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Contact Dermatitis Associated With Nail Care Products

Retrospective Analysis of North American Contact Dermatitis Group Data, 2001–2016

Warshaw, Erin M. MD, MS*,†,‡; Voller, Lindsey M. BA*,‡,§; Silverberg, Jonathan I. MD; DeKoven, Joel G. MD; Atwater, Amber R. MD**; Maibach, Howard I. MD††; Reeder, Margo J. MD‡‡; Sasseville, Denis MD§§; Belsito, Donald V. MD∥∥; DeLeo, Vincent A. MD¶¶; Fransway, Anthony F. MD***; Fowler, Joseph F. Jr MD†††; Taylor, James S. MD‡‡‡; Pratt, Melanie D. MD§§§; Mathias, Toby MD∥∥∥; Marks, James G. Jr MD¶¶¶; Zug, Kathryn A. MD****; Zirwas, Matthew J. MD††††

Author Information
doi: 10.1097/DER.0000000000000583
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Abstract

Nail care products have long been used cosmetically. Embellishments include liquid nail polish, nail wraps, gel nails, dipping powders, and acrylics (Table 1). Nail care products may also be used to strengthen the nail plate, soften cuticles, and promote nail hydration.1 These products are popular; spending on nail salon services in the United States was estimated to be at least $8.5 billion in 2017.2 This estimate does not include data from smaller nail salons or the cost of newer, do-it-yourself, home gel nail polish products.

TABLE 1
TABLE 1:
Descriptions of Common Nail Techniques1,2

Nail treatments may lead to adverse effects. Irritant contact dermatitis (ICD) can result in nail plate yellowing, nail dystrophy, and cuticle disruption.3 Allergic contact dermatitis (ACD) to nail polish in consumers has been reported to most commonly present as ectopic dermatitis involving the face and neck, as allergens are transferred by direct contact from partially dried polish.4,5 Özkaya and Ekinci6 estimated the prevalence of nail polish allergy in a Turkish population at 1% of all patch-tested patients. The prevalence was notably higher in Brazil, where 8% of patients with presumed ACD had patch test reactions to at least 1 nail polish ingredient.7

Historically, tosylamide—a synthetic resin added to polish to enhance flexibility and shine—has been the most common nail polish–associated allergen.2,8 However, the prevalence of ACD to tosylamide may be declining, largely due to a shift toward newer “hypoallergenic” or “tosylamide-free” polish alternatives.9 Contact allergy to (meth)acrylate chemicals, conversely, is on the rise.10,11 Many authors attribute this increase to emerging long-lasting nail techniques such as gel nail polishes, some of which utilize a light-based curing system to induce polish hardening.1,12,13 Although fully cured (meth)acrylate polymers are thought to rarely cause cutaneous sensitization, monomers have significant allergenic potential.12 Sensitization occurs when polish is cured inadequately and residual monomers contact the skin.14,15 Select literature on the prevalence of contact allergy specifically to nail care products associated with tosylamide and (meth)acrylates is summarized in Table 2. In addition to these well-known allergens, other contact sensitizers associated with nail care products include cyanoacrylates, formaldehyde (and related compounds), phthalates, benzophenones, and epoxy resin.12,18,19

TABLE 2
TABLE 2:
Select Literature on the Prevalence of Sensitization to Tosylamide and (Meth)acrylates Associated With Nail Care Products

Although previous studies have investigated ACD to nail care products, updated estimates from a large US cohort have been lacking. Our primary goals were to determine (1) the frequency of nail care products as a source of clinically relevant positive patch test reactions, (2) the frequency of nail care products as a source of ICD, (3) primary body sites affected in nail care product–associated dermatitis, and (4) commonly associated allergens and nail care product sources among patients patch tested by the North American Contact Dermatitis Group (NACDG).

