# Burden of atopic dermatitis in paediatric patients: an international cross-sectional study

Stephan Weidinger, Eric L Simpson, Jonathan I Silverberg, Sebastien Barbarot, Laurent Eckert, Paola Mina-Osorio, Ana B Rossi, Lysel Brignoli, Tarek Mnif, Isabelle Guillemin, et al.

<figure><img src="image_1.png" /></figure>

## ► To cite this version:

Stephan Weidinger, Eric L Simpson, Jonathan I Silverberg, Sebastien Barbarot, Laurent Eckert, et al.. Burden of atopic dermatitis in paediatric patients: an international cross-sectional study. British Journal of Dermatology, 2024, 190 (6), pp.846-857. 10.1093/bjd/ljad449. hal-04901234

HAL Id: hal-04901234

https://hal.science/hal-04901234v1

Submitted on 20 Jan 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>
# Burden of atopic dermatitis in paediatric patients: an international cross-sectional study

Stephan Weidinger,<fnref n="1" /> Eric L. Simpson,<fnref n="2" /> Jonathan I. Silverberg,<fnref n="3" /> Sebastien Barbarot,<fnref n="4" />

Laurent Eckert,<fnref n="5" /> Paola Mina-Osorio,<fnref n="6" /> Ana B. Rossi,<fnref n="7" /> Lysel Brignoli,<fnref n="8" /> Tarek Mnif,<fnref n="8" />

Isabelle Guillemin,<fnref n="5" /> Miriam C. Fenton,<fnref n="7" /> Dimitri Delevry,<fnref n="6" /> Chien-chia Chuang,<fnref n="7" /> Marine Pellan<fnref n="8" />
and Abhijit Gadkari<fnref n="6" />

Correspondence: Stephan Weidinger. Email: sweidinger@dermatology.uni-kiel.de

Linked Article: Chiesa Fuxench *Br J Dermatol* 2024; **190**:783–784.

## Abstract

**Background** Few large-scale international studies have broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents.

**Objectives** To better characterize the AD burden in paediatric patients by disease severity.

**Methods** This cross-sectional, web-based survey of paediatric patients (6 months to < 18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia and East Asia. Patients with diagnosed AD were identified based on the International Study of Asthma and Allergies in Childhood criteria and self-/parent-report of ever being told by a physician that they or their child had eczema. AD severity was assessed using the Patient-Oriented Eczema Measure and Patient Global Assessment. Outcomes included measures of itch, skin pain, sleep, health-related quality of life (HRQoL), missed school days and atopic comorbidities.

**Results** The survey included 1489 children aged 6 months to < 6 years; 2898 children aged 6 to < 12 years; and 3078 adolescents aged 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, paediatric patients with moderate or severe AD had more itch, skin pain, sleep problems and impaired HRQoL, and missed more school days relative to those with mild AD; greater burden was observed among those with severe relative to moderate AD. At least one atopic comorbidity was present in 92.5% of all respondents.

**Conclusions** These results highlight the burden of AD in paediatric patients, especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life.

### What is already known about this topic?

* Atopic dermatitis (AD) is associated with a substantial patient burden in adults, but there is a gap in the quantitative characterization of the burden in the paediatric population.

### What does this study add?

* Paediatric patients with AD were characterized by a multidimensional disease burden including itch, pain, sleep disturbance, impaired health-related quality-of-life, presence of atopic comorbidities and a negative effect on school attendance.

* The impact of AD on the multidimensional burden increased with greater disease severity.

* The disease burden associated with AD was generally consistent across age ranges and geographic regions.

<footnote n="1">¹Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany</footnote>

<footnote n="2">²Oregon Health and Science University, Portland, OR, USA</footnote>

<footnote n="3">³Northwestern University Feinberg School of Medicine, Chicago, IL, USA</footnote>

<footnote n="4">⁴Centre Hospitalier Universitaire de Nantes, Nantes, France</footnote>

<footnote n="5">⁵Sanofi, Chilly-Mazarin, France</footnote>

<footnote n="6">⁶Regeneron, Tarrytown, NY, USA</footnote>

<footnote n="7">⁷Sanofi, Cambridge, MA, USA</footnote>

<footnote n="8">⁸Kantar – Health Division, Paris, France</footnote>
* This study reinforces the burden of AD in the paediatric population, especially in patients with moderate-to-severe disease.

* The results also suggest a major unmet need for effective therapies with demonstrated safety for moderate-to-severe AD in paediatric patients.

The onset of childhood atopic dermatitis (AD) usually occurs in infants and early childhood,¹ although adolescent- and adult-onset AD is also recognized and may be characterized by differences in phenotype.² The course of childhood AD is variable and may range from transient disease to relapsing remitting AD, long periods of remission followed by recurrence, or progression into adulthood in those with more severe disease or other predisposing risk factors.¹ AD is associated with a substantial multidimensional patient burden in adults that includes impaired health-related quality of life (HRQoL) and work productivity.³⁻⁵ While the burden of AD in paediatric populations has been suggested to be multidimensional, including effects on sleep and HRQoL,⁶⁻⁸ there remains a gap in the broader quantitative characterization of the disease burden by AD severity across age groups (infants, children and adolescents).

