Discussion
Our Subset I Study indicated that a high TC level correlated with the
severity of atopic dermatitis in school-age children, and our Subset II
Study (a single center long-term study using OMOP-CDM) indicated that
the high TC group had a slightly greater HR for the onset of atopic
dermatitis than the normal TC group.
Several previous studies examined the relationship of hyperlipidemia
with atopic dermatitis in adults.7,10-14 The results
of the present study of children are consistent that reported a positive
correlation of hyperlipidemia with atopic dermatitis in
adults.7,10 However, very few studies have examined
the association of atopic dermatitis with lipid parameters in children.
A database study by Augustin et al.14 showed a
significantly increased prevalence rate of hyperlipidemia in children
with atopic dermatitis compared to those without atopic dermatitis
(prevalence ratio: 1.29; 95% CI: 1.12, 1.49; P <
0.05). However, their study defined atopic dermatitis based only on ICD
code, did not directly measure TC, LDL-C, HDL-C, or TG, did not report
the severity of atopic dermatitis, and was a cross-sectional study.
Previous research indicated that dyslipidemia is a type of chronic
inflammatory response.26 In particular, elevated TG
and LDL-C lead to increased pro-inflammatory signaling and increased
expression of TNF-α and interleukin (IL)-6.26,27 In
contrast, HDL-C has an anti-inflammatory effect, in that it modulates
T-cell activation.26,27 This supports the
interpretation that the presence of a chronic inflammatory state (as
indicated by dyslipidemia) is responsible for chronic skin inflammation,
and provides a possible mechanism for the relationship between atopic
dermatitis and hyperlipidemia.
We used the SCORAD score to grade the severity of atopic dermatitis, and
found that this score had positive associations with TC and TG and a
negative association with HDL-C. Thus, our results indicate an
association of hyperlipidemia with the severity of atopic dermatitis.
However, another previous case-control study of adults in Germany
reported conflicting results in the relationship of dermatitis with
HDL-C.7 This study found that the HDL-C level was
significantly higher in subjects with atopic dermatitis (61.0 vs.54.9 mg/dL; P < 0.01) and that after stratification by
gender, there was a significant positive association of HDL level and
atopic dermatitis in men.7 Our results indicated that
disease severity (SCORAD score), erythema, excoriation, lichenification,
and pruritus scores in children had positive correlations with the
levels of TC and TG, and negative correlations with HDL-C level. Thus,
cholesterol might be related to the chronicity of atopic dermatitis in
children.
The results of our Subset II Study indicated that the high TC group had
a greater HR for the onset of atopic dermatitis during a median
follow-up time of 1,750 days. The Observational Health Data Sciences and
Informatics (OHDSI) initiative is a large-scale international
collaborative that is investigating the value of analyzing health
data.20
We used a retrospective long-term follow-up study (Subset II) to
complement our cross-sectional study (Subset I) and examine the casual
relationship of hyperlipidemia and atopic dermatitis. Nonetheless, there
were several limitations to this study. We did not perform repeated
objective clinical assessments and there are data quality issues
inherent to working with health care databases, in that covariates,
exposures, and outcomes may be inadequately or incorrectly measured.
However, our use of data standardization into a common data model,
propensity-score matching, and calibration via negative controls
helped to prevent erroneous conclusions. Also, the case definition of
atopic dermatitis was based on ICD-10 diagnostic codes, so there may be
questions about the validity of our definition. To address this issue,
we defined atopic dermatitis as at least 5 diagnoses of atopic
dermatitis from ICD codes plus 2 treatment codes for atopic dermatitis
drug therapy.22
Our study has many merits. To the best of our knowledge, this is the
first large-sample study of urban children to comprehensively
investigate the association between blood lipid level and the severity
of atopic dermatitis. Moreover, trained physicians directly assessed the
severity of atopic dermatitis. Most previous studies of the association
between atopic dermatitis and hyperlipidemia were surveys, and none of
these previous studies examined the disease severity. In our study,
pediatricians specializing in allergies determined all SCORAD scores.
Another strength is a longitudinal cohort analysis to supplement and
valify the cross-sectional analysis.
In conclusion, our results indicated that hyperlipidemia in children has
a positive association with the presence and severity of atopic
dermatitis. These findings suggest that atopic dermatitis should be
considered a systemic disorder that shares certain characteristics with
other chronic inflammatory disorders.