5 gliadin (n = 7), patients with HWP-IWA who satisfied the diagnostic criteria described in Table E2 (n = 20), subjects who had used soaps containing Glupearl 19S but who did not satisfy the diagnostic criteria (ie, skin prick test negative using 0.1% Glupearl 19S solution, n = 20), and healthy controls without wheat allergy (n = 7). The study was approved by the Ethics Committee of Fujita Health University (11-210), and informed consent was obtained from each patient. This study was carried out in accordance with the Declaration of Helsinki. Details of the ELISA method were described previously.E4Varjonen E. Petman L. Makinen-Kiljunen S. Immediate contact allergy from hydrolyzed wheat in a cosmetic cream.Allergy. 2000; 55: 294-296Crossref PubMed Scopus (73) Google Scholar Briefly, 1 mg/mL Glupearl 19S was plated on a Nunc MaxiSorp flat-bottom 96-well plate (Thermo Fisher Scientific). The plate was blocked with 1% skim milk/PBS containing 0.1% Tween 20. After washing, diluted patients' sera was added to each well, and the plate was incubated. The plate was washed, 0.1 μg/mL antihuman IgE antibody horseradish peroxidase conjugate (KPL, Gaithersburg, Md) was added to each well, and the plate was incubated. The plate was washed, and the colorimetric reaction was developed by adding 1-Step Ultra TMB-ELISA (Thermo Fisher Scientific). Absorbance values at 450 nm were measured by VersaMax (Molecular Devices, Sunnyvale, Calif), and were converted into units, as described previously, and cutoff values were set at 5.0 units. A list of non-Japanese patients allergic to HWP in cosmetic products is given in Table E1.E4Varjonen E. Petman L. Makinen-Kiljunen S. Immediate contact allergy from hydrolyzed wheat in a cosmetic cream.Allergy. 2000; 55: 294-296Crossref PubMed Scopus (73) Google Scholar, E5Sanchez-Perez J. Sanz T. Garcia-Diez A. Allergic contact dermatitis from hydrolyzed wheat protein in cosmetic cream.Contact Dermatitis. 2000; 42: 360PubMed Google Scholar, E6Pecquet C. Lauriere M. Huet S. Leynadier F. Is the application of cosmetics containing protein-derived products safe?.Contact Dermatitis. 2002; 46: 123Crossref PubMed Scopus (51) Google Scholar, E7Pecquet C. Bayrou O. Vigan M. Raison N. Lauriere M. Hydrolysed wheat protein: a new allergen in cosmetics and food.Contact Dermatitis. 2004; 50: 182-183Crossref Google Scholar, E8Codreanu F. Morisset M. Cordebar V. Kanny G. Moneret-Vautrin D.A. Risk of allergy to food proteins in topical medicinal agents and cosmetics.Eur Ann Allergy Clin Immunol. 2006; 38: 126-130PubMed Google Scholar, E9Lauriere M. Pecquet C. Bouchez-Mahiout I. Snegaroff J. Bayrou O. Raison-Peyron N. et al.Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities.Contact Dermatitis. 2006; 54: 283-289Crossref PubMed Scopus (103) Google Scholar, E10Hann S. Hughes M. Stone N. Allergic contact dermatitis to hydrolyzed wheat protein in a cosmetic cream.Contact Dermatitis. 2007; 56: 119-120Crossref PubMed Scopus (22) Google Scholar, E11Livideanu C. Giordano-Labadie F. Paul C. Contact dermatitis to hydrolyzed wheat protein.Contact Dermatitis. 2007; 57: 283-284Crossref PubMed Scopus (15) Google Scholar, E12Bouchez-Mahiout I. Pecquet C. Kerre S. Snegaroff J. Raison-Peyron N. Lauriere M. High molecular weight entities in industrial wheat protein hydrolysates are immunoreactive with IgE from allergic patients.J Agric Food Chem. 2010; 58: 4207-4215Crossref PubMed Scopus (23) Google Scholar, E13Olaiwan A. Pecquet C. Mathelier-Fusade P. Frances C. Contact urticaria induced by hydrolyzed wheat proteins in cosmetics.Ann Dermatol Venereol. 2010; 137: 281-284Crossref PubMed Scopus (20) Google Scholar, E14Barrientos N. Vazquez S. Dominguez J.D. Contact urticaria induced by hydrolyzed wheat protein in cosmetic cream.Actas Dermosifiliogr. 2012; 103: 750-752Crossref PubMed Scopus (3) Google Scholar, E15Airaksinen L. Pallasaho P. Voutilainen R. Pesonen M. Occupational rhinitis, asthma, and contact urticaria caused by hydrolyzed wheat protein in hairdressers.Ann Allergy Asthma Immunol. 