Clofent et al. Allergy Asthma Clin Immunol (2020) 16:7 Allergy, Asthma & Clinical Immunology https://doi.org/10.1186/s13223-020-0404-8 CASE REPORT Open Access Sudan red dye: a new agent causing type‑2 occupational asthma David Clofent1, Miquel de Homdedeu1,2, Mariana Muñoz‑Esquerre3, María Jesús Cruz1,2* and Xavier Muñoz1,2,4 Abstract Background: Sudan red or 1-[(2-methoxyphenyl)azo]-2-naphthol is a low molecular weight azoic agent widely used in industry, particularly in the production of hair dyes. The use of this product in the food industry is prohibited due to its potential carcinogenic effect, but no respiratory involvement has been reported to date. Case presentation: We present the case of a 46-year-old female patient who had been working in a cosmetics packaging company for 20 years. The patient developed occupational asthma to a red azo dye known as Sudan red. The diagnosis was confirmed by specific bronchial provocation test. Induced sputum samples were obtained previously and in the 24 h following the procedure, with a rise in the percentage of eosinophils from 10 to 65%. Conclusions: This report describes the case of a patient who developed OA caused by exposure to an azoic dye called Sudan red. The clinical and analytical features suggest a type 2-related asthma; however, we are not yet able to confirm the specific pathophysiological mechanism. The extensive use of azo dyes in industry means that it is particularly important to describe their implications for health, which are probably underestimated at present. Keywords: Allergy, Specific inhalation challenge, Azoic agent Background relationship to OA and it is likely that dyestuff-related Occupational asthma (OA) is a work-related condition OA is underdiagnosed. characterized by variable airflow obstruction and/or by Sudan red or 1-[(2-methoxyphenyl)azo]-2-naphthol bronchial hyperresponsiveness to the conditions of a is a low molecular weight azoic agent widely used in specific working environment. Hundreds of agents are industry, particularly in the production of hair dyes. The known developers of OA, among them more than 100 use of this product in the food industry is prohibited due chemical entities, whose mechanism of action is often to its potential carcinogenic effect, but no respiratory unknown [1, 2]. involvement has been reported to date [13]. Various dyestuffs are considered to be causes of occupational respiratory diseases, which are mainly Case presentation described in workers in textile and cosmetic industries We report the case of a 46-year-old female non-smoker [3–11]. Azoic dyes, which are synthesized from primary without medical history of interest, who had been aromatic amines, are the most extensively used synthetic working in a cosmetics packaging company for 20 years. organic colorants worldwide [12]. Despite the widespread She had undergone daily exposure to several substances use of these products, there are few reports of their including a red azo dye known as Sudan red. Over the past 15 years, the patient had experienced dyspnea, dry cough, occasional wheezing, facial *Correspondence: mj.cruz@vhir.org edema, rhinitis and conjunctivitis. These symptoms 1 Servicio de Neumologia, Hospital Universitario Vall d’Hebron, Passeig had worsened in the last 3 years; she had frequently Vall d’Hebron 119, 08035 Barcelona, Spain required emergency-room assistance for acute episodes Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat​iveco​ mmons​.org/licen​ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/publi​cdoma​in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Clofent et al. Allergy Asthma Clin Immunol (2020) 16:7 Page 2 of 3 of bronchospasm and had been admitted to hospital on Discussion four times. The patient’s symptoms responded to inhaled To our knowledge, this is the first reported case of OA long acting beta-2 agonist and inhaled corticosteroids, caused by Sudan red dye. The increase of eosinophils and were clearly work-related since they improved on in induced sputum is a particularly relevant finding, weekends, during vacations, and after she finally