BJD
British Journal of Dermatology
E P I DE M I O L O G Y
Atopic and nonatopic eczema in adolescence: is there a difference?* €m,4 I. Kull4,5 and C.-F. Wahlgren1,6 E.K. Johansson,1,2 N. Ballardini,3,4 A. Bergstro 1
Dermatology and Venereology Unit, Department of Medicine Solna and 4Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Dermatological and Venereal Clinic and 3Sachs’ Children and Youth Hospital, S€odersjukhuset, Stockholm, Sweden 5 Department of Clinical Science and Education, S€odersjukhuset, Karolinska Institutet, Stockholm, Sweden 6 Department of Dermatology, Karolinska University Hospital Solna, Stockholm, Sweden 2
Linked Comment: von Kobyletzki, Br J Dermatol 2015; 173: 889.
Summary Correspondence Emma K. Johansson. E-mail: [email protected]
Accepted for publication 27 April 2015
Funding sources Funding for this study was provided by the Swedish Asthma and Allergy Association Research Foundation, the Welander–Finsen Foundation, Karolinska Institutet, Stockholm County Council, Swedish Research Council for Working Life and Social Welfare and the European Commission’s Seventh Framework 29 Programme MeDALL grant agreement 261357
Conflicts of interest None declared *Plain language summary available online DOI 10.1111/bjd.13901
Background There is limited information on clinical manifestations of atopic eczema (AE) and non-AE in teenagers. Objectives To describe the characteristics of adolescent eczema in the general population and to identify potential differences between AE and non-AE in teenagers. Methods Overall, 3108 teenagers were included from the population-based BAMSE cohort and 2529 of these teenagers provided blood samples for analysis of specific IgE. At age 16 years, the teenagers answered questionnaires regarding the symptoms of eczema, asthma and rhinitis for the previous year. Results The prevalence of eczema in adolescence was 96% (n = 297). More girls than boys had eczema (125% vs. 65%; P < 0001). The age at onset was usually within the first 2 years of life (488%), but onset in adolescence was also common (256%). Eczema was mild in 727% of cases, moderate in 168% and severe in 104%. Body folds were most frequently affected (734%). More than half of the teenagers with eczema had AE (59%). The teenagers with AE had more severe and more chronic eczema. Onset in infancy was most common in AE and onset in adolescence was most common in non-AE. There were no major differences in location or seasonal variance between AE and non-AE in adolescence. Conclusions AE is more common than non-AE among teenagers. More than one in four teenagers with eczema has moderate-to-severe disease. Onset in adolescence is common, especially for non-AE. AE in adolescence has an earlier onset and is more chronic and more severe than non-AE.
What’s already known about this topic?
• •
The 1-year prevalence of eczema in adolescence is around 10%. More girls than boys have eczema in adolescence.
What does this study add?
• • •
962
One in four teenagers with eczema at age 16 years have onset in adolescence and one in four adolescents with eczema have moderate-to-severe disease. Atopic eczema (AE) in adolescence has an earlier onset and is more chronic and more severe than non-AE. Location and seasonality do not differ between AE and non-AE in adolescence.
British Journal of Dermatology (2015) 173, pp962–968
© 2015 British Association of Dermatologists
Eczema in adolescence, E.K. Johansson et al. 963
Eczema (atopic dermatitis)1 is an inflammatory skin disease characterized by skin dryness and itchy skin lesions. It has a negative impact on the quality of life of patients.2 The prevalence has increased in Sweden3 and in other countries4 over past decades; 15–30% of children and 2–10% of adults are affected.2 Clinical manifestations with age-specific locations in infancy, childhood and adulthood have been described, but this information is derived mainly from patients seen in hospitals.5 However, about 30% of schoolchildren with symptoms of allergy-related disease have not visited a doctor for their symptoms.6 Thus, the characteristics of eczema in adolescence in the general population have not been previously described in detail even though eczema is common in teenagers. According to the World Allergy Organization nomenclature, eczema is divided into atopic eczema (AE) and non-AE. The classification of AE includes the presence of IgE antibodies to either food or inhalant allergens. Non-AE in children may evolve into AE, and the diagnosis of AE and non-AE cannot be reached without an IgE-antibody determination or skin prick test.1 A study among 5-year-old children suggests that AE and non-AE are two different entities. The AE variant is more common, presents early in infancy, has a male predominance and is more persistent, and the non-AE variant has later onset and no relation to asthma or hay fever.7 Others argue that IgE sensitization is associated with an increased risk of more severe and more persistent eczema, but it is not a useful diagnostic tool when other clinical signs have been taken into account.8 Data on differences concerning clinical presentation and risk factors between AE and non-AE in teenagers are scarce. The aim of this study was to describe the characteristics of adolescent eczema in the general population, and to identify potential differences in the clinical manifestations of AE and non-AE in teenagers.
exposure to common contact allergens, hand eczema, quality of life and the use of moisturizers and topical glucocorticoids. The teenagers were invited to participate in a clinical examination, which included giving blood samples. Serum collected at age 16 years was analysed for IgE antibodies to common inhalant allergens (cat, dog, horse, birch, timothy, mugwort, Dermatophagoides pteronyssinus and Cladosporium herbarum, olive, pellitory) with Phadiatopâ (Thermo Fisher, Uppsala, Sweden) and a mix of common food allergens (milk, egg, cod, soy, peanut and wheat) with Fx5 ImmunoCAP systemâ (Thermo Fisher). Study population In the follow-up at age 16 years, completed in March 2013, 76% (n = 3115) of the teenagers in the original cohort answered the questionnaires and 64% (n = 2605) of the teenagers participated in the clinical examination. Blood samples were obtained from 62% (n = 2549) of the teenagers. The study population consisted of 3108 teenagers (76% of the original cohort) who had answered the questions regarding eczema. Their mean age was 166 years (range 157–190). Data on atopic sensitization at age 16 years were available for 814% (2529 of 3108) of these teenagers. Figure 1 shows a flowchart of the study population. Definition of outcome and background variables Health outcomes at age 16 years were based on questionnaires answered by the study subjects. Eczema at age 16 years was defined as dry skin and itchy skin rash on specific locations (arm/leg flexure, wrist/ankle and/or neck) reported by the teenager in the last 12 months. Atopic sensitization was defined as positive Phadiatop and/or Fx5 (allergen-specific IgE ≥ 035 kU L 1) at age 16 years.