EPIdemiology of Children with Atopic dermatitis Reporting on their Experience (EPI-CARE) was a survey conducted in 18 countries worldwide, representing five geographic regions, with the objective of providing current information on the prevalence and burden of AD in paediatric populations. Epidemiological results from EPI-CARE showed a 12-month prevalence of AD that ranged from 2.7% to 20.1% among the countries surveyed.⁹ EPI-CARE included questions designed to capture information on how AD affects these paediatric patients and their families, and the family impact has been previously reported.¹⁰ The current analysis describes the patient burden in the paediatric AD population by disease severity.

# Methods

## Study design

EPI-CARE was an international, cross-sectional study designed to be representative of the general paediatric populations of countries encompassing five geographic regions including North America (Canada and the USA), Latin America (Argentina, Brazil, Colombia, Mexico), Europe (France, Germany, Italy, Spain and the UK), the Middle East/Eurasia (Israel, Russia, Saudi Arabia (SA), Turkey and the United Arab Emirates (UAE)) and East Asia (Japan and Taiwan). Three paediatric age groups were considered: 6 months to 5 years old (infants and young children), 6 to < 12 years old (older children) and 12 to < 18 years old (adolescents).

Data collection was according to the ethical codes of the British Healthcare Business Intelligence Association (BHBIA), the European Society for Opinion and Marketing Research (ESOMAR) and the European Pharmaceutical Market Research Association (EphMRA), and was compliant with the EU General Data Protection Regulation (GDPR) and the US Health Insurance Portability and Accountability Act (HIPAA). All parents provided informed consent prior to participation; adolescents were required to provide assent in addition to parental consent.

Participant recruitment was via parents who were members of online quality-checked, opt-in panels across a range

of consumer, business and professional connection sources in their respective countries. To reduce selection bias, panels were blinded to the research topic when invited. Panel members who completed the questionnaire received points redeemable for items in a prize catalogue.

Data were collected through a web-based survey conducted between 26 September 2018 and 5 March 2019 for all countries except Taiwan and Turkey, which were surveyed between 7 October and 2 December 2019. The questionnaire was administered in the native language of each country including linguistically validated translations of previously developed outcome measures; questionnaire completion took a maximum of 30 min.

In families with more than one eligible child, an algorithm selected the child to be surveyed based on the birthday closest to the survey date, but if this child belonged to a category for which the quota was reached, another child with the following birthday was chosen. In cases of identical birth date, the algorithm selected the child alphabetically using the first letter of the first name.

## Questionnaire and outcomes

The questionnaire consisted of two sections. The first section included questions that enabled the selection algorithm for families with multiple children, confirmed participant eligibility and collected demographic information. Eligible participants were those who were classified as 'diagnosed AD' (Figure S1; see Supporting Information), and were required to fully meet the International Study of Asthma and Allergies in Children (ISAAC) criteria.¹¹ This includes three criteria: (i) itchy rash that was coming and going for at least 6 months; (ii) had this itchy rash in the past 12 months; and (iii) this itchy rash affected any of the regions including the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes; and, additionally, self-reporting ever being told by a physician that they suffer from eczema. Because AD in children presents with age-dependent characteristics that include facial, scalp and extensor involvement in infants and young children,¹² children < 6 years old were required to meet two additional criteria: the itchy rash affecting at any time the face (cheeks and forehead) and affecting at any time elbows to wrist or knee to ankle.

The second section assessed disease severity and collected information on the burden of AD. This section was completed by parents for children < 4 years old. For children 4 to < 12 years old, parents were requested to pass control to their child as much as possible for scales that were validated for completion by younger age groups, but had the right to refuse and continue to answer on behalf of their children; adolescents (12 to < 18 years) self-completed this section.

The severity of AD was assessed using the Patient-Oriented Eczema Measure (POEM; self-reported version for children ≥ 12 years and the proxy version for children < 12 years)¹⁰ and the Patient Global Assessment (PtGA) of disease severity for the past week. PtGA was reported as mild, moderate or severe by the participant or their parents. POEM is the core
outcome instrument for assessing patient-reported AD symptoms.¹³ POEM assesses the frequency over the past week of seven symptoms (items) that are meaningful to patients: itch, sleep disturbance, bleeding, oozing of clear fluid ('weeping'), cracked skin, flaking off and dry or rough skin. Each item is rated from 0 (no days) to 4 (every day) for a maximum score of 28, reflecting the highest severity. Scores are stratified by 0-2 (clear/almost clear); 3-7 (mild); 8-16 (moderate); 17-24 (severe) and 25-28 (very severe).¹⁴ The burden of AD was assessed using validated measures and stand-alone questions. Worst itch and skin pain over the past 24 h were assessed using the Pruritus Numerical Rating Scale (NRS: 0, no itch; 10, worst possible itch)¹² and a Pain NRS (0, no pain; 10, worst possible pain). Sleep quality was assessed using an NRS (0, best possible sleep; 10, worst possible sleep) based on the question 'Thinking about all the ways eczema affects your/your child's sleep, select the number that best describes your/your child's sleep last night'. The frequency of sleep disturbances over the past week was evaluated using item 2 from POEM, which was validated for use as a single-item measure, albeit not for a paediatric population.¹⁵

HRQoL was evaluated using either the Children's Dermatology Life Quality Index (CDLQI)¹⁶ for children ≥4 years old or the Infant's Dermatology Quality of Life Index (IDQOL), which is a parent-completed measure for children <4 years old; the IDQOL was also used for children 4 to < 12 years old whose parents did not agree to pass control.¹⁷ Both measures have a 1-week recall period, with a 0-30 score range and higher scores indicating poorer HRQoL. Bands indicative of the magnitude of effect of AD on a child's life were estimated for the CDLQI with scores 0-1 (no effect on a child's life), 2-6 (small effect), 7-12 (moderate effect), 13-18 (very large effect) and 19-30 (extremely large effect);¹⁸,¹⁹ effect bands have not been established for the IDQOL.

