Scent-sitive skin

By Emily Margosian, Assistant Editor, November 1, 2024

Ask a contact dermatitis expert — what’s one of the toughest allergies to manage?

“Probably fragrance,” said Christen Mowad, MD, FAAD, director of the Contact and Occupational Dermatitis Clinic at Geisinger Medical Center. “Fragrance ingredients are very common, and allergies to fragrance are a challenge to manage because of the way they’re listed on product labels. It’s evolving all the time because the industry continues to introduce new ingredients into our environment.”

“It’s a large group of potential allergens, with over 3,000 chemicals that can be labeled as a fragrance,” agreed JiaDe (Jeff) Yu, MD, FAAD, director of Occupational and Contact Dermatitis and assistant professor of dermatology at Massachusetts General and Harvard Medical School. “In the European Union, they have regulations that require labeling of top fragrance allergens found in personal care products. In the United States, however, this is not the case.”

This month, DermWorld digs into regulatory quirks of fragrance labeling requirements and regulation in the United States and speaks with contact dermatitis experts about tips for identifying and managing allergies to fragrance.

What classifies as a “fragrance”?

Most fragrances and fragrance products are regulated as cosmetics by the FDA. However, some belong to other product categories and are regulated differently, depending on how the product is intended to be used.

What determines if a fragrance product is regulated as a cosmetic? According to the FDA, if the product is intended to be applied to a person’s body to make them more attractive (for example, perfume, cologne, aftershave, etc.), it’s a cosmetic under the law.

However, some fragrance products applied to the body are intended for therapeutic uses. Products intended for this type are treated as drugs under the law. Examples of labeling statements causing a product containing fragrances to be treated as a drug include “easing muscle aches,” or “helping people sleep.”

Other products that may contain fragrance ingredients, but are not applied to the body, are regulated by the Consumer Product Safety Commission. Examples include products like laundry detergent, fabric softener, and dryer sheets.

“Fragrance free” vs. “unscented”

Given the prevalence of fragrance ingredients in personal care products, how should consumers interpret marketing claims that a product is “fragrance free”?

“Not all fragrance-free products are truly fragrance free. You have to check the ingredient labeling to make sure there are no fragrance chemicals, and this can be challenging as some ingredients are not added to products for the purpose of imparting fragrance, but as an emulsifier, for example,” explained Dr. Yu. “Therefore, the product can still be considered ‘fragrance-free’ though it has potential fragrance allergens in it.”

“There’s also the concept of ‘unscented,’ in which products contain some sort of masking fragrance,” explained Walter Liszewski, MD, FAAD, assistant professor of dermatology and preventative medicine at Northwestern Feinberg School of Medicine, and board member of the American Contact Dermatitis Society. “Consumers may not see ‘fragrance’ listed on a bottle, but fragrance essential oils could be present. The reality is that for non-medical products, the FDA doesn’t have tremendous authority to regulate manufacturers’ claims. It’s challenging, because what companies write on their product disclaimers aren’t necessarily what companies actually do.”

“One study of best-selling moisturizers found that 45% of products labeled fragrance-free contained fragrance or a botanical cross-reactor.”

Fragrance chemicals may also function as a preservative in a product, allowing it still to be marketed as “fragrance free,” explained Jennifer Chen, MD, FAAD, clinical professor of dermatology at Stanford University School of Medicine and president of the American Contact Dermatitis Society. “One study of best-selling moisturizers found that 45% of products labeled fragrance-free contained fragrance or a botanical cross-reactor,” she said.

This seemingly misleading marketing harkens back to how fragrances are classified by the FDA, explained Dr. Mowad. “A fragrance, as defined by the FDA, is a substance used for the sole purpose of imparting an odor to a product,” she explained. “That means that if a fragrance substance has another use, such as being a preservative, and if a company is using that fragrance ingredient for the purpose of being a preservative, and not for the purpose of imparting fragrance, it can be put into a fragrance-free product.”

These “covert fragrances” can make avoiding fragrance very difficult for patients suffering from contact allergies. Potential covert fragrance allergens found in consumer products include:

• ethylene brassylate

• benzyl alcohol

• benzaldehyde

• essential oils

• bisabolol

While not all claims of “fragrance free” can be taken at face-value, patients with a known fragrance allergy can look for certain products for additional labeling. “Products with the National Eczema Association Seal of Acceptance are generally fragrance-free as one of the criteria for getting the seal is to be devoid of all fragrances,” recommended Dr. Yu.

