ARTICLE
Auteur(s) : Noriko Fukiwake1, Norihiro
Furusyo2,3, Hiroaki Takeoka2,3, Kazuhiro
Toyoda2,3, Norihiko Kubo2,3, Makiko
Kido3, Sayaka Hayashida3, Hiroshi
Uchi3, Yoichi Moroi3, Kazunori
Urabe3, Naoko Kinukawa4, Yoshiaki
Nose5, Jun Hayashi2,3, Masutaka
Furue1
1Department of Dermatology, Kyushu University
Hospital, Maidashi 3-1-1, Higashiku, 812-8582, Fukuoka, Japan
2Department of General Medicine, Kyushu University
Hospital, Maidashi 3-1-1, Higashiku, 812-8582, Fukuoka, Japan
3Department of Environmental Medicine and Infectious
Disease, Faculty of Medical Sciences, Kyushu University, Maidashi
3-1-1, Higashiku, 812-8582, Fukuoka, Japan
4Department of Medical Information Science, Kyushu
University Hospital, Maidashi 3-1-1, Higashiku, 812-8582, Fukuoka,
Japan
5Department of Medical Information Science, Graduate
School of Medical Science, Kyushu University, Maidashi 3-1-1,
Higashiku, 812-8582, Fukuoka, Japan
accepté le 30 Avril 2008
Atopic dermatitis (AD) is a common and chronic inflammatory skin
disease that is characterized by relapsing itch and eczema [1]. AD
is considered to be a multifactorial disease, and both genetic and
environmental factors are involved in its etiology [2, 3]. Although
the prevalence and risk factors for AD have been the source of many
studies, very few population-based epidemiological studies
assessing related factors for AD or allergic disorders among
children aged 6 years and under have been published [4-8]. We
established the prevalence of AD and serum total and specific IgE
levels among children in Ishigaki Island, Okinawa, Japan, in 2001
[9, 10].
In the present study, we evaluated the associated factors for AD
on the same island by physical examination of the skin and a
questionnaire for family and past history.
Methods
Study population
We performed physical examinations of children in 11 nursery
schools in Ishigaki Island, Okinawa, Japan in 2004. The climate of
Ishigaki is subtropical, and the average temperature and humidity
are 25.4 °C and 76%, respectively. Enrolled were 460 children
aged 6 years or younger. Written informed consent allowing the
children to participate in the study was obtained from parents or
guardians. Approval for the study was obtained from the Ethics
Committee of Kyushu University Hospital as well as from the
directors and classroom teachers of the schools.
Physical and laboratory examinations
Medical examinations of all children were carried out by three
dermatologists from the Department of Dermatology, Kyushu
University Hospital. AD was diagnosed according to the Japanese
Dermatological Association criteria [11]. All children were tested
for total and specific IgE antibodies. Total IgE levels were
determined by a radioimmunoassay with a detection limit of 20 IU/mL
(Shionoria IgE, Shionogi & Co., Ltd. Osaka, Japan). A total IgE
level > 230 IU/mL was considered abnormal for the purpose of
statistical analysis. Specific IgE antibodies against
aeroallergens, such as house dust, Dermatophagoides pteronyssinus,
Dermatophagoides farinae, and food allergens, such as chicken egg
white and cow’s milk, were tested with the Pharmacia Enzyme CAP
procedure (Pharmacia CAP System Specific IgE FEIA, Pharmacia
Diagnostics AB, Uppsala, Sweden). A level of specific IgE
antibodies > 0.34 IU/mL was regarded as abnormal. Family history
and the subject’s history of AD, asthma, rhinitis and Food allergy
(FA) or antibiotic use in infancy were assessed in the
questionnaire answered by parents or guardians of the children.
Definition of groups
The AD group consists of those who were diagnosed as having AD at
the physical examination.
Asthma, rhinitis, and FA groups were comprised of children with
a history of these disorders. Pupils who had displayed adverse
effects by suspicious food intake were diagnosed as FA.
Statistical analysis
To compare related factors between subjects with and without each
allergic disorder, the chi-square test was used. Of the 460
children, data from the 360 who had no missing blood samples and
answers on the questionnaires were subjected to multivariate
analysis. Stepwise logistic regression analysis adjusting for age
was used. P value < 0.05 was considered statistically
significant.
