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Allergic contact dermatitis from resacetophenone (2′,4′‐dihydroxyacetophenone; CAS no. 89‐84‐9) in an antifungal nail preparation

2022; Wiley; Volume: 87; Issue: 6 Linguagem: Inglês

10.1111/cod.14202

1600-0536

María A. Pastor‐Nieto, P. González‐Muñoz, Eva Martín‐Alcalde, María E. Gatica‐Ortega,

Pesticide Exposure and Toxicity

Contact DermatitisVolume 87, Issue 6 p. 539-541 CONTACT POINTSOpen Access Allergic contact dermatitis from resacetophenone (2′,4′-dihydroxyacetophenone; CAS no. 89-84-9) in an antifungal nail preparation María A. Pastor-Nieto, Corresponding Author María A. Pastor-Nieto [email protected] orcid.org/0000-0001-8382-5419 Dermatology Department, University Hospital of Guadalajara, Guadalajara, Spain Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Spain Universidad de Castilla-La-Mancha, Castile-La Mancha, Spain Correspondence María A. Pastor-Nieto, Dermatology Department, University Hospital of Guadalajara. C/Donantes de Sangre s.n. 19002. Guadalajara, Spain. Email: [email protected] Contribution: Conceptualization, ​Investigation, Writing - original draft, Methodology, Validation, Visualization, Writing - review & editingSearch for more papers by this authorPatricia González-Muñoz, Patricia González-Muñoz Dermatology Department, University Hospital of Guadalajara, Guadalajara, Spain Contribution: ​InvestigationSearch for more papers by this authorEva Martín-Alcalde, Eva Martín-Alcalde Pharmacy Department, University Hospital of Guadalajara, Guadalajara, Spain Contribution: ​InvestigationSearch for more papers by this authorMaría E. Gatica-Ortega, María E. Gatica-Ortega orcid.org/0000-0002-8203-5834 Universidad de Castilla-La-Mancha, Castile-La Mancha, Spain Dermatology Department, Toledo Hospital Complex, Toledo, Spain Contribution: Conceptualization, ​Investigation, Writing - original draft, Methodology, Validation, Visualization, Writing - review & editingSearch for more papers by this author María A. Pastor-Nieto, Corresponding Author María A. Pastor-Nieto [email protected] orcid.org/0000-0001-8382-5419 Dermatology Department, University Hospital of Guadalajara, Guadalajara, Spain Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Spain Universidad de Castilla-La-Mancha, Castile-La Mancha, Spain Correspondence María A. Pastor-Nieto, Dermatology Department, University Hospital of Guadalajara. C/Donantes de Sangre s.n. 19002. Guadalajara, Spain. Email: [email protected] Contribution: Conceptualization, ​Investigation, Writing - original draft, Methodology, Validation, Visualization, Writing - review & editingSearch for more papers by this authorPatricia González-Muñoz, Patricia González-Muñoz Dermatology Department, University Hospital of Guadalajara, Guadalajara, Spain Contribution: ​InvestigationSearch for more papers by this authorEva Martín-Alcalde, Eva Martín-Alcalde Pharmacy Department, University Hospital of Guadalajara, Guadalajara, Spain Contribution: ​InvestigationSearch for more papers by this authorMaría E. Gatica-Ortega, María E. Gatica-Ortega orcid.org/0000-0002-8203-5834 Universidad de Castilla-La-Mancha, Castile-La Mancha, Spain Dermatology Department, Toledo Hospital Complex, Toledo, Spain Contribution: Conceptualization, ​Investigation, Writing - original draft, Methodology, Validation, Visualization, Writing - review & editingSearch for more papers by this author First published: 18 August 2022 https://doi.org/10.1111/cod.14202Citations: 2AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract We report the first two cases of allergic contact dermatitis from resacetophenone in a nail antifungal preparation. Patch tests gave positive reactions to resacetophenone (0.1% and 1% pet.). No cross-reactions with resorcinol or phenylethyl resorcinol were found. Patch testing with individual ingredients is paramount to diagnose new allergens. Resacetophenone (CAS no. 89–84-9; synonyms: 