Top fragrance sensitizers

Among the many fragrance ingredients found in personal care products, a few have emerged as common sensitizers. According to Dr. Yu, among the most common fragrance allergens are cinnamal, eugenol, isoeugenol, and hydroxycitronellal.

As the fragrance industry continues to evolve, new “hot” allergens have also appeared.

Lyral, a synthetic fragrance found in some soaps, aftershaves, and deodorants, has emerged as a top fragrance allergen in recent years. “Lyral was added to the most recent iteration of the American Contact Dermatitis Society standard patch testing series about three years ago as an increasingly common, emerging fragrance molecule,” said Dr. Liszewski. “It traditionally was 80 allergens. It’s now been expanded to 90 of the most common allergens in North America, and Lyral was one of those new additions.”

Other emerging fragrance allergens include linalool and limonene, natural terpenes found in essential oils, fruits, trees, grasses, and tobacco. “Linalool and limonene are fragrances that have been found to cause allergic contact dermatitis in more children and adults compared to before,” said Dr. Yu. “These are considered natural essential oil compounds. Linalool is a component of lavender, bergamot, jasmine, and rosewood scents while limonene is more citrusy, consisting of orange oil and lemon oil.”

While linalool and limonene alone are not allergenic, their oxidation results in allergenic hydroperoxides, which can be found in several consumer personal products including shampoo, conditioner, face wash, perfumes, cologne, and deodorant.

Consumer-driven desire for “clean” ingredients has also led to product reformulations containing new fragrance sensitizers. “One of the bigger issues we’re seeing now is that instead of using synthetic or individual fragrance molecules, consumers want this concept of clean products. They want natural. As a result, companies will use a lot of botanicals, and a consumer may not realize that these products contain fragrance,” explained Dr. Liszewski.

Botanicals present a particular challenge for patch testers, according to Dr. Mowad. “They’re hard to test for, because they don’t cross-react. You can’t screen to one chemical and catch all the botanicals that are out there,” she explained. “For example, if you’re dealing with a massage therapist who’s using a lot of botanicals in their work, you need to know what to test for. You can’t test to one and say, ‘Okay, well, you’re allergic to all botanicals.’ It also depends on where people are getting the botanicals from. Who’s manufacturing them? What season were they harvested in? What part of the botanical are they using?”

As consumer appetites and industry norms shift over time, top allergens will only continue to change as new fragrance ingredients are introduced, predicts Dr. Mowad. “Lyral was the allergen that led to Fragrance Mix II, and the hydroperoxides of limonene and linalool are catching a lot of attention now. The world of contact dermatitis is ever evolving. When I first started 25 years ago, quaternium-15, which is a formaldehyde-releaser, was one of the hottest allergens. Now it’s essentially obsolete. Whereas methylisothiazolinone — which was not even on our radar 20 years ago — is the most common allergen we see after nickel. Industry changes and allergens change. That’s why you really have to stay current with what you’re testing to in order to be able to find out what people are reacting to.”

Labeling challenges in managing contact dermatitis to fragrance

Managing fragrance contact dermatitis allergies presents some key challenges not seen with other allergens. Much of this has to do with how fragrance ingredients are listed on product labels in the United States.

“Fragrance ingredients are often labeled under the non-specific term ‘fragrance,’ which may make it difficult for patients to find products that don’t contain their particular allergen,” said Dr. Chen. “Many fragrance chemicals are also found in naturally occurring plants, and if only the plant name is listed in the ingredients, patients who are fragrance allergic may not realize that a product contains their allergen.”

This labeling convention differs from other countries, which have more robust labeling requirements for fragrance ingredients. “Up until recently, the European Union had 26 different fragrance chemicals that had to be declared on the list of ingredients,” said Dr. Mowad. “Last June, the E.U. added 56 more fragrance chemicals that must be included, which comes out to a total of about 80 chemicals that must be disclosed on cosmetic labels. We are starting to see more of that type of labeling in the United States, but it’s not required.”

