INTRODUCTION

Cosmetics have been around for centuries. Cosmetics are defined by the Food, Drug and Cosmetic Act as ‘articles intended to be rubbed, poured, sprinkled or sprayed or introduced into or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance’ and should not alter the structure or function of the skin. Drugs are defined as ‘articles intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease in man’. Cosmeceuticals are cosmetic products that contain bioactive ingredients with the intent to have a beneficial physiologic effect. There is no legal definition of cosmeceuticals. Cosmeceuticals fit somewhere between cosmetics and drugs. However, even water could be classified as a cosmeceutical given its effects on the hydration of the stratum corneum.

Unfortunately, sometimes the cosmeceutical products intended to enhance beauty can lead to a dermatitis that can be quite unsightly, uncomfortable, annoying and perplexing to the patient and the physician. Contact dermatitis is one of these adverse reactions and can be either irritant or allergic in nature, with the former being more common. Allergic contact dermatitis to cosmetics, personal care products, make-up, body washes, moisturizers, creams, nail, lip and hair care products, and the devices (i.e. sponges, applicators) used to apply them can result in a clinical dermatitis. These reports are well documented in the literature and clinically can appear as a well-demarcated reaction at the location of product application. However, the dermatitis can be ectopic to the location the product is applied through transfer to a more sensitive area such as the face or eyelids. Reports of allergic contact dermatitis to cosmeceuticals are not as frequently reported in the literature as one would expect given their widespread usage. This may be due in part to difficulty in testing these products and the lack of standardized allergens.

VITAMINS

Contact dermatitis to cosmeceutical vitamins such as vitamin A (retinol), vitamin C (ascorbic acid), and vitamin E (tocopherol) has been reported in the literature. Vitamin A and its derivatives such as retinol, retinaldehyde, and retinyl palmitate typically produce an irritant contact dermatitis with dryness and skin irritation. This irritation is an unwanted side effect of retinization of the face, but cannot be avoided if the beneficial collagen regenerative effects are to be experienced. Irritant contact dermatitis can sometimes present identically to allergic contact dermatitis, but vesiculation and facial swelling are never an expected part of early retinization of the face. Allergic contact dermatitis to vitamin A is rare, but can be confirmed by positive patch testing. The vitamin A-containing cream can be closed patch tested ‘as is’, but many times it is impossible to determine which of the many ingredients in the preparation is the culprit. Most large cosmeceutical manufacturers can provide a sample of the vitamin A raw material they use in their formulation for individual ingredient patch testing. The person to contact at the company and the address can be obtained from the Cosmetic Industry On Call brochure published as a joint effort between the American Contact Dermatitis Society (ACDS) and the Personal Care Products Council (PCPC; formerly the Cosmetic, Toiletry, and Fragrance Association). More information can be obtained at the PCPC website at http://www.personalcarecouncil.org.

Vitamin C, also known as ascorbic acid, is another vitamin used topically to reverse signs of aging. It is difficult to formulate because it is easily oxidized to inactive products upon exposure to ultraviolet (UV) radiation or oxygen. Allergic contact dermatitis to topical vitamin C is rare, but irritation can occur due to the low pH effects of the ascorbic acid on the skin. The same discussion regarding closed patch testing and ingredient procurement for vitamin A also applies to vitamin C.

Vitamin E, part of a family of compounds called tocopherols, is a common cause of both irritant and allergic contact dermatitis. Its role as a contact allergen is well documented, thus vitamin E represents the most common cosmeceutical vitamin to cause allergic contact dermatitis. Some of the reports have dealt with allergic reactions experienced to vitamin E found in a line of colored cosmetics manufactured in Europe. It appears that the manufacturer used food grade vitamin E instead of cosmetic grade vitamin E which accounted for the allergic contact dermatitis. Many of the casually reported cases of vitamin E allergy appear to be due to consumers breaking open vitamin E capsules intended for oral consumption and rubbing the oil onto wounds or scars to promote healing. While vitamin E formulated in this manner is safe for human oral consumption, it is not intended for topical application. Cosmetic grade vitamin E properly formulated in a moisturizing cream is rarely allergenic.