MATERIALS AND METHODS

NACDG Database

Deidentified data from the NACDG screening series database between 2001 and 2016 were analyzed. Patch testing was conducted in accordance with NACDG standards, which have been described previously.20 Collected data included patient demographics (age, sex, race, occupation), history of atopy (asthma, eczema, hay fever), body sites of dermatitis (maximum of 3 sites), final diagnosis (maximum of 3 diagnoses), and associated allergens. The number of tested allergens varied by 2-year cycle. Sixty-five allergens were tested between 2001 and 2006 and 70 allergens between 2007 and 2016; not all allergens were tested during every cycle. For each patch test reaction, clinical relevance, occupational relevance, strength of reaction, and source codes were documented. Current relevance encompassed reactions coded as “definite” (positive patch test or use test with a skin contactant verified to contain the allergen), “probable” (allergen verified in skin contactant with a consistent clinical presentation), and “possible” (skin contactant possibly contained the allergen); past relevance included previous exposures likely containing the allergen in question. Occupation was coded using the 1980 Census Classified Index of Industries and Occupations.21 Occupational relevance was determined from history and clinical presentation. For each positive allergen, an exposure source was classified. Sources were also coded for positive relevant non-NACDG nail care product–associated allergens, although the names of those specific allergens were not recorded.

In addition to allergens, an assessment of ICD (based on clinical history and examination) was coded for each patient. If an irritant was considered clinically relevant, the source of ICD was coded.

Study Population

Nail care products (nail polish/coatings/gels/strengtheners, artificial nails/extenders, nail adhesives, nail moisturizers, and nail care products not otherwise specified) were added as source codes to the NACDG database in 2001; the study population therefore consisted of NACDG patch–tested patients between 2001 and 2016. Patients with nail care product sources specifically associated with any of the following were included: (1) positive patch test reaction to an NACDG screening allergen, (2) positive patch test reaction to a non-NACDG allergen, and (3) ICD. Allergens with both current and past clinical relevance were included. Patients with reactions of unknown clinical relevance or with negative final readings were excluded. Patients with reactions to nail allergens associated with a non–nail care product source (eg, methyl methacrylate [MMA] allergic reaction associated with a dental adhesive source) were not included.

Data Analysis

Data were entered at a centralized location using Access software (Access 2010; Microsoft Corporation, Redmond, WA) and subsequently analyzed with Microsoft Excel (Excel 2019; Microsoft Corporation). Demographics, clinical relevance, occupational relevance, strength of reactions, and exposure sources were presented using descriptive analyses including frequencies, counts, and proportions. Allergens and sources were compared using χ2 test with GraphPad Prism software (version 8.2.1 for Mac OS X; GraphPad Software, La Jolla, CA). The Cochran-Armitage test was used to evaluate trends over time (eight 2-year cycles; SAS System; SAS Institute, Cary, NC). P < 0.05 was considered statistically significant.

RESULTS

Frequency of Sensitivity

Of the 38,775 patients patch tested between 2001 and 2016, 769 patients (2.0%) had clinically relevant positive patch test reactions and/or ICD associated with a nail care product (Fig. 1). Of these 769 patients, 746 patients (97.0%) had allergic reactions only, 14 patients (1.8%) had ICD only, and 9 patients (1.2%) had both. Of those with allergic patch test reactions attributed to a nail care product, 17.1% had reactions to allergens not on the NACDG screening series. As compared with the previous 7 cycles, the most recent cycle found a significant increase in overall nail care product reactions (1.9% vs 2.4%, P = 0.0171).

Figure 1
Figure 1:
Participant flow diagram.

