Atopic dermatitis (AD) is a bothersome and common skin disease affecting ∼10.7% of children in the United States. This skin condition significantly decreases quality of life in not only patients, but in their families as well. Pediatricians are often the first physicians to diagnose and manage these patients and thus are relied on by families to answer questions about this disease. AD is complex, multifactorial, and has historically had limited therapeutic options, but the landscape of this disease is now rapidly changing. Pathways contributing to the pathogenesis of this disease are continually being discovered, and new therapies for AD are being developed at an unprecedented rate. With this article, we will review the current guidelines regarding the management of AD, outline updates in the current understanding of its pathophysiology, and highlight novel developments available for the treatment of this burdensome disease.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects ∼10.7% of children in the United States1 and is becoming increasingly prevalent.2,4 Pediatricians are often the first physicians providing treatment to patients with new-onset AD and disease flares,5 and ∼50% of patients with AD are treated in a primary care setting.6 Therefore, pediatricians play a key role in the overall management of patients with AD and should be well informed about recent developments in the clinical management of this disease.7 

Despite its high prevalence, this complex disease has historically been poorly understood. With this article, we provide an update on recent advances in our understanding of the clinical presentation and pathophysiology of AD and highlight new therapeutic developments for this disease.

AD is a bothersome skin condition often referred to as the “itch that rashes” because of the pruritus that patients experience. This hallmark symptom of AD is responsible for its significant negative impact on quality of life (QoL).8 Patients with AD often present with severe pruritus and xerosis, with variable lesion distribution based on age. Young infants up to 2 years of age often present with scaly, crusted erythematous patches on the scalp, face, and extensor surfaces, whereas prepubertal children present with erythematous patches in a flexural distribution.9 Adolescents and adults typically present with more lichenified skin changes.

The progression of AD is unpredictable, but the following 4 phenotypes have recently been identified: early-onset transient (9.2% of children), early-onset persistent (6.5%), late-onset (4.8%), and absent or infrequent AD (79.5%).10 Patients with AD have alternating periods of exacerbated disease and symptom resolution. Thus, both the alleviation of symptoms and prevention of flares are important in the management of AD.

Patients commonly present during acute flares with intense pruritus, xerosis, erosions, excoriations, and ill-defined patches of erythema with a distribution that varies with age.7,11 AD is clinically diagnosed on the basis of history, morphology, distribution of skin lesions, and associated clinical signs.11 Other important factors suggesting a diagnosis of AD include early onset (<2 years of age), atopy, and family history of disease.11,12 This diagnosis should be reevaluated frequently, particularly in patients not responding to appropriate treatment, to verify the accuracy of this diagnosis and exclude the possibility of other conditions, such as scabies, contact dermatitis, psoriasis, tinea infections, or viral exanthems.7,13 

AD is thought to “kick off” the atopic march, predisposing patients to other atopic disorders later in life.14,15 Patients with AD with early sensitization to foods have an increased risk of developing asthma, allergic rhinitis, and food allergies.16 Therefore, early diagnosis and management of AD and its associated risk factors may reduce the risk of developing other allergic diseases and improve overall QoL.16 

AD has been associated with an increased risk of developing a peanut allergy specifically,17 but previous clinical practice guidelines on food allergy prevention were constantly changing. Most recently, the Learning Early About Peanut Allergy trial revealed that an early introduction of peanut-containing foods reduces the risk of developing a peanut allergy in high-risk patients, including infants with severe AD.18 Current consensus guidelines recommend an introduction of peanut-containing foods such as peanut butter or peanut puffs as early as 4 months of age to patients with AD to reduce this risk of future allergy.19,20 

Children with AD have significant cutaneous immune dysregulation and an impaired skin barrier, which contribute to an increased susceptibility of developing skin infections.21,22 Because of a decreased antimicrobial peptide expression,23 >75% of affected children are colonized by Staphylococcus aureus, compared with <25% of healthy children in control groups.24Staphylococcus colonization worsens inflammation and pruritus,24 increasing the risk of colonization and/or superinfection with Streptococcus pyogenes, viruses, or fungi.21 AD can also predispose patients to disseminated eczema herpeticum and molluscum contagiosum outbreaks.21 

Currently well-known comorbidities of AD are mostly atopic, but AD may have a broader impact on health. Authors of recent studies have shown that patients with AD are more likely be obese25,26 and have elevated serum cardiovascular risk markers than healthy patients,27 contributing to increased cardiovascular disease risk.28,30 However, severe AD in children and adolescents has also been associated with impaired growth and short stature.31,34 Patients with AD are also at an increased risk of developing depression, anxiety, attention-deficit/hyperactivity disorder, and conduct disorder,35,37 with risk correlated with AD disease severity.35 AD is not just skin deep, and management should be used to address the comorbidities, in addition to skin symptoms, associated with this systemic disease.

Although skin disease is often perceived to be relatively benign, children with generalized AD report QoL deficits similar to that of children with other serious chronic diseases, including renal disease and cystic fibrosis.38,39 Because of the ever-present nature of the itch–scratch cycle, AD can be extremely burdensome and infringe on all areas of affected patients’ lives, including sleep, social functioning, work productivity, and income.

AD has a well-characterized negative impact on sleep in children40,41 and their families42 because of debilitating pruritus and the constant care needed for this disease. Children with moderate-to-severe AD experience more restless sleep, increased waking, greater difficulty falling asleep, and increased daytime sleepiness compared with healthy patients; these are behaviors that worsen with the severity of AD and with flares.21,43 Parents of affected children also experience significant sleep loss (∼1–3 hours per night) while providing overnight care to soothe their children and help them return to sleep.42,44 The severity of sleep disruption associated with AD is comparable to that of other chronic conditions requiring constant care, including autism spectrum disorder, mental retardation, and seizure disorders.45 An effective treatment plan is necessary to minimize the QoL impairment because of poor sleep in both affected patients46 and their families.47 

AD affects children during critical stages of childhood development, causing significant QoL impairment at ages when patients are most vulnerable. Children with AD can be severely impacted by fear of embarrassment46,48 and constant anxiety about future flares.49 Patients with AD are often socially isolated and bullied because of the fear of contagion and stigma,50 leading to poor self-esteem in these young and impressionable patients.51 As a result, patients with AD often withdraw socially, avoid group activities, or may even skip school to prevent further embarrassment.46,52 Affected patients will often also have impaired concentration because of sleep loss, antihistamine sedation, and irresistible itch, which, combined with stunted social development and missed school time, may decrease scholastic achievement and ultimately diminish future career prospects.46,49,52,54 

Additionally, AD is economically burdensome, costing the United States $5.3 billion in 2004,55 a number that will likely rise with the rapidly increasing price of topical corticosteroids (TCSs).56 In 1 study, families of affected patients spent 34.8% ($274) of their available monthly income on AD care, which can be a significant financial burden especially for low-income families.57 Caregivers for patients with AD often miss work to care for their children’s health issues,42 which can contribute to impaired work performance and decreased income. It is important for pediatricians to be aware that the negative impact of AD on the QoL for patients and their families is multimodal. Skin symptoms represent a small portion of the negative impact of AD, which also profoundly affects sleep, childhood development, and finances.