HYDROXY ACIDS

Hydroxy acids are a group of chemicals frequently found in cosmeceutical products. Contact dermatitis to alpha hydroxy acids (AHAs), beta hydroxy acids (BHAs), and polyhydroxy acids (PHAs) is typically in the form of irritant contact dermatitis. The larger size of PHAs reduces skin penetration, which also lessens the opportunity for irritant contact dermatitis to occur. More irritant reactions are seen with the AHAs, in the form of stinging and burning due to the low pH of these cosmeceuticals that rapidly penetrate the stratum corneum to reach the nerve endings in the dermis. AHAs that have been partially neutralized produce less contact dermatitis, but also do not produce dramatic antiaging effects. BHAs, such as salicylic acid, are oil soluble and do not penetrate the stratum corneum well. For this reason, irritant contact dermatitis is lessened, but can still occur in patients with compromised barrier function.

BOTANICALS

Botanicals form one of the largest categories of cosmeceutical ingredients in today’s marketplace. Given the push to nature in our increasingly health conscious society, botanicals are often seen by consumers as natural safer alternatives to their synthetic counterparts. As a result of a strong driving force within the cosmetic industry toward natural products, botanicals are a common cosmeceutical active ingredient. Botanical additives are made from various parts of the plant including the leaves, root, fruits, stems, or flowers. The concentration, composition, efficacy, and antigenicity of a given plant extract may differ depending on the part of the plant from which it was obtained. Different antigens may also be present depending on the time of year the botanical was harvested, where the plant originated, and how the plant material was processed prior to incorporation into a cosmeceutical. Therefore the antigenic component of a particular botanical can vary significantly based on these factors.

There are few systematic reviews on the subject of contact dermatitis and botanicals. Although there are many cases of contact dermatitis to botanicals and essential oils in the literature, most cases of allergic reactions that have been documented are single case reports. With the increasing use of botanicals in the cosmetic and cosmeceutical arena, more reactions to these extracts are expected. This section will not review all of the individual case reports of allergic reactions to botanicals; rather it will serve to highlight some of the more common botanical culprits.

Aloe is a commonly used botanical extract for its soothing properties on wounds, burns, and irritated skin (Fig. 21.1). It is a mucilage containing thousands of individual chemical entities. This makes determination of the exact allergen impossible. Yet, case reports of allergic contact dermatitis are found in the literature. Patients who have experienced a suspected allergic contact dermatitis to aloe should simply learn to read ingredient labels and avoid products containing this botanical extract. It is not hard to avoid cosmeceuticals containing aloe.

Fig. 21.1 Aloe vera mucilage is a possible cause of allergic contact dermatitis

Ginkgo biloba is another common botanical used primarily for its anti-inflammatory effects. There have been no reports of allergic contact dermatitis to products containing this botanical documented in the literature.

Tea tree oil or melaleuca oil is derived from the Cheel shrub in Australia (Fig. 21.2). It has gained increasing popularity in a variety of over-the-counter (OTC) products, including antibacterials, antifungals, shampoos, and OTC salon treatment products designed to minimize dandruff or seborrheic dermatitis. Tea tree oil can cause allergic contact dermatitis and in one study was found to be the most allergenic botanical extract. Although there are several antigenic components of this oil, the constituents of the oil thought to cause the majority of allergic reactions are d-limonene and terpinen-4-ol; however, not all patients who react to tea tree oil react to these components.

Fig. 21.2 Homeopathic dandruff shampoos may be a source of tea tree oil exposure

Curcumin is an antioxidant derived from turmeric root. Curcumin is a common additive to Middle Eastern and Indian food as a hot spice. Its use in these cultures dates back to the prerefrigeration era when curcumin was used as a food preservative. It is used in some cosmeceuticals to prevent the product from discoloring or oxidizing on the store shelf. Several currently marketed cosmeceutical moisturizers contain curcumin to prevent the degradation of ceramides added to enhance the skin barrier. Curcumin is a cutaneous irritant and can cause stinging, burning, and itching in patients with atopic dermatitis or other barrier defects. There are also rare reports of allergic contact dermatitis resulting from topical contact with curcumin.

Witch hazel has been used as a cosmeceutical astringent, acne agent, and vasoconstrictor. It is a cause of allergic contact dermatitis. Currently, witch hazel is a common additive to cosmeceutical eye creams designed to minimize puffiness and bags under the eyes. Witch hazel allergy should be suspected in patients with periorbital swelling who have begun using a new eye area cosmeceutical.