Patients and methods Study design and setting The BAMSE project is a longitudinal population-based birth cohort in which children were included at birth and followed throughout their childhood.9 The parents of all children born between 1994 and 1996, living in predefined areas of Stockholm County, were invited to participate. The final study cohort of 4089 children constituted 75% of the eligible children. Detailed data on residential characteristics, environmental factors and parental allergy were obtained from a baseline parental questionnaire when the child was 2 months old. When the children were aged 1, 2, 4, 8, 12 and 16 years old, the parents filled out questionnaires about manifestations of eczema, asthma and rhinitis during the previous 12 months. The children also filled out the questionnaires at 12 and 16 years of age. The questionnaire at age 16 years covered questions about dry skin, itchy skin rash, its localization and seasonal variation and nocturnal sleep disturbance due to itching. There were also questions regarding contact allergy, © 2015 British Association of Dermatologists
Fig 1. Flowchart of the study population. British Journal of Dermatology (2015) 173, pp962–968
964 Eczema in adolescence, E.K. Johansson et al.
The definitions of additional outcome and background variables are provided in this article’s online supplement (Data S1; see Supporting Information).
with STATA Statistical Software release 121 (StataCorp, College Station, TX, U.S.A.). Ethics
Evaluation of eczema severity To assess eczema severity, a modified scale of the BAMSE Eczema Severity Score (BESS) was used. BESS, scale 3–14, was constructed and used in the 12-year follow-up.10 In our study it was modified to BESS(3–12), scale 3–12, due to the way the questions were written in the questionnaire for those aged 16 years and based on the answers to the three questions shown in Table 1. Teenagers were classified as having mild (3–7), moderate (8–9) or severe eczema (10–12). Statistics Background characteristics were expressed as a percentage of the total number of individuals observed and 95% confidence intervals were calculated by applying a finite population factor. The prevalence of eczema, asthma and rhinitis was assessed over a 12-month period and expressed as a percentage of the total number of study subjects. For dichotomous variables v2-tests were used and P-values less than 005 were considered statistically significant. Study subjects with and without eczema were stratified for sex when the prevalence of asthma and rhinitis were calculated and when comparing AE with non-AE. All statistical calculations were performed
Table 1 Description of BAMSE Eczema Severity Score [BESS(3–12)] Questionnaire Score options Disease severity Has your sleep been disturbed by itching during the last 12 months?
1 2 3
Disease course For how long, in total, have you 1 had eczema over the last 12 months? 2 3 4 Extent of body surface involvement Where has the itchy rash been 2 located for the last 12 months?a 3 4 5 Total score 3–12
No Less often than once a week Once a week or more often < 1 month 1–3 months 4–6 months > 6 months 2 body sites 3–4 body sites 5–6 body sites > 6 body sites
When summarizing the score the teenagers were classified as having mild (3–7), moderate (8–9) or severe eczema (10–12). a The teenagers could choose between 14 different specified locations (scalp; face, ears, neck/throat, trunk, armpits, extensor surfaces of arms and legs, flexural surfaces of arms and legs, wrists/ ankles, hands, buttocks, inside of the thighs, genital area/groins, feet). The number of body sites was categorized. British Journal of Dermatology (2015) 173, pp962–968
This study was approved by the Regional Ethical Review Board at Karolinska Institutet, Stockholm. Informed consent was provided by teenagers and guardians.
Results The 3108 teenagers in the study population were comparable with the original cohort regarding the background factors of parental smoking at birth, maternal age and gestational age. There were minor significant differences concerning sex, socioeconomic status, heredity, any parent born outside of Scandinavia and exclusive breastfeeding for the first 4 months of life (Table S1; see Supporting Information). The prevalence of eczema in adolescence was 96% (297 of 3108). Eczema was significantly more common in girls than in boys [197 of 1579 (125%) vs. 100 of 1529 (65%)]. The prevalence of asthma was 76% and the prevalence of rhinitis was 271%. Of all teenagers who provided blood, 459% (1161 of 2529) showed some sensitization. Sensitization to airborne allergens (434%) was more common than sensitization to foods (132%). Data on sensitization were available for 246 (828%) of the teenagers with eczema. In this subgroup 593% (n = 146) had AE and 407% (n = 100) had non-AE. AE was more common in girls than in boys (71% vs. 43%; P = 0003). Also nonAE was more common in girls compared with boys (58% vs. 20%; P < 0001). Teenagers in the study population who did not provide blood more commonly had parents with low socioeconomic status compared with teenagers who did provide blood (191% vs. 151%; P = 0018). There were no other significant differences concerning background characteristics or eczema prevalence between the groups. Age at onset Onset before 2 years of age was prevalent among teenagers with eczema (145 of 297; 488%). The second most common age at onset was after 12 years of age (256%). Onset after age 12 years was more common among girls (P = 0016) while onset in the first year of life was more common in boys (P < 0001). There was no significant difference between sexes for other ages of onset. The onset of eczema for teenagers with AE occurred more often at 1 or 2 years of age compared with teenagers with non-AE (616% vs. 300%; P < 0001). This difference was still significant when the analysis was stratified for sex (Table 2). Among teenagers with non-AE, onset at 12 years of age or later was more common than in teenagers with AE (480% vs. 226%; P < 0001). A comparable pattern was seen when stratified for sex (Table 2). © 2015 British Association of Dermatologists
Eczema in adolescence, E.K. Johansson et al. 965 Table 2 Age at onset based on when eczema was reported (by teenager or parent) the first time in the BAMSE cohort
Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls
AE (n = 146)
Non-AE (n = 100)
n
%
n
%
P-value
418 57 33
13 4/24 9/76
13 17 12
< 0001 0001 0001
199 17 22
17 4/24 13/76
17 17 17
0572 0973 0473
89 6 11
15 4/24 11/76
15 17 14
0139 0120 0466
68 4 9
7 4/24 3/76
7 17 4
0963 0051 0222
68 2 10
8 3/24 5/76
8 12 7
0734 0052 0467
158 15 16
40 5/24 35/76
40 21 46
< 0001 0533 < 0001
1 year 61 30/53 31/93 2 years 29 9/53 20/93 4 years 13 3/53 10/93 8 years 10 2/53 8/93 12 years 10 1/53 9/93 16 years 23 8/53 15/93
Internal missing data ranged between 0 and 60%. Individuals with missing data were classified as having no disease for that particular follow-up. The analysis was stratified by sex: boys (n = 77; 53 with AE, 24 with non-AE) and girls (n = 169; 93 with AE, 76 with non-AE). Bold indicates statistically significant differences.