The effect of AD on school was evaluated among school-age children by determining the mean number of days missed in the past 4 weeks. For children in the youngest age group, <6 years old, only those 4-5 years old were considered as school age.

Participants/parents reported on the presence of atopic comorbidities including allergic conjunctivitis, allergic rhinitis, allergic urticaria, asthma, atopic keratoconjunctivitis, chronic rhinosinusitis, eosinophilic oesophagitis, food allergies, hay fever, nasal polyps and seasonal allergies. The proportion of participants with at least one atopic comorbidity was determined as were the most prevalent atopic comorbidities. Hay fever, allergic rhinitis and seasonal allergies were considered together to account for overlap (i.e. participants with at least one of these atopic conditions).

## Statistical analysis

Quota apportionment²⁰ was used prior to data collection to ensure that sampled participants were representative of the paediatric population of the countries for sex and age for all countries (https://www.census.gov/), geographic regions (country-specific databases) and urban vs. rural for all countries except for Argentina, Brazil, Colombia, Mexico, SA, Turkey and the UAE (https://knoema.fr).²⁰,²¹ If quota objectives were not exactly met at a country level, a weighting adjustment was applied to have the structure of the total number of respondents per country match exactly the structure of the general population on the quota variables.

Results were analysed by region: North America, Latin America, Europe, Middle East/Eurasia and East Asia. The disease burden was characterized by age group and AD severity using POEM and PtGA. Descriptive statistics include means and standard deviations for continuous variables, and number and proportions for categorical variables. Pairwise comparisons across AD severity levels (mild, moderate and severe) were conducted using the t-test and Pearson's χ² test for continuous and categorical variables, respectively.

## Results

### Populations

A total of 7465 paediatric participants with diagnosed AD were included: 1489 young children (< 6 years), 2898 older children (6 to < 12 years) and 3078 adolescents (12 to < 18 years). Regional distribution within each country reflected the study goals as being representative of the countries surveyed. The demographic characteristics show

<table><caption>**Table 1** Demographic and clinical characteristics of the prevalent paediatric atopic dermatitis (AD) population by age group</caption><thead><tr><th></th><th>All</th><th>North America</th><th>Latin America</th><th>Europe</th><th>Middle East/Eurasia</th><th>East Asia</th></tr></thead><tbody><tr><td>6 months to &lt; 6 years, n</td><td>1489</td><td>198</td><td>368</td><td>518</td><td>197</td><td>208</td></tr><tr><td>Age, mean years (SD)</td><td>3.0 (1.6)</td><td>3.0 (1.7)</td><td>3.1 (1.6)</td><td>3.1 (1.6)</td><td>2.8 (1.5)</td><td>3.1 (1.5)</td></tr><tr><td>Male, %</td><td>51.5</td><td>53.6</td><td>53.3</td><td>44.6</td><td>49.9</td><td>55.2</td></tr><tr><td>Mild/moderate/severe AD, %</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>POEM</td><td>48.6/43.7/6.9</td><td>46.8/42.7/10.2</td><td>45.3/48.7/5.8</td><td>46.5/46.1/7.2</td><td>50.4/41.6/8.0</td><td>59.9/35.9/4.1</td></tr><tr><td>PtGA</td><td>62.1/31.5/6.2</td><td>62.3/30.9/6.6</td><td>58.5/36.6/4.6</td><td>59.9/31.2/8.7</td><td>63.0/32.7/4.3</td><td>75.6/21.1/3.3</td></tr><tr><td>6 to &lt; 12 years, n</td><td>2898</td><td>367</td><td>718</td><td>1112</td><td>429</td><td>272</td></tr><tr><td>Age, mean years (SD)</td><td>9.0 (1.7)</td><td>9.0 (1.7)</td><td>9.1 (1.6)</td><td>9.1 (1.7)</td><td>9.0 (1.7)</td><td>8.8 (1.8)</td></tr><tr><td>Male, %</td><td>52.9</td><td>50.1</td><td>52.9</td><td>56.3</td><td>52.4</td><td>50.8</td></tr><tr><td>Mild/moderate/severe AD, %</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>POEM</td><td>57.6/36.1/6.3</td><td>52.9/35.2/11.9</td><td>57.4/36.5/5.9</td><td>59.1/34.4/6.4</td><td>51.0/43.4/5.6</td><td>62.3/33.4/4.2</td></tr><tr><td>PtGA</td><td>61.5/33.9/3.5</td><td>65.4/29.4/4.8</td><td>56.9/39.3/3.5</td><td>64.3/32.3/3.4</td><td>57.1/38.7/4.3</td><td>75.0/22.5/2.5</td></tr><tr><td>12 to &lt; 18 years, n</td><td>3078</td><td>415</td><td>873</td><td>1070</td><td>457</td><td>263</td></tr><tr><td>Age, mean years (SD)</td><td>14.9 (1.7)</td><td>15.2 (1.7)</td><td>14.8 (1.7)</td><td>15.1 (1.7)</td><td>14.7 (1.6)</td><td>15.4 (1.8)</td></tr><tr><td>Male, %</td><td>48.7</td><td>48.6</td><td>46.8</td><td>55.4</td><td>47.5</td><td>46.0</td></tr><tr><td>Mild/moderate/severe AD, %</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>POEM</td><td>51.5/39.4/9.1</td><td>44.0/41.8/13.6</td><td>52.5/39.4/8.1</td><td>52.9/39.1/8.0</td><td>42.3/45.5/11.5</td><td>63.6/29.2/7.2</td></tr><tr><td>PtGA</td><td>57.6/37.1/5.2</td><td>50.4/40.5/8.5</td><td>55.8/38.6/5.5</td><td>60.8/34.3/5.0</td><td>55.2/38.8/5.4</td><td>64.2/34.3/1.5</td></tr></tbody></table>

