Atopic Dermatitis: Early Life Interventions
Which factor is most important in early life development of atopic dermatitis (AD)? Could it be early antibiotic exposure, transepidermal water loss, the microbiome of the patient, or time spent in the NICU? Lisa Swanson, MD, pediatric dermatologist at Ada West Dermatology in Meridian, Idaho, and a partner at St. Luke’s Children’s Hospital, in Boise, explained these all could factor into the development of AD, but as of now there is no clear answer to which is most important.1
She went on to describe how food allergies and AD have growing evidence of an association, something that the American Academy of Dermatology (AAD) has recently explored, and cautioned that, while the 2 may be connected, avoiding foods would be harmful for pediatric patients.2 Food avoidance can cause malnutrition and lead to increased risk of an allergy or anaphylaxis. A Japanese study that included a 3-year evaluation of 117 patients less than 1 year old who started treatment with topic steroids for severe AD found that less patients in the treated group had food allergies.3
“So, the best thing that families can do to prevent food allergy is treat their child's [AD],” Swanson said.
Besides food allergies, many parents are asking for natural therapy options for their children who have AD, Swanson continued, which can be hard to make suggested treatments for because of the lack of formal studies.
She talked through the natural therapies that have been studied, such as:
There are many impacts of AD that she thinks of as adverse effects (AE) of having the condition, like increased risk of mental health issues, allergies, and cardiovascular disease. Perhaps one of the most devasting issues with having AD is the lack of sleep, which both pediatric patients and parents struggle with. With less sleep, many children with AD end up missing out on growth hormones that secrete during that time, Swanson explained, so they end up smaller on growth curves.
“Growth hormone also plays a huge role in bone formation,” Swanson said. “There's your link to osteoporosis osteopenia and fractures.” There have also been studies that the over-activity of interleukin (IL)-4 also has a negative effect on brain development. Which is why IL-4 suppressants could be a huge asset to treating AD, according to Swanson.
She discussed what medications were available to treat the pediatric population such as fluocinolone 0.01% (Synalar; Medimetriks Pharmaceuticals, Inc) and the Aron Regimen—which is made of 30g of betamethasone valerate 0.1, 24g of mupirocin, and 400g of Vanicream). Additionally, she touched on bleach baths, which has been determined to not kill Staphylococcus bacteria, as was previously thought, but do still have some benefits against AD. Swanson explained this is probably due to an anti-inflammatory effect on the skin.
Currently, the biggest game changer for AD has been dupilumab (Dupixent; Sanofi and Regeneron Pharmaceuticals), which is currently approved for AD in patients ages 6 years and older. The company has also applied for a supplemental biologics license application (sBLA) for children aged 6 months to 5 years with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies, or those therapies are not advisable.7
Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways and is not an immunosuppressant. Swanson explained that she does not do a loading dose for her pediatric patients. “My personal style has been to not do a loading dose in kids, it's just too hard on them. I don't want the first experience to be so traumatizing that they don't come back,” she said. In patients 2 years and younger during the Liberty AD PRESCHOOL (NCT03346434) trial, there was no loading dose.
The other development in AD includes Janise kinase (JAK) inhibitors. Swanson explained that while there is a black box warning on these JAK treatments, it is important to keep in mind that the AEs seen were not studied in the AD population, but physicians should still monitor their patients when needed.
Ruxolitinib cream (Opzelura; Incyte), which is approved in patients 12 years and older, is a topical treatment for AD that also has a black box warning. It can be used in patients with 20% or less effected body surface area.8
For oral JAK inhibitors, she explained that a patient should have a complete blood count (CBC) taken, a comprehensive metabolic panel (CMP) done, and a lipid panel at baseline, 1 month, and every 3 months after. She continued that a QuantiFERON-TB Gold, hepatitis B, and hepatitis C tests should also be done at baseline and, depending on the patient, annually. Swanson also said that while creatine kinase (CK) elevations were observed in past studies, they were transient and not clinically relevant so it’s her opinion that there is no need to test a patient for them.
Other things to consider when treating patients with oral JAKs is hepatic or renal impact at baseline, having patients avoid live vaccines, and having patients avoid becoming pregnant or breast feeding. “Consider talking about [herpes simplex virus] suppression if a patient has a history of cold sores and consider the Zoster vaccination if they're old enough to qualify for it,” Swanson said. “Because there is an HSV/VZV signal with these [treatments].”
Swanson is a speaker for Valeant and Bayer, and on the advisory board of Allergan.