The pathogenesis of AD involves a complex interplay of immunologic dysfunction, genetics, environmental exposures, and skin barrier disruption. Loss-of-function filaggrin gene mutations were implicated early on as a major predisposing risk factor for AD,58 suggesting skin barrier defects to be key drivers of this disease. However, authors of more recent research have found that filaggrin is deficient in most affected adults regardless of genotype59 but not in patients with new-onset AD.60 Therefore, filaggrin deficiency is not necessary for disease onset but may be a downstream result of disease chronicity. Authors of recent findings have also found skin barrier disruption to occur early in life, with increased neonatal transepidermal water loss predicting future development of AD.61 Nevertheless, most recent developments with respect to therapeutics and pathogenesis of this multifactorial condition have been in the understanding of the immunology of this disease.

However, much of the current understanding of AD immunology is based on studies in adults, who present different clinically and have a longer duration of disease than pediatric patients. Given that the immune system changes with age,62 findings in adults may not represent the immunologic processes occurring in children. Authors of recent studies have characterized immunologic differences in AD observed with age,63 ethnicity,64 and disease subtype,65 suggesting that several distinct inflammatory mechanisms likely contribute to this complex, heterogeneous skin disease. Significant recent advances have increased our understanding of the underlying mechanisms of both adult and pediatric AD, contributing to the development of novel therapies for this complex disease.

AD has historically been described as a biphasic T-cell–mediated disease, in which an initial T helper (Th) 2 (Th2) activation drives acute disease, whereas a later Th1 response maintains chronic AD.66 Authors of recent studies corroborate the role of early Th1 axis suppression in this disease, finding low Th1 T-cell levels in acute AD lesions in adults67 and children recently diagnosed with AD.63 However, chronic AD lesions reveal intensification, rather than withdrawal, of Th2-related inflammation.67 Strong activation of the Th2 and Th22 inflammatory responses are observed in the lesional skin of both children and adults with AD, but affected children demonstrate greater induction of the Th17 axis to levels comparable to that of patients with psoriasis.60 Interestingly, the nonlesional skin of young children60 and adults68 also already harbors significant inflammation with increased Th2 and Th17 expression, suggesting that AD involves early systemic involvement. Thus, the progression of AD may not be as clear-cut as previously thought.

Despite major immunologic similarities to AD in adults, pediatric AD also reveals features that may be unique to new-onset disease. The skin of affected children reveals T-cell predominance as compared with healthy children and affected adults, implicating T-cell activation as a key driver of early AD.69 Additionally, these children exhibit lymphocyte distributions similar to that of healthy adults, implying that accelerated lymphocyte development may play a role in disease initiation.69 The lesional skin of affected children also uniquely reveals gene expression more similar to psoriatic lesions than that of adult AD or healthy pediatric skin, which may have implications for future treatment.60 Significant inroads are being made to understand the pathogenesis of both adult and pediatric AD and the overlap and differences between the 2, which may help guide the development of future, more targeted therapies.

Although various additional pathways contribute to AD, the Th2 immune response remains the main focus of AD pathogenesis and therapeutic development. Th2 cells are the main producers of Th2 cytokines interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in AD, but type 2 innate lymphoid cells (ILC2s), found in increased numbers in lesional AD skin,70 have recently been characterized as an additional source of Th2 cytokine release.70,72 The recent discovery of these cells in AD may link several abnormalities known to occur within AD and may serve as a target for new therapies in the near future.

ILC2s express killer cell lectin-like receptor G1, which normally binds E-cadherin to inhibit ILC2 proliferation and IL-5 and/or IL-13 production.70 E-cadherin is normally expressed by epidermal cells but is downregulated in AD73 and patients with filaggrin deficiency.70 Because barrier dysfunction is a key pathogenic factor for AD, this model provides a novel barrier-sensing mechanism that contributes to the pathogenesis of AD.

Additionally, ILC2s proliferate in response to elevations in thymic stromal lymphopoietin (TSLP), a pro-inflammatory cytokine produced by epithelial cells in response to stress74 found at increased levels in AD skin lesions.75 TSLP selectively increases basophil hematopoiesis and promotes peripheral basophilia.76 These basophils subsequently release IL-4, causing ILC2s to proliferate in an IL-4–dependent manner.77,78 ILC2s release IL-5 and IL-13, further contributing to the upregulated Th2 response observed in AD. IL-13 also upregulates TSLP release by keratinocytes, creating a positive feedback loop for the worsening of AD.79 However, the role of ILC2s specifically in AD pathogenesis is poorly understood and in the early stages of investigation. Further characterization of the mechanisms of AD-related immune dysfunction will aid the development of future therapeutics.

AD is often managed successfully in the pediatric primary care setting with topical agents, but recalcitrant disease has been historically difficult to address because of a lack of approved second-line therapies for AD.80 However, great strides have been made recently in the development of treatments for AD.

The basic management of AD has not changed significantly in recent years, still centering around gentle skin care and the prevention of disease exacerbation.7,81 Skin hydration and liberal use of moisturizers is essential for all patients with AD both during flares and for maintenance, because skin barrier disruption in this disease results in xerosis and increased transepidermal water loss.82 Adequate moisturization significantly decreases AD symptoms, including pruritus83 and lichenification,84 and decreases the amount of prescription medications needed for treatment.85,87 In fact, applying moisturizer to neonates with a family history of AD reduces the risk of future development of the disease88,89 and should be considered for patients at high risk of developing atopic disease.

Trigger avoidance is also important to prevent recurrent symptoms or disease worsening. A careful history should be taken to characterize relationships between suspected triggers and skin symptoms. Age can be used to guide the discussion of likely triggers (ie, younger children are more likely to have a food allergy than older children, who are more often triggered by aeroallergens).90 Indiscriminate allergy testing without a history that suggests allergic triggers is not recommended, because these tests have low positive predictive values.90 Skin-prick or specific immunoglobulin E testing should only be done when there is a high clinical suspicion of allergy-induced dermatitis.90 If patients are found to have trigger-induced disease exacerbation, trigger avoidance can greatly decrease the frequency and severity of flares.90 

Acute management of AD is largely focused on controlling pruritus, which is responsible for significant QoL impairment. Acute flares are often managed with topical therapies, but oral antihistamines may provide additional benefit in certain situations.91 Nonsedating antihistamines are not recommended for routine treatment of AD, but short-term use of first-generation antihistamines such as diphenhydramine, in combination with topical therapies, may be helpful for patients with sleep loss secondary to itch because of their sedative effect.91 Young patients should be monitored for paradoxic excitation, a sign of antihistamine toxicity that occurs at higher rates in children.92,93 Sedating therapies should only be used short-term,94 because long-term use can be detrimental to school performance.95,96 

Although their clinical evidence is conflicting,97 bleach baths are recommended for patients with moderate-to-severe AD with signs of secondary bacterial infection because of their presumed antistaphylococcal and antiseptic properties.82 These may also be useful for maintenance treatment of patients suffering from recurrent infections to decrease bacterial colonization and the risk of secondary skin infection and to improve disease severity.7,24,98 These patients should bathe twice weekly in 0.005% sodium hypochlorite (∼0.5 cups of 6% bleach in a full bathtub of water [∼40 gal])24 but may use bleach baths daily if they have severe disease.7 Intranasal mupirocin and sodium hypochlorite cleansers may provide additional benefit,24,99 but consensus guidelines for these have not yet been developed.100 

Vigilant skin care and trigger avoidance may often be sufficient for patients with mild disease, but patients with symptoms not adequately managed by these measures require further pharmacologic interventions, including topical and systemic agents.82 