POEM, Patient-Oriented Eczema Measure; PtGA, Patient-reported Global Assessment.
that the mean age within each age group was similar across regions, and the proportion of males ranged from 44.6% to 56.3%, with no clear pattern of distribution (Table 1). On both POEM and PtGA, AD severity was primarily reported as mild (42.3–75.6%) or moderate (21.1–48.7%) across age categories and geographic regions, and severe AD was consistently low (1.5–13.6%) (Table 1); POEM generally resulted in a slightly higher proportion of moderate and a lower proportion of mild AD than PtGA.

## Itch and pain

Participants with mild AD assessed by POEM had substantial itch and pain in the previous 24 h (Figures 1 and 2) as

indicated by mean NRS scores that ranged from 2.0 to 4.0 and 1.7 to 3.9 for itch and pain, respectively, across age and geographic regions. Itch NRS scores ranged from 4.3 to 6.5 and 6.2 to 7.5 for moderate and severe AD, respectively (Figure 1), with pain NRS scores 3.5–6.4 and 4.9–7.3 for moderate and severe AD, respectively (Figure 2); most pairwise comparisons showed a significantly higher burden with increasing AD severity. There were no clear patterns with regard to itch or skin pain severity based on age group or geographic region, although score ranges were slightly higher when AD severity was assessed using the PtGA (Figures S2 and S3; see Supporting Information). However, there was large variability in scores across all severity levels.

<figure><img src="image_3.png" /><figcaption>**Figure 1** Worst-itch severity over the past 24 h, assessed using the Pruritus Numerical Rating Scale (NRS; 0–10), by atopic dermatitis (AD) severity based on the Patient-Oriented Eczema Measure. (a) < 6 years old; (b) 6 to < 12 years old; (c) 12 to < 18 years old. Higher scores on the NRS indicate higher itch severity.</figcaption></figure>
Sleep

Sleep NRS scores [Figure 3 (POEM) and Figure S4 (PtGA); see Supporting Information] indicated that while participants with mild AD had impaired sleep quality, sleep quality was even poorer among participants with moderate and severe AD. Severe AD was also associated with worse sleep quality than moderate AD. Almost all pairwise comparisons between AD severity levels were statistically significant (*P*<0.05). As with itch and skin pain, there was large variability in sleep scores within each AD severity level, although 48.9–66.9% and 51.1–71.0% of patients with severe AD on POEM and PtGA, respectively, had NRS sleep scores ≥7 (data not shown).

In the overall population, the distribution on the POEM sleep item showed a shift towards more frequent sleep disturbances at higher AD severity [Figure 4 (POEM) and Figure S5 (PtGA); see Supporting Information]. While >90% of participants with mild AD had either ‘no days’ or ‘1–2 days’ of sleep disturbances per week, more than 70% of those with severe AD had sleep disturbances at least 5 days in the past week. Individual geographic regions showed similar shifts towards more frequent sleep disturbances at higher AD severity [Figures S6 (POEM) and S7 (PtGA); see Supporting Information]. No clear patterns were observed based on age for either sleep quality or sleep disturbances frequency.

<figure><img src="image_4.png" /><figcaption>**Figure 2** Worst skin pain severity over the past 24 h, assessed using a Numerical Rating Scale (NRS; 0–10), by atopic dermatitis (AD) severity based on the Patient-Oriented Eczema Measure. (a) <6 years old; (b) 6 to <12 years old; (c) 12 to <18 years old. Higher scores on the NRS indicate higher pain severity.</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>**Figure 3** Sleep quality the past night, assessed using a numerical rating scale (0–10) by dermatitis severity based on the Patient-Oriented Eczema Measure. (a) 6 months to <6 years old; (b) 6 to <12 years old; (c) 12 to <18 years old. Higher scores on the NRS indicate poorer sleep quality.</figcaption></figure>

## Health-related quality-of-life

Across age groups and geographic regions, mean IDQOL and CDLQI scores increased with more severe AD [Figure 5 (POEM) and Figure S8 (PtGA)]; see *Supporting Information*, indicating lower HRQoL. However, standard deviations were large and severe AD was present in a low number of participants. Mean CDLQI scores indicated very large effects on HRQoL among those with moderate and severe AD (Figure 5b-d and Figure S8B-D).

