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Curr Treat Options Allergy. Author manuscript; available in PMC 2018 September 01.
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Published in final edited form as:

Curr Treat Options Allergy. 2017 September ; 4(3): 355–369. doi:10.1007/s40521-017-0140-6.

Atopic Dermatitis: Early Treatment in Children

Amy Huang, MD1, Christine Cho, MD2, Donald Y.M. Leung, MD, PhD2, and Kanwaljit Brar,
MD2
1Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn,
NY
2Department of Pediatrics, National Jewish Health, Denver, CO
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OPINION STATEMENT
Therapeutic regimens for the treatment and long-term management of AD traditionally had a two-
fold objective of decreasing skin inflammation and repairing the defective skin barrier. Essential
treatments for AD in children should include topical moisturizers for skin hydration and
prevention of flares, topical anti-inflammatory medications (e.g. corticosteroids, calcineurin
inhibitors, PDE4 inhibitor), allergen/irritant avoidance, and treatment of skin infections. Treatment
regimens should be severity-based, and implemented in a stepwise approach tailored to the
individual patient. This stepwise approach includes initial use of emollients, gentle skin care, and
escalating to more potent anti-inflammatory treatments as the disease severity increases. Currently
available systemic medications should be reserved for the presence of recalcitrance to topical
therapies due to associated toxicities.
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We believe that early treatment of AD is not only essential in treating the skin disease, but also in
preventing the development of additional atopic diseases, such as food allergy, asthma and allergic
rhinitis. The defective skin barrier of AD permits a route of entry for food and environmental
allergens, and upon exposure, keratinocytes secrete TSLP, which activates the TH2 pathway. This
TH2 differentiation sets off the atopic march and the subsequent diseases that are seen. This review
highlights treatment options and strategies in pediatric AD therapy with an emphasis on early
therapy. Supporting evidence on the efficacy and safety of each intervention will be discussed.

Keywords
atopic dermatitis; eczema; atopic march; allergy; corticosteroids; immunosuppression
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Corresponding author: Kanwaljit Brar, MD: brark@njhealth.org.

COMPLIANCE WITH ETHICS GUIDELINES
Conflict of Interest:
Dr. Amy Huang, Dr. Christine Cho, Dr. Kanwaljit Brar, and Dr. Donald Y.M. Leung declares that they have no conflict of interest.
Donald Y.M. Leung is supported by the National Institutes of Health under grant number R01AR41256. The content is solely the
responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Human and Animal Rights and Informed Consent:
This article does not contain any studies with human or animal subjects performed by any of the authors.
 Huang et al. Page 2

INTRODUCTION
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Atopic dermatitis (AD), or atopic eczema, is the most common inflammatory skin condition
of childhood. It affects 15–30% of children and it is particularly common in industrialized
countries worldwide [1]. In the United States, there were 7.4 million visits of children
younger than 18 years to physicians for AD [2]. The disease is characterized by chronic and
relapsing pruritic skin lesions that generally develop in early childhood, usually between 3
and 6 months of age. Approximately 60% of patients develop eczematous lesions in the first
year of life and 90% by 5 years of age [3].

The distribution of AD lesions also differs with age, as neonates and infants (0–2 years)
generally have pruritic, erythematous, weeping patches on the cheeks, scalp, and extensor
surfaces of extremities. These lesions progress to xerosis, thickened plaques, papules, and
excoriations on the wrists and flexural surfaces of extremities in childhood (2–12 years).
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There are currently 12 various diagnostic criteria for AD, the first of which is the Hanifin
and Rajka criteria, which was developed in 1980 [4]. The Hanifin and Rajka criteria is
composed of four major and 23 minor clinical criteria, and is often used in clinical trials for
the diagnosis of AD.

