DISCUSSION
In this cross-sectional epidemiological study on atopic eczema in
Kosovo, within the GAN collaboration, we have found very low prevalence
of any of the three atopic eczema markers as compared with other GAN
centres. In fact, only three centres, two in India (Lucknow, 1.9% and
Mysuru, 1.4%) and the one in Sri-Lanka (Anuradhapura, 1.1%) had lower
prevalence of symptoms of current eczema than Ferizaj (2.2%); and this
centre had the lowest prevalence of severe eczema symptoms, with only
five cases in the whole population surveyed (<0.5%). With
respect to eczema ever, only nine into sixteen Mexican centres and one
Indian (Mysuru) had a prevalence lower than 3.0%, the one found in
Ferizaj. The centre with the highest prevalence of those markers in
Kosovo is Gjakova with 5.5%, 0.7% and 6.8% respectively for current
eczema symptoms, severe eczema symptoms, and eczema ever. Those figures
are also quite low as compared to the rest of GAN
centres3.
Although there has not been any other previous study on the epidemiology
of atopic eczema in Kosovo, there have been some in the Balkan region.
In the ISAAC phase III survey5, carried out around
2002, Tiranë (Albania) reported the prevalence of eczema markers defined
as in the present study as follows: current eczema symptoms, 2.0%;
severe eczema symptoms, 0.2%; and eczema ever, 2.9%, respectively.
Furthermore, the corresponding figures for Rijeka (Croatia) and Skope
(Republic of Macedonia) were 2.9%, 0.2% and 8.5%; and 2.7%, 0.3%
and 3.7%, respectively. There were also data from five centres in
Serbia and Montenegro, which ranged 2.8%-8.0%, 0.5%-1.3%, and
8.2-17.9%, respectively. The report by Zivković et al.7 on Serbia and Montenegro expands further the data
included in the ISAAC phase III report and showed low prevalence rates
of other eczema markers.
Apart from offering the first epidemiological data on atopic eczema in
Kosovo it is also interesting to study epidemiological factors which
might be associated to this condition in a geographical area with very
low prevalence where, to the best of our knowledge, those factors have
not been yet studied among adolescents. Of those studied factors in the
meta-analyses of the six centres, male sex is independently associated
to both a significant lower prevalence of current eczema symptoms and of
eczema ever (if Prizren is excluded in the latter case) (figure 1). The
prevalence of severe eczema symptoms is too low to allow any
multivariate statistics. The influence of sex in atopic eczema has been
previously studied in adolescents in the Balkan area: Stipic-Markovic et
al. 9 found no association between eczema markers and
sex in Zagreb among adolescents included in the ISAAC phase III survey.
However, other studies have found that different eczema markers are
significantly more prevalent in female sex in this age group, like that
by Mercer et al. carried out in Cape Town (South Africa)16. In the EPI-CARE study, a recent international
cross-sectional study in children (6 months to <12 years old)
and adolescents (12 to <18 years old) using ISAAC methods and
defining atopic dermatitis with the same criteria as in the present
study found that prevalence differences by sex, in one or the other
direction, existed in some countries but not in
others17. However, the authors did not report those
differences separately in the two age groups studied. In the BAMSE
study, a longitudinal population-based cohort study, carried out in
Stockholm, the follow-up visit at age 11-14 years did show a
significantly higher prevalence among females when using an eczema
questionnaire specifically designed for the study18.
The same was found in a large international cross-sectional study among
adults 18–65 years old19, and previously in a Swedish
study on individuals 17-75 years of age which used the
GA2LEN questionnaire to assess eczema
symptoms20. These findings are shared by other
studies21,22. A recent BAMSE report after the visit at
24 years of age of the individuals in the cohort, further extends the
finding of male sex is associated to lower prevalence of eczema
markers23. Sex hormones seem to play a role in this
difference after puberty24.Current eczema symptoms and
eczema ever were also associated to exercise in an apparently not
dose-response fashion. Making regular exercise was significantly
associated with the increase of prevalence of both atopic eczema markers
overall, although this was not the case in some of the centres (figure
2).
