Update on Alkyl Glucosides

Given the increased incidence of allergic contact dermatitis to alkyl glucosides, it is important for the dermatologic and industrial communities to be aware of this clinically relevant allergen. 

Allergic contact dermatitis (ACD) is a socially and economically significant condition, estimated to affect more than 72 million Americans each year.¹ In addition to physical morbidity, ACD can have a significant impact on quality of life; it may lead to missed work days and lost income, inability to enjoy leisure activities, and loss of sleep. 

Often, numerous doctor visits and medications result in significant expenditures for the patient before the underlying cause is discovered. In 2004, the total direct cost (ie, prescription drugs, office visits, etc.) associated with treatment for contact dermatitis was 1.6 billion.¹ 

Patch testing is the gold standard for diagnosis of ACD.² Once the offending allergen is identified, avoidance is critical for sustained remission. However, because time from sensitization or exposure to an allergen to elicitation of the ACD is delayed, it may be difficult to make the association. Therefore, when ACD is suspected, a patient-centered educational approach focusing on pathophysiology, risk of recurrence, and avoidance strategies should be initiated to break the ACD cycle. 

Experimental design studies indicate that antigenic potency, in addition to concentration of the antigen, are important factors in determining whether an exposure to an antigen will result in sensitization. For weakly sensitizing allergens, exposures can occur over many years before a reaction develops. However, for strong sensitizers, sensitization can occur more rapidly. If there is skin barrier compromise or exposure to a supra-potent antigen, even a single exposure could induce primary sensitization.

ACD to alkyl glucosides, which are an eco-friendly group of compounds found in household and personal care products, has risen in recent years. This article reviews alkyl glucosides and why it is named Allergen of the Year for 2017.

History

Emil Fischer, a German chemist, first synthesized alkyl glucosides in 1893. His method of synthesis, termed the “Fischer glycosidation,” involved a reaction between glucose and hydrophilic alcohols such as methanol, ethanol, and glycerol, catalyzed by acidic conditions to create the alkyl glucosides.^3,4 For the next several decades this discovery remained primarily of academic interest only, with the first patent for use as a detergent being filed some 40 years later in Germany (c.1934). 

In the 1980s, a technical processes in alkyl glucoside manufacturing was discovered based on Fischer’s original work, which allowed for more varied (from 2 to 22 carbons long) and mass production.^3,5 The alcohols used to synthesize alkyl glucosides can be obtained from coconut, palm, or rapeseed oil, and the glucose or polysaccharide obtained from corn, potato, or wheat starch.^4-6 The subsequent refinement in the production led to the use of alkyl glucosides beyond the chemical industry into household and consumer products.³ 

In 2013, the Cosmetic Ingredient Review (CIR) Expert Panel released their safety assessment on alkyl glucosides. The CIR works with the FDA and cosmetic industry, reviewing and assessing the safety of ingredients used in cosmetics. The panel concluded that the alkyl glucoside family was indeed safe for use in cosmetics when formulated at low concentrations to remain nonirritating.⁴ Table 1 lists the different alkyl glucosides.

Sources of Exposure

Alkyl glucosides are favored in household products and cosmetics for their nonionic surfactant, cleansing, and/or emulsifying properties.^5,7 They are considered gentle in nature as they have low irritancy and thus are frequently marketed as hypoallergenic or safe for sensitive skin. Additionally, they are considered eco-friendly as their synthesis can be completed with natural and renewable sources and the compounds are biodegradeable.^4-6,8,9

Since the 1990s, the alkyl glucosides are increasingly being used in both rinse-off and leave-on products such as shampoos, soaps, cleansers, hair dyes, disinfectants, lotions, creams, fragrances, sunscreens, deodorants, and tanning products.^5,7 They can also be found in certain baby products such as wipes and cleansers.⁵ Decyl glucoside is the most frequently used alkyl glucoside (Figure 1), commonly found in rinse-off products because it is mild, does not alter product stability, and has superior foaming properties.^4,10 Cetearyl glucoside, lauryl glucoside, and coco-glucoside (Figure 2) are the next most frequently used alkyl glucosides, respectively. Cetearyl glucoside is common in leave-on products, other than sunscreens, for its moisturizing properties.^4,5 Lauryl glucoside is used to enhance foaming, emulsifying, and skin conditioning properties, and exhibits thickening properties when combined with other surfactants.¹⁰ Coco-glucoside is used to also enhance foaming, emulsifying, and conditioning properties.¹⁰