## Impact on school attendance

The number of school days missed in the past 4 weeks due to AD ranged across regions and age groups from 1.4–7.5 days

in mild AD, to 3.2–10.4 days for moderate and 2.0–25.3 days for severe (Figure 6; POEM), with similar results for PtGA severity (Figure S9; see *Supporting Information*). There was large variability and not all pairwise comparisons were significant. No clear trends in missed school days were observed with regard to age groups.

## Atopic comorbidities

Across all respondents, 92.5% of participants reported the presence of at least one atopic comorbidity. The proportion of participants with at least one atopic comorbidity was generally incrementally higher with increasing AD severity assessed on both POEM (Figure 7) and PtGA (Figure S10; see *Supporting Information*). Based on POEM severity, the
<figure><img src="image_6.png" /><figcaption>**Figure 4** Overall frequency of sleep disturbances in the past week, assessed using the sleep item of the Patient-Oriented Eczema Measure (POEM), by age and atopic dermatitis severity based on POEM.</figcaption></figure>

proportions of participants with at least one atopic comorbid-
ity ranged from 76.5% to 96.6% for mild, 80.2% to 99.9%
for moderate and 73.6% to 100% for severe AD (Figure 7);
ranges were similar for PtGA severity (Figure S10). Based on
POEM (Figure 7), there appeared to be a slight increase in
prevalence with increasing age, with ranges of 73.6–100%,
79.2–100% and 83.0–100% for 6 months to < 6 years, 6
to < 12 years, and 12 to < 18 years, respectively.

Across age groups and regions, 58.6–91.7% of partici-
pants reported at least one of the overlapping atopic comor-
bidities of hay fever, allergic rhinitis or seasonal allergies,
representing the most prevalent atopic condition. Asthma
was the second most frequent atopic comorbidity, with
prevalence of 57.4–58.5%.

Discussion

This large, international web-based survey showed a high
multidimensional burden associated with AD that is com-
parable in infants, children and adolescents and across geo-
graphic regions. This burden was higher with more severe
AD, as previously reported among adults with AD.³,⁴ While
paediatric participants with moderate or severe AD had
higher levels of itch, skin pain, sleep problems and greater
impairment of HRQoL, indicative of a moderate-to-high
impact of AD, even those with mild AD reported substan-
tial effects of AD on these outcomes. A potential reason
for the substantial burden among participants with mild AD
may be that AD is a fluctuant disease and because severity
was captured for the week prior to the survey, participants
who were considered to have mild disease may have been
moderate or severe previously. A higher burden was also

observed among those with severe AD relative to moder-
ate AD. However, comparisons between AD severity levels
were not always statistically significant, likely as a result of
large inter-participant variability and/or small sample sizes
in some of the subgroups. Reported outcomes were con-
sistent between POEM- and PtGA-based assessments of
AD severity, although a slightly higher burden among par-
ticipants with mild AD and a corresponding lower burden
among those with moderate AD was observed on several
outcomes when assessed using PtGA.

This study was unique in evaluating three age groups
that encompassed infancy through adolescence, and there
did not appear to be any patterns that could be ascribed
to differences in age, although such differences were not
formally tested. There was also variability across geographic
regions, and no clear patterns were observed except for
a consistent tendency towards a lower reported burden in
East Asia on most outcomes. While it is possible that at
least some of the variability across geographic regions may
have resulted from cultural differences in survey responses,
it should also be considered that this variability may relate to
the clinical and immunological heterogeneity of AD that has
been reported across geographic regions.²²,²³

Outcomes assessed using NRS scores (itch, skin pain and
sleep quality) were comparable in magnitude across geo-
graphic regions. While itch is the hallmark symptom of AD,
skin pain is increasingly recognized as an important symp-
tom of AD in adults²⁴⁻²⁶ and, along with sleep disturbances,
these three symptoms represent a triad of the most com-
mon complaints of adults with AD;²⁷ pain may be at least
partially independent of itch, as they only moderately corre-
late in AD.²⁸,²⁹ The results of this study further support pain
as part of the paediatric burden of AD,⁸ especially among
<figure><img src="image_7.png" /><figcaption>**Figure 5** Effects of atopic dermatitis (AD) on quality of life in children and adolescents by AD severity based on Patient-Oriented Eczema Measure (POEM). (a) Parent-reported Infant's Dermatology Quality of Life (IDQOL) among children < 4 years old and those 4 to < 12 years old whose parents did not agree to pass control. Self-reported Children's Dermatology Life Quality Index (CDLQI) in participants (b) 4 to < 6 years old whose parents agreed to pass control, (c) 6 to < 12 years old whose parents agreed to pass control and (d) 12 to < 18 years old. Higher scores on both IDQOL and CDLQI indicate poorer quality of life, with CDLQI bands indicative of the magnitude of effect of AD on a child's life by scores 0-1 (no effect), 2-6 (small effect), 7-12 (moderate effect), 13-18 (very large effect) and 19-30 (extremely large effect).¹⁸,¹⁹</figcaption></figure>
<figure><img src="image_8.png" /><figcaption>**Figure 6** Days missed from school in the last 4 weeks by atopic dermatitis (AD) severity based on the Patient-Oriented Eczema Measure. (a) 4–5 years old; (b) 6 to < 12 years old; (c) 12 to < 18 years old.</figcaption></figure>

those with moderate or severe AD. Sleep was substantially impaired based on frequency of sleep disturbances and NRS scores, which appeared to parallel NRS scores for itch and pain. These results are consistent with other studies that reported an impact of AD on sleep quality and quantity in paediatric populations,³⁰⁻³³ with greater impairment of sleep quality at higher levels of AD severity.³¹,³³ Furthermore, an association between sleep disturbances and AD in children was documented objectively using actigraphy, and these disturbances were shown to be independent of itch/scratching.³⁰,³⁴

