ARTICLE
Auteur(s) : Noriko
Fukiwake1, Norihiro Furusyo2,3, Norihiko
Kubo2,3, Hiroaki Takeoka2,3, Kazuhiro
Toyoda2,3, Keisuke Morita1, Satoko
Shibata1, Takeshi Nakahara1, Makiko
Kido1, Sayaka Hayashida1, Yoichi
Moroi1, Kazunori Urabe1, Jun
Hayashi2,3, Masutaka Furue1
1Department of Dermatology, Kyushu University
Hospital, Maidashi 3-1-1, Higashiku, 812-8582, Fukuoka, JapanFax:
(+81) 92 642 5600
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
accepté le 12 Avril 2006
Atopic dermatitis (AD) is a common and chronic inflammatory skin
disease that is characterized by relapsing itch and eczema [1]. It
is a major skin disease of children that is increasing in both
developed [2-4] and developing countries [5]. A similar trend has
been documented in Japan, [6-8] although one study has reported
that AD is no longer increasing [8]. There have been many studies
of the prevalence of AD [6-15]. However, there are very few
population-based epidemiological studies assessing prevalence among
children aged 5 years and less. In a previous study, we established
the prevalence of AD and serum total and specific IgE levels among
children in Ishigaki Island, Okinawa, Japan, in 2001 [16].In the
present study, we monitored children in Ishigaki Island by means of
annual physical examinations from 2001 to 2004.
Methods
Study population
We performed physical examinations of children in 15 nursery
schools in Ishigaki Island, which has a population of 45,000, in
Okinawa Prefecture, Japan. All the children were aged 5 years or
less. Approval for the study was obtained from the Ethics Committee
of Kyushu University Hospital as well as from the directors and
class teachers of the schools. Informed consent to allow
participation of the children was obtained from the parents and
guardians. The yearly average temperature and humidity were 25.4 °C
and 76% on Ishigaki Island.
The physical and laboratory examination was continued annually
from 2001 to 2004. The number of children examined was 631 in 2001,
836 in 2002, 844 in 2003, and 764 in 2004 (table 1)( Table 1 ). Of these, 862 were examined only once;
466 were followed for one year; 297 were followed for 2 years; and
106 were followed for 3 years. 1731 individuals were thus enrolled
in total, which represented 42.1% of the 4112 kindergarten pupils
in Ishigaki City. The physical and laboratory examination was
completed in July and August each year (summer season, average
temperature 28 °C).
Table 1 Prevalence of atopic dermatitis in nursery
school children in Ishigaki Island
|
Male
|
Female
|
Total
|
|
Number
|
AD (%)
|
Number
|
AD (%)
|
Number
|
AD (%)
|
Mean age ± SD
|
|
2001
|
342
|
19 (5.6)
|
289
|
20 (6.9)
|
631
|
39 (6.2)
|
3.0 ± 1.3
|
|
2002
|
446
|
23 (5.2)
|
390
|
30 (7.7)
|
836
|
53 (6.3)
|
2.9 ± 1.3
|
|
2003
|
455
|
44 (9.7)
|
389
|
49 (12.6)
|
844
|
93 (11.0)
|
3.2 ± 1.2
|
|
2004
|
412
|
15 (3.6)
|
352
|
13 (3.7)
|
764
|
28 (3.7)
|
3.0 ± 1.3
|
Physical and laboratory examination
The medical examinations for all children were done by two
dermatologists from the Department of Dermatology, Kyushu
University Hospital. AD was diagnosed according to the Japanese
Dermatological Association criteria (table 2)( Table 2 )[17]. 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. 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,
Japanese cedar pollen, Dermatophagoides pteronyssinus,
Dermatophagoides farinae, Candida, Malassezia, and food allergens,
such as chicken egg white, cow’s milk, rice, and soy were tested
with the Pharmacia Enzyme CAP procedure (Pharmacia CAP System
Specific IgE FEIA, Pharmacia Diagnostics AB, Sweden). A level of
specific IgE antibodies over 0.7 UA/mL was considered abnormal.