2013; 111: 577-579Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Many of the patients used facial creams, and some used sprayable hair conditioner containing HWP.E15Airaksinen L. Pallasaho P. Voutilainen R. Pesonen M. Occupational rhinitis, asthma, and contact urticaria caused by hydrolyzed wheat protein in hairdressers.Ann Allergy Asthma Immunol. 2013; 111: 577-579Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar As shown in Table E1, some had no symptoms related to ingestion of food, whereas others showed allergic symptoms after eating foods containing wheat. Interestingly, most of the patients tolerated traditional wheat products, such as bread and pasta, but allergic reactions occurred after eating processed food containing HWP, such as ham and liver pâté.E9Lauriere M. Pecquet C. Bouchez-Mahiout I. Snegaroff J. Bayrou O. Raison-Peyron N. et al.Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities.Contact Dermatitis. 2006; 54: 283-289Crossref PubMed Scopus (103) Google Scholar, E12Bouchez-Mahiout I. Pecquet C. Kerre S. Snegaroff J. Raison-Peyron N. Lauriere M. High molecular weight entities in industrial wheat protein hydrolysates are immunoreactive with IgE from allergic patients.J Agric Food Chem. 2010; 58: 4207-4215Crossref PubMed Scopus (23) Google Scholar, E13Olaiwan A. Pecquet C. Mathelier-Fusade P. Frances C. Contact urticaria induced by hydrolyzed wheat proteins in cosmetics.Ann Dermatol Venereol. 2010; 137: 281-284Crossref PubMed Scopus (20) Google Scholar Among hospitals/clinics eligible for proper diagnosis, 270 clinics/hospitals reported confirmed cases of HWP-IWA by the facial soaps to the Special Committee. After a careful examination at the clinics/hospitals, 2111 subjects were confirmed to be satisfied with the diagnostic criteria. Doctors who treated the confirmed cases were asked to participate in an online survey, and clinical details of 899 patients were reported to the Special Committee (Table I). Causality between Glupearl 19S and HWP-IWA was considered as follows. (1) Patients showed symptoms related to type I allergy after using soap containing Glupearl 19S, and showed symptoms repeatedly. (2) Skin prick test, ELISA, or basophil activation test against Glupearl 19S was positive. This reactivity was not observed in patients with traditional WDEIA and in healthy controls (Fig E3). (3) These symptoms, including allergic reactions after ingestion of wheat products, had not been observed before starting use of soap containing Glupearl 19S. Among 2111 confirmed cases, the past/present history of allergic diseases was available in 899 patients. Allergic rhinitis/pollinosis, atopic dermatitis, urticaria, and asthma were observed in 297 (33%), 107 (12%), 42 (5%), and 17 (2%), respectively. There was no increase in the prevalence of allergic rhinitis/pollinosis and asthma in HWP-allergic patients compared with the prevalence in a general population survey of allergic rhinitis/pollinosis (47.2%) and adult asthma (5.4%), but the incidence of atopic dermatitis, the prevalence of which in the general population was reported to be 9.4% for those in their 20s, 8.3% in the 30s, and 4.8% in the 40s, slightly increased.E16Ministry of Health, Labor and Welfare Japan: Preliminary Report on Measures against Allergic Disease. Available at: http://www.mhlw.go.jp/stf/shingi/2r98520000016819-att/2r9852000001684w.pdf. Accessed May 12, 2017.Google Scholar Fig E3 shows an SDS-PAGE image of Glupearl 19S and gluten. Glupearl 19S was produced by acid treatment of gluten (pH, 0.5-1.2) at 95°C for 40 minutes. The acid treatments at high temperature for a short time produce random degradation of gluten, and mixed short and long peptides, leading to smear pattern by electrophoresis. Other researchers also showed a similar smear pattern of electrophoresis using Glupearl 19S.E17Nakamura R. Adachi R. Itagaki Y. Fukutomi Y. Teshima R. Evaluation of allergenicity of acid-hydrolyzed wheat protein using an in vitro elicitation test.Int Arch Allergy Immunol. 