Demographics and Primary Sites of Involvement

Patient demographics are listed in Table 3. Most patients were female, white, and older than 40 years. Overall occupational relevance was found in 98 of 767 patients (12.8%). The most common occupation was hairdressers/cosmetologists (includes nail technicians; 66.3%). Nail care product allergy was most commonly associated with dermatitis involving the face (43.0%; with the eyelids affected in 14.4% of patients), hands (27.6%), or a scattered/generalized distribution (12.1%; Table 4). Subgroup analysis of individuals with only tosylamide or only (meth)acrylate allergy (excluding those with both) found that patients with tosylamide allergy had significantly greater involvement of the face as compared with those with (meth)acrylate allergy (60.5% vs 33.2%, P < 0.0001), whereas those with (meth)acrylate allergy had greater involvement of the hands (35.8% vs 10.9%, P < 0.0001).

TABLE 3
TABLE 3:
Demographics of Patients With an Allergic Patch Test Reaction or ICD Associated With a Nail Care Product
TABLE 4
TABLE 4:
Primary Body Site of Involvement Among Patients With a Positive Patch Test Reaction or ICD Associated With a Nail Care Product

Allergens

The top 5 NACDG screening allergens associated with nail care products were (2-hydroxyethyl methacrylate [2-HEMA] [273/482, 56.6%], MMA [210/755, 27.8%], ethyl acrylate [EA] [190/755, 25.2%], ethyl-2-cyanoacrylate [ECA] [12/175, 6.9%]) and tosylamide (273/755, 36.2%; Table 5). Of patients with reactions to nail care products, the percentage of patients with a positive patch test reaction to 2-HEMA (P = 0.0069) and EA (P = 0.0024) significantly increased over the study period, whereas allergy secondary to tosylamide significantly decreased (P < 0.0001; Fig. 2). Frequency of positive reactions to MMA did not significantly change over time (P = 0.5329). Other allergens, including epoxy, fragrance chemicals, and formaldehyde-releasing preservatives, demonstrated frequencies less than 2%.

TABLE 5
TABLE 5:
Top 5 NACDG Allergens Associated With a Nail Care Product Source: Final Reaction Reading, Clinical Relevance, and Occupational Relevance
Figure 2
Figure 2:
Trends in the top 5 NACDG allergens associated with a nail care product source between 2001 and 2016.

Reaction strength noted at final patch test reading and clinical relevance of the top 5 allergens are summarized in Table 5. More than half of all reactions to 2-HEMA, tosylamide, and MMA were ++ or +++; EA and ECA were most commonly +. The majority of reactions were of current relevance. 2-Hydroxyethyl methacrylate (16.5%) and EA (15.3%) were most commonly related to occupation. The number of occupationally related positive patch test reactions to EA (P = 0.0078) and MMA (P = 0.0075) significantly increased over the study period, whereas occupationally related positive patch test reactions to 2-HEMA (P = 0.5507) and tosylamide (P = 0.0774) did not significantly change over time.

Allergen Sources

Artificial nails, nail polishes/coatings/gels/strengtheners, and nail adhesives were the most common sources (Table 6). Artificial nails were primarily responsible for patch test reactions to 2-HEMA (69.6%), MMA (66.2%), and EA (62.6%). Most reactions to tosylamide were associated with nail polish (83.9%), whereas the primary source for ECA was nail adhesives (50.0%).

TABLE 6
TABLE 6:
Sources of Nail Care Product Allergy

Irritant Contact Dermatitis

Twenty-three (3.0%) of 769 patients had ICD (14 patients with ICD only and 9 with both ICD and ACD attributed to nail care product sources). Irritant contact dermatitis was most commonly associated with artificial nails/extenders (39.1%), nail adhesives (34.8%), and nail care products not otherwise specified (13.0%). Nail adhesives caused a significantly greater proportion of irritant reactions as compared with allergic (34.8% vs 12.4%, respectively; P = 0.0014), although these numbers were small (n = 12).

