Cosmetics have been in vogue for many centuries. While evidence of their use reaches back to the ancient Egyptians, the cosmetics industry is still booming today. Cosmetics have come a long way from the original kohl, antimony-based makeup that was once used on the eyelids, eyebrows, and eyelashes.1 According to Global Cosmetics Industry magazine, the cosmetic industry generates some $290.9 billion in sales annually.2 Cosmetics are defined by the U.S. Food and Drug Administration as “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and articles intended for use as a component of any such articles; except that such term shall not include soap.”3 Therefore, cosmetics encompass a broad range of products including shampoo, lotion, deodorant, hair dye, makeup and nail polish. Cosmetic Reactions Despite product testing by cosmetic companies before new product releases to the public, adverse reactions are still experienced by consumers of cosmetics. Cosmetics can cause reactions such as, but not limited to, irritant contact dermatitis, allergic contact dermatitis, photocontact dermatitis, contact urticaria, pigmentary changes and acneiform reactions.4 Irritant Reactions Irritant reactions to cosmetics, including subjective and objective irritation, make up the majority of reactions. There are two types of irritation; objective irritation, which is characterized by burning, itching or stinging sensations, with visible skin changes upon application;5 and subjective irritation, which does not cause visible changes in the skin.6 Adaptive Immune Delayed Type IV Hypersensitivity Responses Unlike irritant contact dermatitis, which is not mediated by an immune reaction, both allergic contact and photocontact dermatitis are adaptive immune delayed type IV hypersensitivity responses to chemical compounds penetrating the skin or mucous membranes.7,8 Photocontact dermatitis causes dermatitis in a photodistribution when ingredients such as sunscreens and fragrances are exposed to UVA light.7 Three to four decades ago, a fragrance called “musk ambrette” was the leading cause of photocontact dermatitis.9 Today ingredients in sunscreens like PABA, oxybenzone, cinnamates and avobenzone are all currently implicated as causes of photoallergy.10 Allergic contact dermatitis to cosmetics, though less common than irritant contact dermatitis, can still be a nuisance to cosmetic users. One U.S. study showed that 0.3% of general dermatology patients had a cosmetic allergy.11 Still, it is postulated that the actual prevalence of cosmetic allergies is higher because mild allergic and irritant reactions usually result in discontinuation of the cosmetic product without a need for medical attention.12 Prevalence among patients receiving patch testing for suspected allergic contact dermatitis is much higher, as studies have yielded prevalence rates of allergic contact dermatitis to cosmetics ranging from 2.4% to 36.3%, with a pooled rate of 9.8%.13 These rates differ among males and females. The North American Contact Dermatitis Group (NACDG) found that during a period from 2001 to 2004, 24% of females patch tested were cosmetic allergic vs. 18% of males.14 Displaying a subset of cosmetics, a study done by Adams and Maibach showed that facial and eye makeup made up 11% and 4% of contact dermatitis cases caused by cosmetics, respectively.11 This illustrates that there are a large number of consumers of makeup who may be affected by makeup- induced allergic contact dermatitis. Many ingredients in cosmetics have been cited as causes of allergic contact dermatitis, with fragrances and preservatives being the most common.11,14,15,16 This review focuses on discussing common allergens found in mascara, lipstick, eye shadow and blush. Similar to cosmetics in general, common color cosmetics allergens include preservatives and fragrances as well as red dye. Preservatives Preservatives are ubiquitous and have been added to color cosmetics to protect against product degradation and overgrowth of bacteria and fungi. Some common makeup preservatives are: formaldehyde; formaldehyde-releasing agents like diazolidinyl urea, quaternium-15 (Q-15); non-formaldehyde releasers like parabens; and antioxidants such as gallates and butylhydroxyanisole (BHA). Preservatives are, however, a frequent cause of cosmetic-induced contact dermatitis. Goossens et al found that among patients with cosmetic allergies, 19% had an allergic reaction to preservatives in makeup.16 Formaldehyde is commonly used in mascara, nail polish and hair straightening products. Derivatives of formaldehyde and agents that release formaldehyde are also found in products, which makes reading the label an insufficient indicator of the presence of formaldehyde. One study proved that labels could be misleading by testing for formaldehyde in Swedish moisturizers that did not have it listed as an ingredient by the manufacturer or supplier. They found 10% of their samples did in fact contain the chemical.17 The samples they tested contained a formaldehyde-releasing preservative, which likely released the formaldehyde moiety found in the samples. Many