As found in the present study, exercise has been associated to eczema
previously, although the information is quite limited. In a systematic
review and metanalysis by Kim et al. 25 in 2016 only
seven manuscripts were included after searching all relevant literature
databases since their existence. Three studies found some association
between exercise an eczema; three showed an inverse relationship and one
did not find any association. Only five of them had enough data to be
included in metanalysis which yield non-significant summary effects, but
interestingly, the only study in adolescents26 showed
a significant positive association. Both the two other studies (not
included in the metanalysis) which found positive associations were also
performed in in children or adolescents27,28. Only one
of the studies showing no association was in adolescents. It should be
noted that this one only included 481 individuals29.
All those studies in adolescents and children used the ISAAC
methodology, which requires a sample size of 3000. More recent studies
offer additional information. For instance, Jago et al.30, using accelerometers in a ALSPAC population of
6473 adolescents, concluded that the number of minutes of vigorous
exercise is not related either to asthma or to eczema, but it is
inversely associated to obesity. The nature of the ISAAC studies
(cross-sectional) vs. de ALSPAC (longitudinal) and the different ways of
measuring exercise (simple questionnaire vs. accelerometer) can explain
the discrepancy. However, it cannot be ruled out that low to moderate
exercise is associated to higher prevalence of eczema, while moderate to
vigorous is not. It well might be that low intensity exercise with skin
exposure to environment and climate aggression and sweat could
facilitate mild eczema flares in not highly predisposed individuals;
and, in contrast, those highly predisposed avoid vigorous exercise to
escape from severe flares. In fact, higher disease severity is
associated with decreased levels of physical activity secondary to itch,
in adults, has been previously shown31. The curve of
the association between the amount of exercise and the severity of
eczema (and thus, awareness in self-reported surveys) might have an
inverted U shape.
On the other hand, Honjo et al. 32 found a positive
independent association of exercise induced wheeze with eczema in a
group of 12,405 asthmatic children 6 to 18 years of age following ISAAC
definitions. This is probably in keeping with our findings that the
association of exercise with eczema is higher in those adolescents who
also reported current wheeze (table 2). We cannot say whether the
proportion of atopy was higher in the individuals who wheeze than in
those who did not wheeze, but this possibility cannot also be ruled out.
The third variable that was consistently associated to eczema markers
was taking paracetamol, both at least once last year and at least once
last month (figure 3). This was more consistent for current eczema
symptoms than for eczema ever and was probably driven by those
individuals who have both eczema and wheeze (table 2). There have been
several reports linking the use of paracetamol with eczema, even showing
that this association is higher when several allergic diseases
coexist33-36. Thus, it cannot be said whether the
association between paracetamol and eczema might be driven by asthma
and/or rhino-conjunctivitis and/or allergy. The present study shows that
the association with frequent use (at least one last month) holds even
among those adolescents without current wheeze, but only for current
symptoms of the condition. The effect of early paracetamol intake on
eczema in children 6-7 years of age with neither asthma nor
rhino-conjunctivitis symptoms, has been previously
shown37. This probably indicates that the drug impairs
the antioxidant system which is crucial to maintain skin integrity after
aggression38.
The present study has a main weakness which is its cross-sectional
nature, precluding to obtain any causal relationship. On the other hand,
the study was conducted using validated methods, on a quite large sample
with high participation rate, which is representative of the whole
country of Kosovo. It has the additional interest of being an area with
quite low prevalence of atopic eczema.
In summary, this study shows that, in an area of low prevalence of
atopic eczema, both sex, exercise and paracetamol intake are associated
to the number of eczema cases, also in those adolescents without current
asthma symptoms. Male sex is associated to lower prevalence while mild
to moderate exercise and frequent use of paracetamol are associated to
higher prevalence of the condition.