Abstract: Atopic dermatitis (AD) is a common chronic recurrent inflammatory skin disease associated with genetic allergic qualities that affects 10% to 20% of children. Its etiology and pathogenesis are complex, involving genetic, environmental and immune factors, and the weakening or destruction of skin barrier function, such as the reduction or absence of filoproteins in the epidermis, are important factors in its pathogenesis. There are 3 clinical stages, namely infancy, childhood, and adolescence and adulthood. Some of them may be accompanied by asthma and allergic rhinitis. Topical glucocorticoids are the first line of treatment, and topical glucocorticoids combined with calcineurin phosphatase inhibitors are the first choice for the long-term management of AD. Patient education is the foundation of good long-term treatment management of AD.
Atopic dermatitis (AD), also known as atopic eczema, formerly known as “atopic dermatitis” and “genetic allergic dermatitis”, is a common chronic recurrent inflammatory skin disease associated with genetic allergic qualities. AD is one of the most prevalent skin diseases in the world, and in most countries, about 20% of children are affected by AD. In 2012, the epidemiological survey in Shanghai showed that the prevalence of AD in children aged 3-6 years was 8.3% (8.5% in males and 8.2% in females), which was significantly higher in urban areas than in rural areas (10.2% and 4.6%).
I. Etiology and pathogenesis
The etiology and pathogenesis of AD are complex, involving genetic, environmental and immune factors. Genetic factors mainly affect skin barrier function and immune homeostasis. Patients often have Th2-dominantly mediated immunological abnormalities and reduced or disrupted skin barrier function, such as reduced or absent filoproteins in the epidermis and reduced ceramide lipids. Environmental factors mainly involve allergens and microorganisms, and the earlier the age of onset and the more severe the disease, the higher the correlation with food allergy in children with AD. Food allergies are most common in infants and children under 3 years of age, with eggs, milk, peanuts and soybeans being the most common; children over 3 years of age have increased sensitivity to inhaled antigens, with dust mites and pollen being the most common. Due to impaired skin barrier function, AD patients have changed skin micro-ecological environment and weakened natural immune response, which are prone to secondary infections such as Staphylococcus aureus, herpes virus, Malassezia, etc. These microbial antigens and super-antigens can in turn trigger or aggravate skin hypersensitivity reactions, leading to worsening of AD condition.
II. Atopic and atopic process
Atopy (atopy) was initiated by Coca and Cooke in 1925. Its meaning is.
(1) a frequent familial predisposition to asthma, allergic rhinitis, and eczema.
(2) Self-allergy to heterogeneous eggs.
(3) Elevated serum IgE levels.
(4) Increased peripheral blood eosinophilia. Typical AD has all four of these manifestations in addition to the specific eczema manifestations. The atopic process (atopicmarch) is the progression from skin inflammation to respiratory inflammation in young AD patients as they age. Studies have shown that early intervention in AD can interrupt the atopic process and prevent the development of respiratory allergic diseases later.
III. Diagnosis
1. Clinical manifestations of AD are basically characterized by intense pruritus, chronic eczema-like dermatitis, dry skin and recurrent attacks. According to the age and characteristics of lesions, there are 3 clinical stages, namely infancy, childhood, adolescence and adulthood.
(1) Infancy ((birth to 2 years old): The rash often develops within the first 6 months of life, with the majority appearing within 2 months of birth. The initial lesions are pruritic erythema on the cheeks, followed by pinpoint-sized papules and papules on the basis of erythema, which appear in dense patches, with polymorphic lesions and indistinct boundaries. The nose and nasolabial folds are rarely involved. The rash is often symmetrical, intensely itchy, and recurrent, but 80% will gradually improve and heal by age 2 years, and some children may continue into childhood. Severe infantile AD is often associated with food allergy.
(2) Childhood (>2 to 12 years old): Most of them occur after infantile AD remission for 1 to 2 years and gradually worsen, and a few of them continue to occur since infancy. The rash is mainly papules, infiltrative erythematous plaques and mossiness, with less exudation than in infancy, accompanied by dry skin. It often involves the flexors or extensors of the extremities, followed by the eyelids, face and neck. Intense pruritus. Typical plaques or mossiness in the elbow and N fossa are characteristic of this stage. Some children have a combination of asthma, allergic rhinitis and allergic conjunctivitis.
