Allergies without borders

The UCD Derma Seminar series recently heard a talk by Consultant Dermatologist
Prof Carsten Flohr on how children can become allergic to foods through the skin

The Charles Institute, Ireland’s national dermatology research and education centre, hosts a range of guest speakers who cover a variety of topics ranging from skin cancer to psoriasis, among others. The series, which is currently supported by an Educational Grant from Johnson & Johnson, is designed to provide expert advice from a range of distinguished national and international experts in their respective fields and is chaired by Prof Desmond Tobin, Full Professor of Dermatological Science, UCD School of Medicine and Director of the Charles Institute of Dermatology. The seminars are broadcast to attendees with a special interest in dermatology and cutaneous science in other locations, who access the talks remotely via an audio-visual link.

Attendees heard a presentation from Prof Carsten Flohr, Consultant Dermatologist and Chair in Dermatology and Population Health Science, St John’s Institute of Dermatology, King’s College London. He also directs the Global Atopic Dermatitis Atlas and is a Founding Director of the International Eczema Council. Among his many distinctions, Prof Flohr was the first UK National Institute for Health and Care Research (NIHR) Clinician Scientist in dermatology and the first dermatologist to be awarded a senior Career Development Fellowship from the NIHR.

In his current research, Prof Flohr has a special interest in examining novel ways to prevent atopic dermatitis. He is also researching the role of the microbiome in atopic dermatitis, and the links between atopic dermatitis and food allergies and therapeutics in severe disease. He co-led the landmark Enquiring About Tolerance (EAT) trial, which showed that introducing allergenic foods from three months old significantly reduces the risk of food allergies and that early-onset eczema is a key risk factor for food allergy development through the skin. Based on findings from the EAT trial, Carsten Flohr now leads a European Union Horizon 2020-funded research consortium called TRANS-FOODS to further investigate the mechanisms behind transcutaneous sensitisation to foods.

In his talk, Prof Flohr discussed the latest understanding of how children become allergic to foods through the skin – which is now understood to be the main route of food allergy development – and what clinicians and parents can do to prevent this from happening.

The role of the skin barrier in the development of food allergy

Prof Flohr started off presenting case studies to illustrate the development of allergies in babies and young children and observational data from population-based studies suggest that well over 90 per cent of food allergies are preceded by eczema. Referencing a Danish study, Prof Flohr told the seminar: “More than 60 per cent of children presenting to a hospital dermatology department with eczema have a challenge-proven food allergy. In the community, the risk is lower, but is still a significant 15 per cent.”

He also referenced previous work from the EAT trial, showing a more than six times higher risk of food sensitisation already by three months of age, if a child has eczema. This relationship was disease severity-dependent and enhanced further in those with an impaired skin barrier (raised transepidermal water loss in unaffected skin).

Intervention studies to prevent atopic dermatitis and food allergy

Prof Flohr went on to address the question: If eczema and skin barrier impairment is actually the cause of most food allergies, then preventing skin barrier impairment and eczema should prevent the food allergy. “We had originally shown an up to 50 per cent reduction in eczema risk with an emollient intervention in high-risk babies in a feasibility trial,” Prof Flohr told the attendees. These and other findings led to the much larger Barrier Enhancement Eczema Prevention (BEEP, n~1400) trial, which looked at the use of regular emollients versus standard of care as a way to prevent eczema more comprehensively. While there was no benefit of regular emollient use, the researcher observed an unexpected borderline increase in food allergy risk. Prof Flohr and his colleagues therefore posed the question of whether regular contact of parents’ hands with their children’s skin might facilitate transcutaneous sensitisation to the examined foods (milk, egg, or peanut allergies), in particular, as no hand hygiene advice had been provided in the BEEP trial.

“Without prior hand washing, it is likely that parents’ hands were contaminated with small amounts of food protein, in regular contact with a child’s skin because we told parents in the trial that they needed to put the emollient on twice a day, but we gave them no advice about hand-hygiene because we never thought about it as a potential problem,” he explained.