The recommended first-line pharmacologic therapy for AD continues to be TCSs,81,82,101 which have proven to be effective for children over several decades. However, TCS phobia remains a significant concern for patients102 and providers,103 and is a significant source of treatment nonadherence.102,104 AD persists on average for 6.1 years and can be active well into adulthood for some patients,105,106 so physicians often fear long-term TCS effects such as skin atrophy, striae development, or systemic effects. This has resulted in an increased use of second-line treatments, such as the topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus, in the management of pediatric AD.107 However, TCIs are associated with increased rates of burning sensations and pruritus and have higher costs, with no additional benefit over TCSs with respect to long-term safety or efficacy.101 Thus, TCSs, when used appropriately, are a safe and effective first-line option for the treatment of pediatric AD.82,108 

As the underlying mechanisms of AD have become better understood, new topical therapies have been developed for AD, most notably crisaborole. Crisaborole is a topical phosphodiesterase-4 (PDE-4) inhibitor approved in 2016 for the treatment of mild-to-moderate AD for patients ≥2 years of age.109 PDE-4 inhibition inhibits intracellular cyclic adenosine monophosphate degradation, ultimately decreasing pro-inflammatory cytokine release via downregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway.110 Two phase III trials revealed that nearly one-third of patients using twice-daily crisaborole therapy for 28 days demonstrated Investigator’s Static Global Assessment of clear or almost clear with at least a 2-grade improvement from baseline, significantly more than patients applying vehicle ointment (AD-301: 32.8% vs 25.4%; P = .038; AD-302: 31.4% vs 18.0%; P < .001).110 Notably, crisaborole is well tolerated by patients in the short-term110 and the long-term (48 weeks).111 Application-site burning and/or stinging was experienced by 4.4% of patients in the first 4 weeks,110 with decreased incidence over time.111 A far greater proportion of patients experience stinging in the authors’ clinical experience, but crisaborole still provides a fairly well-tolerated, albeit expensive, nonsteroidal alternative to TCSs and TCIs for the management of mild-to-moderate adult and pediatric AD (Fig 1).

FIGURE 1

Guide to site-based topical therapies for AD. (Adapted with permission from Bhutani T, Kamangar F, Cordoro KM. Management of pediatric psoriasis. Pediatr Ann. 2012;41[1]:e13.)

FIGURE 1

Guide to site-based topical therapies for AD. (Adapted with permission from Bhutani T, Kamangar F, Cordoro KM. Management of pediatric psoriasis. Pediatr Ann. 2012;41[1]:e13.)

Close modal

Several other topical PDE-4 inhibitors have completed phase II studies and have revealed efficacy for AD.112,113 An ointment preparation of tofacitinib, a Janus kinase inhibitor, also significantly improved AD severity and pruritus in a phase II trial.114 Other topical agents being investigated for AD include toll-like receptor antagonists, serotonin inhibitors, aryl hydrocarbon receptor agonists, and leukotriene antagonists.115,117 Clinical trials are currently ongoing to investigate the efficacy and safety of crisaborole for patients 3 months to 2 years in age (NCT03356977).

Safe usage of topical therapies requires a careful and deliberate approach. Patients generally should be treated with the least potent TCS that is effective, to minimize the risk of TCS-related side effects.82 TCSs have greater penetration in sensitive and occluded areas such as the face, neck, and skin folds, so lower potency or nonsteroidal agents should be used in these areas to decrease the risk of systemic corticosteroid absorption (Fig 1).118 Long-term use of high-potency TCSs should be avoided in pediatric patients, because of the increased risk of atrophy and striae as patients grow.118 Because AD often persists for years, long-term maintenance management should alternate TCSs with nonsteroidal agents such as TCIs or crisaborole as appropriate to reduce the risk of treatment-related side effects.

Another important consideration in selecting topical therapies is vehicle choice. Children notoriously have poor adherence to topical medications,119 so physicians must prescribe treatments their patients will actually tolerate and use. Ointments are considered the most efficacious vehicle because of their occlusive nature and are well tolerated by infants and young children.120 However, adolescents often dislike the greasy feel and thus avoid using ointments during the daytime.118 Physicians must aim to optimize treatment adherence and may compromise by recommending nighttime ointment use while suggesting daytime application of thinner vehicles, such as creams or lotions.118 However, choosing topical therapies requires a personalized approach, and vehicle selection should be evaluated on a case-by-case basis.

Because of a historic lack of safe and efficacious options, the threshold for considering the initiation of systemic therapies has traditionally been high.121 UV-B phototherapy is a safe and effective treatment, without increased skin cancer risk, for patients with AD uncontrolled by topical agents.91,121,123 However, phototherapy can be inconvenient, requiring 2 to 3 treatments per week for several months. Patients deriving minimal benefit from phototherapy should consider systemic therapy. Traditionally, azathioprine, cyclosporine, methotrexate, and mycophenolate were the only systemic therapies that were efficacious for recalcitrant AD,121 but these therapies are associated with potentially serious side effects and require close monitoring (Table 1). Because these medications are not frequently used by pediatricians in the outpatient setting, physicians may be hesitant in using them to treat patients with pediatric AD.

TABLE 1

Off-label Systemic Therapies for the Treatment of AD in Children

DrugDoseSide EffectsMonitoring
Azathioprine 1–4 mg/kg per d Myelosuppression, nausea, vomiting, hepatotoxicity Baseline TPMT levels, CBC, CMP 
Cyclosporine 2.5–6 mg/kg Hypertension, renal insufficiency CBC, CMP, Mg2+, uric acid, lipids, blood pressure 
Dupilumab 2–4 mg/kga Conjunctivitis, injection-site reactions None 
Methotrexate 0.2–0.7 mg/kg per wk Nausea, ulcerative stomatitis, hepatotoxicity, myelosuppression CBC, CMP 
Mycophenolate mofetil 20–50 mg/kg daily Nausea, vomiting, abdominal cramping CBC, CMP 
DrugDoseSide EffectsMonitoring
Azathioprine 1–4 mg/kg per d Myelosuppression, nausea, vomiting, hepatotoxicity Baseline TPMT levels, CBC, CMP 
Cyclosporine 2.5–6 mg/kg Hypertension, renal insufficiency CBC, CMP, Mg2+, uric acid, lipids, blood pressure 
Dupilumab 2–4 mg/kga Conjunctivitis, injection-site reactions None 
Methotrexate 0.2–0.7 mg/kg per wk Nausea, ulcerative stomatitis, hepatotoxicity, myelosuppression CBC, CMP 
Mycophenolate mofetil 20–50 mg/kg daily Nausea, vomiting, abdominal cramping CBC, CMP 

CBC, complete blood count; CMP, complete metabolic panel; Mg2+, magnesium ion; TPMT, thiopurine methyltransferase.

a

The dose used in the phase 2a trial is not currently approved for pediatric use.