(3) Adolescence and adulthood (over 12 years of age): It can develop from childhood or occur directly, and is mainly characterized by a flexural mossy rash. The wrists, ankles, neck, and eyelids are common sites of onset. Most patients may present with infiltrative plaques with small blisters, vesicles, scratches, or mossiness.
Patients with AD may present with a range of manifestations that are helpful in diagnosis, including dry skin, auricular fissures, palmaris, papular eczema, periorbicular keratosis, periorbicular bullae, nonspecific hand and foot dermatitis, white furunculosis, recurrent ocular conjunctivitis, ichthyosis, and white scratching signs.
2.Complications
(1) Bacterial infection: AD in infancy and childhood is easily combined with bacterial infection, manifested as vesicles, oozing and pustules and other impetigo-like changes, more than 90% are staphylococcal infections, severe cases combined with sepsis.
(2) Herpetic eczema: also known as Kaposi’s varicella-like rash. It is caused by herpes simplex virus infection on the basis of AD. Most often seen in infants and young children. The rash is often febrile, with a sudden worsening of AD and the appearance of a variety of rashes, mainly blisters, which quickly turn into pustules, rupture, vesicles and black crusts, with the rash mostly clustered on the head, face or extremities, and scattered in other areas, and may be accompanied by severe itching, discomfort, diarrhea and swollen lymph nodes.
(3) Hypoproteinemia: AD combined with hypoproteinemia is a serious manifestation of AD, which may be accompanied by generalized edema in addition to eczema-like rash.
(4) Erythroderma: untimely treatment of AD or improper treatment can cause rash generalization and secondary erythroderma, which is manifested as diffuse erythema, infiltration, hypertrophy and desquamation.
3.Laboratory examination of AD should focus on blood routine and allergen detection for AD with pancytosis or exudation as the main manifestation, the total number of white blood cells can be elevated, especially eosinophils are elevated and can exceed the normal value by 5 to 10 times. Common allergen screening methods in children include skin prick test, serum specific IgE test and specific patch test. Some AD have elevated total IgE, and most AD have positive environmental and food-specific IgE, such as combined respiratory allergy, which is 100% positive for inhalant-specific IgE and 80% positive for food-specific IgE. The atopicpatchtest (APT) is an allergen detection method used for AD in recent years. The allergen is applied to the skin and the results are observed for 48 to 72 h. If an eczema-like rash appears, the test is positive and the AD positive rate is 10% to 52%. At present, it is believed that APT of inhalants can be used as one of the diagnostic indicators for AD. However, the diagnostic significance of food APT is still debated.
4, diagnostic criteria currently used abroad include Hanifin-Rajka criteria, Williams criteria. After comprehensive analysis, Williams diagnostic criteria (Table 1) are simple and easy to use, and their specificity and sensitivity are similar to Hanifin-Rajka criteria, which are suitable for the current clinical practice in China and were recommended by the “Chinese atopic dermatitis diagnosis and treatment guidelines” in 2014. There is no unified diagnostic criteria for AD in infancy, so clinical work can refer to the diagnostic criteria for AD in infants in the modified Hanifin criteria in 1990 and the diagnostic criteria for AD in infants proposed by the British Atopic Dermatitis Diagnostic Criteria Working Conference in 2003 (Table 2 and Table 3).
Table 1 Williams’ diagnostic criteria developed by the British Atopic Dermatitis Working Group in 1994
Pruritus of 12 months’ duration (or parents complaining of scratching or rubbing), plus 3 or more of the following criteria
(1) History of flexural dermatitis eczema, including elbow fossa, N fossa, anterior ankle, and neck (including cheek rash in children under 10 years of age)
(2) History of asthma or allergic rhinitis (or a history of atopic disease in a first-degree relative of a child under 4 years of age)
(3) History of generalized dry skin
(4) flexural eczema-like lesions ((including cheeks, forehead, or extensor aspect of extremities in children under 4 years of age)
(5) Onset before 2 years of age (for patients over 4 years of age)
Note: Information from the literature
Table 21990 Modified Hanifin criteria for the diagnosis of atopic dermatitis in infants
Primary criteria and 2 secondary criteria should be met at the time of diagnosis
Primary criteria Family history of atopic dermatitis
Secondary criteria (1) evidence of chronic or chronic recurrent pruritic dermatitis
(2) typical facial or extensor eczema-like or mossy dermatitis
(3) Absence of rash at the diaper site and/or mouth and nose
(4) Dry skin, ichthyosis, or palpebral dermatitis
(5) peri-hair keratosis
(6) chronic scalp dermatitis
(7) perifollicular augmentation
Note: Information from the literature
Table 3 Working meeting on diagnostic criteria for atopic dermatitis in the UK in 2003
Proposed diagnostic criteria for infantile atopic dermatitis
Diagnosis should meet the necessary conditions and 3 or more secondary conditions at the same time.
