Clinical Review

Update on Pediatric Atopic Dermatitis

Author and Disclosure Information

Recent studies have led to new insights into atopic dermatitis (AD) pathogenesis and epidemiology as well as its impact on the quality of life of affected children and adolescents. In addition, there are several novel topical and systemic agents recently approved and in late-stage clinical development programs. Epidemiologic insights include relative prevalence rates in different countries and studies of subsets of pediatric patients with different disease longevity and persistence. Studies on quality of life have shown tremendous impact on sleep, not only in affected individuals but in their parents/guardians. The impact of bathing regimens is discussed. Newer topical therapies are reviewed, including topical crisaborole, with a new indication for infants as young as 3 months of age. Topical Janus kinase (JAK) inhibitors are being developed, with some studies including adolescents and children. Other novel therapies include the topical aryl hydrocarbon receptor agonist tapinarof and oral JAK inhibitors; adolescents are being included in the initial clinical trials for several of these therapies. Dupilumab, the first biologic agent approved for AD, has now been well studied in patients aged 6 years and older, with expanded indication down to 6 years of age.

Practice Points

  • There has been tremendous growth in our understanding of atopic dermatitis, with further insight into epidemiology, the impact on quality of life of affected individuals and their families, best bathing practices, and expanding treatment options.
  • There are several novel topical and systemic agents recently approved and in late-stage clinical development programs that are evolving therapeutic approaches to pediatric disease.


 

References

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease that occurs most frequently in children but also affects many adolescents and adults. There has been a tremendous evolution of knowledge in AD, with insights into pathogenesis, epidemiology, impact of disease, and new therapies. A variety of studies examine the epidemiology of AD and associated comorbidities. The broad developments in disease state research are reflected in new publication numbers of AD citations on PubMed. A PubMed search of articles indexed for MEDLINE at the end of 2010 using the term atopic dermatitis would have shown 965 citations during the preceding 1-year period. In the 1-year period of June 2019 to June 2020, there were more than 2000 articles. The large body of research includes work of great significance in pediatric AD, and in this article we review recent findings that are important in understanding the progress being made in the field.

Epidemiology and Comorbidities

The epidemiology of AD has evolved over the last few decades, with emerging trends and novel insights into the burden of disease.1 In a recent cross-sectional study on the epidemiology of AD in children aged 6 to 11 years, the 1-year diagnosed AD prevalence estimates worldwide included the following: United States, 10.0%; Canada, 13.3%; the EU5 Countries, 15.5%; Japan, 10.3%; and all countries studied, 12.2%.2 Another recent paper that analyzed data from the Fragile Families and Child Wellbeing Study showed that the prevalence and persistence of AD in urban US children was 15.0%.3Although pediatric AD may spontaneously remit over time, disease continuing into adolescence and adulthood is common. Paternoster et al4 studied the longitudinal course of AD in children from 2 birth cohort prospective studies, showing distinct AD phenotypes having differing course trajectories over time. Disease subsets included patients with early-onset-persistent and early-onset-late-resolving disease.4 Whether phenotyping or subgroup analysis can be used to predict disease course or risk for development of comorbidities is unknown, but it is interesting to consider how such work could influence tailoring of specific therapies to early disease presentation.

Atopic dermatitis poses a serious public health burden owing to its high prevalence, considerable morbidity and disability, increased health care utilization, and cost of care.1 Recent studies have found notably higher rates of multiple medical and mental health comorbidities in both children and adults with AD, including infections, atopic comorbidities (eg, allergic rhinitis, asthma, food allergies), eye diseases (eg, keratitis, conjunctivitis, keratoconus), and possible cardiovascular diseases and autoimmune disorders.1,5-9 Allergic comorbidities are quite common in pediatric AD patients.10 In a recent study examining the efficacy and safety of dupilumab monotherapy in 251 adolescents with moderate to severe inadequately controlled AD, most had comorbid type 2 diseases including asthma (53.6%), food allergies (60.8%), and allergic rhinitis (65.6%).11

Quality of Life/Life Impact of AD

Pediatric AD has a major impact on the quality of life of patients and their families.12 The well-being and development of children are strongly influenced by the physical and psychosocial health of parents/guardians. Two studies by Ramirez and colleagues13,14 published in 2019 examined sleep disturbances and exhaustion in mothers of children with AD. Data for the studies came from the Avon Longitudinal Study of Parents and Children. Children with active AD reported worse sleep quality than those without AD, with nearly 50% higher odds of sleep-quality disturbances. Analysis of the cohort data from 11,649 mother-child pairs who were followed up with a time-varying measure of child AD activity and severity as well as self-reported maternal sleep measures repeated at multiple time points for children aged 6 months to 11 years showed that mothers of children with AD reported difficulty falling asleep, subjectively insufficient sleep, and daytime exhaustion throughout the first 11 years of childhood.13,14 These data suggest that sleep disturbance may be a family affair.

A cross-sectional, real-world study on the burden of AD in children aged 6 to 11 years assessed by self-report demonstrated a substantial and multidimensional impact of AD, including itch, sleep disturbance, skin pain, and health-related quality-of-life impact, as well as comorbidities and school productivity losses. The burden associated with AD was remarkable and increased with disease severity.15

Drucker et al16 completed a comprehensive literature review on the burden of AD, summarized as a report for the National Eczema Association. Quality-of-life impact on pediatric patients included high rates of emotional distress; social isolation; depression; limitations in activities due to lesions with fear of triggers; and behavioral problems such as irritability, crying, and sleep disturbance resulting in difficulty performing at school.16 The psychological impact on children as well as emotional and behavioral difficulties may impact the ability for parents/guardians to implement treatment plans.17

There is a striking association between mental health disorders and AD in the US pediatric population, with a clear dose-dependent relationship that has been observed between the prevalence of a mental health disorder and the reported severity of the skin disease. Data suggest children with AD may be at increased risk for developing mental health disorders. The National Survey of Children’s Health found statistically significant increases in the likelihood of attention deficit hyperactivity disorder (odds ratio [OR], 1.87), depression (OR, 1.81), anxiety (OR, 1.77), conduct disorder (OR, 1.87), and autism (OR, 3.04).6

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