Published On: Apr 2, 2023
Last Updated On: Apr 4, 2023
A diagnosis of atopic dermatitis (AD) can result in multiple physical burdens for affected individuals, as well as reduced quality of life and negative social and economic impact.1 Eczema patients and caregivers, healthcare providers, and AD researchers would love to be able to prevent AD symptoms from developing in the first place. While decades of research into prevention of AD has been performed, this ideal remains elusive and challenging to solve.2
The causes of AD are plentiful and so, similar to the fact that there is no one-size-fits-all treatment for AD, there is also no single approach to try to prevent AD. AD is a complex disease involving a defective skin barrier, an abnormally activated immune system, skin microbiome alterations and environmental exposures, among other contributing factors.3 Methods of AD prevention examined in research have focused on improving the skin barrier through use of emollients and moisturizers, reducing exposure to allergens or altering the development of the immune system both before and after birth, and altering the microbiome through use of probiotic supplements taken by either a mother or an infant.4
There are three components to the overall concept of prevention that also guide the direction of research, termed primary, secondary and tertiary (Figure 1). Primary prevention is about identifying strategies that intervene before symptoms occur to prevent the onset of disease, for example using fluoride to prevent cavities or protecting from the sun to prevent skin cancer. Secondary prevention is about detecting a disease or the risk of a disease at an early stage to prevent worsening. For instance, a doctor will monitor cholesterol and when it reaches abnormally high levels may begin treatment of the patient with statins. Tertiary prevention is the reduction of symptoms or improvement in quality of life for those with established disease – this typically means working with healthcare providers to treat the disease and manage symptoms. In the case of AD, this can involve using various topical and systemic treatments.4 This article will focus most on what we currently understand about primary prevention with some commentary on secondary and tertiary prevention for AD.
Understanding who is at high risk for developing AD and how to detect if a person will get AD are important aspects of research focused on preventing disease from developing in the first place. Research has shown that several risk factors contribute to a diagnosis of AD. We know that children born to parents with a current or past history of AD are at higher risk.5 Having a genetic mutation in the gene filaggrin (FLG; which makes a protein involved in creating the skin barrier) is one of the highest risk factors for developing AD.5 Maternal exposure to things like pollutants, cigarette smoke and perhaps antibiotics while pregnant or nursing has been associated in a few studies6 with development of allergies, which may start with AD and then proceed to asthma, food allergies and rhinitis in an “atopic march”. Still, not everyone who has even these highest of risk factors for developing AD will go on to do so. Therefore, researchers are looking for biological markers (biomarkers) that will more accurately predict who is most likely to be diagnosed with AD so preventative steps can be taken. Research to predict disease course and find the perfect treatment regimen for a single individual (personalized medicine) is also being done.
In the past, research into biomarkers to predict AD has been slowed by the fact that full thickness biopsies were required from infants or young children to analyze skin components. As biopsies result in a wound, can be painful and potentially scar, parents often have concern about this type of invasive tissue collection for research.7 However, recent years have seen rapid development of a minimally-invasive method of collecting skin called tape stripping,8,9 which does not leave a wound, is less painful and allows analysis of components of the top layers of skin including lipids (fatty molecules that help make the barrier and keep the skin from losing water), immune markers, genetic alterations and other molecules.7 Both AD-affected and non-affected skin can be examined for changes in immune profile and other molecular changes. In addition to the method of skin collection, timing of collecting the sample may be important. A recently published study showed that skin samples taken from infants at birth using tape stripping were ineffective to predict the eventual development of AD, while samples taken at two months revealed differences in immune markers from infants that would eventually go on to develop AD, sometimes months later.10 Lipid composition of the top layers of skin collected at two months via tape stripping may also be predictive of AD development.11 The question remains whether the development of AD had already been set in motion or whether intervening at two months could have prevented the process.
