How do some chemicals in popular cosmetics triggering allergic contact dermatitis ?

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Allergic reactions in the skin can be caused by many different chemical compounds found in creams, cosmetics, and other topical consumer products, but how they trigger the reaction has remained somewhat mysterious.

A new study suggests the way some chemicals displace natural fat-like molecules (called lipids) in skin cells may explain how many common ingredients trigger allergic contact dermatitis, and encouragingly, suggests a new way to treat the condition.

The study was led by researchers at Columbia University Irving Medical Center, the Brigham and Women’s Hospital, and Monash University and published online today in Science Immunology.

Why some chemicals trigger dermatitis is a mystery

Poison ivy is a commonly known trigger for allergic contact dermatitis, an itchy skin rash. But many ingredients found in nonprescription topical products can trigger a similar type of rash.

An allergic reaction begins when the immune system’s T cells recognize a chemical as foreign. T cells do not directly recognize small chemicals, and research suggests that these compounds need to undergo a chemical reaction with larger proteins in order to make themselves visible to T cells.

“However, many small compounds in skincare products that trigger allergic contact dermatitis lack the chemical groups needed for this reaction to occur,” says study co-leader Annemieke de Jong, PhD, assistant professor of dermatology at Columbia University Vagelos College of Physicians and Surgeons.

“These small chemicals should be invisible to T cells, but they’re not.”

Skin cells unmask allergy-inducing chemicals

De Jong and her colleagues suspected that CD1a, a molecule that’s abundant on Langerhans cells (immune cells in the skin’s outer layer), might be responsible for making these chemicals visible to T cells.

In the current study, conducted with human cells in tissue culture, the researchers found that several common chemicals known to trigger allergic contact dermatitis were able to bind to CD1a molecules on the surface of Langerhans cells and activate T cells.

These chemicals included Balsam of Peru and farnesol, which are found in many personal care products, such as skin creams, toothpaste, and fragrances.

Within Balsam of Peru, the researchers identified benzyl benzoate and benzyl cinnamate as the chemicals responsible for the reaction, and overall they identified more than a dozen small chemicals that activated T cells through CD1a.

“Our work shows how these chemicals can activate T cells in tissue culture, but we have to be cautious about claiming that this is definitively how it works in allergic patients,” de Jong says. “The study does pave the way for follow up studies to confirm the mechanism in allergic patients and design inhibitors of the response.”

New Ideas for Treatment

CD1a molecules normally bind the skin’s own naturally occurring lipids in its tunnel-like interior. These lipids protrude from the tunnel, creating a physical barrier that prevents CD1a from interacting with T cells.

Structural work done at Monash University showed that farnesol, one of the allergens identified in this study, can hide inside the tunnel of CD1a, displacing the natural lipids that normally protrude from the CD1a molecule. “This displacement makes the CD1a surface visible to the T cells, causing an immune reaction,” de Jong says.

A new study suggests the way some chemicals displace natural fat-like molecules (called lipids) in skin cells may explain how many common ingredients trigger allergic contact dermatitis and, encouragingly, suggests a new way to treat the condition.

This discovery raises the possibility that allergic contact dermatitis could be stopped by applying competing lipids to the skin to displace those triggering the immune reaction.

“From previous studies, we know the identity of several lipids that can bind to CD1a but won’t activate T cells,” she says.

Currently, the only way to stop allergic contact dermatitis is to identify and avoid contact with the offending chemical.

Topical ointments can help sooth the rashes, which usually clear up in less than a month. In severe cases, physicians may prescribe oral corticosteroids, anti-inflammatory agents that suppress the immune system, increasing the risk of infections and other side effects.

The other study co-leaders are Jamie Rossjohn of Monash University (Melbourne, Australia) and Cardiff University School of Medicine (Cardiff, Wales, United Kingdom) and D. Branch Moody of Brigham and Women’s Hospital, Harvard Medical School (Boston, MA).

The study is titled “Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products.” The other contributors are Sarah Nicolai (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA), Marcin Wegrecki (Monash University, Clayton, Victoria, Australia), Tan-Yun Cheng (Brigham and Women’s Hospital), Elvire A. Bourgeois (Brigham and Women’s Hospital), Rachel N. Cotton (Brigham and Women’s Hospital), Jacob A. Mayfield (Brigham and Women’s Hospital), Gwennaëlle C. Monnot (Columbia), Jérôme Le Nours (Monash University), and Ildiko Van Rhijn (Brigham and Women’s Hospital).

