Discussion
This study describes the current demographics, disease characteristics,
comorbidities, and aggravating factors of patients with mild, moderate,
and severe AD in all age groups in China. In moderate to severe group,
the proportion of men was higher relative to the proportion of women
(67.44% vs 59.78%, P<0.001). A cross-sectional study in Europe and
Canada revealed that the proportion of women was higher in the mild AD
group than in the moderate and severe AD groups (61.2% vs 50.5%; P
< 0.001).16 Based on the POEM score, a study
in the United States observed that most adult patients with AD had mild
disease (60.1%, 95% CI: 56.1, 64.1) followed by moderate disease
(28.9%, 95% CI: 25.3, 32.7).17 In contrast, our
findings showed that most of the patients with AD in China had moderate
disease severity followed by mild and severe disease. As the results of
previous studies and ours varied, the differences in the results can be
attributed to the varying definitions between the studies. Additionally,
our results suggest that AD in Chinese individuals is poorly controlled
in all age groups. Consistent with findings of previous
studies,6 the proportion of AD was generally lower in
rural settings than in urban settings. Meanwhile, marital status and
education level did not have a significant effect on AD severity.
In our study, the issue of relationship between the AD severity and
patient distribution in China was explored. The amount of severe AD in
the northern provinces was dominantly
higher than in the western and central provinces. Additionally, there
were more patients with severe AD in the economically developed southern
regions. Aggravating factors, low temperatures, and an arid climate in
northern China may have negative effects on the skin that may aggravate
pruritus in patients.18 Regional specific plants and
flowers are also important components of environmental allergens. South
China belongs to the subtropical and tropical regions, with subtropical
grass pollens being more abundant.19 Emerging evidence
showed that exposure to grass pollen induced a significant worsening of
AD.20 Our data showed that incidence of severe AD is
very high in Guangdong province. In the future, recognition of
subtropical grass pollen allergens by transcriptomic, proteomic and
bioinformatic approaches is essential for study to increase the efficacy
of allergen-specific immunotherapy for AD.
Early-onset AD usually develop atopic comorbidities such as allergic
rhinitis, asthma, food allergies, and allergic conjunctivitis. The
percentage of infants with AD who complicated with allergic rhinitis,
22.4%; food allergy, 15.9%; allergic conjunctivitis 14.1% in the
study of United Stated.21 Allergic rhinitis, food
allergy not asthma or allergic conjunctivitis developed significantly
more often in infants with greater AD severity at baseline. The
relationship of adult-onset AD and atopic comorbidities has been poorly
studied. At all ages of prevalence of allergic rhinitis with AD was
25.88%; food allergy with AD was 6.2%, asthma was with AD 4.22%,
allergic conjunctivitis with AD was 2.2% in our research. Compared to
the children study above, the prevalence of asthma and food allergy
decreased significantly in the multi-age group, suggesting that asthma
and food allergy are main comorbidities of early-onset AD. In terms of
non-atopic comorbidities, AD patients who have identified as having at
least one non-atopic comorbidity, hypertension had the highest
prevalence, followed by diabetes and coronary heart disease. This is not
uncommon as other studies have also found significant associations
between AD, hypertension, diabetes, and cardiovascular diseases.
Silverberg et al. have found higher odds of diabetes, high blood
pressure, and heart disease in both adults and paediatric patients with
AD compared to healthy control.22,23 Additionally, we
found hypertension to be a significant risk factor of AD where patients
with hypertension comprised a significantly higher proportion of severe
AD compared to mild and moderate AD. Similarly, a recent study by
Abdallah & Vestergaard found that moderate-to-severe AD was
significantly associated with hypertension while mild AD was
not.24 This indicate that when managing AD patients,
clinicians have to pay attention to and take care of non-atopic
comorbidities at the same time as performing other AD-specific
interventions. In addition to comorbidities, patient-identified
aggravating factors also contributing to AD development and progression.
Various exogeneous aggravating factors lead to persistence and
recurrence of AD. Our findings revealed that the severity of AD was
associated with exposure to irritants, including fish, shellfish, chili
peppers, dust, pollen, and temperature and humidity changes. Tropomyosin
is the common allergen in fish and shellfish.25Remarkably, tropomyosin shares a significant homology to allergens found
in house dust mites.25 Therefore, we suppose that
house dust mite immunotherapy could improve seafood tolerance in
moderate-to-severe AD.
Aside from comorbidities and exogenous aggravating factors,
psychological factors have also been shown to play a critical role in
increasing the disease burden of AD. In our study, stress, emotional
problems, and sleep disorders have contributed to a significantly higher
proportion of severe AD. In prior studies of adolescent AD, men who
reported with high stress had 46% higher risk of developing severe AD
than participants who reported with no stress.26 Early
studies found that high level of stress may trigger TNF-alpha,
eosinophil, and IgE release, swaying the immune system towards T helper
type 2 (Th2) responses.27,28 Patients with AD have
blunted reactivity of the HPA axis and an overactive sympathetic
adrenomedullary system that results in immune imbalance that favors Th2
responses.29 Sleep disorders are strongly associated
with AD; they have been reported in 47–80% of children and in
33–87.1% of adults with AD.30 Specifically, itching
and scratching can cause tissue damage and sleep disturbance, while
pruritus-induced sleep deprivation can further impede immune functions
and exacerbate AD. This suggests that the management of psychological
conditions is a vital part of the management of AD. Recently, the
American Academy of Dermatology (AAD) published guidelines for managing
comorbidities associated with AD. Within these guidelines, the AAD
advised clinicians to assess and treat patients with unaddressed mental
health issues after adequate control of AD in a case-by-case
manner.31 In the future, with more evident
associations between psychological aggravating factors and AD,
dermatologists may arrive at a consensus for the management of
psychological aspects of AD.
Furthermore, the treatment and management of AD in China has its own
characteristics and unmet needs. According to several guidelines, the
use of moisturizers, topical glucocorticoids, TCI, and topical
antimicrobials are recommended as topical anti-inflammatory
treatments.32-34 For more severe AD, systemic
immunomodulating medications like cyclosporine, azathioprine,
methotrexate, or mycophenolate mofetil, and phototherapy were
recommended.32-35 Meanwhile, the use of antihistamines
to reduce pruritus was found to be ineffective, while systemic steroids
are not recommended due to their severe adverse
effects.32-38 More recently, the use of biological
agents and JAK inhibitors were also recommended for treatments of severe
AD.39-42 However, the therapeutic pattern observed in
our cohort suggested insufficient treatment of patients with AD in
China. For instance, moisturizers containing emollients have been proven
to lessen the symptoms of AD,43,44 yet in our cohort,
there was only 19.58% of AD patients used topical moisturizers.
Additionally, a large proportion of patients used antihistamines
(43.46%) and systemic steroids (8.51%) as their primary treatment,
which are not in line with most guidelines. Furthermore, the proportion
of patients using systemic immunomodulatory medications and biological
agents was low in our cohort. Some patients also relied on Chinese
medicine, such as tripterygium and glycyrrhizin, which lack evidence on
their efficacy in treating AD. These patterns of undertreatment may
explained the high proportion of patients with severe AD in this study.
To solve these problems, an increased use of systemic immunomodulating
therapies, promotion of the use of biological agents, and educational
interventions are needed.
In conclusion, our study firstly revealed the severity distribution and
demographic characteristics of patients with AD across all-ages in
China. Effective long-term management of chronic comorbidities is
AD-related challenges faced by dermatologists and allergists.
Undertaking reasonable measures to avoid aggravating factors can
alleviate AD.