Often patients with a known fragrance allergy are instructed to avoid all fragrance due to a lack of transparency about individual fragrance chemicals on U.S. labels. “If we clear them, they can add one fragrance product back every two weeks or so, to see if they can tolerate that product,” said Dr. Mowad. “If they happen to get a rash during that two-week time, then you know that there’s something in that product that’s causing them trouble. Occasionally, you can reach out to the company and they’ll work with you, but that’s a whole separate process.”

Why is the labeling of fragrance ingredients so vague? There are several reasons. In the United States, if a cosmetic is marketed on a retail basis to consumers, it must have a list of ingredients. In most cases, each ingredient must be listed individually. However, under U.S. regulations, fragrance and flavor ingredients can be listed simply as “fragrance” or “flavor.” This is because the FDA requires a list of ingredients under the Fair Packaging and Labeling Act. However, this law is not allowed to be used to force a company to tell “trade secrets.” Fragrance and flavor formulas are complex mixtures of many different natural and synthetic chemical ingredients and are the kind of cosmetic components that are most likely to be considered “trade secrets.”

“The FDA has a broad interpretation of trade secrets, and so companies can opt in to disclose what they use, but they don’t have to. If a company invests money creating a unique scent to their product, they do not have to disclose certain ingredients,” said Dr. Liszewski. “This creates problems in patch testing, because even if we identify a specific fragrance allergy — for example, limonene — they may be allergic to that precise fragrance, but we don’t know if a product has that allergen if the label just says ‘fragrance.’ Therefore, if we do patch testing and someone reacts to a fragrance molecule, we oftentimes have to avoid all products that contain fragrance, because we don’t know what’s safe and what’s not.”

While the United States has been slow to follow E.U. labeling convention, more transparency may be coming soon. “There are some upcoming changes to fragrance labeling that we are expecting to come soon, following the Modernization of Cosmetics Regulation Act, where certain fragrance chemicals will need to be disclosed,” said Dr. Chen. The Modernization of Cosmetics Regulation Act of 2022 (MoCRA) is the most significant expansion of FDA’s authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic (FD&C) Act was passed in 1938. While the law took effect at the end of 2023, the FDA extended the deadline for companies to register their products and facilities until July 2024. By the end of 2024, the agency is expected to propose rules requiring companies to disclose the ingredients of their fragrances to flag allergens. Learn more about MoCRA.

Tips on identifying and managing a fragrance allergy

Identification

According to experts, most fragrance allergies manifest consistently as allergic contact dermatitis- or eczema-like rashes in key areas of contact depending on the source of the fragrance allergen. “If the allergen is found in shampoos or conditioner, you’ll often see rashes over the eyelids, lateral face, and neck. If the fragrance is in deodorants, then usually the skin around the armpit will have eczema,” said Dr. Yu.

“The rash may occur at sites of direct and indirect contact with the fragrance in question and thus may occur anywhere,” added Dr. Chen. “The most commonly occurring sites include the eyelids, face, neck, anogenital area, leg, and hands, although all sites are possible and even a generalized rash may be commonly seen.”

Prior to patch testing, allergen identification also involves investigative work between patient and physician to determine the source of exposure. This includes a thorough history about a patient’s occupation, hobbies, and whether they are living with another person who might put them in contact with a product causing the dermatitis.

“As part of a thorough history for patch testing, you should always ask patients about their occupation and about what their hobbies are. When it comes to fragrance allergies, I also discuss the concept of connubial dermatitis,” said Dr. Liszewski. “That’s where an individual may react to someone with whom they have close contact. That could be a spouse, or, if a patient has small children at home, they’re potentially coming into contact with a lot of products that they aren’t necessarily using themselves. I think it’s helpful to plant the seed for patients that when they have fragrance allergies, not only do they personally need to avoid certain products, but they also need to avoid things that will aerosolize, like scented candles or essential oil diffusers, and may also need to have a conversation about changing up the products that their spouse or children are using.”

Testing

In terms of allergen detection, experts agree patch testing is the gold standard. The most-used patch tests are the Thin-Layer Rapid Use Epicutaneous Test (T.R.U.E. Test), American Contact Dermatitis Society (ACDS) Core Allergen Series, and North American Contact Dermatitis Group (NACDG) Standard Series.