AD often heralds the onset of the atopic march, a natural progression of atopic disorders that
begins with AD in infancy and leads to allergic rhinitis, food allergies, and asthma in later
childhood [5••]. A recent systematic review showed a strong association between AD, food
sensitization, and food allergy, especially in AD of increased severity and chronicity. In
addition, the study also found evidence that AD precedes the development of food
sensitization and allergy [6]. AD and progressive atopy have a complex pathogenesis that
can involve environmental stressors, mutations in the filaggrin gene and the epidermal
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differentiation complex that encodes epidermal structure and immune effectors, as well as
dysfunctional immune responses [5]. These dysregulated immune responses include a
selective decrease in skin-homing TH1 cells and an increase in TH2 cells, especially in
patients with severe AD [7•]. A study by Czarnowicki et al. found that patients with severe
AD have significantly lower CLA + (skin homing) IFN-γ producing T cells than control
subjects indicating a significant role for IFN-γ, a regulatory cytokine in the pathogenesis of
AD [7•].

The impaired epidermal barrier in AD contributes to transepidermal water loss, leading to

xerosis and promoting colonization and secondary infection with Staphylococcus aureus,
which can enhance type 2 inflammation resulting in downregulation of FLG expression [8].
Patients colonized with S. aureus have higher total serum IgE levels, as well as higher
peripheral eosinophilia [9]. Children with early-onset, severe, persistent AD, and elevated
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levels of total and specific IgE antibodies, are at increased risk of developing asthma and
allergic rhinitis later in life [10, 11]. This may be due to the defective skin barrier in AD
permitting epicutaneous exposure of environmental antigens to a local skin milieu primed
toward type 2 immune responses [12, 13]. Cytokines, such as thymic stromal lymphopoietin
(TSLP) and IL-33, are released by keratinocytes when the skin barrier is disrupted,
activating dendritic cells to trigger an aberrant TH2-mediated immune response [5••].

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There is also evidence that early sensitization to foods or aeroallergens in the first year of
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life increase the risk of persistent AD and asthma [14–16]. In fact, food-induced AD flares
occur in one-third of infants and young children with moderate-to-severe AD, but are
uncommon in adults [17]. Infants with moderate-to-severe AD are also at high risk of food
allergy at 2 years of age, with studies demonstrating that percutaneous exposure to food
proteins is allergenic. In contrast, enteral exposure is tolerogenic [18–20]. As such, it is
believed that early optimal treatment of AD, would prevent epicutaneous sensitization,
which may halt or attenuate the atopic march including food allergies, though there is no
data to date to support this hypothesis.

It is important to note the timing of solid food introduction or withholding of allergenic

foods in both maternal and infant diets does not seem to have a protective effect against AD
[21]. However, clinical trials have shown that hydrolyzed protein formula, probiotic
supplementation, and early introduction of allergenic foods can be beneficial in preventing
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and improving AD in high-risk infants and children [22–28]. The Learning Early About
Peanut Allergy (LEAP) Study showed that food allergy can be avoided in this high-risk
population with moderate to severe AD [29••] by early introduction of peanut. This is an
effective and feasible method to prevent peanut allergy in high-risk atopic infants, without
negatively affecting nutrition and growth.

TREATMENT
Non-Pharmacologic Interventions
Topical Moisturizers—Moisturizers are the cornerstone of all AD regimens. Xerosis is
one of the main clinical features of AD, and results from a dysfunctional epidermal barrier
that leads to increased transepidermal water loss. Topical moisturizers combat xerosis
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through a combination of ingredients that maintain skin hydration, such as emollients (e.g.
glyceryl stearate, soy sterols) that lubricate the skin, occlusive agents (e.g. petrolatum,
dimethicone, mineral oil) that prevent water evaporation, and humectants (e.g. lactic acid,
urea, glycerol) that attract and hold water into the stratum corneum [30••].