The Compositae family comprises a group of plants that have sensitizing capabilities. Arnica montana is an important medicinal plant that has been reported to cause allergic contact dermatitis (Fig. 21.3). Screening patients with sesquiterpene lactone mix, found on the traditional dermatologic patch test tray, may miss some of these reactions and therefore testing to the plant or other chemical constituents of the plant is recommended. Chamomile, another member of the Compositae family, is also a cause of allergic contact dermatitis (Fig. 21.4). This is interesting given the fact that a chamomile extract, known as bisabolol, is used as an anti-inflammatory in cosmeceutical moisturizers. However, echinacea and marigold are two members of this family that have not been reported to cause allergic contact dermatitis. This indicates that there must be subtle differences in each of these plant extracts accounting for the presence or absence of the dermatitis-causing allergen.

Fig. 21.3 Arnica montana is a medicinal plant capable of causing allergic contact dermatitis

Fig. 21.4 Bisabolol is a chamomile extract found in products designed for sensitive skin and may be a rare cause of allergic contact dermatitis

Lavender oil and peppermint oil have also been reported to induce allergic contact dermatitis. These botanicals are used in aromatherapy oils and other OTC products.

Patch testing for botanical allergens is difficult as standardized allergens for these newer compounds are not readily available. Furthermore, screening allergens are not adequate to indicate the possibility of botanical allergy. In a study of those with known botanical allergy, fragrance mix was positive in only 33.3% of patients, balsam of Peru in 30%, Compositae mix in 20%, and sesquiterpene lactone in only 6.7%. Therefore, in those suspected of contact allergy, if a botanical is being used, testing to the individual botanical is recommended.

SUNSCREENS

Our attention now turns to another common component of cosmeceuticals that can cause contact dermatitis—sunscreens. Sunscreens are added to cosmetic and cosmeceutical products and can be the cause of irritant contact dermatitis, allergic contact dermatitis, and photoallergic contact dermatitis. Sunscreens are traditionally divided into physical sunscreens that reflect or scatter ultraviolet light and chemical sunscreens that absorb the ultraviolet radiation. There are several classes of sunscreens including para-aminobenzoic acid (PABA) and its esters, cinnamates, salicylates, benzophenones, anthranilates, and dibenzoylmethanes to which contact dermatitis has been reported. Irritant contact dermatitis is the most common adverse reaction to sunscreens, but reports of allergic and photoallergic contact dermatitis are present in the literature. With increasing usage of sunscreens, reports of contact dermatitis to these chemicals have increased. PABA was the most common cause of allergic and photoallergic contact dermatitis reactions, but as a result PABA is rarely used in currently marketed sunscreens. Benzophenone-3 (oxybenzone) is currently one of the most common causes of photo contact allergy and has also been demonstrated to cause allergic contact dermatitis, contact urticaria, photo contact urticaria, and anaphylaxis.

Although other sunscreen chemicals have been reported to cause contact dermatitis, chemicals such as cinnamates, salicylates, and 4-tert-butyl-4-methoxydibenzoylmethane (Parsol 1789) cause allergy less frequently and no reports to anthranilates or ecamsule (Mexoryl) have been reported to date. Patch testing and photo patch testing are necessary to confirm the diagnosis in suspected cases of allergic contact dermatitis or photoallergic contact dermatitis to sunscreen ingredients. Sunscreens can be closed patch tested ‘as is’. However, most sunscreens contain a ‘cocktail’ of active ingredients to provide broad-spectrum sun protection. Furthermore, the inactive ingredients of the sunscreen product (i.e. the preservatives) and fragrances more commonly cause cutaneous reactions. Therefore, it is best to patch test to an expanded series of allergens as well as individual sunscreen ingredients. It can also be helpful to contact the sunscreen manufacturer through the Cosmetic Industry On Call brochure, as discussed previously, to obtain individual raw material sunscreen actives for patch testing.

FRAGRANCES

Many cosmeceutical products are fragranced and an allergic or irritant reaction may be due to the fragrance component. Fragrances are the most common cause of allergic contact dermatitis to cosmetics. Patch testing to fragrance is typically done via a fragrance mix that contains the individual fragrance ingredients listed in Box 21.1.