Severity Eczema was classified as mild in 727% of teenagers at 16 years of age, moderate in 168% and severe in 104%, with no significant difference between boys and girls. Disturbed night sleep once a week or more was reported by 61% and less than once a week by 158%. The duration of eczema over the last year was < 1 month in 502%, 1–3 months in 195%, 4–6 months in 84% and > 6 months in 219%. Severe eczema was more common among those with AE (Fig. 2). All of the variables included in the BESS were higher in those with AE than in those with non-AE. These included disturbed night sleep once a week or more in the last year (82% vs. 50%), duration of eczema > 6 months in the last year (247% vs. 200%) and eczema in more than six locations in the last year (185% vs. 80%). Eczema was more common in the winter than in other seasons (Fig. 3). There were no major differences in seasonal variation between AE and non-AE, or between the sexes. Location The teenagers with eczema over the last year reported where the eczema had been located. The majority had three locations © 2015 British Association of Dermatologists
Fig 2. Severity of eczema at 16 years of age among study participants with atopic eczema (AE) and non-AE. Each bar illustrates the proportion of teenagers with mild, moderate or severe eczema. NS, not significant.
each and very few reported > 10 locations. The flexural surfaces of the extremities were the most frequently affected (734%) (Fig. 4) with no significant difference between the sexes (720% vs. 741%), nor between AE and non-AE groups (760% vs. 670%). The extensor surfaces of the extremities were more commonly affected in boys than girls (470% vs. 345%; P = 0037). Teenagers with AE had eczema located on the ears more frequently than those with non-AE (110% vs. 30%; P = 0022), and tended to have more eczema on the face (247% vs. 150%; P = 0066). There were no other significant differences in eczema location between boys and girls, and no major differences between AE and non-AE groups. A larger proportion of teenagers with onset of eczema after 12 years of age had an itchy rash located only on the throat and/or the neck (i.e. no rash in body folds or wrists/ankles) compared with those with onset at other ages (24 of 76, 32% vs. 19 of 221, 86%; P < 0001). We therefore compared reported reactions to possible contact allergens in teenagers with onset at 16 years of age with those with onset at 12 years of age or earlier and there was no difference between the groups (data not shown). Eczema history among teenagers with eczema Almost 11% (32 of 297) of teenagers with eczema had chronic disease with eczema reported at every previous follow-up. Internal missing data ranged between 20 and 84% at each age as the teenagers had not participated in all earlier follow-ups. Individuals with missing data were classified as having no disease for that particular follow-up. Chronic eczema was more common among boys than girls (170% vs. 76%; P = 0014). Those with AE at age 16 years had a significantly higher prevalence of eczema in all previous follow-ups compared with teenagers with non-AE. Figure 5 illustrates the differences in the history of eczema from birth to 16 years among teenagers with AE and teenagers with non-AE. Almost one-third (329%) of British Journal of Dermatology (2015) 173, pp962–968
966 Eczema in adolescence, E.K. Johansson et al.
Fig 3. Seasonal variation of eczema among 16-year-old adolescents (n = 280). Each bar illustrates the proportion of teenagers with eczema in each month over the last year. There were 19 teenagers with no data on seasonality.
Fig 4. Proportions of teenagers with eczema on different locations in the last 12 months. Each subject could choose between 14 specified locations, and reported a mean of 35 (range 1–14) locations each (n = 297).
the teenagers with AE had reported eczema in four or five of the five previous questionnaires compared with only 130% of teenagers with non-AE. The majority (600%) of teenagers with non-AE reported eczema only at age 16 years or in one other previous questionnaire, which is twice as common when compared with adolescents with AE (308%).
Discussion This large population-based birth cohort with a follow-up rate of 76% at 16 years of age, and data on sensitization at age 16 years, gave us the opportunity to describe eczema, AE and non-AE in adolescence. The 1-year prevalence of eczema in adolescence was 96% and more girls than boys had eczema. Although age at onset usually occurred within the first 2 years of life (488%), onset in adolescence was also common (256%). More than one in four (273%) had moderate-tosevere eczema. The eczema was located mainly in body folds and on the neck/throat, but was also frequently present on the extensor surfaces of the extremities. AE was more prevalent than non-AE at 16 years of age. AE had earlier onset and British Journal of Dermatology (2015) 173, pp962–968
was more severe and more chronic compared with non-AE among adolescents. There were no major differences between AE and non-AE concerning seasonal variation or location. One strength of this study is the large number of study subjects with complete data up to 16 years of age. Due to the population-based design, our results on AE and non-AE are likely to be generalizable to populations with comparable rates of allergy-related diseases and background factors. A weakness of the study is that the classification of eczema was based on questionnaire data. However, the eczema definition used is rather strict compared with other epidemiological studies (e.g. Odhiambo et al.).11 To be classified as having eczema, the teenagers had to have experienced dry skin and also an itchy rash on one of three specific locations chosen from 14 specified body locations. This reduces the risk of misclassification in the eczema group. On the other hand this definition might underestimate the prevalence of eczema. It is possible that reported skin symptoms vary across different age groups and that teenagers either over- or underestimate the severity of their symptoms, for example xerosis. Moreover, it has been shown that questionnaires provide adequate © 2015 British Association of Dermatologists
Eczema in adolescence, E.K. Johansson et al. 967
(a)
Fig 5. Eczema history among teenagers with (a) atopic eczema (AE) and (b) non-AE. Previous eczema from age 1 year through to age 16 years among 16-year-old teenagers with eczema and data on sensitization (n = 246) in the BAMSE birth cohort. Missing data in one or more previous follow-ups is classified as no disease at that particular age. Each row contains 100 squares and each square represents 1% of the children. The course of each per cent of the subjects can be traced vertically. Filled boxes represent children with eczema. The different colours illustrate the number of questionnaires (one to six) in which eczema was reported; green for chronic eczema (eczema in six of six follow-ups), red for five of six, blue for four of six, orange for three of six, purple for two of six and yellow for one of six.