DISCUSSION

This retrospective study demonstrated several key findings. Nail care products represented a small portion of overall reactions; 2.0% of all NACDG patch–tested patients had positive patch test reactions or ICD linked to a nail care product source. The predominant body sites of nail care product–associated dermatitis were the face (especially tosylamide) and hands (especially [meth]acrylates) or included a scattered/generalized distribution. The top 5 allergens associated with nail care products were 2-HEMA, MMA, EA, ECA and tosylamide; notably, none of these top 5 allergens are present on T.R.U.E. Test.22 The prevalence of allergy secondary to tosylamide decreased significantly over the study period, whereas 2-HEMA and EA allergy increased. Finally, nearly one-fifth of all nail care product–associated allergens would have been missed without additional screening beyond the NACDG screening series, underscoring the need for testing to a broad array of allergens in suspected allergy to nail care products.

Frequency of ACD

Nail care product allergy among the general population has previously been estimated at 1% to 3%.18 Summary reports of patients referred for patch testing indicate a frequency of nail care product allergy of 1% to 8%.6,7,23 We found an overall frequency of 1.9% of NACDG patch–tested patients with more than 1 allergen associated with nail care products. Although this estimate comprises a relatively small percentage of overall ACD cases, nail care product allergy may have important consequences for affected individuals, particularly if allergy occurs secondary to (meth)acrylates. In fact, sensitization to (meth)acrylate-based nail care products has been reported to lead to adverse outcomes when patients are exposed to (meth)acrylates in other sources, such as dental work24 and joint prostheses.25

Frequency of ICD

Anecdotally, ICD is commonly associated with nail care products; certain chemicals including toluene, formaldehyde, acetone, and (meth)acrylates are recognized irritants and can cause significant damage to the nail plate and surrounding soft tissues.26 Yet ICD to nail care products represented a small portion of our overall study population (0.06% of all patch tested patients). This finding is most likely due to clinical recognition of ICD to nail care products,26,27 obviating the need for patch test referral.

Demographics and Primary Sites of Involvement

Not surprisingly, our study population was predominantly female (>97%), similar to prior reports (Table 2). Ages ranged from 12 to 86 years, reflecting the ubiquitous usage of nail care products in all stages of life.

This study confirmed that nail care product dermatitis often affects the face (43.0%), including the eyelids (14.4%). These findings are consistent with previous studies; Lazzarini et al7 found the face to be affected by nail polish allergy in 86% of cases, with the periorbital region (71%), perioral region (30%), and chin (23%) most commonly involved. Özkaya and Ekinci6 documented a greater proportion of cases with eyelid involvement (94%), followed by the face and neck (81%). In both studies, tosylamide was the most commonly identified allergen, affecting more than 87% of patients. Subgroup analysis of our data found that individuals with tosylamide-only allergy had a significantly higher frequency of facial involvement as compared with (meth)acrylates (60.5% vs 33.2%, respectively). Conversely, hand dermatitis was significantly more common among our patients with (meth)acrylate reactions, consistent with prior reports of predominant involvement of the hands with (meth)acrylate allergy.11,12,17 This distribution may be explained by more occupational cases associated with (meth)acrylate nail care products (from application to clients), as well as incomplete curing in home gel nail products.16

Occupational

Nail care product–related dermatitis was associated with occupation in 12.8% of our patients. Hairdressers/cosmetologists were affected most frequently (66.3% of occupationally relevant cases). A previous NACDG study found that 17.1% of occupationally related allergic reactions in cosmetologists (including hairdressers) were related to a nail source.28 Nail technicians are at high risk of sensitization to (meth)acrylates given contact with allergenic monomers before curing, penetration through gloves, and airborne exposures.12,29,30 Protective gloves should be worn by sensitized beauticians. Double nitrile gloves provide up to 60 minutes of protection, but thicker, 4H plastic polymer gloves offer complete protection.13,31 However, those gloves inhibit the fine manual dexterity required by nail technicians; thus, Roche et al32 proposed the “fingerstall technique,” which involves cutting the fingers from 4H gloves and wearing these under more flexible gloves (eg, nitrile) to allow for better agility. Gatica-Ortega et al11 investigated this technique in 22 beauticians with (meth)acrylate allergy and found that it was successful in 36%. In the United States, the National Institute for Occupational Safety and Health has provided guidelines for nail technicians,33 and in the United Kingdom, the Cosmetic, Toiletry, and Perfumery Association has provided detailed techniques for minimizing sensitization from artificially enhanced nails.33,34

Registered nurses and dental assistants/hygienists were the second most common occupation. These workers may become sensitized through occupational exposures,35,36 but our data do not include this information.