left her since it strongly suggests a type 2 mechanism of airway job. inflammation. Physical examination and chest radiograph were Since the first reports of dye-induced OA in 1978 by normal. Blood tests showed eosinophilia (500 cells/mm3) Alanko et al. [8], several cases have been published, and increased total serum IgE (846 KU/L). Lung function most of them caused by exposure to reactive dyes study revealed an obstructive ventilatory pattern with in textile industries. In the early 1990s, on the basis a forced vital capacity (FVC) of 3.14 L (91%), a forced of positive skin prick and RAST-inhibition tests in expiratory volume in one second (FEV1) of 2.12 L (76%) workers who developed allergic lower respiratory and FEV1/FVC of 67%. Methacholine challenge test was symptoms, authors such as Park HS [10], Docker positive, with a PC20 of 0.85 mg/mL and a fractional [7] and Nilsson [3] proposed an IgE-mediated exhaled nitric oxide test (FENO) of 47.2 ppb. immunological mechanism. It was suggested that With a suspected diagnosis of OA, the patient airborne dye molecules may act as haptens and induce underwent a specific inhalation challenge (SIC) with IgE-mediated hypersensitivity reactions, However, the azoic dye, in accordance with the recommendations none of these reports obtained cytological analysis in in the European Respiratory Society guidelines [14]. induced sputum. The patient was exposed to a mixture of 2 g of “Sudan Various pathophysiological pathways have been Red” and 100 g of lactose powder, tipped from one tray described in OA, depending on whether it is induced to another 30 cm away from her face for 10 min; she by a sensitizing or an irritant agent. While irritant- continued treatment with inhaled long acting beta-2 induced asthma is attributed to a non-immunological agonist and inhaled corticosteroids due to the persistence mechanism, sensitizing agents induce asthma through of bronchospasm. During the procedure, she suffered mechanisms which may or may not be type-2- dyspnea and cough, and experienced a dual positive dependent. In fact, a recent study showed that both response with a fall in FEV1 of 22% in the first 20 min and high-molecular-weight agents (with an IgE-mediated another of 33% approximately 10 h after the exposure. No mechanism) and low-molecular-weight agents (with as significant changes in FEV1 were observed in response to yet undefined mechanisms) may generate eosinophilic a control challenge of lactose powder alone conducted on or neutrophilic responses [15]. a separate day (Fig. 1). In the present case report, the rise of eosinophils in Induced sputum samples were obtained previously and induced sputum after the SIC suggests the involvement in the 24 h following the procedure, with a rise in the of a type-2 mechanism of airway inflammation. In percentage of eosinophils from 10 to 65%. Methacholine addition, the presence of high levels of IgE and the and FENO tests did not present significant variations dual positive response to the SIC may support an IgE- from the results obtained prior to the SIC. The diagnosis mediated mechanism and consequently a possible of OA due to Sudan Red was established, and the patient Th2 enrollment. However, the increase in eosinophils was advised to avoid the causal agent. cannot rule out a response mediated by innate lymphocytic immunity (ILC2) or a combination of both. Conclusions This report describes the case of a patient who developed OA caused by exposure to an azoic dye called Sudan red. The clinical and analytical features suggest a type 2-related asthma; however, we are not yet able to confirm the specific pathophysiological mechanism. The extensive use of azo dyes in industry means that it is particularly important to describe their implications for health, which are probably underestimated at present. Fig. 1 Result of specific inhalation challenge to Sudan red Clofent et al. Allergy Asthma Clin Immunol (2020) 16:7 Page 3 of 3 Abbreviations 2. Quirce S, Sastre J. Occupational asthma: clinical phenotypes, biomarkers, FENO: fractional exhaled nitric oxide test; FEV1: forced expiratory volume in and management. Curr Opin Pulm Med. 2019;25:59–63. one second; FVC: forced vital capacity; OA: occupational asthma; SIC: specific 3. Nilson R, Norlinder R, Wass U, Meding B, Belin L. Asthma, rhinitis inhalation challenge. and dermatitis in workers exposed to reactive dyes. Br J Ind Med. 1993;50:65–70. Acknowledgements 4. Helaskoski E, Suojalehto H, Virtanen H, Airaksinen L, Kuuliala O, Aalto- Not applicable. Korte K, Pesonen M. Occupational asthma, rhinitis, and contact urticaria caused by oxidative hair dyes in hairdressers. Ann Allergy Asthma Authors’ contributions Immunol. 