STUDY

Development of Atopic Dermatitis

During the First 3 Years of Life
The Copenhagen Prospective Study on Asthma in Childhood Cohort Study
in High-Risk Children
Liselotte Brydensholt Halkjær, MD; Lotte Loland, MD, PhD; Frederik F. Buchvald, MD, PhD;
Tove Agner, MD, DMSci; Lone Skov, MD, PhD; Matthew Strand, PhD; Hans Bisgaard, MD, DMSci

Objectives: To describe the development of atopic der-
matitis (AD) during the first 3 years of life and identify
the localization of the early skin lesions that predicts the
development of AD.
Design: Prospective,longitudinal,birthcohortstudyofchil-
dren born to mothers with a history of asthma, followed up
for 3 years with scheduled visits every 6 months as well as
visits for onset or acute exacerbations of skin symptoms.
Setting: The cohort was recruited from greater Copenha-
gen, Denmark, and followed up at a clinical research unit,
whichcontrolledalldiagnosesandtreatmentofskindiseases.
matitis) index. Predictive odds ratios of early skin lesions
for those who developed AD vs those who did not were
calculated.
Results: The cumulative incidence of AD by age 3 years
was 44% (155/356). The prevalence rate peaked at age 2
years for boys and at age 2.5 years for girls, but there were
no other sex differences in the proportion of children de-
velopingAD.SkininvolvementininfantswithADwasfound
to begin at the scalp, forehead, ear, and neck in a balaclava-
like pattern and continue to the extensor sides and trunk,
finally affecting the flexor sides of the extremities. Early skin
lesions of arms and joints best predicted AD at age 3 years.

Participants: A total of 411 infants were enrolled in the
cohort; 55 had incomplete follow-up and were excluded
from certain analyses.
Main Outcome Measures: Atopic dermatitis was de-
fined based on the criteria of Hanifin and Rajka, and se-
verity was assessed by the SCORAD (Scoring Atopic Der-
Conclusions: Atopic dermatitis begins at the scalp, fore-
head, ear, and neck in a balaclava-like pattern. Eczema
at the arms and joints provides the highest predictive value
for the development of AD at age 3 years. This may be
used for early prediction and intervention of AD.
Arch Dermatol. 2006;142:561-566

Author Affiliations: Danish
Pediatric Asthma Centre,
Department of Pediatrics
(Drs Brydensholt Halkjær,
Loland, Buchvald, and
Bisgaard), and Danish Research
Centre of Allergy, Department
of Dermatology (Drs Agner and
Skov), Copenhagen University
Hospital, Gentofte, Denmark;
and Division of Biostatistics,
National Medical Jewish and
Research Center, Denver, Colo
(Dr Strand).
A
TOPIC DERMATITIS (AD) IS A
chronically relapsing in-
flammatory skin disease,
which usually presents in
the first years of life1-3 and
is often associated with a family history of
atopy.1,4,5 The cumulative incidence of AD
has increased in the previous 4 decades,
especially in countries with a Western
lifestyle.6-8
See also pages 555 and 633
The diagnosis of AD is based on a syn-
drome of clinical criteria in which the ma-
jorfeaturesarepruritus,typicalmorphologic
features and distribution of the lesions,
chronicrelapsingcourse,andpersonalorfam-
ily history of atopy. The diagnosis is particu-
larlyimpreciseinearlyinfancy,partlybecause
itching, as one of the cardinal symptoms, is
difficult to recognize. The morphologic fea-
tures are therefore instrumental to the diag-
nosis at this young age. The predilection sites
in the first years of life have been reported
to be the head, the trunk, and the extensor
surfaces of the extremities,9-12 although, to
our knowledge, the early presentation and
progression of eczema lesions have not been
described prospectively in detail.
CME course available at
www.archdermatol.com
The primary aim of this study was to de-
scribe the progressively changing predilec-
tion skin lesion pattern of AD during the first
3 years of life in a cohort of high-risk in-
fants. Second, we aimed to identify an early
localization pattern of skin lesions that may
predict AD within 3 years of life.
METHODS
MATERIALS
The Copenhagen Prospective Study on Asthma
in Childhood (COPSAC) is a prospective lon-
gitudinal birth cohort study of 411 children (208