Despite these potential side effects, the “cost of not treating” should be a key consideration in selecting treatment for patients. AD is often thought of as “just a skin disease,” but it is also associated with significant comorbidity and QoL deficits, as discussed previously. This disease typically affects patients during critical stages of development, and abnormal development may ultimately cause lifelong impairment. Pediatric providers must be mindful of these considerations when deciding the optimal course of therapy for their patients. Fortunately, more targeted biological therapies are in development for AD that will create more safe and effective systemic therapies for this disease.121 

One such biological therapy is dupilumab, a human monoclonal immunoglobulin G4 antibody targeting IL-4Rα that was approved in 2017 for the treatment of moderate-to-severe AD for adults.124 Dupilumab inhibits IL-4- and IL-13-mediated inflammatory responses, because the IL-4Rα subunit is shared by the receptor complexes for both of these cytokines. Two phase III trials revealed that more than one-third of patients on dupilumab monotherapy every 2 weeks for 16 weeks demonstrated Investigator’s Global Assessment (IGA) of clear or almost clear with at least a 2-grade improvement from baseline, significantly more than patients receiving the placebo (Study of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis 1 [SOLO1]: 37.9% vs 10.3%; SOLO2: 36.1% vs 8.5%).125 Dupilumab use was associated with an increased risk of conjunctivitis (4%–5% of patients) and injection-site reactions (8%–14%) over the placebo.125 

Topical therapies can be combined with dupilumab for additional benefit and to treat patients with recalcitrant disease. In the phase III trial LIBERTY AD CHRONOS, 38.7% of patients receiving combination therapy with both twice-weekly dupilumab and TCS achieved an IGA of 0 or 1 at week 16 with a ≥2-grade improvement from baseline, as compared with 12.4% of patients using only TCS.126 This response with combination therapy persisted through week 52, with 36.0% of patients receiving combination therapy achieving this same end point, as compared with just 12.5% of patients in the control group.126 Additionally, combination therapy with TCS and twice-weekly dupilumab therapy improved disease severity in patients not responding to cyclosporine, with 40.2% achieving an IGA of 0 or1 with a ≥2-grade improvement at week 16 as compared with 13.9% on TCS alone in the phase III LIBERTY AD CAFÉ trial.127 Patients receiving combination therapy demonstrated no increased risk of serious adverse events over TCS monotherapy but still yielded an increased risk of conjunctivitis and injection-site reactions, consistent with the results of SOLO1 and SOLO2.126,127 

Dupilumab is currently only approved for adults, but investigations into its use for pediatric indications are currently ongoing (NCT02407756, NCT02612454, NCT03054428, NCT03345914). Various other biological therapies for AD have revealed promising results in phase II trials, including interleukin 12 and interleukin 23 inhibitor ustekinumab,128 IL-13 inhibitors lebrikizumab129 and tralokinumab,130 interleukin 22 inhibitor fezakinumab,131 and oral Janus kinase inhibitor baricitinib.132 Several other promising therapies are still in the early stages of investigation and include PDE-4 inhibitor apremilast, interleukin 17A inhibitor secukinumab, TSLP inhibitor tezepelumab, and neurokinin-1 inhibitor serlopitant.130 As AD is increasingly considered to be a systemic disease, a diverse range of safe, effective systemic therapies will be critical in the management of this disease.

Despite its high prevalence, AD has historically been poorly understood, resulting in a paucity of approved treatment options for this burdensome disease. However, several important recent advances have been made to increase our understanding of the mechanisms and physiology of this complex multifactorial disease. The approval of crisaborole and dupilumab for the treatment of AD marks the beginning of an exciting new era, with several other novel therapeutic options on the horizon.

The landscape of AD is rapidly evolving. Perceptions of the burden of this disease, as well as guidelines for the optimal treatment approach for patients, have changed drastically over the past decade. It is now apparent that AD extends beyond cutaneous manifestations to impair sleep,40,41 social function,46 school performance,54 and overall development.52 As such, the treatment paradigm for AD is shifting, and considering deficits beyond physical symptoms is recommended when developing treatment plans.121 The management of affected patients will likely continue to progress in the coming years as the underlying mechanisms of this disease become better understood and new therapies become available. Primary pediatric care providers must stay aware of these updates, because they are the go-to provider for most patients with AD and will continue to be the first-line defense against this burdensome disease.

     
  • AD

    atopic dermatitis

  •  
  • IGA

    Investigator’s Global Assessment

  •  
  • IL-4

    interleukin 4

  •  
  • IL-5

    interleukin 5

  •  
  • IL-13

    interleukin 13

  •  
  • ILC2

    type 2 innate lymphoid cell

  •  
  • PDE-4

    phosphodiesterase-4

  •  
  • QoL

    quality of life

  •  
  • SOLO1

    Study of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

  •  
  • SOLO2

    Study of Dupilumab [REGN668/SAR231893] Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

  •  
  • TCI

    topical calcineurin inhibitor

  •  
  • TCS

    topical corticosteroid

  •  
  • Th1

    T helper 1

  •  
  • Th2

    T helper 2

  •  
  • Th17

    T helper 17

  •  
  • Th22

    T helper 22

  •  
  • TSLP

    thymic stromal lymphopoietin

Mr Yang, Dr Sekhon, Ms Sanchez, and Drs Beck and Bhutani participated in the drafting and revising of this manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