However, allergens included in these tests do not change frequently, and supplemental panels may be required to adequately evaluate patients. “The T.R.U.E. Test is the only FDA-approved patch test series, and tests to 35 allergens. However, it’s been shown to potentially miss up to 50% of allergens. Even the standard series, like the ACDS series or the NACDG series, probably only touch about 90% of allergens,” explained Dr. Liszewski. “The core series does get changed every couple of years, but there’s not a specific frequency. Allergens that become more prevalent get added — for example, something like Lyral — and some will get removed if they’re not really being used anymore. As the cosmetic market changes formulation, it impacts which chemicals consumers are being exposed to, and whether we still need to test them to those.”

According to Dr. Liszewski, the process for determining if a new allergen should be added to a core patch testing series is largely determined by specialty society groups. “This is interpreted by groups like the American Contact Dermatitis Society who follow this data,” he explained. “There’s a committee that basically determines what allergens should be included or removed for the next core set. They’re looking at case reports. They’re looking at data. They’re also pulling from their own experience as high-volume patch testers. For context, I direct the patch test allergic contact dermatitis clinic at Northwestern.”

Common fragrance markers used to detect suspected fragrance allergies include Fragrance Mix I (a mixture of 8 chemicals), Fragrance Mix II (a mixture of 6 chemicals), and Balsam of Peru, which were introduced to keep up with the fragrance industry. “A basic screening panel for patch testing should include Fragrance Mixes I and II, Balsam of Peru, as well as hydroperoxides of limonene and hydroperoxides of linalool. If possible, it would be ideal to also patch test to essential oils, which are commercially available from patch testing companies as haptens,” said Dr. Chen. “Other botanical allergens should be patch tested when possible, such as colophony, Compositae mix, and propolis. Many patch testers may employ additional botanical and fragrance series to supplement a baseline series. It is also helpful to patch test directly to a patient’s products, which can help to catch new and emerging allergens, so long as the product has been confirmed not to contain chemicals that are toxic or highly irritating to the skin.”

“If you have a high suspicion that a patient is reacting to a product that contains fragrance, it can be very helpful to actually test their own individual products in addition to the standard allergens,” agreed Dr. Liszewski. “I think that’s the important part. Part of what’s challenging about testing fragrance is that many of our screening allergens are broadly good at identifying if someone has a sensitivity to fragrance. For me, my interpretation is that you’re either allergic to fragrance or you’re not, and due to the limitations in labeling, it becomes very challenging. We can spend a lot of resources and money testing patients to individual fragrance molecules, but I don’t always find that as helpful as testing to a patient’s products.”

Management

Once an allergen is identified, the patient can receive narratives that include where the allergen is found, what it’s potentially called on labels (if by another name), and what products can be used in place of the original. “The most important job of the patch testing dermatologist is to help patients figure out what the culprit is, and more importantly, how to avoid the allergen and find alternative products,” said Dr. Yu. “This requires a thorough review of patient products and their ingredients, as well as knowledge regarding the sources of certain fragrance allergens.”

According to Dr. Chen, it’s important to highlight to patients that ACD can be delayed, so any product a patient has been using on the affected site should be considered, even if a rash did not immediately appear after application of that product. “Similar products are often made using similar ingredients, so changing products from one brand to another won’t necessarily help. Skin allergies do not require a patient to have recently started a new product. Just because a product was used safely in the past, doesn’t mean that it cannot now be the cause of the rash,” she explained.

While patients with fragrance allergies are generally advised to avoid products with fragrance, an elimination method can be used to determine what products can be tolerated. “If a patient does want to use a product that has fragrance, we avoid all fragranced products until their contact dermatitis improves. Then patients can do what’s called a ‘ROAT,’ which stands for Repeat Open Application Test, where they test the products in the crux of the arm, twice a day for seven days. If they can tolerate that product without getting rash, then it probably doesn’t contain an ingredient they’re sensitive to, or it’s not in a concentration they would react at,” said Dr. Liszewski.

Patients can also access databases of “safe” product lists either for a fee, or through their physician. One example is the Contact Allergen Management Program (CAMP) database, which is managed by the American Contact Dermatitis Society. “The ACDS has a robust database that is extremely useful for patients. It’s available to anybody who’s a member of ACDS,” said Dr. Mowad. “It provides a list of products that are free of the allergen or anything that cross reacts with it. It’s constantly updated and now available on smartphones as well. It really allows patients to stay current with their allergens and avoid them.”

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