Allergic Contact Dermatitis 

In 2003, the first cases of ACD to glucosides were reported. Le Coz and colleagues¹¹ reported on a 29-year-old woman who was using a chlorhexidine digluconate-based antiseptic gel around the umbilicus after receiving an umbilical piercing. She developed an acute eczematous rash, and patch testing was positive to decyl glucoside, an ingredient found within the antiseptic gel. 

Goossens and colleagues¹² also reported on 2 separate cases of ACD to alkyl glucosides: A 55- year-old man was found to have positive patch test results to coco-glucoside and lauryl glucoside, both of which were contained within different shower gels; a 46-year-old nurse was also found to have positive patch test results to coco-glucoside and lauryl glucoside, both of which were ingredients in a cleansing hand lotion, body lotion, and sunscreen that she had come into contact with. 

Several subsequent case reports have been published regarding ACD to various alkyl glucosides: Horn and coleagues¹³ reported a case of ACD to decyl glucoside found in hair mousse, Anderson and Goossens¹⁴ described a case of ACD to decyl glucoside from the sunscreen agent Tinosorb M, and Krehic and Avenel-Audran ¹⁵ reported 2 cases of ACD to decyl glucoside found in an antiseptic lotion. In 2014, Gijbels and colleagues⁷ published a series of 30 patients with ACD to various alkyl glucosides, noting that allergy to this substance was more frequent than previously suspected.

Special mention of ACD from decyl glucoside in Tinosorb is warranted, as there are multiple reports on this specific allergy. Tinosorb M is an UV filter introduced in the early 2000s for use in Europe, Asia, and Australia (it has not yet been approved by the FDA for use in the United States). It is composed of methylene bis-benzotriazolyl (MBBT), decyl glucoside, propylene glycol, xanthan gum, and water. The very first studies investigating ACD to Tinosorb M may have falsely reported MBBT as the sensitizing agent, as pure MBBT was not available for patch testing until 2014. After testing patients to the individual ingredients contained within Tinosorb M, it is now believed that decyl glucoside was in fact the sensitizing agent. As such, decyl glucoside is considered the “hidden allergen” within Tinosorb M that was only recently discovered.⁵ 

Patch Testing 

The North American Contact Dermatitis Group (NACDG) has been patch testing to decyl glucoside since 2009 and has noted an increase in sensitization rates among patch-tested patients. Sensitization to decyl glucoside was 1.5% from 2009 to 2012, increased to 1.7% from 2013 to 2014, and is predicted to continue to rise in the coming years.^5,6,8,9 This most likely still underestimates the prevalence of allergy to alkyl glucosides as large well-designed studies investigating this family of compounds have yet to be performed. Additionally, routine patch testing to multiple alkyl glucosides is not yet widely adopted.⁹  

It is important to note that alkyl glucosides are not included on T.R.U.E. Test, and therefore, could go unrecognized if only this screen is performed. The glucosides can be individually purchased from Allergeze (www.allergEAZE.com) and Dormer (www.dormer.com).

It is common for patients to react to more than 1 alkyl glucoside on patch testing.^5,7,9 This may be because of cross-reactivity of the substances due to structural similarities at the molecular level.^5,7 However, simultaneous sensitization (co-reaction) is also possible as several alkyl glucosides can be present within 1 product.⁷ This may be purposeful or unrealized: In the production of alkyl glucosides, a mixture of alkyl chain lengths are often created, and these glucoside impurities can persist into the final product. Nevertheless, as not all patients react to multiple alkyl glucosides, it is recommended that testing be to a variety of the compounds, as allergy may otherwise be missed.^5,9 It is also recommended that patients be tested specifically to decyl glucoside if allergy to Tinosorb M in sunscreen is suspected.⁵ 

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Characteristics of ACD to Alkyl Glucosides  