1
Shaw
TE
,
Currie
GP
,
Koudelka
CW
,
Simpson
EL
.
Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health.
J Invest Dermatol
.
2011
;
131
(
1
):
67
73
[PubMed]
2
Flohr
C
,
Mann
J
.
New insights into the epidemiology of childhood atopic dermatitis.
Allergy
.
2014
;
69
(
1
):
3
16
[PubMed]
3
Jackson
KD
,
Howie
LD
,
Akinbami
LJ
.
Trends in allergic conditions among children: United States, 1997-2011.
NCHS Data Brief
.
2013
;(
121
):
1
8
[PubMed]
4
Asher
MI
,
Montefort
S
,
Björkstén
B
, et al;
ISAAC Phase Three Study Group
.
Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys.
Lancet
.
2006
;
368
(
9537
):
733
743
[PubMed]
5
Saavedra
JM
,
Boguniewicz
M
,
Chamlin
S
, et al
.
Patterns of clinical management of atopic dermatitis in infants and toddlers: a survey of three physician specialties in the United States.
J Pediatr
.
2013
;
163
(
6
):
1747
1753
[PubMed]
6
Totri
CR
,
Diaz
L
,
Eichenfield
LF
.
2014 update on atopic dermatitis in children.
Curr Opin Pediatr
.
2014
;
26
(
4
):
466
471
[PubMed]
7
Eichenfield
LF
,
Boguniewicz
M
,
Simpson
EL
, et al
.
Translating atopic dermatitis management guidelines into practice for primary care providers.
Pediatrics
.
2015
;
136
(
3
):
554
565
[PubMed]
8
Blome
C
,
Radtke
MA
,
Eissing
L
,
Augustin
M
.
Quality of life in patients with atopic dermatitis: disease burden, measurement, and treatment benefit.
Am J Clin Dermatol
.
2016
;
17
(
2
):
163
169
[PubMed]
9
Rudikoff
D
,
Lebwohl
M
.
Atopic dermatitis.
Lancet
.
1998
;
351
(
9117
):
1715
1721
[PubMed]
10
Roduit
C
,
Frei
R
,
Depner
M
, et al;
the PASTURE Study Group
.
Phenotypes of atopic dermatitis depending on the timing of onset and progression in childhood.
JAMA Pediatr
.
2017
;
171
(
7
):
655
662
[PubMed]
11
Eichenfield
LF
,
Tom
WL
,
Chamlin
SL
, et al
.
Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.
J Am Acad Dermatol
.
2014
;
70
(
2
):
338
351
[PubMed]
12
Williams
HC
,
Burney
PG
,
Pembroke
AC
,
Hay
RJ
.
The U.K. Working Party’s diagnostic criteria for atopic dermatitis. III. Independent hospital validation.
Br J Dermatol
.
1994
;
131
(
3
):
406
416
[PubMed]
13
Krakowski
AC
,
Eichenfield
LF
,
Dohil
MA
.
Management of atopic dermatitis in the pediatric population.
Pediatrics
.
2008
;
122
(
4
):
812
824
[PubMed]
14
Bantz
SK
,
Zhu
Z
,
Zheng
T
.
The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma.
J Clin Cell Immunol
.
2014
;
5
(
2
):
202
[PubMed]
15
Dharmage
SC
,
Lowe
AJ
,
Matheson
MC
,
Burgess
JA
,
Allen
KJ
,
Abramson
MJ
.
Atopic dermatitis and the atopic march revisited.
Allergy
.
2014
;
69
(
1
):
17
27
[PubMed]
16
Dharma
C
,
Lefebvre
DL
,
Tran
MM
, et al;
CHILD Study Investigators
.
Patterns of allergic sensitization and atopic dermatitis from 1 to 3 years: effects on allergic diseases.
Clin Exp Allergy
.
2018
;
48
(
1
):
48
59
17
Martin
PE
,
Eckert
JK
,
Koplin
JJ
, et al;
HealthNuts Study Investigators
.
Which infants with eczema are at risk of food allergy? Results from a population-based cohort.
Clin Exp Allergy
.
2015
;
45
(
1
):
255
264
[PubMed]
18
Du Toit
G
,
Roberts
G
,
Sayre
PH
, et al;
LEAP Study Team
.
Randomized trial of peanut consumption in infants at risk for peanut allergy.
N Engl J Med
.
2015
;
372
(
9
):
803
813
[PubMed]
19
Fleischer
DM
,
Sicherer
S
,
Greenhawt
M
, et al;
LEAP Study Team
.
Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants.
Pediatrics
.
2015
;
136
(
3
):
600
[PubMed]
20
Togias
A
,
Cooper
SF
,
Acebal
ML
, et al
.
Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.
Pediatr Dermatol
.
2017
;
34
(
1
):
e1
e21
[PubMed]
21
Gupta
D
.
Atopic dermatitis: a common pediatric condition and its evolution in adulthood.
Med Clin North Am
.
2015
;
99
(
6
):
1269
1285, xii
[PubMed]
22
Sun
D
,
Ong
PY
.
Infectious complications in atopic dermatitis.
Immunol Allergy Clin North Am
.
2017
;
37
(
1
):
75
93
[PubMed]
23
Ong
PY
,
Ohtake
T
,
Brandt
C
, et al
.
Endogenous antimicrobial peptides and skin infections in atopic dermatitis.
N Engl J Med
.
2002
;
347
(
15
):
1151
1160
[PubMed]
24
Huang
JT
,
Abrams
M
,
Tlougan
B
,
Rademaker
A
,
Paller
AS
.
Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity.
Pediatrics
.
2009
;
123
(
5
). Available at: www.pediatrics.org/cgi/content/full/123/5/e808
[PubMed]
25
Silverberg
JI
,
Becker
L
,
Kwasny
M
,
Menter
A
,
Cordoro
KM
,
Paller
AS
.
Central obesity and high blood pressure in pediatric patients with atopic dermatitis.
JAMA Dermatol
.
2015
;
151
(
2
):
144
152
[PubMed]
26
Zhang
A
,
Silverberg
JI
.
Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis.
J Am Acad Dermatol
.
2015
;
72
(
4
):
606
616.e4
[PubMed]
27
Brunner
PM
,
Suárez-Fariñas
M
,
He
H
, et al
.
The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins [published correction appears in Sci Rep. 2018;8(1):8439].
Sci Rep
.
2017
;
7
(
1
):
8707
[PubMed]
28
Silverberg
JI
,
Greenland
P
.
Eczema and cardiovascular risk factors in 2 US adult population studies.
J Allergy Clin Immunol
.
2015
;
135
(
3
):
721
728.e6
[PubMed]
29
Kwa
MC
,
Silverberg
JI
.
Association between inflammatory skin disease and cardiovascular and cerebrovascular co-morbidities in US adults: analysis of nationwide inpatient sample data.
Am J Clin Dermatol
.
2017
;
18
(
6
):
813
823
[PubMed]
30
Silverberg
JI
.
Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population-based studies.
Allergy
.
2015
;
70
(
10
):
1300
1308
[PubMed]
31
Silverberg
JI
,
Paller
AS
.
Association between eczema and stature in 9 US population-based studies.
JAMA Dermatol
.
2015
;
151
(
4
):
401
409
[PubMed]
32
Silverberg
JI
.
Association between childhood atopic dermatitis, malnutrition, and low bone mineral density: a US population-based study.
Pediatr Allergy Immunol
.
2015
;
26
(
1
):
54
61
[PubMed]
33
Wu
CY
,
Lu
YY
,
Lu
CC
,
Su
YF
,
Tsai
TH
,
Wu
CH
.
Osteoporosis in adult patients with atopic dermatitis: a nationwide population-based study.
PLoS One
.
2017
;
12
(
2
):
e0171667
[PubMed]
34
Drury
KE
,
Schaeffer
M
,
Silverberg
JI
.
Association between atopic disease and anemia in US children.
JAMA Pediatr
.
2016
;
170
(
1
):
29
34
[PubMed]
35
Yaghmaie
P
,
Koudelka
CW
,
Simpson
EL
.
Mental health comorbidity in patients with atopic dermatitis.
J Allergy Clin Immunol
.
2013
;
131
(
2
):
428
433
[PubMed]
36
Strom
MA
,
Fishbein
AB
,
Paller
AS
,
Silverberg
JI
.
Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults.
Br J Dermatol
.
2016
;
175
(
5
):
920
929
[PubMed]
37
Yu
SH
,
Silverberg
JI
.
Association between atopic dermatitis and depression in US adults.
J Invest Dermatol
.
2015
;
135
(
12
):
3183
3186
[PubMed]
38
Beattie
PE
,
Lewis-Jones
MS
.
A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases.
Br J Dermatol
.
2006
;
155
(
1
):
145
151
[PubMed]
39
Kiebert
G
,
Sorensen
SV
,
Revicki
D
, et al
.
Atopic dermatitis is associated with a decrement in health-related quality of life.
Int J Dermatol
.
2002
;
41
(
3
):
151
158
[PubMed]
40
Dahl
RE
,
Bernhisel-Broadbent
J
,
Scanlon-Holdford
S
,
Sampson
HA
,
Lupo
M
.
Sleep disturbances in children with atopic dermatitis.
Arch Pediatr Adolesc Med
.
1995
;
149
(
8
):
856
860
[PubMed]
41
Eckert
L
,
Gupta
S
,
Amand
C
,
Gadkari
A
,
Mahajan
P
,
Gelfand
JM
.
Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: an analysis using the National Health and Wellness Survey.
J Am Acad Dermatol
.
2017
;
77
(
2
):
274
279.e3
[PubMed]
42
Su
JC
,
Kemp
AS
,
Varigos
GA
,
Nolan
TM
.
Atopic eczema: its impact on the family and financial cost.
Arch Dis Child
.
1997
;
76
(
2
):
159
162
[PubMed]
43
Fishbein
AB
,
Mueller
K
,
Kruse
L
, et al
.
Sleep disturbance in children with moderate/severe atopic dermatitis: a case-control study.
J Am Acad Dermatol
.
2018
;
78
(
2
):
336
341
[PubMed]
44
Reid
P
,
Lewis-Jones
MS
.
Sleep difficulties and their management in preschoolers with atopic eczema.
Clin Exp Dermatol
.
1995
;
20
(
1
):
38
41
[PubMed]
45
McCann
D
,
Bull
R
,
Winzenberg
T
.
Sleep deprivation in parents caring for children with complex needs at home: a mixed methods systematic review.
J Fam Nurs
.
2015
;
21
(
1
):
86
118
[PubMed]
46
Lewis-Jones
S
.
Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema.
Int J Clin Pract
.
2006
;
60
(
8
):
984
992
[PubMed]
47
Beattie
PE
,
Lewis-Jones
MS
.
An audit of the impact of a consultation with a paediatric dermatology team on quality of life in infants with atopic eczema and their families: further validation of the Infants’ Dermatitis Quality of Life Index and Dermatitis Family Impact score.
Br J Dermatol
.
2006
;
155
(
6
):
1249
1255
[PubMed]
48
Roosta
N
,
Black
DS
,
Peng
D
,
Riley
LW
.
Skin disease and stigma in emerging adulthood: impact on healthy development.
J Cutan Med Surg
.
2010
;
14
(
6
):
285
290
[PubMed]
49
Zuberbier
T
,
Orlow
SJ
,
Paller
AS
, et al
.
Patient perspectives on the management of atopic dermatitis.
J Allergy Clin Immunol
.
2006
;
118
(
1
):
226
232
[PubMed]
50
Chamlin
SL
,
Frieden
IJ
,
Williams
ML
,
Chren
MM
.
Effects of atopic dermatitis on young American children and their families.
Pediatrics
.
2004
;
114
(
3
):
607
611
[PubMed]
51
Magin
P
,
Adams
J
,
Heading
G
,
Pond
D
,
Smith
W
.
Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study.
Scand J Caring Sci
.
2008
;
22
(
3
):
430
436
[PubMed]
52
Brenninkmeijer
EE
,
Legierse
CM
,
Sillevis Smitt
JH
,
Last
BF
,
Grootenhuis
MA
,
Bos
JD
.
The course of life of patients with childhood atopic dermatitis.
Pediatr Dermatol
.
2009
;
26
(
1
):
14
22
[PubMed]
53
Anderson
RT
,
Rajagopalan
R
.
Effects of allergic dermatosis on health-related quality of life.
Curr Allergy Asthma Rep
.
2001
;
1
(
4
):
309
315
[PubMed]
54
Sibbald
C
,
Drucker
AM
.
Patient burden of atopic dermatitis.
Dermatol Clin
.
2017
;
35
(
3
):
303
316
[PubMed]
55
Drucker
AM
,
Wang
AR
,
Li
WQ
,
Sevetson
E
,
Block
JK
,
Qureshi
AA
.
The burden of atopic dermatitis: summary of a report for the national eczema association.
J Invest Dermatol
.
2017
;
137
(
1
):
26
30
[PubMed]
56
Song
H
,
Adamson
A
,
Mostaghimi
A
.
Medicare part D payments for topical steroids: rising costs and potential savings.
JAMA Dermatol
.
2017
;
153
(
8
):
755
759
[PubMed]
57
Filanovsky
MG
,
Pootongkam
S
,
Tamburro
JE
,
Smith
MC
,
Ganocy
SJ
,
Nedorost
ST
.
The financial and emotional impact of atopic dermatitis on children and their families.
J Pediatr
.
2016
;
169
:
284
290.e5
[PubMed]
58
Liang
Y
,
Chang
C
,
Lu
Q
.
The genetics and epigenetics of atopic dermatitis-filaggrin and other polymorphisms.
Clin Rev Allergy Immunol
.
2016
;
51
(
3
):
315
328
[PubMed]
59
Pellerin
L
,
Henry
J
,
Hsu
CY
, et al
.
Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin.
J Allergy Clin Immunol
.
2013
;
131
(
4
):
1094
1102
[PubMed]
60
Esaki
H
,
Brunner
PM
,
Renert-Yuval
Y
, et al
.
Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin.
J Allergy Clin Immunol
.
2016
;
138
(
6
):
1639
1651
[PubMed]
61
Kelleher
M
,
Dunn-Galvin
A
,
Hourihane
JO
, et al
.
Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.
J Allergy Clin Immunol
.
2015
;
135
(
4
):
930
935.e1
[PubMed]
62
Gasparoni
A
,
Ciardelli
L
,
Avanzini
A
, et al
.
Age-related changes in intracellular TH1/TH2 cytokine production, immunoproliferative T lymphocyte response and natural killer cell activity in newborns, children and adults.
Biol Neonate
.
2003
;
84
(
4
):
297
303
[PubMed]
63
Czarnowicki
T
,
Esaki
H
,
Gonzalez
J
, et al
.
Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.
J Allergy Clin Immunol
.
2015
;
136
(
4
):
941
951.e3
[PubMed]
64
Noda
S
,
Suárez-Fariñas
M
,
Ungar
B
, et al
.
The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.
J Allergy Clin Immunol
.
2015
;
136
(
5
):
1254
1264
[PubMed]
65
Suárez-Fariñas
M
,
Dhingra
N
,
Gittler
J
, et al
.
Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis.
J Allergy Clin Immunol
.
2013
;
132
(
2
):
361
370
[PubMed]
66
Thepen
T
,
Langeveld-Wildschut
EG
,
Bihari
IC
, et al
.
Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study.
J Allergy Clin Immunol
.
1996
;
97
(
3
):
828
837
[PubMed]
67
Gittler
JK
,
Shemer
A
,
Suárez-Fariñas
M
, et al
.
Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis.
J Allergy Clin Immunol
.
2012
;
130
(
6
):
1344
1354
[PubMed]
68
Suárez-Fariñas
M
,
Tintle
SJ
,
Shemer
A
, et al
.
Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities.
J Allergy Clin Immunol
.
2011
;
127
(
4
):
954
964.e1–e4
69
Czarnowicki
T
,
Esaki
H
,
Gonzalez
J
, et al
.
Alterations in B-cell subsets in pediatric patients with early atopic dermatitis.
J Allergy Clin Immunol
.
2017
;
140
(
1
):
134
144.e9
[PubMed]
70
Salimi
M
,
Barlow
JL
,
Saunders
SP
, et al
.
A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