The main areas of research into the primary prevention of AD can be categorized according to timing of the intervention, i.e. altering risk factors in the mother prior to infant birth (prenatal) or changing things about the experience of the at-risk infant at and shortly after birth (peri-natal). Methods that have been explored for predicting AD primarily include improving the skin barrier using emollients and moisturizers, altering dietary intake, limiting or altering the environment and changing the microbiome using probiotics to allow “good bacteria” to develop on the skin and in the gut rather than colonization of disease producing bacteria such as Staphylococcus aureus.4,5
In an initial study of 124 infants known to be at high risk for developing AD (a parent or sibling have AD, asthma or allergic rhinitis) parents were instructed to apply full-body emollient therapy at least once a day starting three weeks post-birth while the control group of parents were instructed not to apply emollients. Daily emollient use significantly reduced the incidence of AD development at six months, with 43% of the infants not given emollients developing AD while only 22% of infants receiving emollients daily developed AD (50% reduced risk).2 Many other researchers repeated or improved upon this study and recently (within the last two years) different groups have analyzed all the cumulative data of these trials using what is called a systematic review and meta-analysis.12-14 Researchers found around 30 studies about skin care regimens that could potentially enhance skin barrier function, reduce dryness or reduce subclinical inflammation in healthy term infants (at least 37 weeks gestation, ≤ 12 months post-natal) without pre-existing eczema, food allergy or other skin condition up to September 2021.12 One of these reports concluded that while continual use of emollients from early infancy in high-risk infants seemed to improve AD, it did not necessarily prevent it.14 They hypothesize that emollients may more delay rather than prevent onset of AD. Another meta-analysis found that early application of emollients is effective for preventing AD in high-risk infants and indicated that liquid emollients may be better than creams that cover and lubricate the skin.13
Special formulations of emollients have also been attempted to try to find the best “formula”.4 However, one of the largest emollient as prevention studies to date (Barrier Enhancement for Eczema Prevention, BEEP) that followed 1,394 infants either given emollients (693 infants) or just general skin care advice (701 infants) for three, four or five years, found that emollients did not prevent AD, asthma, food allergy or rhinitis. This 2022 publication also reported a possible (slight) increase in development of food allergies in the moisturizer group compared to controls, which may indicate that some moisturizers actually increase skin permeability to allergens.15 Other studies with more sophisticated formulations including ceramides to build up the skin barrier are ongoing, as a pilot study found a trend toward a ceramide moisturizer reducing the incidence of AD in the first six months of life and lower food allergy sensitization up to 12 months of life.16 Current data also suggests that infants need to be followed for longer periods of time to better understand what symptoms they go on to develop and if emollients may be better at delaying rather than preventing AD development. The American College of Allergy, Asthma and Immunology recently published a paper stating that, “Further studies are needed to determine the effects of moisturization on allergic sensitization and inflammation and to investigate whether moisturizer type, frequency, duration and age of application substantially affect the prevention and development of these allergies.”15 Dr. Eric Simpson of Oregon Health Sciences University further added, “We continue to have some positive signals using all of these approaches in some studies, but the results are mixed. It is challenging to determine whether the intervention failed in general or whether we tailor a prevention strategy to a genetic subgroup or a group in a specific environment. Emollients are well known to prevent flares, so we were hoping to apply that approach to the initial flare of AD, but we are not there yet.”
Research exploring the diet of the mother or infant to prevent AD has included exclusive breastfeeding, either delay or early introduction of foods other than milk, maternal or infant dietary restrictions and ingesting dietary supplements such as Vitamin D. While some of these things may be important for the general health of an infant, none to date have showed clear evidence of preventing AD.4,5 Like the above study that followed infants for three, four or five years, more long-term studies are needed to understand any benefits of prenatal and early life dietary and nutritional interventions to prevent AD. Unfortunately, these studies are very difficult to perform and difficult to control because each family has different dietary preferences, approaches and content.17
A recent large study of over 2,000 mothers and infants examined use of emollients and complementary feeding of things like peanut, cow’s milk, wheat and egg introduced around three to four months post-birth found that neither emollients nor early complementary feeding reduced incidence of AD.18 A group that studied maternal dietary restriction, breastfeeding, specific food formulas, and timing of introduction of allergenic complementary foods found that there may be a slight lengthening of developing AD symptoms in infants fed exclusively breast milk until 3–4 months of age, but this does not prevent the disease.19 Interestingly, longer term breastfeeding beyond four months seemed to result in decreased wheezing and asthma symptoms before 2 years old and even some long-term breast milk in the diet may keep asthma symptoms at bay past 5 years old.19
While AD is a global disease, we know that aspects of an individual’s environment can play a role in the development of AD. For example, there is much higher prevalence of AD in industrialized nations.20 Further, exposure to allergens like dust mite and cockroaches, or to conditions that impact skin colonization of S. aureus impact AD development. Skin moisture, which may change depending on how warm a living environment is, as well as things like detergents and cleansers can impact the skin and its acidity. Regulating the acidity of the skin (acidic skin is needed for maintaining lipid metabolism to form the skin barrier) or skin inflammation provides a new avenue for research.3 An acidic cream formulation was recently shown to inhibit AD-like skin lesions and development of airway allergic reactions in mice.3
While there is little that most people can control related to where they live and work, research is examining the possibility of examining things that can be controlled within the home. For example, water composition, i.e. “soft” vs. “hard” (>250 mg/L calcium carbonate) water can play a role in development of AD, as in observational studies, people living in areas with hard water were more susceptible to AD development.21,22 A pilot feasibility study to test the preventative benefit of a water softener inside the home was conducted with 80 individual families.21 A lower proportion of infants in the water softener arm of the study developed AD compared to those whose homes remained with hard water. Dr. Carsten Flohr of King’s College in London, who led the study commented on this initial finding stating, “We know that we need to include about 750 to 800 families in order to statistically power a definitive randomized controlled trial, but it would be a heavy lift to get a company to go into these homes to install the softeners. We remain very interested in doing the study.”
Environmental components that impact the skin microbiome are also a new direction of research. A very recent paper shared preliminary results of a search of the Environmental Protection Agency’s databases for pollutants and comparing high incidence of these pollutants with incidence of AD.20 The study found that exposure to pollutants called isocyanates which are found in carpets, paints, bedding and furniture, and even some sports uniforms clearly associated with higher AD incidence.20 The researchers found the mechanism for this to be isocyanates’ ability to disrupt bacteria’s ability to produce important lipid molecules that make up the bacterial cell wall.20 These findings also need further study as with myriad environmental exposures across a lifetime, it is very difficult to tease out specific molecules that may be impacting risk of developing AD and take specific action to limit or prevent exposure to them.