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©2006 American Medical Association. All rights reserved.

female) born of mothers with a history of asthma as previously tory of AD. Of the fathers, 16% had a history of asthma and 13%,
described in detail.13 The study was conducted in accordance with a history of AD.
all applicable regulatory requirements and the guiding prin-
ciples of the Declaration of Helsinki. The study was approved PARTICIPANTS
by the Copenhagen and Frederiksberg Ethics Committee, with
informed written consent obtained from the caregivers. In brief, The participants were seen in the COPSAC Clinical Research
mothers with a history of asthma were invited during preg- Unit (CRU) at age 1 month and at scheduled visits every 6
nancy, and the infants were enrolled during the first month of months thereafter as well as for any acute onset or exacerba-
age. Infants born before 36 gestational weeks or with known se- tion of symptoms from skin or airways. Skin examinations, di-
vere congenital diseases were excluded. The main catchment area agnoses, and treatment of eczema were handled solely by trained
of the cohort was greater Copenhagen, Denmark. The children medical physicians employed for this purpose in the CRU un-
were born between August 1998 and December 2001, and 397 der the supervision of dermatologists (ie, the population was
were white. All mothers had a history of asthma and 48%, a his- not treated by the family practitioner). At each visit to the CRU,
a history of the symptoms and medication used in the past 6
months were recorded in an online database according to pre-
defined questions and response categories.
50

OBJECTIVE CLINICAL EXAMINATION

40
Cumulative Probability, %

Skin lesions with typical dermatitis morphologic features were de-

30 scribed online according to predefined morphologic categories and
localization. The skin morphologic categories of lesions were reg-
20 istered as erythema, edema, excoriations, lichenification, crusts,
dryness, vesicles, and squamatization and cracks on a scale from
10 0 to 3 (none, mild, moderate, and severe). The localization of the
Boys
Girls
lesions was characterized in 35 predefined skin areas covering the
0 whole body. Skin lesions caused by chicken pox, human parvo-
virus B19, Gianotti-Chrosti syndrome, herpes, seborrheic derma-
0.0 0.5 1.0 1.5 2.0 2.5 3.0 titis capitis, and virus exanthema were excluded from this record-
Age, y
ing.Seborrheicdermatitiscapitiswasdefinedasgreasyscalingsolely
in the scalp with no other skin symptoms.
Figure 1. Estimated cumulative probability of atopic dermatitis diagnosis Atopic dermatitis was defined based on the criteria of Hani-
based on Kaplan-Meier survival analysis, using 411 subjects in the fin and Rajka.14 This diagnosis requires the presence of 3 of 4
Copenhagen Prospective Study on Asthma in Childhood, up to age 3 years. major criteria and at least 3 of 23 minor signs. Major criteria
Fifty-five subjects who withdrew from the study before age 3 years were
right-censored at the time of withdrawal. Estimates across ages were not are defined as (1) pruritus; (2) typical morphologic features
significantly different between boys and girls (P=.82). and distribution (erythema with vesicles/papules and/or scaling/
squamatization in a minimum of 2 regions); (3) chronic der-
matitis (physician-verified dermatitis for a minimum of 6 weeks
or recurrent dermatitis within 6 months); and (4) atopic his-
40
tory (all mothers included had a history of asthma). Of the mi-
nor signs in the criteria, the following 4 were excluded: kera-
toconus and anterior subcapsular cataracts (because they
Prevalence Rate, %

