key: cord-0701007-xwd6i2vu authors: Goh, Choon Fu; Ming, Long Chiau; Wong, Li Ching title: Dermatologic reactions to disinfectant use during the COVID-19 pandemic()() date: 2020-10-02 journal: Clin Dermatol DOI: 10.1016/j.clindermatol.2020.09.005 sha: 9cc6973df766bcaf364f6d98857a669d199e7adf doc_id: 701007 cord_uid: xwd6i2vu Infection preventive practice of using disinfectants against SARS-CoV-2 has become the new normal due to the COVID-19 pandemic. Although disinfectants may not be applied directly to the human body, it remains at high risk of exposure including close skin contact on disinfected surfaces or during handling. This dermal contact, on a regular basis, can induce hazardous skin reactions like irritation, inflammation, and burning in severe conditions. Disinfectants are germicide chemicals that can penetrate the skin and create skin reactions that are usually regarded as irritant and allergic contact dermatitis. More importantly, disinfectants can react with skin components (proteins and lipids) to facilitate their skin penetration and disrupt the skin barrier function. Whereas the antimicrobial actions of disinfectants are well understood, much less is known regarding their dermatologic reactions, including but not limited to irritation and hypersensitivity. We reviewed the skin reactions created by those disinfectants against SARS-CoV-2 approved by the European Chemical Agency and the United States Environmental Protection Agency. antigen-specific T cells (adaptive immunity). The inflammation is not directly caused by the chemicals but rather the response of T cells to the haptenized protein. 5 We have provided a comprehensive summary of dermatologic reactions due to the exposure of disinfectants. The data on percutaneous penetration and interactions with skin components in facilitating skin penetration are also highlighted. We have included only the disinfectants commonly found in consumer products from the lists of disinfectants approved by (i) the European Chemical Agency 6 and (ii) the United States Environmental Protection Agency 7 for use against SARS-CoV-2, where these disinfectants have demonstrated efficacy against a harder-to-kill virus or another type of human coronavirus similar to SARS-CoV-2. Table 1 shows the list of disinfectants commonly found in consumer products based on the various chemical classes and their examples and have included adverse reactions associated with the use of disinfectants and their skin penetration ability in Table 2 and 3. WHO recommends the use of alcohols, namely ethanol (80%v/v) and isopropanol (75%v/v) in handrubs. 8 Percutaneous penetration of both alcohols is generally low even with extensive use. [9] [10] [11] They may create both irritant and allergic contact dermatitis. 8, 12 This could be related to the solvent effect on skin components (Table 3) or pre-irritated skin with disrupted skin barrier. 13 Because isopropanol is more irritating than ethanol, 14 emollients, such as glycerol or propylene glycol, may be added to hand preparations. [15] [16] [17] Allergic reactions, including contact urticarial, have been reported. [18] [19] [20] The triggers may be due to impurities, aldehyde metabolites, or fragrances in the product. 19, 21 Iodophors or polyvinylpyrrolidone (povidone, PVP) iodines (PVP-I) is non-staining, being relatively less toxic and irritating, when compared to iodine. Topical absorption seems to be time-dependent. 43 ICD (usually 10% PVP-I) sometimes occurs with chemical burns, pain, blistering lesions, and tissue necrosis. 44 Percutaneous absorption of silver and its nanoparticle forms is usually low in both intact and damaged skin (< 4%), because its ionized form does not penetrate the skin readily. 56, 57 ACD is known to occur due to the other ingredients. 58 Local skin discoloration (brown-black) is occasionally observed and be seen more frequently with topical application to wounds. 59, 60 This is not true argyria (blue-grayish discoloration) which is more long-lasting and common following chronic exposure through inhalation or oral ingestion. 59 AHA, including citric acid (CA), glycolic acid (GA), and lactic acid (LA), can penetrate the skin but the dermal absorption is pH-, concentration-, and time-dependent. [61] [62] [63] [64] Burning, dermatitis, skin peeling, itching, and moderate sunburns are frequently reported at a concentration ≤ 10% or a pH ≥ 3.5. 65 This can be related to the expression of proinflammatory cytokines, such as TNF-α and IL-1α. 66 An increased epidermal and dermal thickness is common at higher concentrations (CA and GA: 20 - 83 The cause may be due to the excellent lipid solubility of PA and its strong oxidative disruption on the skin lipids and keratin protein. Phenol and its derivative, especially ortho-phenylphenol (OPP) or biphenyl-2-ol and ortho-benzylpara-chlorophenol (OBPCP), have excellent skin-penetrating power. 84, 85 Skin reactions can develop with short contact. ACD related to OPP and OBPCP may occur even at low concentrations (0.1%). 86-88 Chemical burns and digital tip gangrene have occurred, following persistent exposure to 0.5% halogenated phenol; the actual causative compound was not stated. 89 Depigmentation or leukoderma is another clinical concern when applying OPP and OBPCP (1%), 90, 91 although the depigmentation is reversible but with the repigmentation process taking upwards to a year or more. J o u r n a l P r e -p r o o f 100 ACD has been reported at very low concentrations (0.01%), and immediate hypersensitivity is possible. [101] [102] [103] [104] [105] Urticaria, swelling, erythema, and itchiness can be found at higher concentrations (1 -10%). 104, 106 DDAC may produce mixed hypersensitivity that induces both IgE-and T-cell mediated responses. 107-109 DDAC can be a skin irritant and sensitizer, probably stronger than BAC. While the use of disinfectants is inevitable, it is crucial to consider the following points to minimize or avoid any potential dermatological reactions:  Damaged skin is prone to adverse reactions from a direct absorption of disinfectants, and extra care should be given to avoid contact with disinfectants.  While multiple disinfectants may be used together or formulated as a single product to achieve synergistic effects, an enhanced adverse effect is expected.  Whenever dermatitis is known, disinfectants that are weak or non-irritants and sensitizers should be prioritized. Patch testing may be considered. It is important to avoid using disinfectants from a similar class that is known to be allergic to the users in consideration of a potential cross-reactivity. Journal Pre-proof  It is necessary to use protective garments during handling to avoid direct contact from spillage. Even with regular use of protective attires, unnoticeable punctures in the gloves on multiple use and the handling of disinfected surfaces can expose users to contamination. Possible interactions of disinfectants with protective garments may occur. For example, glutaraldehyde at 2 -3.4% may penetrate latex gloves after 45 min and thus, butyl rubber and nitrile rubber gloves are recommended. 110  Emphasis is given only on the dermatological reactions in this review but the exposure through other manners such as ocular route and inhalation is often significant and most probably toxic. For instance, chlorine compounds are known to emit chlorine gas during preparation and application. The exposure to the eyes is thus high and toxic. The dermatologic events are usually, but not always, related to prolonged exposure and contact with concentrated disinfectants. Many dermatologic adverse events remain unreported. Some skin reactions, especially sensitization, can develop for compounds currently known to be a non-irritant or sensitizer. WHO. WHO Virtual press conference on COVID-19. March 11, 2020. 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Results of a multicenter study of the German Contact Allergy Group Interaction of Antiseptic Compounds with Intercellular Lipids of Stratum Corneum Correlation of Water and Lidocaine Flux Enhancement by Cationic Surfactants In Vitro Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for consumers concerning benzethonium chloride. European Commission Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro Factors of importance in the use of triethylene glycol vapor for aerial disinfection. 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