Results
Prevalence of AD and other allergic disorders
The prevalence of AD was 12.2% (confidence limits; 9.3-15.5)
(56/460). The prevalence of asthma, rhinitis and FA was 19.9%
(16.3-23.8) (91/458), 3.3% (1.9-5.4) (15/457), and 5.5% (3.6-8.0)
(25/456), respectively.
Associated factors for AD and other allergic disorders
Family history, personal history, and antibiotic use
Univariate analysis by chi-square test revealed that siblings
having AD and rhinitis and past history of asthma and FA had
association for AD, but parental AD history was not related (table 1).
Table 1 Associated factors of atopic dermatitis with
family and past history
|
AD
|
|
Positive No. (%)
|
|
|
+(n = 56)
|
–(n = 404)
|
p value
|
|
Family history
|
|
Paternal
|
|
|
|
|
|
|
AD
|
3
|
(6.4)
|
12
|
(3.1)
|
NS
|
|
Asthma
|
3
|
(6.4)
|
24
|
(6.1)
|
NS
|
|
Rhinitis
|
9
|
(19.1)
|
51
|
(13.0)
|
NS
|
|
Maternal
|
|
|
|
|
|
|
AD
|
3
|
(5.4)
|
19
|
(4.8)
|
NS
|
|
Asthma
|
7
|
(12.5)
|
32
|
(8.0)
|
NS
|
|
Rhinitis
|
13
|
(23.2)
|
54
|
(13.5)
|
NS
|
|
Siblings
|
|
|
|
|
|
|
AD
|
13
|
(24.1)
|
22
|
(5.7)
|
0.0000
|
|
Asthma
|
10
|
(18.5)
|
50
|
(13.1)
|
NS
|
|
Rhinitis
|
9
|
(16.7)
|
25
|
(6.5)
|
0.0197
|
|
Personal history
|
|
AD
|
-
|
-
|
|
|
Asthma
|
25
|
(44.9)
|
66
|
(16.4)
|
0.0000
|
|
Rhinitis
|
3
|
(5.4)
|
12
|
(3.0)
|
NS
|
|
FA
|
11
|
(19.6)
|
14
|
(3.5)
|
0.0000
|
|
Antibiotic use
|
|
In first 2 months of life
|
3
|
(5.5)
|
18
|
(4.7)
|
NS
|
|
In first year of life
|
27
|
(48.2)
|
162
|
(41.8)
|
NS
|
Total and specific IgE
Serum total IgE and specific IgEs for house dust, Dermatophagoides
pteronyssinus, Dermatophagoides farinae, and chicken egg white were
significantly related to the AD and FA groups, and except chicken
egg white in the rhinitis group. However, no relation between IgE
levels and asthma was observed (table 2).
Table 2 Relation of serum IgE level with atopic
dermatitis and other disorders
|
AD
|
Asthma
|
Rhinitis
|
FA
|
|
Positive No. (%)
|
p value
|
Positive No. (%)
|
p value
|
Positive No. (%)
|
p value
|
Positive No. (%)
|
p value
|
|
+(n = 56)
|
–(n = 404)
|
+(n = 91)
|
–(n = 367)
|
+(n = 15)
|
–(n = 442)
|
+(n = 25)
|
–(n = 431)
|
|
Serum total IgE
|
24
|
(45.3)
|
67
|
(17.2)
|
< 0.0001
|
22
|
(25.6)
|
68
|
(19.1)
|
NS
|
8
|
(57.1)
|
83
|
(19.5)
|
0.0020
|
11
|
(44.0)
|
79
|
(19.0)
|
0.0058
|
|
Specific IgE
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
House dust
|
28
|
(52.8)
|
121
|
(32.4)
|
0.0058
|
34
|
(41.0)
|
115
|
(33.6)
|
NS
|
10
|
(76.9)
|
139
|
(33.9)
|
0.0037
|
14
|
(58.3)
|
134
|
(33.5)
|
0.0239
|
|
D. pteronyssinus
|
29
|
(54.7)
|
121
|
(32.4)
|
0.0025
|
34
|
(41.0)
|
116
|
(33.9)
|
NS
|
10
|
(76.9)
|
140
|
(34.1)
|
0.0040
|
14
|
(58.3)
|
135
|
(33.8)
|
0.0257
|
|
D. farinae
|
27
|
(50.9)
|
108
|
(29.0)
|
0.0022
|
32
|
(38.6)
|
103
|
(30.1)
|
NS
|
9
|
(69.2)
|
126
|
(30.7)
|
0.0086
|
15
|
(62.5)
|
119
|
(29.8)
|
0.0018
|
|
Chicken egg white
|
26
|
(49.1)
|
110
|
(29.5)
|
0.0069
|
24
|
(28.9)
|
111
|
(32.5)
|
NS
|
