This guideline was developed by the Immunology Group of the Dermatology and Venereology Branch of the Chinese Medical Association on the basis of joint discussions with reference to domestic and foreign literature (main authors: Gu Heng, Hao Fei, Zhang Jianzhong). This guideline is for the reference of domestic dermatology colleagues in the diagnosis and treatment, and will be further revised in the future.
Atopic dermatitis (AD) is a chronic, recurrent, pruritic, inflammatory skin disease that seriously affects the quality of life of patients and their families. The disease is associated with genetic allergies and is often accompanied by skin barrier dysfunction. The disease usually begins in infancy, and some data show that about 50% of all patients develop the disease before the age of 1 year. The prevalence of AD can be as high as 10%-20% in developed countries, and epidemiological surveys in China also show an increasing trend in the incidence of this disease, for example, in 2000, the epidemiological survey in China showed that the total prevalence of school-age adolescents (6-20 years old) was 0.70% [1], and in 2004, the prevalence of urban preschool children (1-7 years old) was 2.78% [2]. In general, the incidence of AD decreases with age, and the disease may gradually decrease.
1. Etiology and pathogenesis
The etiology of atopic dermatitis is very complex and has not yet been fully understood. Genetic, environmental and biological factors are closely related to this disease [3]. Children of parents with a history of genetic allergies have a significantly increased chance of developing the disease, but genetics is not the only determining factor. Environmental factors, especially the degree of industrialization, urban living, standard of living and changes in lifestyle are important risk factors for the development of AD. Among allergic factors, diet such as milk, eggs and seafood have an influence on the development of AD, especially in those with severe disease in infancy and early childhood. Dust mites, house dust mites, and pollen may be important airborne allergens. Non-allergic factors such as irritants or detergents that disrupt the skin barrier, scratching, microbial colonization (e.g., Staphylococcus aureus and Malassezia furfur), and psychological factors (e.g., stress, anxiety, depression) also play an important role in the pathogenesis [3,4].
The exact pathogenesis of AD is not known. It is generally believed that it is caused by dysfunction of the body’s skin barrier or direct dysregulation of the body’s immune response in response to certain genetic background and/or environmental factors, leading to allergic or non-allergic inflammatory reactions. Skin barrier dysfunction creates conditions for local sensitization of allergens or microbial colonization, which is an important basis for triggering or aggravating skin inflammation.
The development of atopic dermatitis involves both immune and non-immune aspects. Immune-mediated inflammation involves several components, including the presentation of allergens by Langerhans cells and cutaneous dendritic cells, dysregulation of Th1/Th2 balance and regulatory T cell dysfunction, involvement and amplification of the inflammatory response process by eosinophils and specific IgE, and the production of cytokines and inflammatory mediators by keratinogenic cells involved in the inflammatory response. In recent years it has been noted that non-immune factors such as neuro-endocrine factors or abnormal physiological and pharmacological mediator responses are also involved in the formation of skin inflammation [3-5]. The above inflammatory processes are an important basis for the therapeutics of atopic dermatitis.
2.Clinical manifestations
The clinical manifestations of atopic dermatitis are diverse, and the most basic feature is a chronic recurrent pruritic rash with certain age-stage characteristics. The rash can be divided into three stages: infancy, childhood and adolescent-adult stage according to the occurrence, development and distribution characteristics of the rash. The infantile period (1 month to 2 years) is characterized by infantile eczema, and the lesions are mainly exudative and dry, mainly on the cheeks, forehead and scalp. Childhood (2 to 12 years old), mostly evolving from infancy, may also not go through infancy, its lesions show eczema type and itchy rash type, mostly occurring in the elbow fossa, N fossa and the extensor side of the calf. In adolescent adults (>12 years of age), the lesions are similar to those of childhood and are mostly limited dry dermatitis lesions, mainly occurring in the elbow fossa, N fossa, and anterior aspect of the neck, but also on the face and back of the hands.
Atopic dermatitis can be accompanied by a range of characteristic skin changes, including dry dermatitis, auricular fissures, ichthyosis, palmaris, periorbital keratosis, propensity for skin infections (especially Staphylococcus aureus and herpes simplex), nonspecific hand and foot dermatitis, papular eczema, labyrinthitis, recurrent conjunctivitis, Dennie-Morgan (Dennie-Morgan) infraorbital folds, periorbital dark halo, pale face, white pityriasis, anterior cervical folds, and white scratches/delayed whitening, which are signs that help aid in the diagnosis of AD.
Based on the combination of systemic allergic diseases in AD, it can be divided into simple type, which presents only with skin involvement, and mixed type, which is combined with other atopic diseases such as allergic asthma and allergic rhinitis. The former lacks allergic evidence, while the latter has positive allergen-specific IgE or increased blood IgE levels or peripheral blood eosinophil counts. The endogenous type is easy to be missed clinically and should be taken seriously.
3.Diagnostic criteria
At present, there are several diagnostic criteria used in the diagnosis of atopic dermatitis at home and abroad, including Hanifin and Rajka criteria, Williams criteria and Conkefer criteria, among which Willianms criteria are concise and easy to use, and their specificity and sensitivity are similar to Hanifin and Rajka AD criteria and Conkefer criteria, and they are especially suitable for outpatient work, so they are recommended. Williams’ diagnostic criteria are shown in the table below.
4. Treatment
Because atopic dermatitis has a long duration and is prone to recurrence, the principle of treatment is to restore the normal barrier function of the skin, to find and remove triggering and/or provoking factors, and to reduce or relieve symptoms. When necessary for pharmacological treatment, health education for patients and/or family members is very important so that they have a clear understanding of the disease, treatment methods and processes, and pay attention to various precautions in life such as avoiding or reducing exposure to triggering factors as much as possible; understanding the importance and use of adjuvant treatments such as emollients; avoiding or reducing the search for so-called “potent “special” treatments; understand the effects and adverse effects of relevant drugs, understand the benefits and risks of various treatments, and cooperate with the doctor to obtain the best possible results.