(b)
eczema prevalence estimates at population level.12 The tool for estimating eczema severity, BESS(3–12), is similar to the validated Nottingham Eczema Severity Score.13 However, BESS(3–12) has not been validated, which is a limitation of this study. The prevalence of eczema in adolescence is comparable with earlier results (73–123%).11,14–17 In the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, the global prevalence of eczema at 13–14 years of age was 73% (boys 62%, girls 83%) and the Swedish prevalence was 123%.11 In the 12-year follow-up in the BAMSE project the prevalence of eczema was 119%10 and in a British birth cohort from the Isle of Wight the prevalence at 18 years of age was 123%.17 The prevalence of eczema was lower in our study compared with the Isle of Wight cohort, possibly due to a stricter eczema definition. Our study also had a lower prevalence of eczema compared with the results of ISAAC due to the older age of our participants. Earlier studies have shown that eczema is more common in adolescent girls than in boys,11,17 and in the Isle of Wight cohort non-AE was significantly more common in girls, but AE was not.17 Our study confirms that adolescent eczema and non-AE are more common in girls, but unlike other studies17 we also found AE to be more common in girls, probably due to the larger study population. The prevalence of severe eczema (104%) was higher in our study compared with other population-based studies that © 2015 British Association of Dermatologists
included children. However, these studies included preschool13,18,19 and preadolescent children.10 In the ISAAC study, severe eczema was defined as ‘disturbed night sleep one or more nights per week’ resulting in a prevalence of severe eczema of 00–58% worldwide and 07% in Sweden.11 If the ISAAC definition of severe eczema had been used in our study, 61% would have been classified as having severe eczema. The proportion of severe eczema seems to be higher among 16-year-old adolescents in Stockholm than in earlier reports among younger children. This could partly be due to our strict eczema definition, which might have excluded some milder cases. Another explanation could be that eczema prevalence decreases with age in childhood and that children with mild eczema early in life outgrow the disease before adolescence. It is possible that insufficient treatment of eczema increases when teenagers take responsibility for treatments previously managed by their parents, leading to more severe eczema. Eczema often starts in childhood with onset in infancy being most common.2,5 In our study population, the majority had onset in infancy, but a large proportion (256%) had onset in adolescence. In comparison, 284% of 16-years-old subjects with eczema in the National Child Development Study reported the onset of their eczema after age 7 years.20 Our study shows that onset in adolescence is common among teenagers with eczema. It would be interesting to explore whether the risk factors are the same for eczema that starts in British Journal of Dermatology (2015) 173, pp962–968
968 Eczema in adolescence, E.K. Johansson et al.
adolescence compared with eczema that starts earlier in life. In our study, the teenagers with onset after 12 years of age (compared with all others with eczema) had significantly more often fulfilled the diagnostic criteria of eczema due to an itchy rash located only on the throat and/or neck. We considered whether this large proportion could be explained by a misclassification of contact allergic dermatitis. However, answers concerning reactions to potential contact allergens did not differ between those with onset after 12 years of age and the teenagers with onset at other ages (data not shown). In the present study, we have described differences between AE and non-AE. However, AE does not differ from non-AE in reported clinical signs of eczema and therefore, based on current data, eczema should be considered as one disease phenotype. The analysis performed in this study was based on current sensitization, and non-AE in teenagers might evolve into AE at a later stage. Sensitization is associated with age at onset, disease severity and chronicity but does not justify splitting eczema into two different disease entities as opposed to two subtypes of one disease. Another possible explanation for our findings could be that eczema early in life increases the risk of sensitization through the inflamed skin.21,22 Thus, having AE in adolescence might be a consequence of a defective skin barrier caused by early onset eczema. In conclusion, we found that 96% of teenagers in Sweden had eczema and more than one in four had moderate-to-severe disease. AE was more common than non-AE and onset in adolescence was common among teenagers with eczema. AE in adolescence was characterized by earlier onset, chronicity and more severe current eczema compared with non-AE. However, AE and non-AE did not differ in location or seasonality.
Acknowledgments We would like to thank all the teenagers and parents who participated in the BAMSE project. We would also like to thank all the staff involved in the project, especially Eva Hallner and Sara Nilsson for their practical skills and handling of the study and the data.
References 1 Johansson SG, Bieber T, Dahl R et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004; 113:832–6. 2 Bieber T. Atopic dermatitis. N Engl J Med 2008; 358:1483–94. 3 Aberg N, Hesselmar B, Aberg B, Eriksson B. Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991. Clin Exp Allergy 1995; 25:815–19. 4 Williams H, Stewart A, von Mutius E et al. Is eczema really on the increase worldwide? J Allergy Clin Immunol 2008; 121: 947– 54. e15. 5 Rajka G. Natural history and clinical manifestations of atopic dermatitis. Clin Rev Allergy Immunol 1986; 4:3–26.
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6 Saval P, Fuglsang G, Madsen C, Osterballe O. Prevalence of atopic disease among Danish school children. Pediatr Allergy Immunol 1993; 4:117–22. 7 Kusel MM, Holt PG, de Klerk N, Sly PD. Support for 2 variants of eczema. J Allergy Clin Immunol 2005; 116:1067–72. 8 Johansson SG, Flohr C, Wahlgren CF, Williams H. Role of immunoglobulin E sensitization in eczema, previously referred to as atopic dermatitis. Expert Rev Clin Immunol 2005; 1:257–62. 9 Wickman M, Kull I, Pershagen G, Nordvall SL. The BAMSE project: presentation of a prospective longitudinal birth cohort study. Pediatr Allergy Immunol 2002; 13 (Suppl. 15):11–13. 10 Ballardini N, Kull I, S€ oderh€all C et al. Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort. Br J Dermatol 2013; 168:588–94. 11 Odhiambo JA, Williams HC, Clayton TO et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol 2009; 124: 1251–8 e23. 12 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. 13 Emerson RM, Charman CR, Williams HC. The Nottingham Eczema Severity Score: preliminary refinement of the Rajka and Langeland grading. Br J Dermatol 2000; 142:288–97. 14 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; 131:67–73. 15 Nissen SP, Kjaer HF, Host A et al. The natural course of sensitization and allergic diseases from childhood to adulthood. Pediatr Allergy Immunol 2013; 24:549–55. 16 Finnbogadottir AF, Ardal B, Eiriksson H et al. A long-term follow-up of allergic diseases in Iceland. Pediatr Allergy Immunol 2012; 23:181–5. 17 Ziyab AH, Raza A, Karmaus W et al. Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study. Clin Exp Allergy 2010; 40:1776–84. 18 Eller E, Kjaer HF, Host A et al. Development of atopic dermatitis in the DARC birth cohort. Pediatr Allergy Immunol 2010; 21:307–14. 19 B€ ohme M, Svensson A, Kull I et al. Clinical features of atopic dermatitis at two years of age: a prospective, population-based casecontrol study. Acta Derm Venereol 2001; 81:193–7. 20 Williams HC, Strachan DP. The natural history of childhood eczema: observations from the British 1958 birth cohort study. Br J Dermatol 1998; 139:834–9. 21 Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol 2010; 105:99–106; quiz 107–9, 117. 22 Brough HA, Liu AH, Sicherer S et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol 2015; 135:164–70.
Supporting Information Additional Supporting Information may be found in the online version of this article at the publisher’s website: Data S1. Definition of additional outcome and background variables. Table S1. Background characteristics of children in the original cohort and study population.