4
|
(30.8)
|
131
|
(32.0)
|
NS
|
13
|
(54.2)
|
121
|
(30.3)
|
0.0263
|
|
Cow’s milk
|
14
|
(26.4)
|
73
|
(19.6)
|
NS
|
13
|
(15.7)
|
74
|
(21.6)
|
NS
|
4
|
(30.8)
|
83
|
(20.2)
|
NS
|
6
|
(25.0)
|
80
|
(20.0)
|
NS
|
Multivariate analysis
Multivariate analysis by stepwise logistic regression analysis
revealed that for AD, maternal history of rhinitis, having AD
siblings, past history of asthma and FA, and elevation of total IgE
were significant associated factors; past history of FA had the
highest odds ratio. Maternal and siblings’ asthma, past history of
AD, and antibiotic use in the first year of life were associated
factors for asthma. For rhinitis, only maternal asthma and
elevation of specific IgE for dermatophagoides farinae were
associated factors. For FA, paternal and past histories of AD were
associated factors, and, interestingly, having AD siblings and
antibiotic use in first year of life were negatively related to FA
(table 3).
Table 3 Association factors analysed by stepwise
logistic regression adjusting for age
|
AD
|
Asthma
|
Rhinitis
|
FA
|
|
Odds ratio (95% CI)
|
Odds ratio (95% CI)
|
Odds ratio (95% CI)
|
Odds ratio (95% CI)
|
|
1. Gender, Male
|
NS
|
NS
|
NS
|
NS
|
|
2. Age
|
|
|
|
|
|
0 and 1 y
|
|
|
|
1.00
|
|
2 y
|
|
|
|
0.00 (not calculated)
|
|
3 y
|
NS in the model
|
NS in the model
|
NS in the model
|
0.300 (0.0604-1.49)
|
|
4 y
|
|
|
|
0.138 (0.0233-0.824)
|
|
5 and 6 y
|
|
|
|
0.348 (0.0508-2.38)
|
|
3. Family history
|
|
|
|
|
|
Paternal
|
|
|
|
|
|
AD
|
NS
|
NS
|
NS
|
35.5 (4.89-258)
|
|
Asthma
|
NS
|
NS
|
NS
|
NS
|
|
Rhinitis
|
NS
|
NS
|
NS
|
NS
|
|
Maternal
|
|
|
|
|
|
AD
|
NS
|
NS
|
NS
|
NS
|
|
Asthma
|
NS
|
2.93 (1.25-6.84)
|
8.26 (2.15-31.8)
|
NS
|
|
Rhinitis
|
2.87 (1.17-7.01)
|
NS
|
NS
|
NS
|
|
Siblings
|
|
|
|
|
|
AD
|
7.41 (2.69-20.4)
|
NS
|
NS
|
0.00 (not calculated)
|
|
Asthma
|
NS
|
4.31 (2.11-8.79)
|
NS
|
NS
|
|
Rhinitis
|
NS
|
NS
|
NS
|
NS
|
|
4. Past history
|
|
|
|
|
|
AD
|
|
3.72 (1.67-8.26)
|
NS
|
21.2 (5.63-79.7)
|
|
Asthma
|
4.32 (1.95-9.56)
|
|
NS
|
NS
|
|
Rhinitis
|
NS
|
NS
|
|
NS
|
|
FA
|
10.4 (3.08-35.1)
|
NS
|
NS
|
|
|
5. Antibiotic use
|
|
|
|
|
|
In the first 2months of life
|
NS
|
NS
|
NS
|
NS
|
|
In the first year of life
|
NS
|
2.23 (1.23-4.04)
|
NS
|
0.242 (0.0581-1.01)
|
|
6. Serum total IgE
|
2.90 (1.32-6.36)
|
NS
|
NS
|
NS
|
|
7. Specific IgE
|
|
|
|
|
|
House dust
|
NS
|
NS
|
NS
|
NS
|
|
D. pteronyssinus
|
NS
|
NS
|
NS
|
NS
|
|
D. farinae
|
NS
|
NS
|
6.24 (1.55-25.1)
|
NS
|
|
Chicken egg white
|
NS
|
NS
|
NS
|
NS
|
|
Cow’s milk
|
NS
|
NS
|
NS
|
NS
|
Discussion
In this study, we analyzed the associated factors for AD, asthma,
rhinitis and FA in nursery school children in Ishigaki Island,
which is located to the south of the Japanese mainland. Since
symptoms are known to become apparent during the first 5 years of
life in 85% of children having AD [12], it is worthwhile
determining the associated factors as well as the prevalence of AD
in nursery school children.
