Behind the Bubbles: A Guide to Surfactants as Potential Allergens

Estimated to affect approximately 20% of the general population, allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction of the skin that results from exposure to exogenous allergens.1 Patch testing is the gold standard for diagnosing ACD and involves affixing small amounts of suspected allergens in chambers to unaffected skin for 48 hours, then removing patches and monitoring for delayed reactions over several time points.² Allergen avoidance is the mainstay treatment for ACD. The prevalence of contact allergy to specific allergens may fluctuate with time and reflects changes in the marketing and consumerism of today’s world.

An emerging class of allergens, surfactants are substances that decrease the surface tension of the skin, characterized as having polar and nonpolar moieties within a single molecule. They have numerous uses, including for cleaning, lathering, foaming, softening, and eliminating static.³ To understand the usage of surfactants in the ever-changing skincare industry, it is important to consider their origins. Historically, the earliest types of soaps were made using a mixture of oil, alkali, and water. The mixing of alkali and oil created a surfactant with lathering and cleansing properties, and this reaction was termed saponification. Traditional soaps were made from animal fats and plant ashes containing alkali carbonates, whereas modern soaps use fat derived from plant or nut oils, such as coconut, palm, and castor oils.⁴ The US Food and Drug Administration defines soap as a product made primarily of alkali salts of fatty acids. Today, there are very few “true soaps” that are available commercially, having been replaced by synthetic detergent products.⁵ Synthetic detergents, also called syndets, used as cleaning agents are made from synthetic surfactants, compounds chemically synthesized to contain polar and nonpolar moieties.⁶

The utility of a surfactant is determined by the carboxylic acid salt formed during saponification and is broadly categorized into 4 classes: amphoteric, anionic, cationic, and nonionic (Table 1). The charge of surfactants influences their cleansing and foaming abilities, as well as irritant potential. There are various cleansers available for purchase, each with distinct compositions, typically using 2 or more synthetic surfactants.³ With the rise in contact sensitization to these surfactants, it is essential for dermatologists to consider their role in eliciting skin reactions.

Sulfates

Sulfate surfactants are anionic molecules made of an alkyl chain covalently bonded to a sulfate ester group that is ionized (typically with Na+), with functions in micelle formation and membrane disruption, making them effective cleaning and lathering agents.⁹ Sulfates were one of the first classes of synthetic surfactants developed in the early 21st century in response to significant shortages of soaps after World War I in Germany.¹⁰ Historically, sulfates were the most widely used surfactants in industrial, household, and personal care products, a trend corroborated by a 2019 study by the American Contact Dermatitis Society’s (ACDS) Contact Allergen Management Program (CAMP). This analysis found that laureth/pareth sulfates were the leading surfactant class in shampoos and other hair care products, dish soaps, and laundry detergents, although not in household cleaning and eye products.¹¹ Sodium lauryl sulfate, also called sodium dodecyl sulfate, is the most common sulfate surfactant used in high-foaming personal care products and toothpastes.

While sulfate surfactants are extremely efficient cleansing and foaming agents, they are also harsh and well-known agents of irritant contact dermatitis. In particular, sodium lauryl sulfate has been associated with aphthous ulcers, mucosal irritation, and desquamation from use in toothpastes.¹² Due to the strong irritant potential of sulfates, companies have progressively switched to using gentler surfactants, such as sodium lauryl ether sulfate, which undergoes additional ethoxylation in its production.

Cocamidopropyl Betaine and Related Surfactants

Cocamidopropyl betaine (CAPB) was named the Contact Allergen of the Year in 2004. It is a mild, amphoteric surfactant that creates a rich lather in numerous rinse-off products, including shampoos, conditioners, cleansers, and cosmetics.¹³ CAPB is synthesized from reacting coconut-derived fatty acids with dimethylaminopropylamine (DMAPA), leaving amidoamine and DMAPA as leftover impurities. Consistent findings across studies have reported that sensitization to CAPB is likely from residual amounts of DMAPA and amidoamine, rather than to CAPB itself. Oleamidopropyl dimethylamine (OPDMA), a cationic emulsifier, is synthesized in a similar fashion to CAPB with DMAPA as a starting material, and OPDMA is found in similar products. Allergenicity is thought to arise from primary and tertiary amine groups that are separated by 2 to 3 carbon atoms in CAPB-related compounds, including amidoamine, DMAPA, and OPDMA.¹⁴ There are numerous other chemicals related to CAPB that should be avoided in CAPB-allergic individuals (Table 2). However, patients who are sensitive to CAPB-related surfactants do not need to routinely avoid coconut or other coconut derivatives.

