Feedback AAD 2017

What’s New in Pediatric Dermatology 2017

Key developments in the field of pediatric allergy include newly available products, emerging agents, and importantly, intriguing findings about opportunities to actually prevent the development of some conditions. Sheila Fallon Friedlander, professor of Dermatology and Pediatrics at UCSD and Rady Children’s Hospital, San Diego, California, USA shared some exciting news regarding the atopic dermatitis (AD), peanut allergies, and vascular abnormalities in pediatric patients.

Dermatologists have been using petrolatum vaseline and other emollients on their pediatric patients with AD “forever.” But the news is that using these emollients proactively on susceptible patients can reduce the risk of developing AD. This was demonstrated by Simpson et al. 2014 in a randomized, clinical trial of 124 high risk neonates (<3 weeks old) in the US and UK. A choice of sunflower oil cream or ointment, applied once daily, was compared to control. The risk of developing AD was decreased by 50% (43% for the control group vs 22% for the emollient group), suggesting a simple way to intervene early before AD develops.

Emma Guttman and her colleagues investigated the effects of petrolatum on the skin in 49 patients with and without AD, evaluating the effects of petrolatum applied under occlusion, occlusion alone, or control. On biopsy, patients treated with petrolatum had increased barrier differentiation markers (eg. filaggrin and loracrin) and upregulation of antimicrobial peptides and innate immune genes, increased thickness of the stratum corneum, and decreased T cell infiltrates, compared with those with occlusion-only and controls.

These findings highlight the potential role of antimicrobial peptides, natural antibiotics found on the skin which are shown to be deficient in patients with AD, and the importance of a normal skin microbiome on the skin. Furthermore, patients with AD have more Staphylococcus aureus on their skin, and are more prone to inflammation and infection.

An exciting study by Rich Gallo looking at the skin of patients with AD and those without AD has yielded some clues about differences in the skin microbiome. Those findings suggest that atopic skin is dysbiotic; compared with normal skin, it lacks microbial diversity. Building on this finding, they took normal “good bugs,” such as coagulase-negative Staphylococci and some Corynebacterium from patients with AD and clonally expanded them, grew them out, and put them back on AD skin in both animals and humans. They found that these “good bugs” on the skin produce beneficial antimicrobial peptides which prevent growth of S. aureus, leading to less inflammation. Ultimately, this may lead to development of “anti-dysbiotic cream” that can be applied to help normalize the skin microbiome.

Another notable development is the introduction of crisaborole, a boron-based topical phosphodiesterase-4 inhibitor which can be used in children with mild to moderate AD. By increasing levels of cyclic AMP, crisaborole tilts the balance toward production of anti-inflammatory cytokines. Based on pharmacokinetic studies in pediatric patients, it appears to be minimally absorbed.

For patients with severe AD, dupilumab, a monoclonal antibody that blocks inflammatory receptors, is a potential game changer. In an unpublished study in pediatric and adolescent patients, patients were injected with dupilumab 2 or 4 grams per kilogram of weight every 1 to 4 weeks, and then received an additional series of 4 injections 8 weeks later. In the 6-11 year old group, Eczema Area and Severity Index (EASI) scores fell by 76% at week 12 in patients who received dupilumab, and there was an early improvement of itch as well.

Another story in prevention is the LEAP (Learning Early About Peanut allergy) study. Historically, the conventional wisdom has been to avoid peanut exposure in susceptible infants. Findings from the LEAP study subvert these beliefs, demonstrating that early exposure to peanuts may prevent development of peanut allergies. Importantly, they suggest that how a child is exposed to an antigen may be crucial in whether they develop an allergy. If a child with AD who has an impaired barrier is exposed to an antigen through the skin, the Th2 inflammatory side is stimulated, leading to production of interleukins and inflammation. But if a child is exposed to antigen via the mouth, it is processed by the gut, which favors Th1. The LEAP study took 640 infants aged 4 to 11 months at high risk for peanut allergies and exposed some to orally ingested peanuts, while others avoided exposure. Patients with a history of severe anaphylaxis and those who already had a strong skin prick test and demonstrated allergy to peanuts were excluded. At 60 months, the children who had avoided peanuts had a higher incidence of peanut allergy compared to those who had ingested peanuts. Children with no history of allergy, no positive skin test, and no serum immunoglobulin E (IgE) were protected, but those who had some risk of allergy did even better.

The takeaway for practitioners is that if a child presents with severe eczema or a family history of atopy, look at IgE levels. If it’s negative for peanut allergy, have them eat peanuts. If their IgE is positive, they should be sent to an allergist before making this recommendation.

Friedlander briefly reviewed vascular malformations and the easy-to-use classification ISSVA (International Society for the Study of Vascular Anomalies) which provides clear directions for categorization. Many vascular formations are associated with known somatic mutations such as PIK3CA, RASA1, GNAQ, PK3CA, STAMBP, PIK3CA, AKT1, and PTEN. A biopsy of the actual tumor must be taken to find these mutations and studies show that the genes are not found in the blood or saliva. Timolol provided an effective treatment and should be a consideration for use.