Compared with other allergic disorders [13-17], the prevalence
of rhinitis (3.3%) in Ishigaki Island was remarkably lower than in
other reports (19.9-29.8%) [13, 14]. This is partially because in
Ishigaki there is no Japanese cedar pollen which is one of the
major aeroallergens for rhinitis in Japan; none of the children in
Ishigaki had a specific IgE antibody for this antigen [9]. These
data suggest that cedar pollen might be an important antigen not
only in adults but also in nursery school children.
Both genetic factors [2] and environmental factors [6] are known
to be involved in the etiology of AD. Contrary to previous reports
[8, 18], parental history of AD was not related to AD among nursery
school children in Ishigaki Island, and siblings’ AD and maternal
rhinitis were the only familial associated factors for AD.
Environmental factors rather than genetic factors might have a
critical effect on the occurrence of AD in Ishigaki Island. The
lifestyle in Ishigaki Island is changing very rapidly; houses are
increasingly made of concrete and steel instead of the traditional
wooden houses, and more roads have been paved.
Past history of asthma and FA were significantly associated with
AD in both univariate and multivariate studies. Although the
prevalence of asthma and FA in students with AD varies among
reports, a relatively high prevalence has been observed (asthma;
22.9-46.3% and FA; 9.5-51%) [14, 15, 19-22]. Similar levels of
prevalence were also found in the present study. However, it was
difficult to confirm this association due to the low prevalence of
rhinitis in Ishigaki Island.
Previous studies showed that total IgE and some specific IgEs
were associated with AD in univariate analysis [8, 9, 20]. However,
in this study only the elevation of total IgE remained a
significant associated factor in multivariate analysis. In
addition, another report revealed that children having either
long-term AD or newly developed AD had a higher serum total IgE
level than normal children [10]. These results suggest that a high
value for total IgE is an important associated factor as well as an
indicator of continuous morbidity of AD. It should also be noted
that elevated total IgE was not related to asthma, rhinitis or FA,
although this trend is not consistent with findings from other
studies [23, 24].
In conclusion, siblings’ AD, personal history of asthma and FA,
maternal rhinitis, and the elevation of total IgE were
significantly related to AD in pupils on Ishigaki Island. A high
total IgE level might be an AD-specific associated factor in this
population.
Acknowledgement
This work was supported by grants from the Ministry of Health,
Labor and Welfare.
References
1 Furue M, Terao H, Moroi Y, Koga T,
Kubota Y, Nakayama J, et al. Dosage and adverse
effects of topical tacrolimus and steroids in daily management of
atopic dermatitis. J Dermatol 2004; 31: 277-83.
2 Takeuchi M, Ueda H. Increase of atopic dermatitis
(AD) in recent Japan. Envir Dermatol 2000; 7: 133-6.
3 Yura A, Shimizu T. Trends in the prevalence of
atopic dermatitis in school children: Longitudinal study in Osaka
Prefecture, Japan, from 1985 to 1997. Br J Dermatol 2001; 145:
966-73.
4 Hoffjan S, Epplen JT. The genetics of atopic
dermatitis: recent findings and future options. J Mol Med 2005; 83:
682-92.
5 Sublett JL. The environment and risk factors for atopy.
Curr Allergy Asthma Rep 2005; 5: 445-50.
6 Haileamlak A, Dagoye D, Williams H,
Venn AJ, Hubbard R, Britton J, et al. Early
life risk factors for atopic dermatitis in Ethiopian children. J
Allergy Clin Immunol 2005; 115: 370-6.