2′,4′-dihydroxyacetophenone; 4-acetylresorcinol)1 may be used in cosmetics due to its antioxidant, bleaching and skin conditioning properties.2 CASE REPORTS Case 1 In December 2019, a 53-year-old female non-atopic teacher, presented with acute inflammation involving her right toes which she related to Nailner 2 in 1 (Karo Pharma AB), a nail antifungal preparation (ethyl lactate, aqua, glycerin, lactic acid, citric acid and resacetophenone). She first started applying the product in August on her right third toenail daily and began experiencing inflammation 1 month later (Figure 1A). Her podiatrist, however, recommended that she applied the product on all toenails. Some days later, inflammation spread to all toes (Figure 1B). She recalled the application of semi-permanent polish to her fingernails 7 years before without any consequences but never to her toenails. The reaction fully cleared up with oral steroids after she stopped the application of the product. No flare-ups were observed in a 30-month follow-up period. FIGURE 1Open in figure viewerPowerPoint Case 1. (A) Acute vesicular lesions involving the proximal and lateral nailfolds of the central toes. (B) The lesions thereafter spread to the periungual skin of all toes. (C) Semi-open tests with the antifungal nail product as is gave an extreme vesicular oozing reaction on both Days 2 and 4 (photograph was taken on D4). (D) Patch tests with 0.1% and 1% pet. Resacetophenone gave strong reactions on D2 and D4 (photograph was taken on D4). A positive reaction to hydroxyethyl methacrylate was observed without any evidence of current relevance. Case 2 In May 2022, a non-atopic 48-year-old male construction worker, presented with pruritic reactions following the exposure to the same product as in Case 1. Four years before he had used it for 1 month to treat traumatic nail dystrophy with good tolerance. Recently, he applied it again on his first right fingernail and a pruritic reaction involving his hand, abdomen and limbs developed. Lesions improved with topical corticosteroids and withdrawal of the product. He thereafter re-applied it and accidentally spilled it over his hand and right thigh. Two days later, pruritic reactions involving his hand, trunk, upper limbs and thighs developed (Figure 2A–D). FIGURE 2Open in figure viewerPowerPoint Case 2. (A–D) Lesions consisting of artefact linear erythematous-edematous plaques of asymmetrical distribution. Ectopic mechanism caused by indirect transfer through fingers was suspected. (E) Patch tests with 0.1% and 1% pet. Dilutions of one of its ingredients (namely, resacetophenone) clearly showed an allergic morphology (strong reactions spreading beyond the contact limits) on D2 and D4 (photograph was taken on D2). (F) Semi-open tests with the fungal nail preparation as is also gave positive results on D2 and D4 (photograph was taken on D2). In Case 1, we performed patch tests with the Spanish Contact Dermatitis Research Group (GEIDAC) baseline series (T.R.U.E. Test, supplied by allergEAZE; SmartPractice) and, the candidates for the European baseline series (Chemotechnique Diagnostics). In Case 2, we patch tested the extended 2022 GEIDAC series (T.R.U.E. Test and supplemental allergens supplied by Marti Tor Alergia). Both cases were semi-open tested with the nail product as is and additionally patch tested with in-house 0.1% and 1% pet. Dilutions of resacetophenone (raw substance provided by the manufacturer). In order to check for cross-reactions we also patch tested resorcinol 1% pet. (Chemotechnique) and phenylethyl resorcinol 0.1%, 1% and 2% pet. (available from previous research). Allergens were prepared on Curatest chambers (Lohmann & Rauscher) and fixed with Omnifix E (Hartmann), in Case 1; and, on Finn Chamber Aqua (SmartPractice), in Case 2. Exposure times (48 h) and scoring readings on Days 2 and 4, were conducted according to the ESCD guidelines.3 In these