Discussion
A total of nineteen guidelines for the management of AD in children were included in the study, thirteen of which were CPG and two guidelines were in Chinese. The quality of the included guidelines was evaluated by the AGREE II instrument, and three guidelines were rated A level and eleven were rated B level, which was of high overall quality. Those who received a C-level quality rating were mainly evidence-based expert consensus.
More research has been focused on AD worldwide with the development and advancement of medicine, but it seems that the main treatment of AD has not changed so much. AD occurs predominantly in infancy and early childhood, symptoms are predominantly mild, with a few cases extending into adulthood.41,42 All guidelines suggest that for mild, non-episodic AD without other infections, the primary concern is basic skin care, such as keeping skin moist and clean. Skin moisturization and cleansing can reduce the severity of AD and the frequency of medication use.43 The choice of moisturizer can be based on patient preferences. There is no consensus on the dosage, frequency and timing of application, but most guidelines recommend choosing the dosage based on fingertip units (FTU), and European guideline suggests specific dosages (shown in Table 5). Also, it is recommended to use it together with medication to reduce the side effects when it comes to flares. Skin cleansing is as important as moisturizing. The use of a moisturizer immediately after the end of daily bathing was agreed upon for this recommendation across guidelines. There is no agreement on the time and temperature of bathing water, most recommend 5 to 10 min and a water temperature of 27℃ to 40℃, water temperature too high can cause itching of the skin.44Cleaners refer to patient preferences and try to use neutral or low pH, non-allergenic substances or additives.
This study included AD guidelines published after 2016, and it can be seen that the initial reports on the use of biologics were small sample size studies, and their safety and efficacy could not be confirmed especially in children, who are at high risk of AD and are more cautious about the use of biologics. Dupilumab is the first biologic agent for adult AD approved in Europe and FDA in 2017.45,46Dupilumab is a fully human monoclonal antibody that blocks the common a-chain of the receptor for interleukin-4 and interleukin-13 that shows positive control of the extent of AD lesions and pruritus symptoms. Dupilumab was approved in South Korea in 2018 and China in 2020 for use in adults with moderate to severe AD, respectively. With increased relevant evidence, Dupilumab was approved by FDA in 2019 for adolescent patients aged 12~17 years and in 2020 for pediatrics aged 6~11 years with moderate-to-severe AD. Other biologics such as omalizumab, Ustekinumab, rituximab, mepolizumab, Nemolizumab, and alefacept are not recommended in the guidelines for now due to the limited evidence available. Cost-effectiveness also needs to be considered when using biologics for AD in children.47
Traditional medicine such as Chinese herbal medicine, acupuncture, massage, homeopathy, and aromatherapy, are widely used in some Asian countries. However, the safety and efficiency of traditional medicine are still waiting to be verified. For example, the use of herbal medicine may cause metal element poisoning and increase the nephrotoxicity of patients.48 Therefore, most existing guidelines do not recommend conventional medicine for the treatment of AD, and more research evidence is needed for its application in children. It is noteworthy that 67.4% of AD patients in a survey conducted in Hiroshima, Japan, used herbal medicine. In a questionnaire survey of guardians of children with AD at their first visit in Tokyo, patients with steroid phobia used traditional medicine more frequently than patients without steroid phobia (22.2% vs. 13.0%, P=0.013).27,49 China has published guidelines for Chinese medicine to AD which to guide clinical practitioners in the application of Chinese herbal medicines in 2021, which is currently only available in Chinese and mentions limited evidence of effectiveness, and more clinical studies are needed to confirm the efficacy of these herbal medicines in the future.
In addition to traditional medicine, there are several complementary treatments like dietary restrictions, essential fatty acids, vitamin D, probiotics and allergen immunotherapy, etc. Above all, dietary restrictions are not recommended especially for children, pregnant and lactating women. Unless patients have a clear allergy to food or a positive oral irritation test. Dietary restrictions can cause malnutrition, which is difficult to implement in real life and reduces the quality of life. Patients and family members must be informed of the pros and cons of this method before implementation. Secondly, certain agents such as essential fatty acids, vitamin D, and probiotics are not recommended due to insufficient evidence available. In particular, probiotics have been shown to have no significant effects in pediatrics patients with AD. For allergen immunotherapy, it can be considered in moderate to severe AD with a combination of allergic rhinitis, asthma, dust mite, and pollen allergy, otherwise it is not recommended. However, these conclusions may also be overturned later.
Almost all guidelines have mentioned patient education. Patient education has been proven to reduce disease severity, improve quality of life and improve mental health. Although patient education has never been neglected, it still seems to be ineffective and steroid phobia has not diminished over time. Patient education is an ongoing, time-consuming, and high-volume effort that requires multidisciplinary staff collaboration and includes pediatricians, dermatologists, pharmacists, nursing staff, community workers, etc. There are different forms of patient education in different national backgrounds. Specialized outpatient clinics, brochures, inpatient lectures, online videos and dedicated websites are the main modes of patient education. Some developed countries from Europe carried out eczema action plans and eczema schools, which may benefit from national policy support. The implementation of patient education should take into account the applicability and cost-effectiveness of the region where it is carried out. The target of education is not only patients, but also family members, especially parents of children, to increase patient compliance and ensure the quality of life. Also, it is important to know that patients and families learn to use some self-assessment tools such as POEM so that they can be informed of the degree of control timely. In the future, there is still a need to explore more methods of education that can be satisfied by patients, families and staff to improve compliance with AD treatment.