Sleep problems associated with AD may be especially relevant in a paediatric population.⁶,³⁰ In addition to contributing to reductions in overall health³² and HRQoL in children,³⁰,³³,³⁵ sleep disturbances may be associated with in-class daytime

sleepiness and poor school behaviour,³⁰,³⁶ increased sedentary behaviour,³⁷ and result in a higher likelihood of attention deficit hyperactivity disorder and behavioural problems.³⁸,³⁹

An important aspect of this study concerns the potential impact of AD on school attendance. An association between AD and chronic school absenteeism was previously suggested but with limited quantitative data.⁴⁰⁻⁴² The current study indicates the magnitude of this problem, especially with regard to more chronic absenteeism with increasing AD severity; the mean number of absences generally indicated a week or more of school days was missed in the past month among those with moderate or severe AD. This absenteeism, combined with the high rates of sleep impairment, which was suggested to result in teacher-reported daytime sleepiness,³⁰ supports the potential
<figure><img src="image_9.png" /><figcaption>**Figure 7** Proportion of participants with at least one atopic comorbidity by atopic dermatitis (AD) severity based on the Patient-Oriented Eczema Measure (POEM). (a) 6 months to < 6 years old; (b) 6 to < 12 years old; (c) 12 to < 18 years old.</figcaption></figure>

for AD to affect school performance. Although two studies reported that AD was not associated with negative effects on academic achievement,⁴³,⁴⁴ both of those studies were conducted in adolescents. More recent longitudinal studies suggested that AD reduces educational attainment relative to those without AD,⁴⁵,⁴⁶ but the role of school absenteeism on subsequent educational impairment was not evaluated. Nevertheless, the implications of these studies combined with the results of the current analysis imply that early intervention to control AD may have short-term benefits on school performance and long-term benefits on academic achievement.

Consistent with other studies that showed significant correlations of decreased HRQoL with increased AD severity,³³,³⁵,⁴⁷,⁴⁸ greater impairment was reported on the IDQOL and CDLQI with increasing AD severity. While the mean CDLQI scores suggested at least ‘very large effects’ of moderate and severe AD, even those with mild AD reported moderate effects. The magnitude of these effects is consistent with a meta-analysis which reported that the impact of AD on HRQoL in children is greater than the impact of psoriasis and other common skin conditions.¹⁹

A very high percentage (92.5%) of the paediatric participants with diagnosed AD reported at least one atopic
comorbidity. This proportion is substantially higher than the 59% of a real-world population of children < 12 years old with AD.⁷ Even considering the same age group, the current study found that 73.6–100% of children < 12 years old had at least one atopic comorbidity. While atopic comorbidities tended to increase slightly with increasing age and with AD severity, even those with mild AD were characterized by a substantial atopic comorbidity burden.

The strengths of this study are the external validity and generalizability resulting from the large sample size and use of ISAAC criteria combined with being told by a physician that they suffer from eczema as a consistent method for reliably identifying AD across countries. Participant selection that provided broad representation of populations in each country can also be considered a strength, although pooling of countries within geographic regions may have contributed to the observed variability resulting from cultural differences across countries even within the same geographic region. Study limitations include the use of outcomes that were based on self-report by participants or their parents, introducing the potential for misclassification, recall bias and variability in responses. Furthermore, not all outcomes were assessed using validated measures. Because use of an online survey for data collection presupposes computer literacy and internet access, this approach may represent a form of selection bias. Detection bias should also be considered when interpreting comorbidity data, as all participants were noted to be 'diagnosed' AD cases and may have had more interaction with the healthcare system compared with participants without AD. Finally, the lack of representation of African countries should also be considered a limitation.

In conclusion, this study provides a global perspective on the burden of AD in paediatric populations across five geographic regions. While variability was observed across regions and age groups, the results consistently demonstrate that AD is associated with a substantial and multidimensional disease burden in children and adolescents. Although the magnitude of this burden is higher with greater disease severity, AD affects all patients, and even patients with mild AD report a substantial disease burden that includes impaired HRQoL. Of particular relevance are the observations that skin pain and sleep disturbance parallel the burden of itch and the chronic school absenteeism across all severity levels, which have potential implications for impaired academic performance. In addition to emphasizing the need for appropriate treatment in the paediatric population regardless of AD severity, these results highlight the importance of incorporating a broader assessment that goes beyond clinical signs and symptoms by taking into account the impact of AD and its management on the function and daily life of children afflicted with this disease.

## Acknowledgements

Medical writing support was provided by E. Jay Bienen PhD, an independent medical writer, and was funded by Sanofi and Regeneron Pharmaceuticals, Inc.