J Exp Med
.
2013
;
210
(
13
):
2939
2950
[PubMed]
71
Kim
BS
,
Siracusa
MC
,
Saenz
SA
, et al
.
TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation.
Sci Transl Med
.
2013
;
5
(
170
):
170ra16
[PubMed]
72
Imai
Y
,
Yasuda
K
,
Sakaguchi
Y
, et al
.
Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice.
Proc Natl Acad Sci USA
.
2013
;
110
(
34
):
13921
13926
[PubMed]
73
Trautmann
A
,
Altznauer
F
,
Akdis
M
, et al
.
The differential fate of cadherins during T-cell-induced keratinocyte apoptosis leads to spongiosis in eczematous dermatitis.
J Invest Dermatol
.
2001
;
117
(
4
):
927
934
[PubMed]
74
Liu
YJ
.
Thymic stromal lymphopoietin: master switch for allergic inflammation.
J Exp Med
.
2006
;
203
(
2
):
269
273
[PubMed]
75
Soumelis
V
,
Reche
PA
,
Kanzler
H
, et al
.
Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.
Nat Immunol
.
2002
;
3
(
7
):
673
680
[PubMed]
76
Siracusa
MC
,
Saenz
SA
,
Hill
DA
, et al
.
TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation.
Nature
.
2011
;
477
(
7363
):
229
233
[PubMed]
77
Kim
BS
,
Wang
K
,
Siracusa
MC
, et al
.
Basophils promote innate lymphoid cell responses in inflamed skin.
J Immunol
.
2014
;
193
(
7
):
3717
3725
[PubMed]
78
Mashiko
S
,
Mehta
H
,
Bissonnette
R
,
Sarfati
M
.
Increased frequencies of basophils, type 2 innate lymphoid cells and Th2 cells in skin of patients with atopic dermatitis but not psoriasis.
J Dermatol Sci
.
2017
;
88
(
2
):
167
174
[PubMed]
79
Zheng
T
,
Oh
MH
,
Oh
SY
,
Schroeder
JT
,
Glick
AB
,
Zhu
Z
.
Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling.
J Invest Dermatol
.
2009
;
129
(
3
):
742
751
[PubMed]
80
Paller
AS
,
Kabashima
K
,
Bieber
T
.
Therapeutic pipeline for atopic dermatitis: end of the drought?
J Allergy Clin Immunol
.
2017
;
140
(
3
):
633
643
[PubMed]
81
Schneider
L
,
Tilles
S
,
Lio
P
, et al
.
Atopic dermatitis: a practice parameter update 2012.
J Allergy Clin Immunol
.
2013
;
131
(
2
):
295
299.e1–e27
82
Eichenfield
LF
,
Tom
WL
,
Berger
TG
, et al
.
Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.
J Am Acad Dermatol
.
2014
;
71
(
1
):
116
132
[PubMed]
83
Angelova-Fischer
I
,
Neufang
G
,
Jung
K
,
Fischer
TW
,
Zillikens
D
.
A randomized, investigator-blinded efficacy assessment study of stand-alone emollient use in mild to moderately severe atopic dermatitis flares.
J Eur Acad Dermatol Venereol
.
2014
;
28
(
suppl 3
):
9
15
[PubMed]
84
Korting
HC
,
Schöllmann
C
,
Cholcha
W
,
Wolff
L
;
Collaborative Study Group
.
Efficacy and tolerability of pale sulfonated shale oil cream 4% in the treatment of mild to moderate atopic eczema in children: a multicentre, randomized vehicle-controlled trial.
J Eur Acad Dermatol Venereol
.
2010
;
24
(
10
):
1176
1182
[PubMed]
85
Grimalt
R
,
Mengeaud
V
,
Cambazard
F
;
Study Investigators’ Group
.
The steroid-sparing effect of an emollient therapy in infants with atopic dermatitis: a randomized controlled study.
Dermatology
.
2007
;
214
(
1
):
61
67
[PubMed]
86
Msika
P
,
De Belilovsky
C
,
Piccardi
N
,
Chebassier
N
,
Baudouin
C
,
Chadoutaud
B
.
New emollient with topical corticosteroid-sparing effect in treatment of childhood atopic dermatitis: SCORAD and quality of life improvement.
Pediatr Dermatol
.
2008
;
25
(
6
):
606
612
[PubMed]
87
Tan
WP
,
Suresh
S
,
Tey
HL
,
Chiam
LY
,
Goon
AT
.
A randomized double-blind controlled trial to compare a triclosan-containing emollient with vehicle for the treatment of atopic dermatitis.
Clin Exp Dermatol
.
2010
;
35
(
4
):
e109
e112
[PubMed]
88
Horimukai
K
,
Morita
K
,
Narita
M
, et al
.
Application of moisturizer to neonates prevents development of atopic dermatitis.
J Allergy Clin Immunol
.
2014
;
134
(
4
):
824
830.e6
[PubMed]
89
Simpson
EL
,
Chalmers
JR
,
Hanifin
JM
, et al
.
Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention.
J Allergy Clin Immunol
.
2014
;
134
(
4
):
818
823
[PubMed]
90
Sidbury
R
,
Tom
WL
,
Bergman
JN
, et al
.
Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies and approaches.
J Am Acad Dermatol
.
2014
;
71
(
6
):
1218
1233
[PubMed]
91
Sidbury
R
,
Davis
DM
,
Cohen
DE
, et al;
American Academy of Dermatology
.
Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents.
J Am Acad Dermatol
.
2014
;
71
(
2
):
327
349
[PubMed]
92
Cheng
KL
,
Dwyer
PN
,
Amsden
GW
.
Paradoxic excitation with diphenhydramine in an adult.
Pharmacotherapy
.
1997
;
17
(
6
):
1311
1314
[PubMed]
93
Schad
CA
,
Skoner
DP
.
Antihistamines in the pediatric population: achieving optimal outcomes when treating seasonal allergic rhinitis and chronic urticaria.
Allergy Asthma Proc
.
2008
;
29
(
1
):
7
13
[PubMed]
94
Bender
BG
,
McCormick
DR
,
Milgrom
H
.
Children’s school performance is not impaired by short-term administration of diphenhydramine or loratadine.
J Pediatr
.
2001
;
138
(
5
):
656
660
[PubMed]
95
Vuurman
EF
,
van Veggel
LM
,
Uiterwijk
MM
,
Leutner
D
,
O’Hanlon
JF
.
Seasonal allergic rhinitis and antihistamine effects on children’s learning.
Ann Allergy
.
1993
;
71
(
2
):
121
126
[PubMed]
96
Vuurman
EF
,
van Veggel
LM
,
Sanders
RL
,
Muntjewerff
ND
,
O’Hanlon
JF
.
Effects of semprex-D and diphenhydramine on learning in young adults with seasonal allergic rhinitis.
Ann Allergy Asthma Immunol
.
1996
;
76
(
3
):
247
252
[PubMed]
97
Chopra
R
,
Vakharia
PP
,
Sacotte
R
,
Silverberg
JI
.
Efficacy of bleach baths in reducing severity of atopic dermatitis: a systematic review and meta-analysis.
Ann Allergy Asthma Immunol
.
2017
;
119
(
5
):
435
440
[PubMed]
98
Wong
SM
,
Ng
TG
,
Baba
R
.
Efficacy and safety of sodium hypochlorite (bleach) baths in patients with moderate to severe atopic dermatitis in Malaysia.
J Dermatol
.
2013
;
40
(
11
):
874
880
[PubMed]
99
Ryan
C
,
Shaw
RE
,
Cockerell
CJ
,
Hand
S
,
Ghali
FE
.
Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis.
Pediatr Dermatol
.
2013
;
30
(
3
):
308
315
[PubMed]
100
Eichenfield
LF
,
Ahluwalia
J
,
Waldman
A
,
Borok
J
,
Udkoff
J
,
Boguniewicz
M
.
Current guidelines for the evaluation and management of atopic dermatitis: a comparison of the joint task force practice parameter and American Academy of Dermatology guidelines.
J Allergy Clin Immunol
.
2017
;
139
(
4S
):
S49
S57
[PubMed]
101
Broeders
JA
,
Ahmed Ali
U
,
Fischer
G
.