cases, positive results were observed with both the nail product semi-open tested as is (+++ on D2 and D4) (Figures 1C and 2F), and with resacetophenone patch tested at 0.1% and 1% pet. (+++ on D2 and D4) (Figures 1D and 2E). In Case 1, patch tests also gave positive results to methylisothiazolinone-methylchloroisothiazolinone (++); nickel sulfate (+), gold sodium thiosulfate (++), limonene hydroperoxides 0.3% pet. (+) and hydroxyethyl methacrylate (HEMA) (+), of unknown relevance. Patch tests with resacetophenone 0.1% and 1% pet. in 10 controls were negative. DISCUSSION We hereby report two cases of allergic contact dermatitis (ACD) from a nail antifungal preparation caused by resacetophenone. To our knowledge, no previous cases of ACD from resacetophenone have been reported. However, ACD to related compounds such as hydroxyacetophenone (CAS no. 99-93-4),4 phenylethyl resorcinol (CAS no. 99-93-4)5, 6 and resorcinol (CAS no. 108-46-3)7 have been described in the literature. We did not find evidence of cross-reactions between resacetophenone, resorcinol or phenylethyl resorcinol in our cases. Since resacetophenone is a new allergen, standardized concentration and vehicles for patch testing are lacking. We suggest patch testing with 0.1% pet. This dilution caused allergic patch test reactions in our patients and failed to cause irritation in 10 controls. The role played by the rest of the ingredients, which were not tested, is unknown. We believe, however, that it is unlikely that they participated in the reactions because they are frequent cosmetic ingredients rarely reported to cause sensitization. These cases further stress the importance of patch testing with the individual ingredients to diagnose emerging allergens. The cooperation of manufacturers with investigations of ACD from topical preparations is of paramount importance. AUTHOR CONTRIBUTIONS María A. Pastor-Nieto: Conceptualization; investigation; writing – original draft; methodology; validation; visualization; writing – review and editing. Patricia González-Muñoz: Investigation. Eva Martín-Alcalde: Investigation. María E. Gatica-Ortega: Conceptualization; investigation; writing – original draft; methodology; validation; visualization; writing – review and editing. AKNOWLEDGEMENT The authors would like to acknowledge Karo Pharma AB, Stockholm, Sweden for kindly providing samples of resacetophenone used to patch test our patients. CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1 National Center for Biotechnology Information. PubChem Compound Database; CID=6990. Accessed July 6, 2022. https://pubchem.ncbi.nlm.nih.gov/compound/6990 2 CosIng (The European Commission database for information on cosmetic substances). Accessed July 6, 2022. https://ec.europa.eu/growth/tools-databases/cosing/index.cfm?fuseaction=search.details_v2&id=59061 3Johansen JD, Aalto-Korte K, Agner T, et al. European Society of Contact Dermatitis guideline for diagnostic patch testing—recommendations on best practice. Contact Dermatitis. 2015; 73: 195- 221. 4Sanz-Sánchez T, Valverde Garrido R, Maldonado Cid P, Díaz-Díaz RM. Allergic contact dermatitis caused by hydroxyacetophenone in a face cream. Contact Dermatitis. 2018; 78: 174- 175. 5Pastor-Nieto MA, Sánchez-Pedreño P, Martínez-Menchón T, Melgar-Molero V, Alcántara-Nicolás F, de la Cruz-Murie P. Allergic contact dermatitis caused by phenylethyl resorcinol, a skin-lightening agent contained in a sunscreen. Contact Dermatitis. 2016; 75: 250- 253. 6Mairlot M, Aerts O, Dendooven E, Herman A. Three additional cases of facial allergic contact dermatitis from the powerful pigment-lightening agent phenylethyl resorcinol. Contact Dermatitis. 2021; 85: 259- 261. 7Darcis J, Goossens A. Resorcinol: a strong sensitizer but a rare contact allergen in the clinic. Contact Dermatitis. 2016; 74: 310- 312. Citing Literature Volume87, Issue6December 2022Pages 539-541 FiguresReferencesRelatedInformation