“Good bacteria” that reside on and in the human body are absolutely crucial for development of health. Biodiversity, which is an abundance of all kinds of bacteria rather than reduced diversity such as happens with skin colonization of S. aureus, is important to prevent infections and to stimulate the immune system to appropriately develop.23 The gut microbiome of an infant begins to develop in utero, during pregnancy and continues during the period of breastfeeding or formula treatment. Skin, gut and airway microbiomes are further developed during and after birth and then can be altered throughout life depending on exposures to different types of microorganisms.23 Several studies have examined whether enhancing certain bacteria using probiotics either during pregnancy, during breastfeeding or in the infant at high risk of developing AD may actually help prevent AD.
Once again, research on this concept is complex and sometimes confusing but shows some promise. Supplementation through probiotics with the bacteria Lactobacillus rhamnosus during pregnancy and after birth until 2 years of age and in children 6–7 years old was shown in a meta-analysis to statistically significantly reduce AD.24 Infants who received probiotics through their mother during pregnancy and after birth through breastfeeding had lower incidence of AD.24 Another meta-analysis of 21 published studies on the use of probiotics with a combined total of 5,406 children found that mixes of probiotics all containing various species of Lactobacillus among other bacteria and administered to the pregnant mother, the infant or both mother and infant exhibited reduced risk of AD.25 Dr. Flohr said, “There is still a lot of room for research on probiotics because the studies done so far have largely used different mixtures of probiotics, which can be very hard to compare. The research needs to be done systematically. There can also be bias due to studies being funded by the companies that make probiotics. Network meta-analysis have suggested benefits of Lactobacillus and Acidophilus species. There does not seem to be harm in trying this in mothers at high risk of giving birth to babies who will develop AD”. Because both the microbiome and the immune system very rapidly develop during the first year of life, studies suggest that intervening to alter the microbiome and immune system prenatally and during the first year of life may be the most impactful.23 Dr. Flohr agreed, saying, “Priming of the immune system prior to and around birth seems to be key.”
Once AD has developed, the prevention focus changes to disease management. This means that a person is past primary prevention and into secondary (detecting AD quickly to intervene and prevent it from worsening) and tertiary (reduction of symptoms or improvement in quality of life of those with established disease) prevention. This typically occurs through a combination of self-care and involvement with the medical community to facilitate the use of various prescription-based therapies.4 Aggressive early treatment when AD first develops is an attractive potential secondary prevention strategy as well as interventions that alleviate the itch/scratch cycle that drives the progression of disease.4 Again, ongoing research to develop biomarkers may be useful to predict which patients will and will not respond to certain treatments, as well as potentially predict progression of disease. Knowing exactly how and when to intervene for each individual patient using personalized medicine is an area of very active research aided by the era of non-invasive tape stripping and other screening approaches. Dr. Simpson agreed, stating, “The most important upcoming studies are regarding secondary and tertiary prevention. A couple of studies have shown the timing and type of treatment may impact the natural course of the disease and modify comorbidities like food allergy. Some evidence shows early, aggressive anti-inflammatory therapy in the first four months after disease onset can reduce food allergy at two years. So, even if we cannot prevent the disease, hopefully we can identify a way to treat the disease to promote the disease to resolve at an early age and to reduce the risk of comorbidity development.”
The most important aspect of current and future prevention research is to continue efforts to understand the biological and multifactorial complexity underlying development of AD. Dr. Hywel Williams, who has been researching biology and prevention of AD for decades, urges that researchers learn from past errors in trial design and focus on new and emerging knowledge of AD biology rather than continuing to try methods that have not proven effective to date.4 Further, he recommends that research focus be placed on exploring fetal environment by intervening in mothers at high risk of giving birth to infants who will develop AD and to really do a well-designed meta-analysis of all the research thus far on use of probiotics.4 He suggests this may result in ability to move past cautious recommendations and toward firm implementation of preventive methods.4 Learning more about the microbiome/immune system interactions in production of AD seems to be a great place to continue looking for ways to prevent AD from ever happening in the first place and to slow or prevent progression to asthma, food allergies and rhinitis.3 As with so many aspects of understanding AD, time and evolution of research techniques will tell whether it will ever be possible to prevent AD.
References:
There are many ingredients and products that can cause contact dermatitis — a skin rash caused by an allergic reaction after something touches your skin. Learn more about this type of eczema, including how to diagnose, treat and prevent it.
Amanda Campbell shares how she successfully managed her eczema during one of the toughest backpacking hikes in the United States.
The Food and Drug Administration approved two new treatments for eczema in 2024. Learn more about each treatment option, plus what you can expect in 2025.
In October 2024, the National Eczema Association acknowledged Eczema Awareness Month through the The Ecz-hibition campaign by putting #EczemaOnDisplay.