4.1 Basic treatment
4.1.1 Avoid triggers and aggravating factors Try to avoid all possible stimuli. One should try to wear cotton clothes, with loose-fitting, change clothes and bed sheets and other household items, and avoid forceful scratching and rubbing; avoid excessive washing of the skin, especially scalding and excessive use of soap; pay attention to maintaining a suitable temperature environment to reduce the stimulation of sweat; pay attention to maintaining a clean living environment to reduce allergens such as house dust, mites, animal hair, pollen, fungi, etc.; pay attention to observing the reaction to the food consumed. Avoid eating allergenic food.
4.1.2 Restore and maintain skin barrier function Correcting dry skin, protecting skin barrier function and stopping itching are the key measures for treating AD. In the acute phase, bathing with warm water once or twice a day will increase humidity and help reduce exudation and remove scabs and residual medication; in the chronic phase, bathing can be done once a day.
Whether in the acute phase or in remission, the application of emollients and/or moisturizers is essential and should be applied topically (mostly recommended for systemic use) at least 1 to 2 times daily, especially immediately after bathing, to maintain the hydrated state of the skin and protect the barrier function and reduce pruritus symptoms.
4.2 Drug treatment
4.2.1 Topical treatment (1) Glucocorticoids: Intermittent topical glucocorticoids, together with emollient moisturizers, are the first-line treatment for AD. Different types and strengths of glucocorticoid preparations are selected according to the patient’s age, lesion site and degree of disease in order to quickly and effectively control inflammation and reduce symptoms. However, relatively weak glucocorticosteroids should be used on the face, neck and folds, and strong fluoride preparations should be avoided, and strong glucocorticosteroids should be used with caution in children. Long-term use may cause certain skin adverse reactions (such as skin atrophy, capillary dilation, swelling lines, hirsutism, hormonal acne, bacterial infection, purpura, etc.), and long-term large-scale application may sometimes cause systemic adverse reactions (medical adrenocortical insufficiency, Cushing’s syndrome, psychoneurological symptoms, glaucoma, cataracts, and menstrual cycle disorders, etc.). Therefore, for chronic or thicker lesions topical application should be selected with more potent glucocorticoid preparations, and after controlling the disease in the short term, switch to weak preparations or non-hormonal drugs.
(2) Calcium-regulated neurophosphatase inhibitors: These drugs, including tacrolimus and pimecrolimus, have good efficacy in atopic dermatitis, have strong selective anti-inflammatory effects, and can be used for a relatively long period of time in all sites of pathogenesis, especially on the face and neck and other tender skin areas. Adverse reactions are mainly local burning and irritation for a short period of time after administration, no significant systemic adverse reactions have been found (transdermal absorption of both drugs is low), and there are no adverse reactions of glucocorticoids.
(3) Topical antibiotic preparations: Since bacteria or fungi can induce or aggravate the disease by producing superantigens or acting as allergens, while using glucocorticoids, especially when treating exudative lesions, antibacterial or antifungal drugs should be added early to help control the disease, but long-term use should be avoided.
(4) Anti-pruritic agents: 5% doxepin cream or non-steroidal anti-inflammatory drugs can effectively reduce pruritic symptoms in the short term, and can be used alternately with glucocorticoid preparations or calcium-regulated neurophosphatase inhibitors.
(5) Other: wet compresses, zinc oxide oil (paste), tar, black bean distillate, etc. can also be chosen according to the condition and lesions.
4.2.2 Systemic treatment (1) antihistamines and cell membrane stabilizers: first or second generation antihistamines can be chosen according to different conditions and drug targets.
(2) Anti-infective drugs: For patients with severe disease (especially those with exudate) or proven secondary bacterial or fungal infection, anti-infective drugs can be given for a short period (7-10 days), but do not abuse them.
(3) Glucocorticoids: In principle, such drugs are not used or used sparingly, especially in children. However, patients with serious illness can be given small and medium doses for a short period of time, and use the morning dose method. After the condition improves, the dosage should be gradually reduced and discontinued in time to avoid the adverse reactions brought by long-term use or the rebound of the disease due to too rapid discontinuation.
(4) Immunosuppressants: For patients with severe disease that is not easily controlled by conventional therapy, cyclosporine A, azathioprine and mycophenolate may be used as appropriate. However, they should be used with caution in children, and attention should be paid to systemic adverse reactions when using them.
(5) Anti-leukotriene therapy: Anti-leukotriene agents such as zallust and montelukast have been reported to be effective in the treatment of AD, especially in patients with allergic asthma.
(6) Others: Trinostat, glycopyrrolate and multivitamins can be chosen for the treatment of AD and can have adjuvant therapeutic effects. Interferon-gamma may be effective for AD treatment, but often requires longer-term maintenance medication.
4.2.3 Traditional Chinese medicine (TCM) Treatments are based on clinical symptoms and signs.
4.3 Physical therapy
Ultraviolet light is an effective treatment for atopic dermatitis, and narrow-wave medium-wave ultraviolet light (NB-UVB) and UVA1 are more effective. Care should be taken to use emollients after phototherapy. Because the carcinogenicity of this therapy after long-term repeated use needs to be further evaluated, it is generally believed that UV therapy should be avoided in people younger than 12 years of age.
In conclusion, in the treatment of atopic dermatitis, the patient’s medical history, disease duration, severity and extent of involvement should be evaluated first, and “comprehensive treatment” should be given according to the different conditions. Since this disease is chronic and requires long-term treatment, the cooperation between the doctor and the patient is very important to obtain good results.