© 2015 British Association of Dermatologists
British Journal of Dermatology
E P I DE M I O L O G Y
Atopic and nonatopic eczema in adolescence: is there a difference?* €m,4 I. Kull4,5 and C.-F. Wahlgren1,6 E.K. Johansson,1,2 N. Ballardini,3,4 A. Bergstro 1
Dermatology and Venereology Unit, Department of Medicine Solna and 4Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Dermatological and Venereal Clinic and 3Sachs’ Children and Youth Hospital, S€odersjukhuset, Stockholm, Sweden 5 Department of Clinical Science and Education, S€odersjukhuset, Karolinska Institutet, Stockholm, Sweden 6 Department of Dermatology, Karolinska University Hospital Solna, Stockholm, Sweden 2
Linked Comment: von Kobyletzki, Br J Dermatol 2015; 173: 889.
Summary Correspondence Emma K. Johansson. E-mail: [email protected]
Accepted for publication 27 April 2015
Funding sources Funding for this study was provided by the Swedish Asthma and Allergy Association Research Foundation, the Welander–Finsen Foundation, Karolinska Institutet, Stockholm County Council, Swedish Research Council for Working Life and Social Welfare and the European Commission’s Seventh Framework 29 Programme MeDALL grant agreement 261357
Conflicts of interest None declared *Plain language summary available online DOI 10.1111/bjd.13901
Background There is limited information on clinical manifestations of atopic eczema (AE) and non-AE in teenagers. Objectives To describe the characteristics of adolescent eczema in the general population and to identify potential differences between AE and non-AE in teenagers. Methods Overall, 3108 teenagers were included from the population-based BAMSE cohort and 2529 of these teenagers provided blood samples for analysis of specific IgE. At age 16 years, the teenagers answered questionnaires regarding the symptoms of eczema, asthma and rhinitis for the previous year. Results The prevalence of eczema in adolescence was 96% (n = 297). More girls than boys had eczema (125% vs. 65%; P < 0001). The age at onset was usually within the first 2 years of life (488%), but onset in adolescence was also common (256%). Eczema was mild in 727% of cases, moderate in 168% and severe in 104%. Body folds were most frequently affected (734%). More than half of the teenagers with eczema had AE (59%). The teenagers with AE had more severe and more chronic eczema. Onset in infancy was most common in AE and onset in adolescence was most common in non-AE. There were no major differences in location or seasonal variance between AE and non-AE in adolescence. Conclusions AE is more common than non-AE among teenagers. More than one in four teenagers with eczema has moderate-to-severe disease. Onset in adolescence is common, especially for non-AE. AE in adolescence has an earlier onset and is more chronic and more severe than non-AE.
What’s already known about this topic?
• •
The 1-year prevalence of eczema in adolescence is around 10%. More girls than boys have eczema in adolescence.
What does this study add?
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962
One in four teenagers with eczema at age 16 years have onset in adolescence and one in four adolescents with eczema have moderate-to-severe disease. Atopic eczema (AE) in adolescence has an earlier onset and is more chronic and more severe than non-AE. Location and seasonality do not differ between AE and non-AE in adolescence.
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© 2015 British Association of Dermatologists
Eczema in adolescence, E.K. Johansson et al. 963
Eczema (atopic dermatitis)1 is an inflammatory skin disease characterized by skin dryness and itchy skin lesions. It has a negative impact on the quality of life of patients.2 The prevalence has increased in Sweden3 and in other countries4 over past decades; 15–30% of children and 2–10% of adults are affected.2 Clinical manifestations with age-specific locations in infancy, childhood and adulthood have been described, but this information is derived mainly from patients seen in hospitals.5 However, about 30% of schoolchildren with symptoms of allergy-related disease have not visited a doctor for their symptoms.6 Thus, the characteristics of eczema in adolescence in the general population have not been previously described in detail even though eczema is common in teenagers. According to the World Allergy Organization nomenclature, eczema is divided into atopic eczema (AE) and non-AE. The classification of AE includes the presence of IgE antibodies to either food or inhalant allergens. Non-AE in children may evolve into AE, and the diagnosis of AE and non-AE cannot be reached without an IgE-antibody determination or skin prick test.1 A study among 5-year-old children suggests that AE and non-AE are two different entities. The AE variant is more common, presents early in infancy, has a male predominance and is more persistent, and the non-AE variant has later onset and no relation to asthma or hay fever.7 Others argue that IgE sensitization is associated with an increased risk of more severe and more persistent eczema, but it is not a useful diagnostic tool when other clinical signs have been taken into account.8 Data on differences concerning clinical presentation and risk factors between AE and non-AE in teenagers are scarce. The aim of this study was to describe the characteristics of adolescent eczema in the general population, and to identify potential differences in the clinical manifestations of AE and non-AE in teenagers.
exposure to common contact allergens, hand eczema, quality of life and the use of moisturizers and topical glucocorticoids. The teenagers were invited to participate in a clinical examination, which included giving blood samples. Serum collected at age 16 years was analysed for IgE antibodies to common inhalant allergens (cat, dog, horse, birch, timothy, mugwort, Dermatophagoides pteronyssinus and Cladosporium herbarum, olive, pellitory) with Phadiatopâ (Thermo Fisher, Uppsala, Sweden) and a mix of common food allergens (milk, egg, cod, soy, peanut and wheat) with Fx5 ImmunoCAP systemâ (Thermo Fisher). Study population In the follow-up at age 16 years, completed in March 2013, 76% (n = 3115) of the teenagers in the original cohort answered the questionnaires and 64% (n = 2605) of the teenagers participated in the clinical examination. Blood samples were obtained from 62% (n = 2549) of the teenagers. The study population consisted of 3108 teenagers (76% of the original cohort) who had answered the questions regarding eczema. Their mean age was 166 years (range 157–190). Data on atopic sensitization at age 16 years were available for 814% (2529 of 3108) of these teenagers. Figure 1 shows a flowchart of the study population. Definition of outcome and background variables Health outcomes at age 16 years were based on questionnaires answered by the study subjects. Eczema at age 16 years was defined as dry skin and itchy skin rash on specific locations (arm/leg flexure, wrist/ankle and/or neck) reported by the teenager in the last 12 months. Atopic sensitization was defined as positive Phadiatop and/or Fx5 (allergen-specific IgE ≥ 035 kU L 1) at age 16 years.