Several authors have suggested the addition of other essential oils to the current fragrance mix, such as sandalwood, narcissus, jasmine, and ylang ylang to enhance the detection of fragrance allergy. If testing to the fragrance mix and these other chemicals is negative and a fragrance allergy is still suspected, patch testing to other fragrances on extended series should be considered. Lyral is another fragrance that is not detected with the current fragrance mixture available and further highlights the need to do extended fragrance testing if allergy is suspected and standard patch testing is negative.

Unfortunately, product labeling can be misleading as no specific information regarding fragrance components is usually listed on cosmeceutical products manufactured for sale in the US. Product labels simply list ‘fragrance’ in the ingredient disclosure. Even if patch testing allows identification of specific fragrance allergens, labels do not typically list individual fragrance components. This makes management of the fragrance allergic patient difficult.

To further complicate matters, there are several fragrance chemicals such as benzyl alcohol, benzaldehyde, and ethylene brassylate that can have other functions in addition to being a fragrance component. These chemicals can still be used in a product labeled ‘fragrance free’ if they serve a function other than to impart fragrance in the cosmeceutical. This is often the case with botanical extracts that are frequently not listed as fragrance ingredients because they are used for their medicinal properties and not for the ability to impart fragrance. Patients who are allergic to fragrance should also be instructed to avoid botanical preparations. Initial avoidance of all fragrances is recommended for at least 4–6 weeks and the dermatitis should be cleared. Then, if necessary or desired, introduction of one fragranced product at a time can be initiated. Each product should be used for approximately 2 weeks prior to introducing another fragrance or fragranced product. Physicians must educate patients to the fact that unscented does not mean no fragrance exists, just that it cannot be smelled. Many times unscented products contain masking fragrances designed to mask the chemical odor of the formulation.

PRESERVATIVES

Preservatives used to prevent bacterial growth and oxidation in cosmeceutical products are the second most common cause of allergic contact dermatitis. Preservatives are found in all cosmeceutical products. Formaldehyde and formaldehyde releasers such as quaternium-15, DMDM hydantoin, diazolidinyl urea, imidazolidinyl urea and 2-bromo-2-nitropropane-1,3-diol are common allergens. Quaternium-15 is the most frequently found preservative causing allergic contact dermatitis in cosmeceuticals.

The parabens are widely used cosmeceutical preservatives and are felt to be very safe. The most common parabens used are ethyl, butyl, methyl, propyl, and isobutyl paraben. Although these are generally a well-tolerated class of preservatives, there are isolated reports of allergic contact dermatitis to parabens. However, given the widespread use of these preservatives, the rate of sensitivity is low. Thus, patients with suspected preservative allergies might be advised to select cosmeceuticals that use parabens for preservation.

Methylchloroisothiazolinone (MCI/MI, Kathon CG, Euxyl K 100) is another preservative used in cosmetic preparations that can cause allergic contact dermatitis. The rate of sensitivity as determined by the North American Contact Dermatitis Group is 2.3%. Allergic contact dermatitis to this chemical was initially reported in Europe where the chemical was first introduced. However, with increased usage in the US, reports of allergy to this chemical have been made. At present, methylchloroisothiazolinone is used mainly in rinse-off products such as hair shampoos and conditioners where the short contact time minimizes the chances of an allergic reaction. However, there are a variety of sensitive skin moisturizers that contain this ingredient, which may be problematic.

Methyldibromo glutaronitrile phenoxyethanol is another frequently used preservative that has broad-spectrum antibacterial activity. It has been shown to cause allergic contact dermatitis primarily due to the methyldribromo glutaronitrile component.

PATCH TESTING

The gold standard for diagnosing an allergic contact dermatitis to any product including cosmeceuticals is patch testing. This is a simple easy office procedure that can be extremely helpful in determining the cause of a patient’s dermatitis (Fig. 21.5). Obviously, other causes of the patient’s reaction including irritant contact dermatitis, contact urticaria, acneiform eruptions, rosacea, seborrheic dermatitis, atopic dermatitis, perioral dermatitis, and other skin disorders must be considered. However, in the patient who does not respond to traditional methods of treatment, or who has a persistent or localized dermatitis, or a dermatitis that flares after discontinuation of a treatment regimen, the diagnosis of allergic contact dermatitis should be considered and patch testing should be performed. It is important to note that most patients, and even experienced specialists within the field of allergic contact dermatitis, are unable to reliably and consistently identify the causative allergen prior to patch testing based on history and physical examination alone.