7 Benn CS, Wohlfahrt J, Aaby P,
Westergaard T, Benfeldt E, Michaelsen KF,
et al. Breastfeeding and risk of atopic dermatitis, by
parental history of allergy,during the first 18 months of life. Am
J Epidemiol 2004; 160: 217-23.
8 Purvis DJ, Thompson JM, Clark PM,
Robinson E, Black PN, Wild CJ, et al. Risk
factors for atopic dermatitis in New Zealand children at 3.5 years
of age. Br J Dermatol 2005; 152: 742-9.
9 Hamada M, Furusyo N, Urabe K, Morita K,
Nakahara T, Kinukawa N, et al. Prevalence of atopic
dermatitis and serum IgE values in nursery school children in
Ishigaki Island, Okinawa, Japan. J Dermatol 2005; 32: 248-55.
10 Fukiwake N, Furusyo N, Kubo N, Takeoka H,
Toyoda K, Morita K, et al. Incidence of atopic
dermatitis in nursery school children -A follow-up study from 2001
to 2004, Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).
Eur J Dermatol 2006; 16: 416-9.
11 Tagami H. Japanese Dermatological Association criteria
for the diagnosis of atopic dermatitis. J Dermatol 1995; 22:
966-7.
12 Sampson HA. Pathogenesis of eczema. Clin Exp Allergy
1990; 20: 459-67.
13 Peroni DG, Piacentini GL, Alfonsi L,
Zerman L, Di Blasi P, Visona G, et al. Rhinitis
in pre-school children: prevalence, association with allergic
diseases and diseases and risk factors. Clin Exp Allerg 2003; 33:
1349-54.
14 Kao CC, Huang JL, Ou LS, See LC. The
prevalence, severity and seasonal variations of asthma, rhinitis
and eczema in Taiwanese schoolchildren. Pediatr Allergy Immunol
2005; 16: 408-15.
15 Oh JW, Pyun BY, Choung JT, Ahn KM,
Kim CH, Song SW, et al. Epidemiological change of
atopic dermatitis and food allergy in school-aged children in Korea
between 1995 and 2000. J Korean Med Sci 2004; 19: 716-23.
16 Garcia-Marcos L, Quiros AB, Hernandez GG,
Guillen-Grima F, Diaz CG, Urena IC, Pena AA,
et al. Stabilization of asthma prevalence among adolescents
and increase among schoolchildren (ISAAC phases I and III) in
Spain. Allergy 2004; 59: 1301-7.
17 Rance F, Grandmottet X, Grandjean H.
Prevalence and main characteristics of schoolchildren diagnosed
with food allergies in France. Clin Exp Allergy 2005; 35:
167-72.
18 Miyake Y, Yura A, Iki M. Cross-sectional study
of allergic disorders in relation to familial factors in Japanese
adolescents. Acta Paediatr 2004; 93: 380-5.
19 Tay YK, Kong KH, Khoo L, Goh CL,
Giam YC. The prevalence and descriptive epidemiology of atopic
dermatitis in Singapore school children. Br J Dermatol 2002; 146:
101-6.
20 Illi S, von Mutius E, Lau S, Nickel R,
Gruber C, Niggemann B, Wahn U, Multicenter Allergy
Study Group. The natural course of atopic dermatitis from birth to
age 7 years and the association with asthma. J Allergy Clin Immunol
2004; 113: 925-31.
21 Niggemann B, Sielaff B, Beyer K,
Binder C, Wahn U. Outcome of double-blind,
placebo-controlled food challenge tests in 107 children with atopic
dermatitis. Clin Exp Allergy 1999; 29: 91-6.
22 Hikino S, Nakayama H, Yamamoto J,
Kinukawa N, Sakamoto M, Hara T. Food allergy and
atopic dermatitis in low birthweight infants during early
childhood. Acta Paediatr 2001; 90: 850-5.
23 Anonymous. Worldwide variation in prevalence of symptoms of
asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The
International Study of Asthma and Allergies in Childhood (ISAAC)
Steering Committee. Lancet 1998; 351: 1225-32.
24 Platts-Mills TA. Asthma severity and prevalence: an
ongoing interaction between exposure, hygiene, and lifestyle. PLoS
Med 2005; 2: e34.
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