2014;112(1):46–52. MM-E had full access to all of the data in the study and takes responsibility for 5. Wong GA, King CM. Immediate-type hypersensitivity and allergic contact the integrity of the data and the accuracy of the data analysis. He contributed dermatitis due to para-phenylenediamine in hair dye. Contact Dermat. to the analysis and interpretation of data, drafting the case report for 2003;48(3):166. important intellectual content, and reading and approving the final version. 6. Park HS, Kim YJ, Lee MK, Hong CS. Occupational asthma and IgE MM-E and DC: contributed to data collection, analysis and interpretation of antibodies to reactive dyes. Yonsei Med J. 1989;30(3):298–304. data, drafting the case report for important intellectual content, and reading 7. Docker A, Wattie JM, Topping MD, Luczynska CM, Newman Taylor and approving the final version. MJC and MH: contributed to laboratory AJ, Pickering CA, Thomas P, Gompertz D. Clinical and immunological analysis and interpretation of data and reading, drafting the case report investigations of respiratory disease in workers using reactive dyes. Br J for important intellectual content. All authors read and approved the final Ind Med. 1987;44(8):534–41. manuscript. 8. Alanko K, Keskinen H, Bjorksten F, Ojanen S. Immediate-type hypersensitivity to reactive dyes. Clin Allergy. 1978;8:25–31. Funding 9. Stern MA. Occupational asthma from a reactive dye. Ann Allergy. MJC is a researcher supported by the Miguel Servet programme of the 1985;55:264. Instituto de Salud Carlos III (CPII17/00025). 10. Park HS, Lee MK, Kim BO, et al. Clinical and immunologic evaluation of reactive dye-exposed workers. J Allergy Clin Immunol. 1991;87:639–49. Availability of data and materials 11. Koh DH, Won J, Ahn YS, Kim HR, Koh SB. Asthma mortality in male Yes. workers of the dye industry in Korea. J Occup Health. 2008;50(2):130–5. 12. Chung KT. Azo dyes and human health: a review. J Environ Sci Health C Ethics approval and consent to participate Environ Carcinog Ecotoxicol Rev. 2016;34(4):233–61. Not applicable. 13. The safety review of the use of certain azo-dyes in cosmetic products. Opinion of the scientific committee on cosmetic products and non-food Consent for publication products intended for consumers. 19th plenary meeting of 27 February Yes. 2002. 14. Vandenplas O, Suojalehto H, Aasen TB, Baur X, Burge PS, de Blay F, et al. Competing interests Specific inhalation challenge in the diagnosis of occupational asthma: The authors declare that they have no competing interests. consensus statement. Eur Respir J. 2014;43:1573–87. 15. Vandenplas O, Godet J, Hurdubaea L, Rifflart C, Suojalehto H, Wiszniewska Author details M, et al. Are high- and low-molecular-weight sensitizing agents 1 Servicio de Neumologia, Hospital Universitario Vall d’Hebron, Passeig Vall associated with different clinical phenotypes of occupational asthma? d’Hebron 119, 08035 Barcelona, Spain. 2 CIBER Enfermedades Respiratorias Allergy. 2019;74:261–72. (CibeRes), Madrid, Spain. 3 Servicio de Neumologia, Hospital Universitario de Bellvitge‑IDIBELL, Universidad de Barcelona, Barcelona, Spain. 4 Departamento de Biología Celular, Fisiología e Inmunología, Universitat Autònoma de Publisher’s Note Barcelona, Barcelona, Spain. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Received: 24 October 2019 Accepted: 14 January 2020 References 1. Malo JL, Vandenplas O. Definitions and classification of work-related asthma. 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