Fig. 21.5 Diagram of the patch testing technique

The procedure of patch testing requires an interest and level of suspicion on the part of the clinician as well as a set of allergens in the office. First the physician must take a thorough history detailing the products the patient uses, including make-up, moisturizers, natural products the patient might be using as well as the method of application, and removal of these products. Natural products that a patient uses are frequently omitted when giving a history. Patients often falsely assume that something natural could not be the cause of their problem. They should be reminded that poison ivy is natural and causes many people significant skin problems.

Once the allergens to be tested have been chosen, a nurse within the office, who has been trained on the application of patch testing, applies the patches. This involves applying allergens to the upper back and taping them in place. The allergens applied can be obtained from several different companies including Allerderm (manufacturers of TRUE Test, Petaluma, CA, US), Chemotechnique Diagnostics (Malmo, Sweden), Trolab/Pharmascience (Montreal, Canada) and Smart Practice (manufacturers of AllergEAZE, Calgary, Canada). The TRUE Test is a reasonable starting place for patch testing but studies have shown that expanded sets of allergens are more successful in identifying a causative allergen in the patient who suffers from allergic contact dermatitis. Therefore, if considering the diagnosis of allergic contact dermatitis, expanded testing is often helpful, particularly if the TRUE Test is unrevealing. If expanded allergen series are not available, referral to a center specializing in patch testing may be necessary if the suspicion of allergic contact dermatitis remains. It is usually possible to obtain the specialized allergens required by contacting the company as listed in the Cosmetic Industry On Call brochure. Most companies can also provide information on how to formulate and apply the patches, as well as providing the Material Safety Data Sheets (MSDS) for specific chemical information about the substance.

The initial patches should be kept in place and kept dry for 48 hours. The patches are then removed and a map of the allergens is drawn on the back. The patient should return for a second reading from 96 hours to 1 week later to assess for delayed reactions which are well documented in the literature. If a second reading is not performed, several allergic reactions may be missed (Box 21.2).

As many of the cosmeceuticals are relatively new and standardized allergens are not available, testing to the products themselves can be helpful. If the product is intended to be a leave-on product, it can be tested as is. However, if the product is a rinse-off product intended to be diluted with water, the product must be diluted prior to application so as to avoid irritant reactions. There are guides available to help determine the appropriate dilutions of such products. Controls must be done when using patient products for testing. The standard negative control used is generally petrolatum. It may also be worthwhile to include a positive irritant, such as sodium lauryl sulfate, if an irritant reaction is suspected for comparison.

If an allergic reaction is identified, the patient should be instructed on allergen avoidance, and label reading. The dermatitis can take 6–8 weeks to resolve despite avoidance and patients should be reassured during this time period. A database called the Contact Allergen Replacement Database is available to members of the American Contact Dermatitis Society through the society web page (http://www.contactderm.org) and can be very helpful in identifying products free of a patient’s known allergens. In this member-only database, the physician enters the chemicals to which the patient tested positive and the database provides a listing of products free of these chemical ingredients. The database is extensive but is limited by the products entered into the database. It is updated once yearly. It can prove helpful in identifying products a patient can use and is a helpful resource for patients.

Cosmeceuticals are an increasingly popular arena in the skin care market. Even these products, many containing natural ingredients and intended to enhance beauty, can cause an allergic or irritant contact dermatitis. Contact dermatitis to these products has been reported though not with high frequency. As more people use cosmeceuticals, an increase in adverse reactions might be expected. Fortunately, the cosmetic industry is early to recognize problems and reformulate to minimize consumer difficulties. Nevertheless, the possibility of allergic contact dermatitis should be considered. Patch testing is an important tool to identify and confirm the possible cause of an adverse reaction to a cosmeceutical (Fig. 21.6).

Fig. 21.6 Patch testing. (A) Allergen is placed in metal Finn chambers. (B) Numbered allergens are placed on upper back. (C) Orientation marks are placed for allergen identification upon removal. (D) Positive patch test is present at site D17