Patients and methods Study design and setting The BAMSE project is a longitudinal population-based birth cohort in which children were included at birth and followed throughout their childhood.9 The parents of all children born between 1994 and 1996, living in predefined areas of Stockholm County, were invited to participate. The final study cohort of 4089 children constituted 75% of the eligible children. Detailed data on residential characteristics, environmental factors and parental allergy were obtained from a baseline parental questionnaire when the child was 2 months old. When the children were aged 1, 2, 4, 8, 12 and 16 years old, the parents filled out questionnaires about manifestations of eczema, asthma and rhinitis during the previous 12 months. The children also filled out the questionnaires at 12 and 16 years of age. The questionnaire at age 16 years covered questions about dry skin, itchy skin rash, its localization and seasonal variation and nocturnal sleep disturbance due to itching. There were also questions regarding contact allergy, © 2015 British Association of Dermatologists
Fig 1. Flowchart of the study population. British Journal of Dermatology (2015) 173, pp962–968
964 Eczema in adolescence, E.K. Johansson et al.
The definitions of additional outcome and background variables are provided in this article’s online supplement (Data S1; see Supporting Information).
with STATA Statistical Software release 121 (StataCorp, College Station, TX, U.S.A.). Ethics
Evaluation of eczema severity To assess eczema severity, a modified scale of the BAMSE Eczema Severity Score (BESS) was used. BESS, scale 3–14, was constructed and used in the 12-year follow-up.10 In our study it was modified to BESS(3–12), scale 3–12, due to the way the questions were written in the questionnaire for those aged 16 years and based on the answers to the three questions shown in Table 1. Teenagers were classified as having mild (3–7), moderate (8–9) or severe eczema (10–12). Statistics Background characteristics were expressed as a percentage of the total number of individuals observed and 95% confidence intervals were calculated by applying a finite population factor. The prevalence of eczema, asthma and rhinitis was assessed over a 12-month period and expressed as a percentage of the total number of study subjects. For dichotomous variables v2-tests were used and P-values less than 005 were considered statistically significant. Study subjects with and without eczema were stratified for sex when the prevalence of asthma and rhinitis were calculated and when comparing AE with non-AE. All statistical calculations were performed
Table 1 Description of BAMSE Eczema Severity Score [BESS(3–12)] Questionnaire Score options Disease severity Has your sleep been disturbed by itching during the last 12 months?
1 2 3
Disease course For how long, in total, have you 1 had eczema over the last 12 months? 2 3 4 Extent of body surface involvement Where has the itchy rash been 2 located for the last 12 months?a 3 4 5 Total score 3–12
No Less often than once a week Once a week or more often < 1 month 1–3 months 4–6 months > 6 months 2 body sites 3–4 body sites 5–6 body sites > 6 body sites
When summarizing the score the teenagers were classified as having mild (3–7), moderate (8–9) or severe eczema (10–12). a The teenagers could choose between 14 different specified locations (scalp; face, ears, neck/throat, trunk, armpits, extensor surfaces of arms and legs, flexural surfaces of arms and legs, wrists/ ankles, hands, buttocks, inside of the thighs, genital area/groins, feet). The number of body sites was categorized. British Journal of Dermatology (2015) 173, pp962–968
This study was approved by the Regional Ethical Review Board at Karolinska Institutet, Stockholm. Informed consent was provided by teenagers and guardians.
Results The 3108 teenagers in the study population were comparable with the original cohort regarding the background factors of parental smoking at birth, maternal age and gestational age. There were minor significant differences concerning sex, socioeconomic status, heredity, any parent born outside of Scandinavia and exclusive breastfeeding for the first 4 months of life (Table S1; see Supporting Information). The prevalence of eczema in adolescence was 96% (297 of 3108). Eczema was significantly more common in girls than in boys [197 of 1579 (125%) vs. 100 of 1529 (65%)]. The prevalence of asthma was 76% and the prevalence of rhinitis was 271%. Of all teenagers who provided blood, 459% (1161 of 2529) showed some sensitization. Sensitization to airborne allergens (434%) was more common than sensitization to foods (132%). Data on sensitization were available for 246 (828%) of the teenagers with eczema. In this subgroup 593% (n = 146) had AE and 407% (n = 100) had non-AE. AE was more common in girls than in boys (71% vs. 43%; P = 0003). Also nonAE was more common in girls compared with boys (58% vs. 20%; P < 0001). Teenagers in the study population who did not provide blood more commonly had parents with low socioeconomic status compared with teenagers who did provide blood (191% vs. 151%; P = 0018). There were no other significant differences concerning background characteristics or eczema prevalence between the groups. Age at onset Onset before 2 years of age was prevalent among teenagers with eczema (145 of 297; 488%). The second most common age at onset was after 12 years of age (256%). Onset after age 12 years was more common among girls (P = 0016) while onset in the first year of life was more common in boys (P < 0001). There was no significant difference between sexes for other ages of onset. The onset of eczema for teenagers with AE occurred more often at 1 or 2 years of age compared with teenagers with non-AE (616% vs. 300%; P < 0001). This difference was still significant when the analysis was stratified for sex (Table 2). Among teenagers with non-AE, onset at 12 years of age or later was more common than in teenagers with AE (480% vs. 226%; P < 0001). A comparable pattern was seen when stratified for sex (Table 2). © 2015 British Association of Dermatologists
Eczema in adolescence, E.K. Johansson et al. 965 Table 2 Age at onset based on when eczema was reported (by teenager or parent) the first time in the BAMSE cohort
Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls Onset at All Boys Girls
AE (n = 146)
Non-AE (n = 100)
n
%
n
%
P-value
418 57 33
13 4/24 9/76
13 17 12
< 0001 0001 0001
199 17 22
17 4/24 13/76
17 17 17
0572 0973 0473
89 6 11
15 4/24 11/76
15 17 14
0139 0120 0466
68 4 9
7 4/24 3/76
7 17 4
0963 0051 0222
68 2 10
8 3/24 5/76
8 12 7
0734 0052 0467
158 15 16
40 5/24 35/76
40 21 46
< 0001 0533 < 0001
1 year 61 30/53 31/93 2 years 29 9/53 20/93 4 years 13 3/53 10/93 8 years 10 2/53 8/93 12 years 10 1/53 9/93 16 years 23 8/53 15/93
Internal missing data ranged between 0 and 60%. Individuals with missing data were classified as having no disease for that particular follow-up. The analysis was stratified by sex: boys (n = 77; 53 with AE, 24 with non-AE) and girls (n = 169; 93 with AE, 76 with non-AE). Bold indicates statistically significant differences.
