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.