There has been an abundance of evidence supporting emollient therapy in preventing and
treating pediatric AD. The predictions of one mathematical model of AD confirm that
emollient therapies reduce the ability of environmental stressors to cause TH2 sensitization
[31]. This was defined by a two-fold increase in minimum stress load needed to trigger
systemic TH2 sensitization and subsequent AD flares. Numerous clinical trials have
demonstrated efficacy of emollient therapy in preventing and decreasing the clinical
manifestations of AD, including pruritus, erythema, fissuring, and lichenification, in
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neonates, infants, and children [32–35•] and in adults [36–38]. In neonates, early moisturizer
intervention resulted in a decrease in the cumulative incidence of AD, with a relative risk
reduction of 50% [32•]. Moisturizers have a steroid-sparing effect on treatment of AD. This
was shown in three randomized controlled trials [34, 39, 40], and should be a component in
the regimen for moderate-to-severe disease. Moisturizers should also be used as
maintenance therapy in any AD regimen. There are currently no studies that define an
optimal amount or frequency of moisturizer application, although current guidelines from
the American Academy of Dermatology suggest liberal daily use of moisturizers [30••].

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Special considerations should be made in the treatment of neonates and infants, compared to
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that of adults. The skin of infants under the age of 2 years is characterized by a thinner
epidermis and stratum corneum, higher water content, increased transepidermal water loss,
high skin pH, and high desquamation and proliferation rates [41]. Infants have a high ratio of
body surface area to body weight, resulting in increased absorption of topical medications.
This translates to an increased need for moisturizers to combat skin water loss and lower
doses of topical medications.

Newer formulations of topical moisturizers containing ingredients that mimic components of

the epidermal barrier in distinct ratios have also been effective in treating pediatric AD.
These prescription emollient devices (PEDs) contain ingredients such as ceramide,
palmitoylethanolamide, glycyrrhetinic acid, and other hydrolipids and filaggrin breakdown
products that are reduced in levels in the skin of patients with AD. PEDs have been found to
be just as effective as over-the-counter moisturizers in reducing the clinical signs and
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symptoms of AD, in limited studies in children [42–47], and can be useful adjuncts to
topical corticosteroid therapy. However, they can be cost-prohibitive, and are mostly
available by prescription.

Bathing Practices and Additives—Daily bathing with warm water is beneficial in AD

therapy by hydrating the skin and removing serous crusts, allergens, and irritants [30••].
Cleansers should be hypoallergenic, fragrance-free, and neutral to low pH. This should be
followed by quick towel-drying by patting, and application of moisturizers to prevent
transepidermal water loss [48]. There is a paucity of evidence to determine the best bathing
practices, as most recommendations stem from personal experience. The “soak and smear”
technique of soaking in plain water for 20 minutes, followed by immediate and direct
application of topical corticosteroids, can be beneficial in severely inflamed lesions [49].
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There are no studies to support the use of bath additives, such as oils, emollients, and salts,
in treating AD.

Bleach Baths—The addition of dilute sodium hypochlorite in bath water, or bleach baths,
has demonstrated efficacy in clinically improving moderate-to-severe AD in children [50–
52] and has been recommended as a low-cost and effective adjuvant therapy in these patients
by the American Academy of Dermatology (AAD) and the American Academy of Allergy,
Asthma and Immunology (AAAAI). Bleach baths are thought to reduce skin inflammation
and thereby decrease colonization of Staphylococcus aureus bacteria on the skin. This can
be beneficial, as staphylococcal exotoxins are known to exacerbate AD [53]. However, one
recent study noted that bleach baths did not reduce S. aureus colonization/infection or
improve AD [54]. Common side-effects of bleach baths include exacerbation of xerosis and
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skin and nasal irritation.