Severity Eczema was classified as mild in 727% of teenagers at 16 years of age, moderate in 168% and severe in 104%, with no significant difference between boys and girls. Disturbed night sleep once a week or more was reported by 61% and less than once a week by 158%. The duration of eczema over the last year was < 1 month in 502%, 1–3 months in 195%, 4–6 months in 84% and > 6 months in 219%. Severe eczema was more common among those with AE (Fig. 2). All of the variables included in the BESS were higher in those with AE than in those with non-AE. These included disturbed night sleep once a week or more in the last year (82% vs. 50%), duration of eczema > 6 months in the last year (247% vs. 200%) and eczema in more than six locations in the last year (185% vs. 80%). Eczema was more common in the winter than in other seasons (Fig. 3). There were no major differences in seasonal variation between AE and non-AE, or between the sexes. Location The teenagers with eczema over the last year reported where the eczema had been located. The majority had three locations © 2015 British Association of Dermatologists
Fig 2. Severity of eczema at 16 years of age among study participants with atopic eczema (AE) and non-AE. Each bar illustrates the proportion of teenagers with mild, moderate or severe eczema. NS, not significant.
each and very few reported > 10 locations. The flexural surfaces of the extremities were the most frequently affected (734%) (Fig. 4) with no significant difference between the sexes (720% vs. 741%), nor between AE and non-AE groups (760% vs. 670%). The extensor surfaces of the extremities were more commonly affected in boys than girls (470% vs. 345%; P = 0037). Teenagers with AE had eczema located on the ears more frequently than those with non-AE (110% vs. 30%; P = 0022), and tended to have more eczema on the face (247% vs. 150%; P = 0066). There were no other significant differences in eczema location between boys and girls, and no major differences between AE and non-AE groups. A larger proportion of teenagers with onset of eczema after 12 years of age had an itchy rash located only on the throat and/or the neck (i.e. no rash in body folds or wrists/ankles) compared with those with onset at other ages (24 of 76, 32% vs. 19 of 221, 86%; P < 0001). We therefore compared reported reactions to possible contact allergens in teenagers with onset at 16 years of age with those with onset at 12 years of age or earlier and there was no difference between the groups (data not shown). Eczema history among teenagers with eczema Almost 11% (32 of 297) of teenagers with eczema had chronic disease with eczema reported at every previous follow-up. Internal missing data ranged between 20 and 84% at each age as the teenagers had not participated in all earlier follow-ups. Individuals with missing data were classified as having no disease for that particular follow-up. Chronic eczema was more common among boys than girls (170% vs. 76%; P = 0014). Those with AE at age 16 years had a significantly higher prevalence of eczema in all previous follow-ups compared with teenagers with non-AE. Figure 5 illustrates the differences in the history of eczema from birth to 16 years among teenagers with AE and teenagers with non-AE. Almost one-third (329%) of British Journal of Dermatology (2015) 173, pp962–968
966 Eczema in adolescence, E.K. Johansson et al.
Fig 3. Seasonal variation of eczema among 16-year-old adolescents (n = 280). Each bar illustrates the proportion of teenagers with eczema in each month over the last year. There were 19 teenagers with no data on seasonality.
Fig 4. Proportions of teenagers with eczema on different locations in the last 12 months. Each subject could choose between 14 specified locations, and reported a mean of 35 (range 1–14) locations each (n = 297).
the teenagers with AE had reported eczema in four or five of the five previous questionnaires compared with only 130% of teenagers with non-AE. The majority (600%) of teenagers with non-AE reported eczema only at age 16 years or in one other previous questionnaire, which is twice as common when compared with adolescents with AE (308%).
Discussion This large population-based birth cohort with a follow-up rate of 76% at 16 years of age, and data on sensitization at age 16 years, gave us the opportunity to describe eczema, AE and non-AE in adolescence. The 1-year prevalence of eczema in adolescence was 96% and more girls than boys had eczema. Although age at onset usually occurred within the first 2 years of life (488%), onset in adolescence was also common (256%). More than one in four (273%) had moderate-tosevere eczema. The eczema was located mainly in body folds and on the neck/throat, but was also frequently present on the extensor surfaces of the extremities. AE was more prevalent than non-AE at 16 years of age. AE had earlier onset and British Journal of Dermatology (2015) 173, pp962–968
was more severe and more chronic compared with non-AE among adolescents. There were no major differences between AE and non-AE concerning seasonal variation or location. One strength of this study is the large number of study subjects with complete data up to 16 years of age. Due to the population-based design, our results on AE and non-AE are likely to be generalizable to populations with comparable rates of allergy-related diseases and background factors. A weakness of the study is that the classification of eczema was based on questionnaire data. However, the eczema definition used is rather strict compared with other epidemiological studies (e.g. Odhiambo et al.).11 To be classified as having eczema, the teenagers had to have experienced dry skin and also an itchy rash on one of three specific locations chosen from 14 specified body locations. This reduces the risk of misclassification in the eczema group. On the other hand this definition might underestimate the prevalence of eczema. It is possible that reported skin symptoms vary across different age groups and that teenagers either over- or underestimate the severity of their symptoms, for example xerosis. Moreover, it has been shown that questionnaires provide adequate © 2015 British Association of Dermatologists
Eczema in adolescence, E.K. Johansson et al. 967
(a)
Fig 5. Eczema history among teenagers with (a) atopic eczema (AE) and (b) non-AE. Previous eczema from age 1 year through to age 16 years among 16-year-old teenagers with eczema and data on sensitization (n = 246) in the BAMSE birth cohort. Missing data in one or more previous follow-ups is classified as no disease at that particular age. Each row contains 100 squares and each square represents 1% of the children. The course of each per cent of the subjects can be traced vertically. Filled boxes represent children with eczema. The different colours illustrate the number of questionnaires (one to six) in which eczema was reported; green for chronic eczema (eczema in six of six follow-ups), red for five of six, blue for four of six, orange for three of six, purple for two of six and yellow for one of six.