Contact allergy to CAPB-related surfactants has been extensively reported in the literature. The North American Contact Dermatitis Group’s (NACDG) patch testing results from 2021 to 2022 demonstrated significant increases in the positivity rates of OPDMA (4.1%), DMAPA (3.5%), and amidoamine (2.7%).² At our institution, the most common routes of CAPB exposure in allergic individuals were from rinse-off hair products, particularly shampoos, as well as hand and dish soaps. In our experience of patch testing patients with suspected CAPB allergy, reactions to manufacturing impurities and related compounds (OPDMA, DMAPA, and amidoamine) vary considerably among individuals. Patients may react to 1 or more of these substances but not necessarily all of them. As such, comprehensive testing of each of these compounds is important to ensure CAPB allergy is not missed. Because there are so many compounds related to CAPB, it can be challenging for CAPB-allergic patients to find safe products. Our patients have found success with avoiding CAPB using allergenavoidance databases, such as SkinSafe and ACDS CAMP.

Alkyl Glucosides

Alkyl glucosides are nonionic, mild surfactants that are produced from condensing glucose with palm or coconut oil-derived fatty alcohols.¹⁵ Glucosides are multi-purpose, with emulsifying, cleansing, and lathering properties. Although these surfactants were first introduced in the 1930s, they have become increasingly popular in recent years due to their eco-friendly nature from being entirely biodegradable.¹⁶ There are 19 distinct compounds that fall under this class of surfactants, including decyl, lauryl, coco, and cetearyl glucosides, where cross- and co-reactivity have been reported.^15,16 Glucosides are most frequently used in rinse-off products, such as shampoos, conditioners, body washes, and cleansers.¹⁶

Alkyl glucosides were named Contact Allergen of the Year in 2017 due to the increasing use of glucosides in personal care products coinciding with an upward trend in their sensitivity rates.¹⁶ Indeed, the NACDG has been testing decyl glucoside since 2009, showing the sensitivity rate has risen from 1.5% (2009–2012) to 1.7% (2013–2014) to 2.4% (2021–2022).^2,16 Individuals with a history of childhood eczema, seasonal allergies, or asthma have been particularly noted to be at increased risk for sensitization to this relatively weak sensitizer.¹⁶ This might be attributed to increased susceptibility to allergen penetration from a disrupted skin barrier, as well as glucosides being commonly used in products marketed as hypoallergenic for sensitive skin. Although glucoside contact allergy is frequently associated with the use of rinse-off agents, there have been reports of ACD to glucosides in leave-on products, such as antiseptic lotion,¹⁷ sunscreen,¹⁸ and medicinal honey gel.¹⁹

Alkyl Amphoacetates

Alkyl amphoacetates are a family of imidazoline-derived amphoteric surfactants with long fatty acid (alkyl) chains. Similar to CAPB, amphoacetates are synthesized by forming a fatty acid amide followed by carboxymethylation in an aqueous medium. There are various compounds belonging to the amphoacetate family that diff er based on the type of fat used for synthesis (coconut vs palm kernel oil) and the length of their alkyl chains.²⁰ Examples include sodium cocoamphoacetate, disodium cocoamphodiacetate, sodium lauroamphoacetate, and disodium lauroamphodiacetate. Since the 1950s, amphoacetates have been increasingly used in cosmetics as mild foaming and cleansing agents with a low potential for irritancy.²⁰

Despite widespread use, there are limited reports detailing contact reactions to amphoacetates. Pesonen et al. published a series of 5 cases of occupational contact dermatitis caused by sodium cocoamphopropionate in a hand cleanser.²¹ Hanson et al. reported 2 cases of ACD to a hypoallergenic liquid cleanser attributed to disodium lauroamphodiacetate, alongside sodium lauroyl sarcosinate and isostearamidopropyl morpholine lactate.²² Over the last 5 years at our specialized patch testing center, we have observed 17 allergic reactions (>1+ strength) to disodium lauroamphodiacetate, approximately half of which were found to be clinically relevant (definite or probable relevance).

Conclusion

In summary, contact allergy to surfactants is continuing to rise. Patch testing for possible ACD to surfactants should be considered with dermatitis that presents in a “rinse-off ” distribution (forehead, hairline, eyelids, ears, neck, and/or upper chest and back), flares with use of personal care products, and/or is refractory to prescribed therapies. Common classes of surfactants responsible for ACD include CAPB-related compounds, alkyl glucosides, and alkyl amphoacetates.