30
required identification by an ophthalmologist), delayed blanch
(because it required an injection of methacholine), and im-
paired cell-mediated immunity.
20 The severity of AD was scored using the SCORAD (Scoring
Atopic Dermatitis) index, ranging from 0 to 103 points,15 which
Boys
Girls includes the assessment of (1) extent, (2) intensity (erythema,
10 edema/papules, oozing/crust, excoriation, lichenification, and dry-
0.5 1.0 1.5 2.0 2.5 3.0
ness on a scale from 0 to 3), and (3) subjective symptoms (pru-
Age, y ritus and sleeplessness [using a scale from 0-10 of the parents’
subjective opinion of the child’s degree of pruritus and sleepless-
Figure 2. Atopic dermatitis prevalence rates, by age and sex, up to age 3
ness]). The severity of AD was subsequently categorized into mild
years. Subjects were included in calculations until time of withdrawal from (⬍15 SCORAD points), moderate (15-40 SCORAD points), and
the study. Prevalence rates began to decline slightly before age 3 years for severe (⬎40 SCORAD points) according to the objective com-
both boys and girls. ponents of the index (clinical signs and disease extent), ranging

Table 1. Severity of AD and Sex Differences at Half-Yearly Visits*

Scheduled Visits, y

SCORAD Categories 0.5 1.0 1.5 2.0 2.5 3.0

With mild AD 43 (42/43) 52 (60/45) 63 (58/68) 68 (69/67) 74 (84/65) 81 (83/80)
With moderate AD 56 (58/54) 47 (40/53) 34 (41/27) 29 (30/29) 24 (16/33) 17 (11/20)
With severe AD 2 (0/4) 1 (0/2) 3 (2/5) 3 (2/4) 2 (2/2) 2 (6/0)

Abbreviations: AD, atopic dermatitis; SCORAD, the Scoring Atopic Dermatitis index.
*Data are given as mean percentage (male/female, %).

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from 0 to 83 points16 (ie, excluding subjective components pru-
ritus and sleeplessness from the SCORAD index). Table 2. Progression of Skin Region Involvement
With Respect to Age in 139 Infants Who Developed
TREATMENT OF ECZEMA Skin Lesions by Age 18 Months and AD by Age 3 Years*