(b)
eczema prevalence estimates at population level.12 The tool for estimating eczema severity, BESS(3–12), is similar to the validated Nottingham Eczema Severity Score.13 However, BESS(3–12) has not been validated, which is a limitation of this study. The prevalence of eczema in adolescence is comparable with earlier results (73–123%).11,14–17 In the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, the global prevalence of eczema at 13–14 years of age was 73% (boys 62%, girls 83%) and the Swedish prevalence was 123%.11 In the 12-year follow-up in the BAMSE project the prevalence of eczema was 119%10 and in a British birth cohort from the Isle of Wight the prevalence at 18 years of age was 123%.17 The prevalence of eczema was lower in our study compared with the Isle of Wight cohort, possibly due to a stricter eczema definition. Our study also had a lower prevalence of eczema compared with the results of ISAAC due to the older age of our participants. Earlier studies have shown that eczema is more common in adolescent girls than in boys,11,17 and in the Isle of Wight cohort non-AE was significantly more common in girls, but AE was not.17 Our study confirms that adolescent eczema and non-AE are more common in girls, but unlike other studies17 we also found AE to be more common in girls, probably due to the larger study population. The prevalence of severe eczema (104%) was higher in our study compared with other population-based studies that © 2015 British Association of Dermatologists
included children. However, these studies included preschool13,18,19 and preadolescent children.10 In the ISAAC study, severe eczema was defined as ‘disturbed night sleep one or more nights per week’ resulting in a prevalence of severe eczema of 00–58% worldwide and 07% in Sweden.11 If the ISAAC definition of severe eczema had been used in our study, 61% would have been classified as having severe eczema. The proportion of severe eczema seems to be higher among 16-year-old adolescents in Stockholm than in earlier reports among younger children. This could partly be due to our strict eczema definition, which might have excluded some milder cases. Another explanation could be that eczema prevalence decreases with age in childhood and that children with mild eczema early in life outgrow the disease before adolescence. It is possible that insufficient treatment of eczema increases when teenagers take responsibility for treatments previously managed by their parents, leading to more severe eczema. Eczema often starts in childhood with onset in infancy being most common.2,5 In our study population, the majority had onset in infancy, but a large proportion (256%) had onset in adolescence. In comparison, 284% of 16-years-old subjects with eczema in the National Child Development Study reported the onset of their eczema after age 7 years.20 Our study shows that onset in adolescence is common among teenagers with eczema. It would be interesting to explore whether the risk factors are the same for eczema that starts in British Journal of Dermatology (2015) 173, pp962–968
968 Eczema in adolescence, E.K. Johansson et al.
adolescence compared with eczema that starts earlier in life. In our study, the teenagers with onset after 12 years of age (compared with all others with eczema) had significantly more often fulfilled the diagnostic criteria of eczema due to an itchy rash located only on the throat and/or neck. We considered whether this large proportion could be explained by a misclassification of contact allergic dermatitis. However, answers concerning reactions to potential contact allergens did not differ between those with onset after 12 years of age and the teenagers with onset at other ages (data not shown). In the present study, we have described differences between AE and non-AE. However, AE does not differ from non-AE in reported clinical signs of eczema and therefore, based on current data, eczema should be considered as one disease phenotype. The analysis performed in this study was based on current sensitization, and non-AE in teenagers might evolve into AE at a later stage. Sensitization is associated with age at onset, disease severity and chronicity but does not justify splitting eczema into two different disease entities as opposed to two subtypes of one disease. Another possible explanation for our findings could be that eczema early in life increases the risk of sensitization through the inflamed skin.21,22 Thus, having AE in adolescence might be a consequence of a defective skin barrier caused by early onset eczema. In conclusion, we found that 96% of teenagers in Sweden had eczema and more than one in four had moderate-to-severe disease. AE was more common than non-AE and onset in adolescence was common among teenagers with eczema. AE in adolescence was characterized by earlier onset, chronicity and more severe current eczema compared with non-AE. However, AE and non-AE did not differ in location or seasonality.
Acknowledgments We would like to thank all the teenagers and parents who participated in the BAMSE project. We would also like to thank all the staff involved in the project, especially Eva Hallner and Sara Nilsson for their practical skills and handling of the study and the data.
References 1 Johansson SG, Bieber T, Dahl R et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004; 113:832–6. 2 Bieber T. Atopic dermatitis. N Engl J Med 2008; 358:1483–94. 3 Aberg N, Hesselmar B, Aberg B, Eriksson B. Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991. Clin Exp Allergy 1995; 25:815–19. 4 Williams H, Stewart A, von Mutius E et al. Is eczema really on the increase worldwide? J Allergy Clin Immunol 2008; 121: 947– 54. e15. 5 Rajka G. Natural history and clinical manifestations of atopic dermatitis. Clin Rev Allergy Immunol 1986; 4:3–26.
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6 Saval P, Fuglsang G, Madsen C, Osterballe O. Prevalence of atopic disease among Danish school children. Pediatr Allergy Immunol 1993; 4:117–22. 7 Kusel MM, Holt PG, de Klerk N, Sly PD. Support for 2 variants of eczema. J Allergy Clin Immunol 2005; 116:1067–72. 8 Johansson SG, Flohr C, Wahlgren CF, Williams H. Role of immunoglobulin E sensitization in eczema, previously referred to as atopic dermatitis. Expert Rev Clin Immunol 2005; 1:257–62. 9 Wickman M, Kull I, Pershagen G, Nordvall SL. The BAMSE project: presentation of a prospective longitudinal birth cohort study. Pediatr Allergy Immunol 2002; 13 (Suppl. 15):11–13. 10 Ballardini N, Kull I, S€ oderh€all C et al. Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort. Br J Dermatol 2013; 168:588–94. 11 Odhiambo JA, Williams HC, Clayton TO et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol 2009; 124: 1251–8 e23. 12 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. 13 Emerson RM, Charman CR, Williams HC. The Nottingham Eczema Severity Score: preliminary refinement of the Rajka and Langeland grading. Br J Dermatol 2000; 142:288–97. 14 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; 131:67–73. 15 Nissen SP, Kjaer HF, Host A et al. The natural course of sensitization and allergic diseases from childhood to adulthood. Pediatr Allergy Immunol 2013; 24:549–55. 16 Finnbogadottir AF, Ardal B, Eiriksson H et al. A long-term follow-up of allergic diseases in Iceland. Pediatr Allergy Immunol 2012; 23:181–5. 17 Ziyab AH, Raza A, Karmaus W et al. Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study. Clin Exp Allergy 2010; 40:1776–84. 18 Eller E, Kjaer HF, Host A et al. Development of atopic dermatitis in the DARC birth cohort. Pediatr Allergy Immunol 2010; 21:307–14. 19 B€ ohme M, Svensson A, Kull I et al. Clinical features of atopic dermatitis at two years of age: a prospective, population-based casecontrol study. Acta Derm Venereol 2001; 81:193–7. 20 Williams HC, Strachan DP. The natural history of childhood eczema: observations from the British 1958 birth cohort study. Br J Dermatol 1998; 139:834–9. 21 Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol 2010; 105:99–106; quiz 107–9, 117. 22 Brough HA, Liu AH, Sicherer S et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol 2015; 135:164–70.
Supporting Information Additional Supporting Information may be found in the online version of this article at the publisher’s website: Data S1. Definition of additional outcome and background variables. Table S1. Background characteristics of children in the original cohort and study population.
© 2015 British Association of Dermatologists