Prof Flohr’s team then went back to the EAT study dataset and found that the risk of food allergy increases if moisturisers are used more frequently, in particular if applied more than daily: “Interestingly, this was not dependent on whether the child has eczema at three months or not,” he said. Prof Flohr also referenced previous research showing that the use of peanut protein-containing topical products in early life increases the risk of developing peanut allergy in infants, and noted that these products are now banned in the UK, in part based on their team’s research.

With reference to the TRANS-FOODS project, Prof Flohr noted that his team discovered that mice could be made allergic to peanuts simply by stretching their skin over application of a peanut-protein containing gel. No skin barrier disruption, for instance with tape stripping, was needed. “Importantly, we did not see this effect in hairless mice, which suggests that the action is in the hair follicle,” he added, “and we have also shown that the allergic sensitisation is facilitated by a subtype of dendritic cell.”

In terms of prevention, Prof Flohr told the seminar that maintaining good hand-hygiene is likely an easy way to prevent allergen transfer from parents’ hands to the baby’s skin during moisturisation or baby massage. “Our team has not only shown that peanut protein can be transferred from one body site to another, but also that standardised hand washing removes almost all peanut protein from human skin. As a result, we advocate meticulous hand-hygiene for all parents who are using moisturisers on their children, especially if the child has eczema. This is a message that needs to go out in a standardised way to all healthcare professionals and parents alike, and we are working on that. I also want to stress the importance of avoiding food protein-containing preparations and the need for early introduction of allergenic foods from around three months alongside breastfeeding, as this is the best way to induce tolerance. The babies at the highest risk of transcutaneous sensitisation are those who are exclusively breastfed for longer than three months, as tolerance induction is delayed. If the food protein is first recognised by the human immune system through the skin, especially if cutaneous antigen-presenting cells are already in a hyper-alert state through eczematous inflammation, then the risk of food allergy development appears the highest.”

Treatment

“Transcutaneous sensitisation to foods is a real phenomenon, there is no doubt about that,” Prof Flohr synopsised. “Emollient application does not prevent atopic dermatitis, but it can also facilitate transcutaneous sensitisation. Several other intervention studies are still ongoing with emollients, and some of these are looking at not just preventing skin dryness and eczema, but also treating the eczema proactively, as researchers hope that addressing the barrier dysfunction and inflammation together might provide additional protective benefit against food allergy.”

In terms of the future, Prof Flohr commented: “We have one trial that has just started called CUTIE, which is in healthy babies, because we want to understand the skin immune response to regular massage. In CUTIE, we randomise babies to either no massage, massage twice a week, or massage every day. We have developed a novel non-invasive suction device that allows us to conduct proteomic analyses on interstitial fluid retrieved from the babies’ skin to see what happens to the skin immune system, as well as microbiome in response to regular skin stretching.”

Caesarean vs vaginal delivery

Each UCD Charles Institute seminar is followed by a discussion and Q&A, which is moderated by Prof Tobin. In these, participants in person and online have the opportunity to raise questions and offer input based on the content of the talk. 

Prof Tobin commented: “You stressed several times the sequence in which things happen in this early childhood period, suggesting perhaps that there are windows of more optimal intervention in terms of the switching… but is there any evidence – given that in affluent countries, we see this onward march of increasing evidence of childhood eczema – is there any association in children born via Caesarean rather than natural vaginal delivery in terms of how their skin is ‘set-up’ in the first months of life?”

Prof Flohr responded: “Yes, a number of observational studies have shown a link between mode of delivery and atopic dermatitis risk. The bacterial microbiome of those born during Caesarean section is less diverse than of those born vaginally, and a reduction in bacterial diversity in the gut and on the skin is linked to a higher risk of atopic dermatitis development over the first few years of life.”

Johnson & Johnson has had no input into the content of this article or series of seminars.