Wet Wrap Therapy—Wet wrap therapy (WWT) is used to reduce disease severity in
children with significant AD flares and/or refractory disease. After a soaking bath, a wetted
layer of bandages, gauze, or a cotton suit is applied over a layer of topical corticosteroid or
emollient, followed by a dry outer layer [30••]. WWT serves to increase penetration of the
medication by occlusion, prevents patient scratching, and decreases epidermal water loss. In
our experience, a cotton suit, which covers hands and feet, works best as an outer layer, as

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this physically prevents scratching. In children with refractory AD, WWT improved AD
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severity in a number of studies, especially when used with corticosteroids versus emollients
[55, 56]. A recent systematic review revealed low evidence that WWT is more effective than
conventional treatment with topical corticosteroids in AD [57]. However, the review
included all ages and severities of AD.

Pharmacological Interventions
Topical Corticosteroids—Topical corticosteroids (TCS) are essential anti-inflammatory
agents in the management of AD. They reduce the production of pro-inflammatory
cytokines, interfere with antigen processing, and reduce the activity of immune effector
cells, thus lowering skin inflammation [30••]. TCS are typically administered when the skin
appears inflamed as evidenced by erythema, oozing, crusting, and/or lichenification. TCS
can also be used as maintenance therapy for prevention of relapses. TCS have been used to
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treat AD for over 60 years, and there are more than 110 different randomized-controlled
trials performed to date [30••]. Newer types of TCS are constantly being developed, each
with different potencies, vehicles, and excipients. Patient preference (vehicle, cost, and
availability), lesion site, and disease severity often drive selection in prescribing and
selecting potency of TCS. TCS are well-studied in pediatric patients, and have proven to be
safe and effective in reducing the clinical signs and symptoms of AD [58]. Fluticasone
propionate 0.05% cream, desonide 0.05% gel and foam, and hydrocortisone butyrate 0.1%
lotion are the only topical corticosteroids that are U.S. Food and Drug Administration (FDA)
approved for use in infants as young as three months of age.

TCS range in potencies and are grouped accordingly into seven classes, from very low/
lowest potency (VII) to very high potency (I) (Table 1) [59]. There are currently no
guidelines in optimal dosing and quantity of TCS application [30••]. Low potency (Class
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VII) TCS are generally applied to sensitive and thin areas, such as the face, skin folds, and
genitalia. Special considerations are needed when using topical therapies for children with
AD. Children have a proportionately greater body surface area to weight ratio, resulting in a
higher degree of absorption of topical agents. Higher potency TCS can be used in short-term
courses to rapidly control significant flares, but should be followed by a stepwise decrease in
potency and then tapered to the lowest effective potency for long-term management. This
minimizes the adverse effects of skin atrophy, telangiectasia, acne, and striae, which are
major concerns of parents of children with AD.

There have been multiple studies addressing the short and long-term safety of TCS in infants
and children. A recent systematic review of AD patients less than 12 years of age found that
the evidence supporting long-term TCS use is limited only to low- to mid-potency agents,
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and there was a lack of data supporting the use of long-term monotherapy with mid- to high-
potency TCS in pediatric AD [60]. In fact, continuous, long-term application of high- and
very high-potency agents can lead to significant systemic absorption and increased risk of
systemic adverse effects, such as hypothalamic-pituitary-axis (HPA) suppression, especially
in children concurrently receiving other forms of steroids for asthma [61]. Some
observational studies reported growth delay and abnormal bone turnover in children treated
long-term with TCS for AD, but others have not [62–64]. Sustained, long-term use of a mid-

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potency TCS with one to twice weekly application did not demonstrate adverse effects in a
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clinical trial [65], and one systematic review concluded a good overall safety profile of TCS
[66]. A recent cross-sectional observational study of children with AD on long-term TCS
(weak, moderate, and potent) showed no rates of skin atrophy, both in the TCS treatment
group and in the control group [67]. Nonetheless, allaying parental fears of TCS use in
children is essential in maintaining adherence and appropriate use, which decreases the risks
of adverse effects and relapse [68, 69].