Standard operation procedures at the CRU outlined treatment Median Age at Onset, d No. of
recommendations as skin moisturizers and topical corticoste- Skin Region (25th-75th Percentiles) Infants
roids, mainly mild (hydrocortisone) for eczema located to the Scalp 108 (85-157) 16
head and genitals and mid-strength (hydrocortisone butyrate) Ear 113 (65-199.5) 20
for eczema located at the body and extremities. The amount of Forehead 116 (69-201) 26
treatment used was quantified as number, amount, and dura- Neck 153 (98-201) 37
tion of treatment courses. Elbow, ext 183 (125-368) 21
Wrist, flex 185 (123-369) 22
DATA ANALYSIS Cheek 197 (119-360) 106
Ankle, ext 198 (123-347) 33
Data were entered online into the cohort database. The central Knee, ext 198 (170-362) 25
tendency and dispersion are reported as the arithmetic mean±SD. Nose 198 (182-495) 5
Kaplan-Meier survival analysis methods were used to com- Back, upper 202 (121-370) 41
pute cumulative probabilities of AD diagnosis by age up to 3 Chest 203 (124-362.5) 48
years. Those censored in this analysis were children not com- Ankle, flex 208 (154-370) 14
pleting the study to age 3 years (censored at time of with- Forearm, ext 226 (151.5-381.5) 20
drawal) and those completing visits through age 3 years with- Abdomen 231 (120-462.5) 44
out an AD diagnosis (censored at age 3 years). This analysis Wrist, ext 238 (123-441) 31
was stratified by sex, and the log-rank test was used to com- Upper leg, ext 245 (155.5-424) 44
pare probabilities between sex across age. Upper arm, flex 251 (157-370) 19
The odds of AD diagnosis by age 3 years were computed for Chin 274 (122-475) 63
those with and without a skin lesion observed at the 18-month Foot, back 275 (183-397) 9
visit for each of 10 main body regions. Sample odds ratios (ORs) Lower leg, ext 278 (157.5-393) 32
Upper arm, ext 283 (157-397) 27
were calculated, including 95% confidence intervals (CIs) based
Back of neck 284 (102-414) 34
on asymptotic theory. For this analysis, subjects were restricted
Forearm, flex 320 (191.5-472.5) 20
to those who had had a skin lesion in at least 1 body region by Back, lower 325 (169-502) 39
the 18-month visit and completed the study through age 3 years. Perioral 339 (191-443) 39
Fisher exact and ␹2 tests were used to compare propor- Eye area 344 (157-441) 6
tions. P⬍.05 was considered significant. Diaper region 354 (218.5-476.5) 24
Knee, flex 367 (194-543) 57
RESULTS Upper leg, flex 370 (157-546) 24
Hand, back 370 (170-547) 19
Elbow, flex 397 (359-536) 37
The COPSAC study enrolled 411 neonates at age 1 month, Lower leg, flex 419 (195-549) 18
356 of whom provided complete follow-up data by age Hand, palm 557 (NA) 1
3 years. The earliest sign of dermatitis leading to the AD Foot, sole 576 (NA) 1
diagnosis was recorded at age 1 month, with the highest
incidence rate occurring during the second half-year of Abbreviations: AD, atopic dermatitis; ext, extensor surface; flex, flexure;
NA, not applicable.
life. For those with complete follow-up, the cumulative *Those not completing the study through 3 years of age were not
incidence of AD was 31% (109/356) at age 1 year, 41% included.
(147/356) at age 2 years, and 44% (155/356) at age 3 years
(Figure 1). The prevalence of AD peaked at age 2 years For those who completed 3 years of the study, the cu-
for boys and at age 2.5 years for girls (Figure 2). By age mulative incidence of AD was 43% (78/183) for girls and
18 months, the cumulative incidence of seborrheic der- 45% (77/173) for boys (P=.70 for difference). Kaplan-
matitis capitis was 24% in children with AD, 28% in chil- Meier estimates of the cumulative probability of AD di-
dren with skin lesions but not fulfilling AD diagnosis, agnosis by age 3 years were slightly lower (40% for both
and 21% in children without other dermatitis skin le- boys and girls). However, these estimates incorporated
sions. This mitigates against seborrheic dermatitis capi- all subjects in the cohort until they dropped out of the
tis being mistakenly diagnosed as AD. study. Differences in cumulative AD probabilities across
Most infants presented with mild AD, and only single age (0-3 years) between boys and girls were not signifi-
cases presented with severe AD. The severity of AD de- cant (P=.80). Girls and boys did not differ in AD sever-
clined with age, with an increased fraction of mild cases ity measured by the SCORAD index (objective compo-
and a reduced fraction of moderate severity and no ob- nents) (Figure 1 and Table 1).
vious sex difference (Table 1). Topical corticosteroid Skin involvement in infants who developed AD started
(mild, mid-strength, and potent) was prescribed in 7.6 at the scalp, forehead, ear, neck, and cheek and later spread
(2.9, 4.5, and 0.2, respectively) courses per child during to the extensor side of the extremities and the rest of the
the first 3 years of life, with a mean ± SD of 15 ±14 days face and trunk, finally affecting the flexor sides of the ex-
per treatment period. The non-AD lesions group re- tremities (Table 2). The most commonly involved re-
ceived a total of 4 courses (mean, 16.3 days). Systemic gions in children with AD seen at the scheduled visits
corticosteroid courses were given for respiratory symp- were the cheeks, the flexures of the knee, and the chin,
toms on 8 occasions in 7 children with AD. occurring in at least 1 in 4 infants, whereas the eye area,

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 70 Scheduled Visit
Visit for Acute Exacerbation

60

50

40
Infants, %

30

20

10

0
Cheek

Knee, Flex

Chin

Chest

Upper Leg, Ext

Perioral

Back, Upper

Back, Lower

Abdomen

Neck, Ext

Ankle, Ext

Neck, Flex

Wrist, Ext

Lower Leg, Ext

Wrist, Flex

Upper Leg, Flex

Knee, Ext

Upper Arm, Flex

Diaper Region

Hand, Ext

Forearm, Flex

Lower Leg, Flex

Upper Arm, Flex

Ear

Forearm, Ext

Scalp

Forehead

Ankle, Flex

Foot, Ext

Nose

Hand, Palm

Foot, Sole

Eye Area
Elbow, Flex

Elbow, Ext
Skin Region

Figure 3. Affected skin regions at scheduled (6-, 12-, and 18-month) visits compared with visits for acute exacerbations of skin symptoms. The percentages are
based on 139 infants with skin lesions by 18 months and atopic dermatitis diagnosis by age 3 years. Ext indicates extensor surface; flex, flexure.