Allergy to alkyl glucosides is more common in females than males, likely due to females’ higher use of personal care products.^5,9 The median age of those sensitized is 49.6 years. Conditions such as atopic dermatitis (AD) and occupational irritation may increase the risk of ACD to alkyl glucosides by affecting the skin barrier and allowing greater penetration of the allergen(s).⁵ Furthermore, people with atopy or sensitive skin might self-select those products marketed for sensitive skin, many of which contain alkyl glucosides. A low-grade reaction caused by such an alkyl glucoside may then be missed or mistaken as a simple flare of the AD rather than a new diagnosis of ACD. Personal care products are frequent sources of alkyl glucosides, especially sunscreens, shampoos, skin-cleansing products, facial and body lotions and creams, and hair products (eg, dyes and mousses).⁹ 

The physical dermatitis location from alkyl glucosides depends on which type of product is being used. The hands, scalp, face, and neck are commonly affected areas for products such as shampoos, soaps, and sunscreens. Unexposed skin sites such as the breasts, abdomen, groin, and skin folds imply the use of products such as antiseptics, skin cleansers, and deodorant wipes.⁵ 

Treatment for alkyl glucoside ACD is somewhat straightforward. Confirm the allergen through patch testing, use topical corticosteroids to help hasten the resolution of the dermatitis, and completely avoid any product containing the culprit allergen to prevent ongoing dermatitis.⁵ 

Allergen of 2017

The American Contact Dermatitis Society (ACDS) is an organization that conveys important information on contact dermatitis and occupational skin disease to the medical community. In 2000, the “Allergen of the Year” was developed by the editors of Dermatitis in conjunction with the NACDG to bring recognition to those allergens that are common, remarkably relevant clinically, under acknowledged, or whose exposure patterns have changed.^6,8 

In 2017, with the number of reports of ACD to alkyl glucosides rising to approximately 1.9%, this group of compounds were awarded the distinction of the Allergen of the Year.^5,6,8,9 Alkyl glucosides were felt to be an appropriate recipient as it is important for the dermatologic and industrial communities to be aware of this clinically relevant allergen, especially with the ever-increasing use of glucosides within household, cosmetic, and industrial products.⁶ (Tables 2 and 3)

Conclusion

Alkyl glucosides are eco-friendly compounds, increasingly being used in household and personal care products for their surfactant, cleansing, and/or emulsifying properties. They are considered gentle in nature as they have low irritancy and are frequently marketed as hypoallergenic or safe for sensitive skin.

Since their first synthesis, they are increasingly being used in both rinse-off and leave-on products such as shampoos, soaps, cleansers, hair dyes, disinfectants, lotions, creams, fragrances, sunscreens, and tanning products. Some of the more common alkyl glucosides are decyl glucoside, cetearyl glucoside, lauryl glucoside, and coco-glucoside. In 2003, the first case reports of ACD to an alkyl glucoside were published. Since then, there has been an increase in the incidence of ACD to this family of compounds. It is becoming clear that awareness of ACD to alkyl glucosides is increasingly important, and alkyl glucosides have thusly been named the Allergen of the Year for 2017 by the ACDS. For additional resources for ACD, see Table 4. 

Dr Boyd is with Hennepin County Medical Center, Transitional Year Residency, and Hennepin County Medical Center, department of dermatology, Occupational and Contact Dermatitis Clinic, in Minneapolis, MN.

Dr Hylwa is with Hennepin County Medical Center, department of dermatology, Occupational and Contact Dermatitis Clinic, and the University of Minnesota, department of dermatology, in Minneapolis, MN. 

Dr Jacob, Section Editor of Allergen Focus, is a board-certified dermatologist and professor at Loma Linda University in Loma Linda, CA. She is founder and chief executive officer of the Dermatitis Academy public outreach education campaign.

Disclosure: The authors report no relevant financial relationships.

References

1. Bickers DR, Lim HW, Margolis D, et al; American Academy of Dermatology Association; Society for Investigative Dermatology. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55(3):490-500.

2. Jacob SE, Burk CJ, Connelly EA. Patch testing: another steroid-sparing agent to consider in children. Pediatr Dermatol. 2008;25(1):81-87.

3. Hill K. History of alkyl polyglucosides. In: Hill K, von Rybinski W, Stoll G. Alkyl Polyglucosides: Technology, Properties and Applications. New York, NY:  VCH Publishers Inc; 2008:1-8.