Topical Calcineurin Inhibitors—Topical calcineurin inhibitors (TCIs) are anti-

inflammatory agents and bacteria-derived macrolides that bind intracellular protein
macrophilin-12 (FK-binding protein) and prevents translocation of the nuclear factor of
activated T cells (NFAT), which reduces the expression of T cell activation cytokines, in
particular IL-2 [70]. TCIs do not cause skin atrophy, telangiectasia, and striae, as do potent
TCS, and are effective both as steroid-sparing agents and agents in the treatment of AD
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lesions on the eyelids, face, and skin folds. They are the only FDA-approved treatment for
chronic AD, and are typically prescribed to patients where long-term use of TCS increases
the risk of steroid-related side-effects. Two TCIs are available: Tacrolimus (Protopic) is
available as a 0.03% (approved for children 2 years of age and older) or 0.1% ointment
(approved for children over 16 years of age), and Pimecrolimus (Elidel) is available as a 1%
cream (approved for use in children 2 years of age and older). However, both agents have
been shown in studies to effectively treat AD in infants [71]. Tacrolimus is indicated for
moderate-to-severe AD, although tacrolimus 0.03% has shown efficacy and safety in
pediatric patients with mild-to-moderate AD [72]. Pimecrolimus is indicated for mild-to-
moderate AD [30••]. The FDA’s Pediatrics Advisory Committee issued a black box warning
of cancer risk for topical tacrolimus and pimecrolimus. However, this is mostly a theoretical
risk of malignancy, as most cancers have been seen only with oral tacrolimus use in
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transplant patients [73]. The FDA recommended the medications be avoided for children
younger than age 2. However, since this warning, a number of studies have failed to
demonstrate this causation, and incidence of malignancy in the treated population is similar
to that of the general population [73]. In infants and children with active lesions, both agents
have been shown to be more effective than vehicle in short-term (3 to 12 weeks) and long-
term (up to 12 months) studies [74–79]. Two systematic reviews have shown that TCIs and
TCS have similar efficacy [80, 81••] , though TCIs had a higher incidence of skin irritation
and pruritus, and may cause stinging and burning. TCIs are also often combined with TCS to
control flares, prevent relapse, and spare topical steroid use. TCIs used concomitantly with
TCS have been shown to be more effective than TCI and vehicle or use of either agent alone
[82].
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PDE4 Inhibitor—Crisaborole ointment, a non-steroidal phosphodiesterase 4 (PDE4)

inhibitor, was recently approved by the FDA to treat mild-to-moderate AD in patients 2
years of age and older. PDE4 is a regulator of the cyclic adenosine monophosphate (cAMP)
pathway at an intracellular level to reduce cytokine production of immune effector cells
[83•] . Crisaborole has been shown to be effective and with a favorable safety profile in two
phase III AD studies [83•] . Common side-effects included stinging and burning upon
application.

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Systemic Immunosuppressants
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Systemic immunosuppressants, such as cyclosporine, azathioprine, mycophenolate, and

methotrexate, are administered off-label in the management of chronic and/or moderate-to-
severe AD refractory to topical conventional treatments. These therapies are not FDA
approved for use in AD; and have multiple associated toxicities. However, they may be
effective in children with severe AD, in conjunction with aggressive use of moisturizers and
topical agents.

Cyclosporine—Cyclosporine A (CSA) is a calcineurin inhibitor that inhibits T cell

activation and IL-2 production. CSA can be administered as both short-term and long-term
therapy in severe pediatric AD (ages 2–16 years) [84]. However, CSA has been linked to
lower bone mineral density in children [85]. Dosing guidelines in the pediatric population
recommend 3–6 mg/kg/day, and 150–300mg/day in adults. Patients should be monitored for
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side-effects, which include infection, nephrotoxicity, hypertension, tremor, hypertrichosis,

headache, gingival hyperplasia, and increased risk of skin cancer and lymphoma [86••].