Funding: The research was funded by grants from the National Institutes of Health (T32 AI007306, K01 AR068475, R01 AR048632), the National Health and Medical Research Council of Australia, and the Australian Research Council, an Irving Scholarship from the Irving Institute for Clinical and Translational Research at Columbia University, and a Wellcome Trust Collaborative Award.

The authors declare that they have no competing interests.


Contact dermatitis (CD) is an umbrella term for a group of inflammatory skin conditions that result from contact between a chemical substance and the skin. Irritant CD (ICD) is by far the most prevalent and can occur in anyone (no prior sensitization is necessary). ICD can be thought of as the effect observed when a sensitive area of skin is exposed to too strong a chemical, such as detergents. Allergic CD (ACD), on the other hand, represents the clinical disease state that results from exposure to an allergenic chemical in a person who is already sensitized to that chemical, such as that in poison ivy. ACD is a delayed-type hypersensitivity reaction that is diagnosed through the application of a closed (under occlusion) patch test, in which the suspected allergen is placed on intact skin (on the back or inner arm) for 24 to 48 hours (Lazzarini et al., 2013). These patches are evaluated at removal and again at a later period (72-120 hours; Lazzarini et al., 2013).

Children represent a unique group in terms of ACD, despite the condition being quite prevalent in the pediatric population (20%-25% of all childhood dermatitis; Bruckner and Weston, 2002Militello et al., 2006Seidenari et al., 2005). Notably, patch testing in children with recalcitrant dermatitis is often delayed (Jacob et al., 2008McGowan et al., 2018). This is unfortunate given that there is both an increase in the reported number of children with ACD and the need for patch testing in children with dermatitis (Jacob et al., 2008). Recent studies demonstrate that allergens in personal hygiene products contribute significantly to pediatric CD (Berne et al., 1996Goon and Goh, 2006Jacob et al., 2005Pratt et al., 2004)—hence the role of the Pediatric Contact Dermatitis Registry, which is a collaborative, multidisciplinary registry consisting of > 250 health care providers that provide data from > 1000 patch-tested children in the United States (Jacob et al., 2017).

Bathing practice–associated exposures are important sources of these allergens (Table 1). In addition, several allergens can be in one product and can range from preservatives to fragrances to emulsifiers and detergents (Smaoui and Hlima, 2012Timmermans et al., 2007). It is also important to recognize that these chemicals may serve as a source of ICD (especially in children with eczema who demonstrate lower thresholds for irritation; Fernandez Vozmediano and Armario Hita, 2005Lammintausta et al., 1992Lugovic and Lipozencic, 1997Oranje and Wolkerstorfer, 1999) and may predispose children to ACD (Marty and Cheng, 2005). Therefore, it stands to reason that if the skin has already been damaged by endogenous dermatosis (e.g., atopic dermatitis) or external trauma, skin penetration by allergens may be enhanced. Skin barrier function is often genetically predetermined at birth; however, even healthy skin is more delicate in children (compared with adults) and consequently more prone to irritant and allergic contact dermatitis (Gelmetti, 2001).

Table 1

Children product types used in bathing routines

Baby wipes
Lotion
Shampoo
Baby powder
Diaper cream
Conditioner
Bubble bath
Soap-cleansers

The development of CD (both irritant and allergic types) requires contact with the eliciting chemicals; thus, decreasing the time of exposure may have a clinically relevant impact (Beattie et al., 2007). Furthermore, ICD, but not the elicitation of ACD, depends on the time of exposure.

ICD is dependent on the concentration and duration of exposure. Allergic sensitization is a rate-limited phenomenon of a breached threshold in relation to hapten concentration per unit area of the skin and the immune state of the skin. In addition, inflammation is thought to predispose the epidermal layer to penetration by certain allergens. Thus, decreasing the time of exposure to surfactants may decrease ICD and only indirectly ACD.


Source:
Columbia University
Media Contacts:
Annemieke de Jong – Columbia University
Original Research: Open access
“Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products”. Sarah Nicolai, Marcin Wegrecki, Tan-Yun Cheng, Elvire A. Bourgeois, Rachel N. Cotton, Jacob A. Mayfield, Gwennaëlle C. Monnot, Jérôme Le Nours, Ildiko Van Rhijn, Jamie Rossjohn, D. Branch Moody, Annemieke de Jong..
Science Immunology doi:10.1126/sciimmunol.aax5430.

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