palm of hand, foot sole, and nose regions were very rarely the second half-year of life, with a declining incidence
affected. During the visits for acute exacerbations, the fore- rate thereafter (Figure 1). Such early onset concurs with
head, ear, neck, and eye area were more commonly af- previous reports.1,17,18
fected (Figure 3). Using survival analysis methods, the cumulative inci-
Table 3 shows the pattern of skin lesions that may dence of AD was 40% by 3 years of life in this cohort study
predict AD. Of the 356 subjects who completed 3 years of children born to mothers with a history of asthma. A re-
of the study, 139 (39%) had had a skin lesion in at least cent study based on posted questionnaires in the same geo-
1 body region by the 18-month visit and AD by age 3 years; graphic region reported that 38% of children with single
100 (28%) had a skin lesion by the 18-month visit but parental atopic history developed AD by age 4 years.5
no AD diagnosis by age 3 years; and 117 (33%) had not We used the diagnostic criteria defined by Hanifin and
had any skin lesions at any visit during these first 18 Rajka14 to identify children with AD. This classification
months of life. The risk of AD at age 3 years was esti- has been a matter of debate, especially with respect to
mated for 10 body regions, which were aggregated based the significance of some minor features in younger chil-
on anatomy and the progression seen in the children with dren.19-23 A recent study24 has demonstrated good agree-
AD (Table 2). Early lesions presenting on the arms and ment between Hanifin-Rajka criteria and other criteria
joints showed a strong correlation to later development used to diagnose AD at this young age.
of AD (OR, 7.5-11.8; maximum 95% CI, 2.7-50.9), The specificity of the AD diagnosis is probably high
whereas diaper area demonstrated no correlation to de- in our cohort because the diagnosis, detailed phenotyp-
velopment of AD (OR, 1.9; 95% CI, 0.9-4.1). The cheeks ing, and management of skin lesions was controlled solely
were affected in almost 80% of children with AD, but by the CRU physicians. This reduces the risk of misclas-
cheek involvement was likewise observed in more than sification. This reduced risk of misclassification is of par-
40% of children without AD, indicating that skin le- ticular importance in the clinical evaluation of AD, for
sions on the cheek are not specific for AD. Lesions in the which interobserver variation is a problem.25
children without AD were itchy, eczematous, and indis- The cumulative incidence of seborrheic dermatitis capi-
tinguishable from those in the children with AD. tis was not significantly different in children with AD and
in children with skin lesions not fulfilling AD diagnosis.
COMMENT This suggests that misclassification between AD and seb-
orrheic dermatitis capitis was not a major confounder.
The COPSAC prospective cohort study of high-risk in- The sensitivity of the AD diagnoses in the present study
fants provides new and precise information on the pro- was recently supported by comparing the COSPAC da-
gression of AD during the first 3 years of life. This gives tabase with the records of the family practitioner, which
new insight into early prediction of AD and improves the revealed no diagnoses of AD that was not recorded in the
ability to diagnose and intervene early. COPSAC database.
The first sign of AD was diagnosed from age 1 month. The severity of the disease was mild to moderate in most
The highest dermatitis incidence rate was found during cases (Table 1). This is in line with a recent study of a com-