Azathioprine—Azathioprine (AZA) is a purine analog that inhibits DNA production,

affecting cells with high proliferation rates, such as immune effector cells during active
inflammation. Although it is FDA-approved for rheumatoid arthritis and renal transplant
rejection prophylaxis, AZA has also been used off-label for severe recalcitrant AD. In a
retrospective study of AZA use in severe pediatric AD, 28/48 children had an excellent
response to treatment and 13/48 had a good response [87]. AZA is metabolized by
thiopurine methyltransferase (TPMT), and baseline TPMT activity levels should be
measured in children before administration of the drug. The same study showed that children
with higher TPMT levels responded less well to treatment and had a greater risk of
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hepatotoxicity, while children with lower TPMT levels responded more favorably, but had an
increased risk of myelosuppression [87]. More common adverse effects include nausea,
vomiting, and gastrointestinal symptoms, which may cause the child emotional distress and
result in medication non-compliance. Pediatric dosing varies, but most studies recommend
2.5 mg/kg/day with a maximum of 4 mg/kg/day [86••] . The dose is gradually titrated up to
minimize nausea and vomiting.

Methotrexate—Methotrexate (MTX) is an anti-folate metabolite that blocks DNA

synthesis. It is used in a variety of inflammatory dermatological diseases, such as psoriasis
and cutaneous lupus erythematosus. There was only one prospective study on MTX use in
children with severe AD, and it compared MTX to CSA [88]. The same considerations in
safety and dosing apply for pediatric patients, as in adult patients. Dosing varies greatly with
the patient, and is based on the psoriasis dose regimen (0.2–0.7 mg/kg/week) [86••] .
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Common side-effects include nausea, vomiting, and stomatitis. Patients should be monitored
for severe and potentially irreversible side-effects, such as bone marrow suppression and
pulmonary fibrosis.

Mycophenolate Mofetil—Mycophenolate mofetil (MMF) is an immunosuppressant drug

that inhibits B and T cell growth and proliferation. MMF has been used as monotherapy in
children with severe refractory AD aged 2 years and older, without significant adverse

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effects [89]. Dosing in children (600–1200 mg/m2) is adjusted for increased hepatic
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metabolism in the pediatric population. Although there are currently no long-term efficacy
and safety studies examining the use of MMF in pediatric AD; in one study, use in children
for up to 24 consecutive months did not demonstrate significant adverse effects. Common
side-effects include nausea, vomiting, and abdominal cramping [86••] .

Systemic Corticosteroids—Systemic corticosteroids (prednisone, prednisolone, and

methylprednisolone) should generally be avoided in children with AD, as the risks of
treatment outweigh the benefits [86••]. Risks include severe rebound flares and increased
disease severity when systemic corticosteroids are weaned or stopped. Additionally,
hypertension, glucose intolerance, weight gain, adrenal suppression, increased infections,
and decreased bone density are also common with chronic use. Pediatric patients are at risk
of decreased linear growth, which can be long-term [90]. There is little evidence to support
use of systemic steroids in AD; in one double-blind, placebo-controlled trial, only one
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patient out of 27 taking prednisolone achieved durable remission after two weeks of oral
steroid therapy [91]. The study was also prematurely discontinued due to significant rebound
flaring in the steroid group. Dosing is generally 0.5–1.0 mg/kg, and steroids must be
carefully tapered to decrease the risk of adrenal suppression and severe AD flare [86••].
Pediatric patients on systemic steroids require blood pressure monitoring, growth-velocity
measurements, ophthalmologic examination, and hypothalamic-pituitary-adrenal axis
suppression testing [86••].