brands of mascara and eye shadow also contain formaldehyde-releasing preservatives such as diazolidinyl urea and Q-1518, as do several brands of blush.19 Of patients found to have makeup-induced contact dermatitis by the NACDG from 2001 to 2004, 9.1% had reacted to Q-15.14 Parabens (methyl-, ethyl-, propyl-, butyl-, or benzyl-) are also common ingredients in cosmetics because they rarely cause irritation and are economical to use.20 In fact, parabens are found in 87% to 93% of cosmetic products,21 including most lipstick, mascara, eye shadow, and blush.19 Many consumers warned to avoid parabens often try to avoid products containing parabens; however, unlike other preservatives, parabens rarely cause allergic contact dermatitis. Warshaw et al showed that only 1.1% of cosmetic allergic patients had reactions to paraben mix.14 Fragrances Even though fragrances are used in cosmetics to impart pleasant aromas, they are often the source of cosmetic contact allergies. Surprisingly, even products like blush, mascara, and lipstick contain fragrance.19,22 One literature review found that 1% of allergic contact cheilitis from lipsticks were due to the fragrance cinnamic aldehyde.23 Goossens et al showed that 11% of patients had an allergic reaction to the perfume components in makeup.16 Another study found that of patients with makeup-induced contact dermatitis, 12.5% had reacted to fragrance mix and 10.2% had reacted to balsam of Peru.14 This can be very frustrating for those with fragrance allergy because of how difficult the allergens can be to avoid. Patch testing with fragrance mix can be an effective screening tool to detect fragrance allergy. Although specific allergens can be identified, patients with any fragrance allergy should use “fragrance-free” products. The term “unscented” generally refers to the addition of fragrance-masking chemicals, whereas “fragrance-free” refers to the absence of chemicals added to enhance aroma. Therefore, “unscented” and “fragrance-free” are not synonymous. Unfortunately, some fragrance-free products still contain fragrance. This is because the legal definition of a fragrance is any substance, natural or synthetic, used solely to impart an odor to a cosmetic product. If the fragrance is being used as a preservative in the product rather than to impart odor, in accordance with the legal definition,24 “fragrance-free” products may still contain fragrance. Red Dyes Red color dyes are present in many color cosmetics and, for some, can be sources of cosmetic allergens. When inedible lipsticks were popular in the 1950s, lipstick allergy caused by eosin, a red dye that stains the lips, was the most common type of cosmetic allergy.25 A chemical contaminant in eosin was implicated as the allergen causing the lipstick cheilitis.26 Once the fashion of lipstick colors changed and a more pure form of eosin was implemented in lipstick, the incidence of eosin allergy decreased precipitously.27 Eosin is one of many red colors reported to have caused lipstick cheilitis. Those colors are: carmine,25 D&C Red 7,28 D&C Red 17, D&C Red 19, D&C Red 31 D&C Red 36, FD&C Red 3, and FD&C Red 40.29 Color additives, D&C (drugs and cosmetics) or FD&C (foods, drugs, and cosmetics) are strictly regulated by the federal government. By U.S. law, all color additives used in cosmetics must be approved, certified, meet the requirements of identity and specifications stated in the Code of Federal Regulations (CFR), and be used only for the intended uses stated in the regulations that pertain to them.30 This regulation ensures that any color that is deemed unsafe, ie, carcinogenic, will not be used in a cosmetic product. Allergy-Free Makeup Options For those with a preservative, fragrance or red color allergy, finding a color cosmetic that will not cause an allergic contact dermatitis can be challenging. While options are limited, women can still enjoy the elegance and beauty of mascara, blush, eye shadow and lipstick. It requires thorough reading and understanding of product labels and steering away from color cosmetics that contain the specific allergen. Good alternatives for sufferers of preservative fragrance allergies might consider products from companies such as VMV Hypoallergenics, a product line created by dermatologists that includes mascaras, lipsticks, blushes and skin care. Many large companies such as Revlon, Almay and Covergirl now have formaldehyde-free nail polishes and mascara. Conclusion Lipstick, blush, mascara, and eye shadow do not have to be a source of irritation and frustration for those with cosmetic allergies. With proper avoidance and a good color cosmetic alternative, there is no reason why a person with a cosmetic allergy should have to go without makeup. Ms. Miyar is with the University of Illinois at Chicago. Dr. Baumann is with the Cosmetic Medicine and Research Institute, Miller School of Medicine, University of Miami, Miami Beach, FL. Disclosures: Dr. Baumann is an investigator for Stiefel, Galderma, Medicis, Allergan, Unilever, Avon and Mary Kay. Ms. Miyar has no conflicts of interest with the subject discussed in this column.