Specific Allergens

Tosylamide

Tosylamide—a thermoplastic resin imparting gloss adhesion and hardness introduced into nail polish in 19399—has been a recognized cause of ACD to nail care products, often affecting the neck and eyelids.37 We found a statistically significant decrease over time in reactions to tosylamide associated with nail care products. These results are consistent with the findings of Lee et al,9 who documented a significant decrease in the frequency of tosylamide reactions in 7408 Australian patients patch tested over an almost identical study period (2002–2017). This decrease may represent a shift by manufacturers toward “hypoallergenic” and “nontoxic” polish, in which tosylamide is replaced by polyester resins or cellulose acetate butyrate.38 In addition, a decrease in tosylamide reactions may be due to increased use of other nail polish products such as long-lasting gel nail polish, which contain (meth)acrylates, and powder nails, also known as dipping powder manicure, which contain ECA.9,39

2-Hydroxyethyl Methacrylate

In contrast to tosylamide, the frequency of nail care product–associated 2-HEMA reactions increased throughout the study period. 2-Hydroxyethyl methacrylate has previously been cited as the most commonly positive (meth)acrylate and is present within gel nails and Shellac gel nail polish.10,40–42 Rolls et al40 suggested adding 2-HEMA to the British baseline series after finding that nearly one-third of all cases of (meth)acrylate allergy would have been missed if 2-HEMA were excluded. Drucker and Pratt43 similarly found that adding 2-HEMA increased (meth)acrylate allergy detection from 73% to 91% compared with testing with EA and MMA alone. These findings reflect the overall increasing prevalence of contact allergy to (meth)acrylate nail care products in recent years, particularly in Europe,11,44,45 the United Kingdom,15 and now North America.

Acrylic, gel, and Shellac nails were previously applied only in nail salons; however, home gel nail polish kits are now widely available.16 Most kits come with either a UV or light-emitting diode (LED) light source, which is specific to the type of gel nail polish. Consumers using these kits are potentially at high risk of sensitization due to frequent reapplication rates and lack of proper training. For example, if a consumer uses an LED nail polish with a UV light source, there may be inadequate curing, as curing takes approximately 30 seconds for LED and 2 minutes for UV lights.16 Risk of sensitization and relapsing dermatitis may be mitigated by utilizing appropriate light sources for the recommended amount of time and avoiding cutaneous contact with uncured polish. Guidelines for home use have been developed in the United Kingdom.34 A continued upsurge of allergy to 2-HEMA is expected in coming years as the use of long-lasting nail techniques becomes increasingly widespread.

Methyl Methacrylate

Methyl methacrylate, an inexpensive (meth)acrylate used in nail sculpting,41 was the next most common allergen associated with nail care product allergy in our study. Although the use of 100% MMA was banned by the US Food and Drug Administration in the 1970s, MMA can still be found illegally in certain nail salons and may be found in online products.46–48 Canadian regulations also restrict MMA, with an advisory warning and subsequent ban on MMA in cosmetic nail preparations issued in 2003.49

Ethyl Acrylate

Ethyl acrylate is an acrylic monomer commonly used in the nail industry.2 Our study found EA less commonly associated with nail care products as compared with 2-HEMA or MMA, similar to prior reports,15,50 although other studies have found that EA is more common than MMA.10,51 These differences may be due to variable cross-reactivity between members of the (meth)acrylate family.45 Certain authors have proposed that 2-HEMA is the primary sensitizer, and all other acrylate reactions, including those to EA, result from structural similarities between monomers.45,52 The most conservative approach for affected patients involves avoidance of all (meth)acrylates.