Table 2 Definition and diagnostic criteria for atopic
dermatitis by Japanese Dermatological Association
|
Definition
|
|
AD is a pruritic, eczematous dermatosis, the symptoms of which
fluctuate chronically with remissions and relapses. Most
individuals with AD have atopic diathesis.
|
|
Atopic diathesis: (1) personal or family history (asthma, allergic
rhinitis and/or conjunctivitis and AD), and/or (2) predisposition
to overproduction of immunoglobulin E (IgE) antibodies.
|
|
Diagnostic criteria for atopic dermatitis
|
|
1. Pruritus
|
|
2. Typical morphology and distribution:
|
|
(1) Eczematous dermatitis
|
|
(a) acute lesions: erythema, exudation, papules, vesiculopapules,
scales, crusts
|
|
(b) chronic lesions: infiltrated erythema, lichenification,
prurigo, scales, crusts
|
|
(2) Distribution
|
|
(a) symmetrical: predilection sites: forehead, periorbital area,
perioral area, lips, periauricular area, neck, joint areas of
limbs, trunk
|
|
(b) age-related characteristics
|
|
• infantile phase: starts on the scalp and face, often spreads to
the trunk and extremities
|
|
• childhood phase: neck, the flexural surfaces of the arms and
legs
|
|
• adolescent and adult phase: tendency to be severe on the upper
half of body (face, neck, anterior chest and back)
|
|
3 .Chronic or chronically relapsing course (usually
coexistence of old and new lesions):
|
|
(1) More than 2 months in infancy
|
|
(2) More than 6 months in childhood, adolescence and
adulthood
|
|
Definite diagnosis of AD requires the presence of all three
features.
|
Statistical analysis
Continuous data were expressed as mean values ± standard deviation
(SD) or standard error (SE) of the mean. Unpaired t-tests and
Mann-Whitney U-tests were used to compare the means of samples
between two groups. The chi-square test or Fisher’s exact test was
used for categorical variables for comparisons between two groups.
The Cochran-Armitage test was used to determine the relationship
between the increase or decrease in the prevalence rate of AD and
the IgE abnormality rate. P < 0.05 was considered statistically
significant.
Results
Incidence of AD
Table 1 shows the annual prevalence of AD in the study population,
which ranged from 3.7 to 11% (mean, 6.8%) each year, with no
significant difference between boys and girls. Of the total of 1731
children examined, 869 were followed up for 1 to 3 years, of whom
74 were diagnosed as having AD, while the remaining 795 were
considered to be free of AD at the initial physical examination.
Among the 74 AD cases, 53 were confirmed to have regressed
during the 3-year follow-up (71.6%); 31 cases after one year, 16 at
2 years, and the remaining 6 at 3 years ( (figure 1) ). In contrast,
44 of the 795 non-AD individuals (5.5%) developed AD
newly-developed within this 3-year period ( (figure 2) ), indicating
that the rate of new onset AD was 3.67%/person year in these
nursery school children.
Total IgE levels
Total IgE levels were compared in four different groups with or
without AD, namely the long-term AD group, the regressed AD group,
the newly-developed AD group, and the non-AD group ( (figure 3) ). Total IgE
levels gradually increased with increasing age in all four groups.
However, in the long-term AD group, the increase of total IgE was
significantly more rapid and greater than in the other 3 groups
over the 3-year follow-up period ( (figure 3) ). In contrast,
increases in total IgE levels were very slight both in the
regressed AD group and in the newly-developed AD group. However, it
is interesting that IgE levels were slightly higher in the latter,
and also that the IgE levels of the regressed AD group fell almost
to the same levels as in children without AD.
Discussion
In the present study, we performed a follow-up study of AD in among
children in Ishigaki and found that 71.6% of children with AD
experienced remission during the follow-up period. Furthermore, the
de novo occurrence of AD in these nursery school age children was
estimated as 3.67%/person year.