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munity birth cohort in the same region, which showed that
the mild cases constituted 45%.18 Data from other epide- Table 3. The Risk of AD Development by Age 3 Years
miological studies have equally shown that most AD cases in Children Who Had a Defined Skin Lesion in a Given
Main Skin Region by Age 18 Months Compared
are characterized as mild and moderate and only 1% to 2% With Children Who Did Not*
as severe.26-30 Even if the present cohort is at high risk for
development of AD, the severity of symptoms should not OR (95% CI) for AD
necessarily be expected to be increased compared with chil- Main Skin Region by Age 3 y
dren with AD from a nonrisk population. Arm, flex
Use of topical corticosteroids in the study was almost Upper arm, flex
11.8 (2.7-50.9)
limited to the AD group. Registration of treatment courses Forearm, flex
and number of days was performed carefully by the par- Joints, flex
ents, which in this study was preferred to attempts of quan- Wrist, flex
Ankle, flex
titative measurement of use of topical corticosteroids. Knee, flex
8.1 (4.1-16.2)
In this prospective cohort study, there was no differ- Elbow, flex
ence in cumulated incidence between sexes, although boys Arm, ext
tended to peak 0.5 years earlier than girls. Nor did boys Forearm, ext
7.5 (2.6-21.9)
have more severe disease. Previous studies have pro- Upper arm, ext
Joints, ext
vided conflicting evidence with respect to the impor- Elbow, ext
tance of sex in the incidence of AD in young children. Ankle, ext
No sex effect on AD was found in children younger than 7.5 (3.5-16.0)
Wrist, ext
3.5 years who were studied in a retrospective population- Knee, ext
based postal questionnaire study in the United King- Trunk
Back, upper
dom31 and in children younger than 2 years who were Chest
studied in a prospective population-based case-control 5.6 (2.9-10.6)
Abdomen
study in Sweden.18 In contrast, Harris et al32 found boys Back, lower
to be more affected than girls in a cohort of children re- Leg, ext
cruited before birth and followed up to age 2 years. Upper leg, ext
4.1 (2.1-8.1)
Lower leg, ext
Progression of skin region involvement in infants who Head and neck
develop skin lesions before age 18 months and AD by age Scalp
3 years was found to begin at the scalp, forehead, ear, Forehead
and neck in a balaclava-like pattern and continue to the Ear
extensor sides of the extremities, rest of the face, and Neck
Cheek
trunk, finally affecting the flexor sides of the extremi- Chin 3.6 (1.8-7.4)
ties. Involvement of the palm of the hand and foot sole Back of neck
was seldom seen and the latest to occur (Table 2). Perioral
Cheek, chin, and flexures of the knee were found to Nose
be the most commonly affected skin regions in children Eye area
Leg, flex
who developed AD (Figure 3). Exacerbation of AD, as
Upper leg, flex
evaluated at visits for acute exacerbations, had almost simi- Lower leg, flex 3.6 (1.4-9.1)
lar skin region involvement as AD at scheduled visits Hand and foot
(Figure 3), but the presence of skin lesions at the eye area, Foot, back
forehead, ear, scalp, and neck proportionally led most Hand, back
2.2 (1.0-5.0)
Hand, palm
frequently to visits for acute exacerbations. Possible ex-
Foot, sole
planations for this may be that these skin regions attract Diaper region 1.9 (0.9-4.1)
more attention from the parents compared with lesions
on the extremities and trunk and also that the forehead, Abbreviations: AD, atopic dermatitis; CI, confidence interval; ext, extensor
ear, scalp, and neck front were the first areas to be af- surface; flex, flexure; OR, odds ratio.
fected and therefore caused more concern leading to the *Skin lesions in the arm flexures represent the highest predictive risk of
later AD development. Skin lesions in the diaper region represent little risk of
first visit for acute exacerbation (Table 2). later AD development.
Comparing skin lesions during the first 1.5 years of
life between children who eventually did or did not be-
come diagnosed as having AD at age 3 years showed that The COPSAC cohort is a birth cohort of children at
the presence of eczema at the arms and around the joints high risk for the development of atopic diseases includ-
(Table 3) had the highest predictive value for AD. A skin ing AD. This selection restricts how the findings may be
lesion in the diaper region is generally considered not to generalized, and validation in unselected populations may
represent AD, and in this study, diaper area involve- be needed. Adherence to the study program was good,
ment was confirmed not to predict AD (OR, 1.9; 95% CI, with a high retention rate. The COPSAC study provides
0.9-4.1) (Table 3). While the cheeks were the most com- prospective, longitudinal, follow-up of phenotyping and
monly involved region in children who later developed severity of AD in early infancy. The most important dis-
AD, involvement of this region was also common in chil- tinguishing factor of the COPSAC study was the empha-
dren who did not develop AD. These observations may sis on regular objective skin lesion phenotyping and con-
be useful for early prediction of AD. trol of AD diagnosis and treatment solely by the CRU.