Interventional Procedures
Phototherapy—The usefulness of ultraviolet (UV) light plus oral psoralen in the treatment
of AD has been documented since the late 1970’s [92]. Since then, a variety of light therapy
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have been used as short-term treatment of AD, including natural sunlight, narrow-band
ultraviolet light B (NB-UVB), broad-band ultraviolet light B (BB-UVB), ultraviolet light A
(UVA), topical and systemic psoralen plus UVA (PUVA), and ultraviolet light A and B
(UVAB) [86••] . NB-UVB is the most commonly recommended light therapy, due to its
efficacy, availability, and low risk of side-effects. Phototherapy is generally recommended in
the treatment of AD refractory to conventional topical medications, and can be used as
monotherapy or in combination with TCS. Use with TCIs is not recommended. In children,
phototherapy has demonstrated efficacy and safety in multiple studies [93–95]. Various
lasers (e.g. excimer, diode, and pulse dye) and extracorporeal photochemotherapy (ECP) are
additional modes of treatment for AD; the latter is used in generalized and erythrodermic
AD patients [86••] . There is a theoretical increased risk of skin cancer with long-term
phototherapy, due to exposure to UV light. Although one large study found no significant
association between NB-UVB therapy and skin cancer, treatment with PUVA was found to
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have a slight increase in incidence of basal cell carcinoma [96].

Emerging Therapies
Several promising agents are currently under investigation in the treatment of AD. These
agents, including biologics, are not currently FDA-approved for use in children, though there
are ongoing studies examining their use in pediatric populations.

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Topical Lipoxin—Lipoxins are endogenous, anti-inflammatory molecules derived from

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the metabolic breakdown of arachidonic acid. These molecules are activated during
inflammation and inhibit the production of pro-inflammatory cytokines, such as IL-12,
IL-13, and various leukotrienes [97]. In a study of infantile AD, topical 15(R/S)-methyl-
lipoxin A4 (LXA4) significantly reduced disease severity, induced remission, and improved
quality of life. This was a randomized, double-blind, placebo-controlled, parallel-group trial
of patients 1–12 months of age with varying disease severity that compared the lipoxin
cream with mometasone furoate cream, a mid-potency topical steroid [98]. Extent and rate
of recovery were similar to that of patients in the 0.1% mometasone furoate cohort.

Omalizumab—Another biologic that has been used off-label in pediatric AD is

omalizumab, a humanized monoclonal antibody that binds to free IgE and surface-bound
IgE on mast cells and basophils. A case series of seven patients (aged 6–19 years) with
severe AD demonstrated clinical improvement of symptoms after 3 to 6 months of treatment
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[99]. A recent systematic review, however, stated no concrete evidence of the effectiveness
of omalizumab as a treatment for AD [100].

Recombinant Interferon Gamma—Several studies have examined the use of

subcutaneous recombinant interferon gamma (rIFN-γ) in AD. IFN-γ is a cytokine that is
involved in innate and adaptive immunity. In the first double-blind, placebo-controlled trial
of rIFN-γ in moderate-to-severe AD in children and adults, rIFN-γ was found to have an
age-related, improved clinical response in the pediatric cohort versus adults. 67% of children
ages 3 to 20 reported greater than 50% improvement, compared to 56% of adults ages 21–40
and 44% of adults ages 41–65 [101]. Side-effects included flu-like symptoms, transient
transaminase elevation, and granulocyte suppression [102].
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Dupilumab—Dupilumab, a fully human monoclonal antibody against interleukin-4

receptor alpha, is a biologic that was recently FDA approved for use in adults with
moderate-to-severe AD. Dupilumab blocks signaling from two key cytokines in the TH2
inflammatory pathway, IL-4 and IL-13. In Phase III trials, significantly more patients treated
with 300 mg bi-weekly showed 75% improvement in Eczema Area and Severity Index
(EASI) from baseline compared with the placebo group [103]. In addition, treatment
resulted in improvement of other endpoints, including pruritus, symptoms of anxiety, and
depression, and quality of life. A Phase 2a, open-label trial of 78 children and adolescents,
ages 6–18, with moderate-to-severe AD (NCT02407756) demonstrated mean improvement
of pruritus and EASI scores, especially in the younger cohort, at increasing subcutaneous
doses (from 2–4mg/kg) [104•]. Dupilumab is a promising therapy in AD and is expected to
alter future management of the disease towards a more personalized approach. Though its
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use is currently only approved in adults, it may benefit the younger pediatric population once
studied and found to be safe in children.