Symptoms become apparent during the first year of life in 65% of
children developing AD and in 85% during their first 5 years [18];
it is thus worthwhile to determine the incidence as accurately as
possible in nursery school children. The incidence in Japanese
elementary school students was around 3% in 1981 to 1983 but
increased to around 6 to 7% in the 1990s [7]. In 2000 to 2002, a
research team of the Japanese Ministry of Health, Labor and Welfare
(chief researcher, Dr. S. Yamamoto) performed physical examinations
of 48,072 children living in Asahikawa, Iwate, Tokyo, Gifu, Osaka,
Hiroshima, Kochi, and Fukuoka [19, 20]. In that study, it was found
that the average national prevalence of AD was 12.8% in 4-month-old
children, 9.8% in 18-month-olds, 13.2% in 3-year-olds, 11.8% in 6-
to 7-year-olds, 10.0% in 12- to 13-year-olds, and 8.2% in
18-year-old children in Japan. In the present study, the mean
prevalence of AD in children under the age of 5 years was 6.8% in
Ishigaki Island through 2001 to 2004, which was much lower than
that in mainland Japan [19, 20]. Yemaneberhan et al. studied the
prevalence of AD symptoms and the effects of potential
environmental etiologies in rural and urban areas of Jimma in
southwestern Ethiopia [21]. Lifetime cumulative prevalence of AD
symptoms was generally low with an overall prevalence of 1.2%, but
it was higher in the urban (1.5%) than in the rural areas (0.3%;
odds ratio = 4.45 [95% CI 2.34-8.47]) indicating a marked
urban-rural gradient [21]. In relation to industrialization and
urbanization, air pollution is now believed to be undeniably
involved in the increase of allergic diseases such as asthma and AD
[22-25]. In a recent Spanish epidemiologic study, air pollution was
associated with a higher prevalence of AD with a trend toward
greater severity as well [25]. In accordance with this notion, air
pollution is much lower on Ishigaki Island compared to mainland
Japan.
It is generally believed from clinical experience that
spontaneous regression occurs in the majority of AD patients in the
early period of life. However, few studies have actually addressed
and confirmed this assumption using population-based cohort study
methodology. Kohno reported that 80% of 4-month-old AD patients
became symptom-free at 18-months [26]. In the present cohort, we
determined the regression rate prospectively. Spontaneous
regression was observed in 71.6% of AD patients during the 3-year
follow-up period in the nursery school children studied here. Such
spontaneous regression seemed to occur rather rapidly because 41.9%
of patients no longer showed any symptoms as early as 1 year
later.
Among the 795 initially symptom-free children, AD developed in
25, 14 and 5 cases, one, 2 and 3 years later, respectively. Thus,
44 of 795 children (5.5%) developed AD over the 3 years
(3.67%/person year). Consistent with this finding, it was reported
that 60% of 3 year-old AD patients had not shown any symptoms at
4-months [26]. Considering the spontaneous regression and de novo
development as mentioned above, the clinical course of AD is
clearly extremely diverse in nursery school children.
In our previous study, high levels of total IgE were found in
only 33.3% of those children diagnosed with AD. However, IgE
antibodies specific for one or more allergens were detected in
64.1% of children with AD. The total and specific IgE levels were
both significantly higher in children with AD than in those without
[16]. In the present cohort, we compared IgE levels in long-term AD
patients with those who spontaneously regressed, developed AD de
novo, or never had AD. The IgE levels tended to increase gradually
as the children’s ages increased in all of these groups.
Nonetheless, a much more marked elevation of IgE was observed in
the long-term AD group compared to the others. Other studies have
also found that IgE levels were elevated in 80 to 85% of children
who developed AD and correlated with disease severity [27, 28].
Recently, Yamamoto et al. showed that subcutaneous injection of
culture supernatants from keratinocytes potently enhanced IgE
secretion by splenocytes and increased in vivo IgE levels in mice
[29]. Soumelis et al. demonstrated that thymic stromal
lymphopoietin (TSLP) was highly expressed by keratinocytes from
patients with AD, and that TSLP-activated dendritic cells primed
naive helper T cells to produce the proallergic cytokines IL-4,
IL-5, IL-13 and tumor necrosis factor-alpha, while down-regulating
IL-10 and interferon-γ [30]. These results suggest that continuous
atopic inflammation of the skin may enhance IgE production by
stimulating the secretion of keratinocyte-derived cytokines.
In conclusion, more than 70% of AD children experienced
spontaneous regression within the 3-year follow-up period, while
new onset was estimated at 3.67%/person year in nursery school age
children.
Acknowledgements
This work was supported by grants from the Ministry of Health,
Labor and Welfare.
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