By Abby Van Voorhess, MD, February 01, 2011
In this month's Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Eric L. Simpson, MD, about his recent JAAD article, "A pilot study of emollient therapy for the primary prevention of atopic dermatits."
Dr. Van Voorhees: What is the role of barrier dysfunction in atopic dermatitis?
Dr. Simpson: We’ve known for many years that the skin in atopic dermatitis is abnormal. We’ve known that atopic skin has increased trans-epidermal water loss, it’s drier than normal skin, more prone to irritancy, and in the lab you can find lipid abnormalities as well as serine protease inbalances. The whole filaggrin story came about in 2006 and confirmed that the epidermis is a pretty important part of the story in terms of initiating eczema. What we haven’t known is whether these skin abnormalities are primary to the disorder or secondary to inflammation. That’s been the classic chicken-and-egg argument for years now.
Dr. Van Voorhees: What made you consider exploring barrier protection in atopic dermatitis?
Dr. Simpson: I think it spawned from my mentor, Jon Hanifin, MD, who was pondering whether skin barrier protection or early control of inflammation could potentially prevent the progression of the disease. I took it one step further. We knew that topical therapy could prevent flares of eczema so my idea was, “Can we prevent the first flare?”
Dr. Van Voorhees: Other things that have been tried to prevent eczema are allergen avoidance and probiotic formula. Have they been successful?
Dr. Simpson: Reviewing the literature I was disappointed that there was no one consistent, allergy-based preventive strategy that was effective.
The most recent studies looking at oral probiotic therapy in pregnant moms and neonates and extensively hydrolyzed formula are the most promising. The studies have been a little bit conflicting but a recent meta-analysis showed that there’s potentially some effect from oral probiotics. There’s been some conflicting evidence about the extensively hydrolyzed formula and in my opinion the strategy is limited by the poor palatability and expense of the formula — so it might not be practical for a very common disorder that has a global distribution.
Dr. Van Voorhees: Did you find that there was an optimal time to correct barrier dysfunction?
Dr. Simpson: The main point of this initial pilot study was to determine feasibility; barrier protection from birth for eczema prevention has never been studied so there were no data to guide us. But atopic dermatitis can often start in the first three months of life so any preventive strategy needed to be either prenatal or in the first three months. We arbitrarily picked within the first week of life.
Dr. Van Voorhees: Who did you choose to enroll?
Dr. Simpson: We picked neonates at high risk for developing atopic dermatitis — one parent having a history of atopic dermatitis and one first-degree family member with some type of respiratory atopy. If you look at data from previous studies, that type of population should have a 40 to 50 percent chance of having a child with atopic dermatitis. We followed them for almost two years because the majority of eczema is going to start in the first two years.
Dr. Van Voorhees: What emollient were you using?
Dr. Simpson: There is very limited evidence comparing how effective different emollients are in skin barrier protection or clinical outcomes so I couldn’t use the literature to guide me very well. I used a relatively inexpensive petrolatum-based cream that comes in large quantities, which I really picked for practical reasons. I think any emollient could be used with potentially varying effects, we just don’t know which way is optimal at this point.
Dr. Van Voorhees: Did you allow the parents to use topical steroids? Did you encourage or discourage other conservative maneuvers like bathing?
Dr. Simpson: We tried to keep it as real world as possible, with just the addition of daily moisturization, which we encouraged them to do after a bath. They could bathe as often as they wished. We did give them a recommendation to use a cleanser designed for babies but gave no specifics regarding which one. We wanted to make this a feasibility study and get information from the parents: Were you able to do this? How often could you do this? How many times did you miss their treatments? We wanted to see if this is an approach worth pursuing.
Dr. Van Voorhees: And what did you find out?
Dr. Simpson: We found that topical therapy or barrier protection is a feasible prevention strategy. Parents were able to apply this at least 85 percent of the time to children’s skin on a daily basis. There were no adverse events. Things we were looking for were any signs of irritant or allergic contact dermatitis or potential occlusive-based infectious complications, primarily candida, and we didn’t see any of that during this study.
We had three out of 22 babies develop atopic dermatitis during the course of this study. We would have expected far more than that to develop it by age two when you compare to historical controls. I think the most we can conclude from this small pilot study, however, is that this is a feasible approach and controlled studies are needed. We also found that the use of emollients early on in this patient population kept trans-epidermal water loss and skin barrier function measurements within normal range.
Dr. Van Voorhees: Is there anything known about whether barrier protection might be useful in the prevention of other related things, such as asthma, food allergies, or hay fever? Is there any evidence for that that made you think of barrier protection?
Dr. Simpson: Looking ahead, I think this is a natural progression of where barrier protection in childhood is going to go. There aren’t any data right now about whether protecting the skin early on can prevent respiratory atopy. There’s really intriguing data in mouse models that the skin is a potent organ for IgE sensitization so one would think that potentially protecting the barrier and preventing inflammation and the ingress of antigens and allergens may reduce one’s IgE sensitization over time and, carrying that forward, may reduce IgE-mediated diseases like allergic rhinitis or asthma. We are planning these studies but they’re going to take large patient numbers and many years of study. But those are exciting future directions for this kind of research.
Dr. Van Voorhees: Is sounds like this is an area that’s fertile for future research.
Dr. Simpson: There’s been a lot of international interest so we’re putting together an international consortium to do the final efficacy study that will probably be starting in six months to a year.
This controlled study is looking at different emollients, including sunflower oil, which has been shown in premature nenonates to improve skin barrier. Our thought was that if this could improve skin barrier and reduce the incidence or even the severity of atopic dermatitis that it would be a cheap and effective modality for preventing atopic disease on a more global basis.
Dr. Simpson is associate professor of dermatology and director of clinical studies in the department of dermatology at Oregon Health and Science University. His article was published online by the Journal of the American Academy of Dermatology on Aug. 9, 2010. doi:10.1016/j.jaad.2009.11.011.