Expert stresses use of epidermal repair therapy in managing paediatric atopic dermatitis
Managing paediatric atopic dermatitis (AD) remains a huge challenge mainly because of noncompliance to treatment, but this challenge can be addressed by prescribing nonsteroidal, noncalcineurin inhibitor agents providing epidermal repair therapy, according to an expert who spoke at the 23rd Asian Australasian Regional Conference of Dermatology (RCD 2018) held in Surabaya, Indonesia.
Currently, mild-to-moderate AD is managed by topical corticosteroids (TCSs) or topical calcineurin inhibitors (TCIs), moisturizers and optimal skincare practices. This treatment paradigm is aimed at relieving itch and reducing inflammation, repairing epidermal barrier, and strengthening the barrier in the long term, said Dr Cheong Wai Kwong, director at Specialist Skin Clinic and Associates in Singapore.
However, Kwong noted that TCSs or TCIs, which have been the mainstay treatment for AD, are met with a fear stemming from unwanted side effects, such as burning sensation and erythema, and concerns regarding long-term treatment. Steroid phobia leads to poor treatment compliance, which in turn exacerbates disease.
In severe AD cases, eczema clearance and effective maintenance of clearance is achieved through proactive therapy. In other words, TCSs or TCIs must be firmly applied at an optimum dose over the entire site of rash, even if the symptoms are mild, at least thrice, twice or once weekly. Additionally, a moisturizer should be used all over the entire body daily.
“Epidermal repair therapy is the keyword. So every time you prescribe steroids to your patients, you tell them that you’re also going to prescribe a moisturizer that will repair the skin. Tell the parents they can cut back on the dose of TCSs or TCIs, but they have to apply a moisturizer throughout,” he said.
Such a strategy is in line with existing guidelines strongly recommending that moisturizers be used as first-line therapy or as an integral part of treatment. [J Dermatolog Treat 2016;27:568-576]
As to the question of which moisturizer to use, the MAS063DP cream has been shown to be effective in treating symptoms of mild-to-moderate AD in infants, children and adults. Specifically, improvements in pruritus may be observed 3 days into treatment, with fewer patients requiring TCS supplementation.
The said cream is the only topical emollient supported by more than four randomized controlled trials in a systematic review of different moisturizing products. Those containing urea, ceramides, glycerin and glycyrrhetinic acid also show evidence of efficacy. [G Ital Dermatol Venereol 2018;153:396-402]
More importantly, the addition of moisturizers to topical anti-inflammatory medications in AD management has been found to be more effective than anti-inflammatory treatment alone and results in fewer flares. [Br J Dermatol 2017;177:1256-1271;]
Novel alternatives to TCS, TCI
Meanwhile, there are novel treatments developed to address the need for alternative anti-inflammatory topical therapies without the safety concerns associated with TCSs and TCIs, Kwong said. These include biologics that focus on blockade of inflammatory cytokines.
Dupilumab, a biologic directed against the shared interleukin (IL)-4 receptor alpha subunit, inhibits both IL-4 and IL-13 signalling. This leads to a decreased T helper 2 (Th2) immune response, which is upregulated in AD. Results from an open-label phase IIa trial of this drug showed a significant reduction in disease severity and pruritus scores in children and adolescents with moderate-to-severe AD. [AAD 2017, abstract 5279]
While effective, biologics can be very expensive, and the cost may limit its use in clinical practice, Kwong said. Cheaper alternatives are available, such as nonsteroidal, noncalcineurin inhibitor agents developed to specifically inhibit phosphodiesterase (PDE) 4, and topical probiotics.
PDE4 inhibitors work to increase intracellular cyclic adenosine monophosphate (cAMP) levels, reducing cytokine mediator release and regulating inflammation. Currently available FDA-approved agents in this class include the topical crisaborole and the oral apremilast.
On the other hand, probiotics reduce exposure to allergens by improving intestinal barrier function and promoting immunoregulation to prevent IgE sensitization. When used in AD patients, topical probiotics may address an imbalance of microbes in skin, as well as protect against skin infections by directly killing harmful bacteria such as Staph aureus, Kwong said.
In an open-label clinical study involving 10 adult and five paediatric AD patients, topical microbiome transplantation with Roseomonas mucosa led to an improvement in eczema after 6 weeks. Treatment was associated with significant decreases in disease severity, topical steroid requirement and S. aureus burden. There were no adverse events or treatment complications. [JCI Insight 2018;doi:10.1172/jci.insight.120608]
When dealing with the challenge of integrating these newer agents into the treatment paradigm for paediatric AD in clinical practice, Kwong stressed that clinicians acknowledge that some of the available treatments are less expensive. Specifically, probiotics and topical antioxidants may be more affordable than dupilumab.
He also reiterated the prescription of agents providing epidermal repair therapy. “You have to find a moisturizer capable of repairing the skin of your patients.”