Ethyl-2-Cyanoacrylate

Cyanoacrylates rarely cross-react with (meth)acrylates.2 Therefore, nail wraps and press-on nails, which utilize cyanoacrylate-based adhesives, may be a safe alternative for some (meth)acrylate-sensitive individuals desiring long-lasting nail color. However, cyanoacrylates may lead to sensitization independently.2 Dipping powders, which also utilize ECA,39 may represent a particularly high-risk source of sensitization to cyanoacrylates.17 In the current study, ECA was tested during 2 NACDG cycles, with a frequency of only 6.9% of nail sources. Positive patch test reactions to ECA were also low in a retrospective Portuguese study by Raposo et al,12 which found a frequency of 5.7% (13/230). Interestingly in that study, all patients reacted to other (meth)acrylates. The authors discounted cross-reactivity and implicated a switch by patients from (meth)acrylate-based nail care products (due to allergy) to press-on or silk nails (eg, nail wraps) containing ECA.12

Other Allergens

All other allergens demonstrated frequencies of less than 2%. One patient with generalized dermatitis reacted to every member of the formaldehyde family, including imadazolidinyl urea (aq. and pet.), diazolidinyl urea (aq. and pet.), quarternium-15, DMDM hydantoin, and bronopol, all of which were attributed to a nail care product source. Another patient had a strong (++) reaction to nickel, an allergen that can be present in metal mixing balls to prevent separation of nail polish components,4 as well as metal extension molds for lengthening nails.53,54 Although uncommon, clinicians should keep in mind these additional causative allergens in nail care product dermatitis.

Sources

Artificial nails were the most common specific nail care product source, followed by nail polishes and nail adhesives. These findings align with the general pattern of allergen frequencies described previously (eg, [meth]acrylates present in artificial nails, tosylamide in polish, and cyanoacrylates in nail adhesives and dipping powders). Patients commonly use multiple nail care products, and specification of one source can be difficult. Therefore, differentiation of nail care product sources is somewhat subject to physician interpretation bias, patient recall bias, and availability of nail care product ingredient lists.

Limitations

As a retrospective study, this study is inherently limited by its design. The NACDG database does not document longitudinal outcomes; therefore, we cannot comment on whether patients improved following avoidance of responsible nail care products. Next, the 1980 Census Classified Index of Industries and Occupations includes cosmetologists, hairdressers, and nail technicians all in 1 code,21 so exact, occupation-specific estimates could not be obtained. Finally, names of non-NACDG allergens are not recorded (only sources of those allergens), so specific allergen names (including [meth]acrylates not on the NACDG screening series) cannot be determined. Several other allergens, including phthalates and so on, have also been reported.55–57 These findings underscore the importance of testing to additional series in cases of suspected nail care product allergy.

CONCLUSIONS

Although allergy to nail care products represents a minority of cases of ACD, the increasing popularity of long-lasting nail techniques will likely result in increased prevalence. In this retrospective study of a large North American cohort, patients most often presented with facial (especially those allergic to tosylamide) and/or hand dermatitis (especially those allergic to [meth]acrylates). The most common allergens associated with nail care products included tosylamide, 2-HEMA, MMA, EA, and ECA. Frequency of tosylamide allergy significantly decreased over the study period, whereas allergy to 2-HEMA and EA significantly increased. Importantly, almost one-fifth of nail care product–associated allergens would have been missed if additional allergens were not tested (beyond the NACDG screening series), underscoring the need for testing to a broad array of allergens in suspected allergy to nail care products.

ACKNOWLEDGMENT

This study was supported with resources and the use of facilities at the Minneapolis Veterans Affairs Medical Center. The contents do not represent the views of the US Department of Veterans Affairs or the US government.

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