2013; 160: 259-264Crossref PubMed Scopus (21) Google Scholar Acid treatment of gluten at high temperature for a long period (24 hours) produced only small peptides that are not allergenic,E18Nakamura R. Sakai S. Haishima Y. Fukui C. Suzuki T. Nakamura R. et al.Comprehensive analyses of hydrolyzed wheat protein using shotgun proteomics.Bull Natl Inst Health Sci. 2013; 131: 50-57Google Scholar but Glupearl 19S contains short and long peptides that could cause allergic reaction in the patients. Glupearl 19S itself is not deamidated by transglutaminase in the body, but deamidated peptides were produced during the process of acid and heat treatment of gluten,E18Nakamura R. Sakai S. Haishima Y. Fukui C. Suzuki T. Nakamura R. et al.Comprehensive analyses of hydrolyzed wheat protein using shotgun proteomics.Bull Natl Inst Health Sci. 2013; 131: 50-57Google Scholar and then specific IgE antibodies against Glupearl 19S were produced while patients used the soap repeatedly (Fig E3). Ingested wheat food product such as bread and/or pasta might be deamidated by transglutaminase in the body, and specific IgE antibodies against Glupearl 19S could cross-react with deaminated peptide derived from food gluten, which may lead to anaphylactic/allergic reaction in the patients.Fig E2Age and sex distribution of the Japanese patients allergic to HWP in facial soaps.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig E3IgE antibody levels against Glupearl 19S. A, SDS-PAGE image of Glupearl 19S and gluten. M: molecular weight marker; lane 1: Glupearl 19S, lane 2: gluten. B, Dot plots of serum Glupearl 19S specific IgE levels were quantified by ELISA using sera from patients with conventional WDEIA (CO-WDEIA, n = 7), HWP-IWA who satisfied the diagnostic criteria described in Table E2 (HWP, n = 20), subjects who had used the soaps but who did not satisfy diagnostic criteria (HWP-Negative, n = 20), and healthy controls without wheat allergy (Healthy, n = 7). Units greater than 100 are described as 100. Dashed line indicates a cutoff value (5 units).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table E1Non-Japanese patients allergic to HWP in cosmetic productsYearAuthorsNo. of patientsCountryCosmetic productsSymptoms after applying cosmeticsSymptoms after eating wheat-containing foodReference2000Sanchez-Perez et al1SpainMoisturizing cosmetic creamContact urticariaNAE5Sanchez-Perez J. Sanz T. Garcia-Diez A. Allergic contact dermatitis from hydrolyzed wheat protein in cosmetic cream.Contact Dermatitis. 2000; 42: 360PubMed Google Scholar2000Varjonen et al1FinlandBody creamContact dermatitis/urticariaNAE4Varjonen E. Petman L. Makinen-Kiljunen S. Immediate contact allergy from hydrolyzed wheat in a cosmetic cream.Allergy. 2000; 55: 294-296Crossref PubMed Scopus (73) Google Scholar2002Pecquet et al1FranceEyelid cream, body moisturizerGeneralized urticariaGeneralized urticariaE6Pecquet C. Lauriere M. Huet S. Leynadier F. Is the application of cosmetics containing protein-derived products safe?.Contact Dermatitis. 2002; 46: 123Crossref PubMed Scopus (51) Google Scholar2004Pecquet et al7FranceFacial creamsContact dermatitisAnaphylaxis/urticaria (6 patients)E7Pecquet C. Bayrou O. Vigan M. Raison N. Lauriere M. Hydrolysed wheat protein: a new allergen in cosmetics and food.Contact Dermatitis. 2004; 50: 182-183Crossref Google Scholar2006Codreanu et al3FranceShower gel, shampoo, mascaraGeneralized erythema, contact eczema, facial angioedema with generalized urticariaWDEIA (1 patient)E8Codreanu F. Morisset M. Cordebar V. Kanny G. Moneret-Vautrin D.A. Risk of allergy to food proteins in topical medicinal agents and cosmetics.Eur Ann Allergy Clin Immunol. 2006; 38: 126-130PubMed Google Scholar2006Lauriere et al9FranceFacial creams, body moisturizer, shower gel, hair conditionerContact urticariaGeneralized urticaria (3 patients), anaphylaxis (2 patients), WDEIA (1 patient)E9Lauriere M. Pecquet C. Bouchez-Mahiout I. Snegaroff J. Bayrou O. Raison-Peyron N. et al.Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities.Contact Dermatitis. 2006; 54: 283-289Crossref PubMed Scopus (103) Google Scholar2007Hann et al1United KingdomMoisturizing cosmetic creamContact dermatitisNAE10Hann S. Hughes M. Stone N. Allergic contact dermatitis to hydrolyzed wheat protein in a cosmetic cream.Contact Dermatitis. 2007; 56: 119-120Crossref PubMed Scopus (22) Google Scholar2007Livideanu et al1FranceEmollientContact dermatitisNAE11Livideanu C. Giordano-Labadie F. Paul C. Contact dermatitis to hydrolyzed wheat protein.Contact Dermatitis. 2007; 57: 283-284Crossref PubMed Scopus (15) Google Scholar2010Bouchez-Mahiout et al4FranceSkin tensing cosmetic, facial creamContact urticariaUrticaria (1 patient), exercise-induced food allergy (1 patient)E12Bouchez-Mahiout I. Pecquet C. Kerre S. Snegaroff J. Raison-Peyron N. Lauriere M. High molecular weight entities in industrial wheat protein hydrolysates are immunoreactive with IgE from allergic patients.J Agric Food Chem. 2010; 58: 4207-4215Crossref PubMed Scopus (23) Google Scholar2010Olaiwan et al2FranceCosmeticsContact urticariaGeneralized urticaria (1 patient)E13Olaiwan A. Pecquet C. Mathelier-Fusade P. Frances C. Contact urticaria induced by hydrolyzed wheat proteins in cosmetics.Ann Dermatol Venereol. 2010; 137: 281-284Crossref PubMed Scopus (20) Google Scholar2012Barrientos et al1SpainSkin creamContact dermatitisNo symptoms related to ingestion of the foodE14Barrientos N. Vazquez S. Dominguez J.D. Contact urticaria induced by hydrolyzed wheat protein in cosmetic cream.Actas Dermosifiliogr. 2012; 103: 750-752Crossref PubMed Scopus (3) Google Scholar2013Airaksinen et al2FinlandSprayable hair conditionerOccupational rhinitis, asthma, contact urticariaWDEIA (1 patient), exercise-induced food allergy (1 patient)E15Airaksinen L. Pallasaho P. Voutilainen R. Pesonen M. Occupational rhinitis, asthma, and contact urticaria caused by hydrolyzed wheat protein in hairdressers.Ann Allergy Asthma Immunol. 2013; 111: 577-579Abstract Full Text Full Text PDF PubMed Scopus (15) Google ScholarNA, Not available. Open table in a new tab Table E2Diagnostic criteria for immediate wheat allergy to HWP (Glupearl 19S)Individual must meet all the following criteriaE4Varjonen E. Petman L. Makinen-Kiljunen S. Immediate contact allergy from hydrolyzed wheat in a cosmetic cream.Allergy. 2000; 55: 294-296Crossref PubMed Scopus (73) Google Scholar, E5Sanchez-Perez J. Sanz T. Garcia-Diez A. Allergic contact dermatitis from hydrolyzed wheat protein in cosmetic cream.Contact Dermatitis. 2000; 42: 360PubMed Google Scholar, E6Pecquet C. Lauriere M. Huet S. Leynadier F. Is the application of cosmetics containing protein-derived products safe?.Contact Dermatitis. 2002; 46: 123Crossref PubMed Scopus (51) Google ScholarCriteria 1 (usage of soaps):1.History of usage of Cha-no-Shizuku soap or other products containing hydrolyzed wheat (Glupearl 19S)Criteria 2 (symptoms), either of the following:1.Itching, eyelid edema, nasal discharge, and/or wheals within several to 30 min after using Cha-no-Shizuku soap or other products containing hydrolyzed wheat (Glupearl 19S)2.General symptoms, such as itching, wheals, eyelid edema, nasal discharge, dyspnea, nausea, vomiting, abdominal pain, diarrhea, and decreased blood pressure, within 4 h after eating wheat productsCriteria 3 (laboratory test positive), either of the following:1.Skin prick test using ≤0.1% Glupearl 19S solution2.Immunoassay, such as dot blot, ELISA, and/or western blot to identify specific IgE antibody to Glupearl 19S in the serum/plasma3.Basophil activation test using Glupearl 19SExclusion criterionSkin prick test negative using 0.1% Glupearl 19S solutionDefined by the Special Committee for the Safety of Protein Hydrolysates in Cosmetics on October 11, 2011. Open table in a new tab NA, Not available. Defined by the Special Committee for the Safety of Protein Hydrolysates in Cosmetics on October 11, 2011.