## Funding sources

This study was funded by Regeneron.

## Conflicts of interest

A full list of the authors' conflicts of interest is available in Appendix S1 (see Supporting Information).

## Data availability

All data generated during this study are included in the published article and supplementary material.

## Ethics statement

Data collection was according to ethical codes of the British Healthcare Business Intelligence Association (BHBIA), the European Society for Opinion and Marketing Research (ESOMAR) and European Pharmaceutical Market Research Association (EphMRA), and was compliant with the EU General Data Protection Regulation (GDPR) and the US Health Insurance Portability and Accountability Act (HIPAA). All parents provided informed consent prior to participation; adolescents were required to provide assent in addition to parental consent.

## Supporting Information

Additional Supporting Information may be found in the online version of this article at the publisher's website.

## References

1. Irvine AD, Mina-Osorio P. Disease trajectories in childhood atopic dermatitis: an update and practitioner's guide. *Br J Dermatol* 2019; **181**:895-906.

2. Lee HH, Patel KR, Singam V et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. *J Am Acad Dermatol* 2019; **80**:1526-32.

3. Simpson EL, Guttman-Yassky E, Margolis DJ et al. Association of inadequately controlled disease and disease severity with patient-reported disease burden in adults with atopic dermatitis. *JAMA Dermatol* 2018; **154**:903-12.

4. de Bruin-Weller M, Gadkari A, Auziere S et al. The patient-reported disease burden in adults with atopic dermatitis: a cross-sectional study in Europe and Canada. *J Eur Acad Dermatol Venereal* 2020; **34**:1026-36.

5. Luger T, Romero WA, Gruben D et al. Clinical and humanistic burden of atopic dermatitis in Europe: analyses of the National Health and Wellness Survey. *Dermatol Ther (Heidelb)* 2022; **12**:949-69.

6. Fishbein AB, Cheng BT, Tilley CC et al. Sleep disturbance in school-aged children with atopic dermatitis: prevalence and severity in a cross-sectional sample. *J Allergy Clin Immunol Pract* 2021; **9**:3120-9 e3.

7. Paller AS, Guttman-Yassky E, Schuttelaar MLA et al. Disease characteristics, comorbidities, treatment patterns and quality of life impact in children &lt;12 years old with atopic dermatitis: interim results from the PEDISTAD Real-World Registry. *J Am Acad Dermatol* 2022; **87**:1104-8. https://doi.org/10.1016/j.jaad.2022.01.018.

8. Cheng BT, Paller AS, Griffith JW et al. Burden and characteristics of skin pain among children with atopic dermatitis. *J Allergy Clin Immunol Pract* 2022; **10**:1104-6 e1.

9. Silverberg JI, Barbarot S, Gadkari A et al. Atopic dermatitis in the pediatric population: a cross-sectional, international epidemiologic study. *Ann Allergy Asthma Immunol* 2021; **126**:417-28.
10 Barbarot S, Silverberg JI, Gadkari A *et al.* The family impact of atopic dermatitis in the pediatric population: results from an international cross-sectional study. *J Pediatr* 2022; **246**:220-6.e5.

11 Asher MI, Keil U, Anderson HR *et al.* International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. *Eur Respir J* 1995; **8**:483-91.

12 Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in children: clinical features, pathophysiology, and treatment. *Immunol Allergy Clin North Am* 2015; **35**:161-83.

13 Chalmers JR, Simpson E, Apfelbacher CJ *et al.* Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative). *Br J Dermatol* 2016; **175**:69-79.

14 Charman CR, Venn AJ, Ravenscroft JC *et al.* Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods. *Br J Dermatol* 2013; **169**:1326-32.

15 Lei D, Yousaf M, Janmohamed SR *et al.* Validation of four single-item patient-reported assessments of sleep in adult atopic dermatitis patients: sleep in atopic dermatitis. *Ann Allergy Asthma Immunol* 2020; **124**:261-6.

16 Lewis-Jones MS, Finlay AY. The Children's Dermatology Life Quality Index (CDLQI): initial validation and practical use. *Br J Dermatol* 1995; **132**:942-9.

17 Lewis-Jones MS, Finlay AY, Dykes PJ. The Infants' Dermatitis Quality of Life Index. *Br J Dermatol* 2001; **144**:104-10.

18 Waters A, Sandhu D, Beattie P *et al.* Severity stratification of Children's Dermatology Life Quality Index (CDLQI) scores [abstract]. *Br J Dermatol* 2010; **163** (Suppl. 1):S121.

19 Olsen JR, Gallacher J, Finlay AY *et al.* Quality of life impact of childhood skin conditions measured using the Children's Dermatology Life Quality Index (CDLQI): a meta-analysis. *Br J Dermatol* 2016; **174**:853-61.

20 Deville JC. A theory of quota surveys. *Surv Methodol* 1991; **17**:163-81.

21 Flohr C, Weinmayr G, Weiland SK *et al.* How well do questionnaires perform compared with physical examination in detecting flexural eczema? Findings from the International Study of Asthma and Allergies in Childhood (ISAAC) phase two. *Br J Dermatol* 2009; **161**:846-53.

22 Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. *J Am Acad Dermatol* 2019; **80**:390-401.