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 In conclusion, the present study shows that the pro-
gression of skin region involvement in infants who de-
velop AD begins at the scalp, forehead, ear, and neck in a
balaclava-like pattern. A high predictive OR was found for
eczema at the arms and around the joints, while the pre-
dictive OR was lower for involvement of the head and neck
and the predictive OR for involvement of the diaper re-
gion was not significant. This improved description of the
progression of skin lesions facilitates early diagnosis of AD
in infancy and allows studies examining early interven-
tion and prevention strategies.
Accepted for Publication: August 30, 2005.
Correspondence: Hans Bisgaard, MD, DMSci, Danish Pe-
diatric Asthma Centre, Department of Pediatrics, Copen-
hagen University Hospital, Gentofte, Niels Andersens Vej
65, DK-2900 Hellerup, Denmark (Bisgaard@copsac.dk).
Author Contributions: Study concept and design: Bisgaard.
Acquisition of data: Brydensholt Halkjær, Loland, and
Buchvald. Analysis and interpretation of data: Brydensholt
Halkjær, Agner, Skov, Strand, and Bisgaard. Drafting of the
manuscript: Brydensholt Halkjær and Bisgaard. Critical re-
vision of the manuscript for important intellectual content:
Brydensholt Halkjær, Agner, Skov, and Bisgaard. Statistical
analysis: Strand. Obtained funding: Brydensholt Halkjær, Ag-
ner, and Bisgaard. Administrative, technical, and material sup-
port: Bisgaard. Study supervision: Agner, Skov, and Bisgaard.
Financial Disclosure: Dr Bisgaard has been a consultant
to, paid for lectures by, and holds sponsored grants from
Aerocrine, AstraZeneca, Altana, GlaxoSmithKline,
MedImmune, and Merck. He does not hold stock or op-
tions in any pharmaceutical company in the respiratory field.
Funding/Support: The COPSAC cohort study is spon-
sored by the following funds: the Pharmacy Foundation
of 1991; the Lundbeck Foundation; Ronald McDonald
House Charities; the Danish Medical Research Council; The
Danish Pediatric Asthma Center; The Danish Research Cen-
ter of Allergy; Direktør, Cand Pharm K Gad Andersen og
Hustrus Familiefond; Aage Bangs Fond; Danish Lung As-
sociation; Kai Lange og Gunhild Kai Langes Fond; Direk-
tør Ib Henriksens Fond; Gerda og Aage Hensch’s Fond; Ro-
salie Petersens Fond; Hans og Nora Buchards Fond; Dagmar
Marshalls Fond; Foundation of Queen Louise’ Children
Hospital; the Danish Hospital Foundation for Medical Re-
search, Region of Copenhagen, the Faroe Island, and Green-
land; Gangsted Fond; Højmosegård-Legatet; Fonden til Læ-
gevidenskabens Fremme; A. P. Møller og Hustru Chastine
McKinney Møllers Fond til almene Formaal; The Danish
Ministry of the Interior and Health’s Research Centre
for Environmental Health; AstraZenaca; LEOpharma;
Yamanouchi Pharma; and Pharmacia-Pfizer.
Acknowledgment: We thank all the families participat-
ing in the COPSAC cohort and members of the COPSAC
Clinical Research Unit.
REFERENCES
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Allergy. 1986;4:3-26.
2. Queille-Roussel C, Raynaud F, Saurat JH. A prospective computerized study of
500 cases of atopic dermatitis in childhood, I: initial analysis of 250 parameters.
Acta Derm Venereol Suppl (Stockh). 1985;114:87-92.
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