CONCLUSION
Early treatment of AD in children can delay or prevent the atopic march. Although the
pathogenesis of AD is multivariate and complex, therapeutic interventions target two major
areas of dysfunction: 1) the defective skin barrier leading to early sensitization to allergens

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and 2) the dysfunctional skin immune response to allergens and irritants. Topical
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moisturizers and topical anti-inflammatory medications are the cornerstones of AD

treatment regimens. Although there are a wide variety of both moisturizers and topical
corticosteroids, any combination of both with gentle skin care can effectively control most
mild-to-moderate AD lesions. Moderate-to-severe and recalcitrant AD, however, may
require the addition of phototherapy or systemic medications. Special considerations are
made for pediatric patients, as severe adverse effects of systemic medications and high-dose
topical corticosteroids must be weighed against the benefits of treatment. Emerging
therapies, such as crisaborole and dupilumab, are welcome additions to the current arsenal of
treatments for AD.

References
Papers of particular interest, published recently, have been highlighted as:
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• Of importance

•• Of major importance

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Table 1

Topical Corticosteroid Potencies, Strengths, and Formulations,

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Class I: Superpotent/Very High Potency Class IV: Mid-Strength/Medium Potency

Betamethasone dipropionate (ointment) Desoximetasone, 0.05% (cream, ointment)

Clobetasol propionate, 0.05% (cream, ointment, solution, spray, shampoo) Fluocinolone acetonide, 0.03% (ointment)
Clobetasol propionate (foam) Flurandrenolide, 0.05% (ointment)
Desoximetasone, 0.25% (spray) Hydrocortisone valerate, 0.2% (ointment)
Diflorasone diacetate, 0.05% (ointment) Mometasone furoate, 0.1% (cream)
Fluocinonide, 0.1% (cream) Triamcinolone acetonide, 0.1% (cream, spray)
Flurandrenolide, 0.05% (Cordran Tape)
Halobetasol propionate, 0.05% (cream, ointment, lotion)

Class II: Potent/High Potency Class V: Lower Mid-Strength/Lower-Medium Potency

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Betamethasone dipropionate, 0.05% (cream) Desonide, 0.05% (lotion)

Desoximetasone, 0.25% (cream, ointment) Fluocinolone acetonide, 0.03%/0.01% (cream)
Desoximetasone, 0.05% (gel) Fluocinolone acetonide, 0.01% (shampoo)
Diflorasone diacetate, 0.05% (cream, ointment) Flurandrenolide, 0.05% (cream, lotion, tape)
Fluocinonide, 0.05% (cream, gel, ointment) Fluticasone propionate, 0.05% (cream, lotion)
Halcinonide, 0.1% (ointment, cream) Hydrocortisone, 0.1% (cream, lotion, ointment, solution)
Mometasone furoate, 0.1% (ointment) Hydrocortisone valerate, 0.2% (cream)
Prednicarbate, 0.1% (cream)

Class III: Upper Mid-Strength/Medium Potency Class VI: Mild/Low Potency

Betamethasone valerate, 0.12% (foam) Alclometasone dipropionate, 0.05% (cream, ointment)

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Fluocinonide, 0.05% (cream) Desonide, 0.05% (gel, foam)

Fluticasone propionate, 0.005% (ointment) Fluocinolone acetonide, 0.01% (cream, solution, oil)

Class VII: Least Potent/Lowest Potency

Hydrocortisone, 0.5%/1% (lotion)

Hydrocortisone, 1%/2.5% (cream, lotion)
Hydrocortisone, 2%/2.5% (cream)
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Curr Treat Options Allergy. Author manuscript; available in PMC 2018 September 01.