23 Suaini NHA, Tan CPT, Loo EXL *et al.* Global differences in atopic dermatitis. *Pediatr Allergy Immunol* 2021; **32**:23-33.

24 Vakharia PP, Chopra R, Sacotte R *et al.* Burden of skin pain in atopic dermatitis. *Ann Allergy Asthma Immunol* 2017; **119**:548-52.

25 Huet F, Shourick J, Seite S *et al.* Pain in atopic dermatitis: an online population-based survey. *Acta Derm Venereol* 2020; **100**:adv00198.

26 Silverberg JI, Gelfand JM, Margolis DJ *et al.* Pain is a common and burdensome symptom of atopic dermatitis in United States adults. *J Allergy Clin Immunol Pract* 2019; **7**:2699-706.

27 Wittkowski A, Richards HL, Griffiths CE *et al.* Illness perception in individuals with atopic dermatitis. *Psychol Health Med* 2007; **12**:433-44.

28 Kaaz K, Szepietowski JC, Matusiak L. Influence of itch and pain on sleep quality in atopic dermatitis and psoriasis. *Acta Derm Venereol* 2019; **99**:175-80.

29 Silverberg JI, Simpson EL, Guttman-Yassky E *et al.* Dupilumab significantly modulates pain and discomfort in patients with atopic dermatitis: post hoc analysis of five randomized clinical trials. *Dermatitis* 2020; **32**:S81-91.

30 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**:336-41.

31 Ramirez FD, Chen S, Langan SM *et al.* Association of atopic dermatitis with sleep quality in children. *JAMA Pediatr* 2019; **173**:e190025. https://doi.org/10.1001/jamapediatrics.2019.0025.

32 McKenzie C, Paller AS, Fishbein A *et al.* Association between the longitudinal course of AD, sleep disturbance and overall health in United States children. *J Allergy Clin Immunol Pract* 2020; **8**:812-14.

33 Kong TS, Han TY, Lee JH *et al.* Correlation between severity of atopic dermatitis and sleep quality in children and adults. *Ann Dermatol* 2016; **28**:321-6.

34 Reuveni H, Chapnick G, Tal A *et al.* Sleep fragmentation in children with atopic dermatitis. *Arch Pediatr Adolesc Med* 1999; **153**:249-53.

35 Xu X, van Galen LS, Koh MJA *et al.* Factors influencing quality of life in children with atopic dermatitis and their caregivers: a cross-sectional study. *Sci Rep* 2019; **9**:15990.

36 Manjunath J, Silverberg NB, Silverberg JI. Association of atopic dermatitis with poor school behaviours in US children and adolescents. *J Eur Acad Dermatol Venereol* 2022; **36**:e346-8.

37 Strom MA, Silverberg JI. Associations of physical activity and sedentary behavior with atopic disease in United States children. *J Pediatr* 2016; **174**:247-53 e3.

38 Strom MA, Fishbein AB, Paller AS *et al.* Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults. *Br J Dermatol* 2016; **175**:920-9.

39 Manjunath J, Silverberg JI. Atopic dermatitis is associated with multiple behavioral problems in US children and adolescents. *Dermatitis* 2022; **33** (Suppl. 6):S52-60. https://doi.org/10.1097/DER.0000000000000749.

40 Bridgman AC, Eshtiaghi P, Cresswell-Melville A *et al.* The burden of moderate to severe atopic dermatitis in Canadian children: a cross-sectional survey. *J Cutan Med Surg* 2018; **22**:443-4.

41 Wan J, Margolis DJ, Mitra N *et al.* Racial and ethnic differences in atopic dermatitis-related school absences among US children. *JAMA Dermatol* 2019; **155**:973-5.

42 Cheng BT, Silverberg JI. Association of pediatric atopic dermatitis and psoriasis with school absenteeism and parental work absenteeism: a cross-sectional United States population-based study. *J Am Acad Dermatol* 2021; **85**:885-92. https://doi.org/10.1016/j.jaad.2021.02.069.

43 Brew BK, Soderberg J, Lundholm C *et al.* Academic achievement of adolescents with asthma or atopic disease. *Clin Exp Allergy* 2019; **49**:892-9.

44 Kim SY, Kim MS, Park B *et al.* Allergic rhinitis, atopic dermatitis, and asthma are associated with differences in school performance among Korean adolescents. *PLoS One* 2017; **12**:e0171394.

45 Schmidt SAJ, Mailhac A, Darvalics B *et al.* association between atopic dermatitis and educational attainment in Denmark. *JAMA Dermatol* 2021; **157**:1-9.

46 Palsson K, Slagor RM, Flachs EM *et al.* Childhood atopic dermatitis is associated with a decreased chance of completing education later in life: a register-based cohort study. *J Eur Acad Dermatol Venereol* 2021; **35**:1849-58.

47 Weisshaar E, Diepgen TL, Bruckner T *et al.* Itch intensity evaluated in the German Atopic Dermatitis Intervention Study (GADIS): correlations with quality of life, coping behaviour and SCORAD severity in 823 children. *Acta Derm Venereol* 2008; **88**:234-9.

48 Monti F, Agostini F, Gobbi E *et al.* Quality of life measures in Italian children with atopic dermatitis and their families. *Ital J Pediatr* 2011; **37**:59.