Systematic review and meta-analysis of randomized clinical trials (RCTs) comparing topical calcineurin inhibitors with topical corticosteroids for atopic dermatitis: a 15-year experience.
J Am Acad Dermatol
.
2016
;
75
(
2
):
410
419.e3
[PubMed]
102
Li
AW
,
Yin
ES
,
Antaya
RJ
.
Topical corticosteroid phobia in atopic dermatitis: a systematic review.
JAMA Dermatol
.
2017
;
153
(
10
):
1036
1042
[PubMed]
103
Paller
AS
,
McAlister
RO
,
Doyle
JJ
,
Jackson
A
.
Perceptions of physicians and pediatric patients about atopic dermatitis, its impact, and its treatment.
Clin Pediatr (Phila)
.
2002
;
41
(
5
):
323
332
[PubMed]
104
Charman
CR
,
Morris
AD
,
Williams
HC
.
Topical corticosteroid phobia in patients with atopic eczema.
Br J Dermatol
.
2000
;
142
(
5
):
931
936
[PubMed]
105
Kim
JP
,
Chao
LX
,
Simpson
EL
,
Silverberg
JI
.
Persistence of atopic dermatitis (AD): a systematic review and meta-analysis.
J Am Acad Dermatol
.
2016
;
75
(
4
):
681
687.e11
[PubMed]
106
Margolis
JS
,
Abuabara
K
,
Bilker
W
,
Hoffstad
O
,
Margolis
DJ
.
Persistence of mild to moderate atopic dermatitis.
JAMA Dermatol
.
2014
;
150
(
6
):
593
600
[PubMed]
107
Horii
KA
,
Simon
SD
,
Liu
DY
,
Sharma
V
.
Atopic dermatitis in children in the United States, 1997-2004: visit trends, patient and provider characteristics, and prescribing patterns.
Pediatrics
.
2007
;
120
(
3
). Available at: www.pediatrics.org/cgi/content/full/120/3/e527
[PubMed]
108
Callen
J
,
Chamlin
S
,
Eichenfield
LF
, et al
.
A systematic review of the safety of topical therapies for atopic dermatitis.
Br J Dermatol
.
2007
;
156
(
2
):
203
221
[PubMed]
109
EUCRISA
.
(crisaborole) [package insert]
.
New York City, NY
:
Pfizer Inc
;
2016
110
Paller
AS
,
Tom
WL
,
Lebwohl
MG
, et al
.
Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults [published correction appears in J Am Acad Dermatol. 2017;76(4):777].
J Am Acad Dermatol
.
2016
;
75
(
3
):
494
503.e6
[PubMed]
111
Eichenfield
LF
,
Call
RS
,
Forsha
DW
, et al
.
Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.
J Am Acad Dermatol
.
2017
;
77
(
4
):
641
649.e5
[PubMed]
112
Ohba
F
,
Matsuki
S
,
Imayama
S
, et al
.
Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: an investigator-blinded, vehicle-controlled study.
J Dermatolog Treat
.
2016
;
27
(
5
):
467
472
[PubMed]
113
Hanifin
JM
,
Ellis
CN
,
Frieden
IJ
, et al
.
OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): a phase-II randomized, double-blind, placebo-controlled study.
J Am Acad Dermatol
.
2016
;
75
(
2
):
297
305
[PubMed]
114
Bissonnette
R
,
Papp
KA
,
Poulin
Y
, et al
.
Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial.
Br J Dermatol
.
2016
;
175
(
5
):
902
911
[PubMed]
115
Edwards
T
,
Patel
NU
,
Blake
A
, et al
.
Insights into future therapeutics for atopic dermatitis [published correction appears in Expert Opin Pharmacother. 2018;19(9):1041].
Expert Opin Pharmacother
.
2018
;
19
(
3
):
265
278
[PubMed]
116
Udkoff
J
,
Waldman
A
,
Ahluwalia
J
,
Borok
J
,
Eichenfield
LF
.
Current and emerging topical therapies for atopic dermatitis.
Clin Dermatol
.
2017
;
35
(
4
):
375
382
[PubMed]
117
Nygaard
U
,
Deleuran
M
,
Vestergaard
C
.
Emerging treatment options in atopic dermatitis: topical therapies.
Dermatology
.
2017
;
233
(
5
):
333
343
[PubMed]
118
Bhutani
T
,
Kamangar
F
,
Cordoro
KM
.
Management of pediatric psoriasis.
Pediatr Ann
.
2012
;
41
(
1
):
e1
e7
[PubMed]
119
Krejci-Manwaring
J
,
Tusa
MG
,
Carroll
C
, et al
.
Stealth monitoring of adherence to topical medication: adherence is very poor in children with atopic dermatitis.
J Am Acad Dermatol
.
2007
;
56
(
2
):
211
216
[PubMed]
120
Tollefson
MM
,
Bruckner
AL
;
Section on Dermatology
.
Atopic dermatitis: skin-directed management.
Pediatrics
.
2014
;
134
(
6
). Available at: www.pediatrics.org/cgi/content/full/134/6/e1735
[PubMed]
121
Simpson
EL
,
Bruin-Weller
M
,
Flohr
C
, et al
.
When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.
J Am Acad Dermatol
.
2017
;
77
(
4
):
623
633
[PubMed]
122
Lee
E
,
Koo
J
,
Berger
T
.
UVB phototherapy and skin cancer risk: a review of the literature.
Int J Dermatol
.
2005
;
44
(
5
):
355
360
[PubMed]
123
Hearn
RM
,
Kerr
AC
,
Rahim
KF
,
Ferguson
J
,
Dawe
RS
.
Incidence of skin cancers in 3867 patients treated with narrow-band ultraviolet B phototherapy.
Br J Dermatol
.
2008
;
159
(
4
):
931
935
[PubMed]
124
DUPIXENT
.
(dupilumab) [package insert]
.
Tarrytown, NY
:
Regeneron Pharmaceuticals, Inc
;
Bridgewater, NJ
:
sanofi-aventis US LLC
;
2017
125
Simpson
EL
,
Bieber
T
,
Guttman-Yassky
E
, et al;
SOLO 1 and SOLO 2 Investigators
.
Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.
N Engl J Med
.
2016
;
375
(
24
):
2335
2348
[PubMed]
126
Blauvelt
A
,
de Bruin-Weller
M
,
Gooderham
M
, et al
.
Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.
Lancet
.
2017
;
389
(
10086
):
2287
2303
[PubMed]
127
de Bruin-Weller
M
,
Thaçi
D
,
Smith
CH
, et al
.
Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ).
Br J Dermatol
.
2018
;
178
(
5
):
1083
1101
128
Khattri
S
,
Brunner
PM
,
Garcet
S
, et al
.
Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis.
Exp Dermatol
.
2017
;
26
(
1
):
28
35
[PubMed]
129
Simpson
EL
,
Flohr
C
,
Eichenfield
LF
, et al
.
Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE).
J Am Acad Dermatol
.
2018
;
78
(
5
):
863
871.e11
[PubMed]
130
Nygaard
U
,
Vestergaard
C
,
Deleuran
M
.
Emerging treatment options in atopic dermatitis: systemic therapies.
Dermatology
.
2017
;
233
(
5
):
344
357
[PubMed]
131
Guttman-Yassky
E
,
Brunner
PM
,
Neumann
AU
, et al
.
Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: a randomized, double-blind, phase 2a trial.
J Am Acad Dermatol
.
2018
;
78
(
5
):
872
881.e6
132
Guttman-Yassky
E
,
Silverberg
JI
,
Nemoto
O
, et al
.
Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study [published online ahead of print February 1, 2018].
J Am Acad Dermatol
. doi:
[PubMed]

Competing Interests

POTENTIAL CONFLICT OF INTEREST: Dr Bhutani is an investigator for AbbVie, Janssen, Merck, Eli Lilly, and Strata Skin Sciences; the other authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: Dr Bhutani is an investigator for AbbVie, Janssen, Merck, Eli Lilly, and Strata Skin Sciences but has no direct financial conflicts to report; the other authors have indicated they have no financial relationships relevant to this article to disclose.