Pruritic skin > 1 month for the requisite condition
Secondary conditions (1) head and facial eczema without involvement of the mouth, nose and eye area
(2) simple extensor dermatitis or mixed extensor dermatitis
(3) diaper area is not involved
(4) diffuse dry skin
(5) hand eczema
(6) History of food-induced rash
(7) History of allergic rhinitis, asthma, atopic dermatitis in first-degree relatives
Note: Information from literature
5. Differential diagnosis of AD in children needs to be differentiated from some common diseases, such as chronic simple moss, infantile seborrheic dermatitis, contact dermatitis, scabies, psoriasis, and in a few cases, Langerhans cell histiocytosis, enteropathic acrodermatitis, biotin deficiency, hyper IgE syndrome, Wiskott-Aldrich syndrome, Netherlon syndrome, etc.
(1) Seborrheic dermatitis: manifested as bright red or yellow-red rash with a large number of greasy crusts and scales. In infants, seborrheic dermatitis mainly manifests as erythema on the scalp, diaper area, skin folds (such as behind the ears, neck, umbilicus, axilla, elbow fossa, N fossa). Facial erythema is rare, mainly on the forehead, brow and around the nose. Generally not itchy.
(2) Scabies: The rash of scabies in infants and young children can be generalized and often involves the whole body, and there are often water scars, pustules and papules on the palmoplantar wrists and between the fingers; nodules appear on the trunk, especially in the axillae and external genitalia; a history of similar diseases in family members can be distinguished.
(3) Hyper-IgE syndrome: manifested by intractable eczema-like dermatitis, recurrent infections (especially staphylococcal infections causing cold abscesses of the skin), pulmonary infections causing lung abscesses, and significant increase in blood eosinophils and serum IgE.
(4) Eosinophilic syndrome: The lesions are diverse, and in addition to eczema-like rash, pruritic erythema, nodules, wind masses or angioedema may also appear. The diagnostic criteria for eosinophilic syndrome are.
① peripheral blood eosinophils ≥ 1.5×109/L for at least 6 months.
②Excluding parasites, allergic diseases and other diseases that can cause eosinophilia
(iii) signs and symptoms of organ and systemic involvement.
(5) Wiskott-Aldrich syndrome: also known as eczema, thrombocytopenia with immunodeficiency syndrome, with clinical features of thrombocytopenia, eczema, immunodeficiency, susceptibility to autoimmune diseases and malignancy.
(6) Nethetion syndrome: It has three major clinical features (congenital ichthyosis-like erythroderma, hair abnormalities and atopic manifestations).
IV. Treatment
AD is a chronic recurrent disease, and the treatment day is to relieve or eliminate clinical symptoms, eliminate triggering and/or aggravating factors, reduce and prevent recurrence, and improve patients’ quality of life.
1, treatment principles on the basis of health education, moderate, standardized, long-term comprehensive treatment of mild and moderate AD is based on topical treatment.
2.Basic treatment emphasizes skin cleansing care and moisturizing and emollient skin. Moisturizing and emollient skin is the basis of treating AD and helps to restore skin barrier function. Adhere to daily bathing, water temperature 32-38℃ is appropriate, soak for 10-15min, and use emollient within 3min immediately after bathing. It is recommended to use water for bathing, and if necessary, use hypoallergenic and non-irritating weak acidic (pH about 6) skin cleansers. Choose a suitable emollient for the child and insist on using it more than 2 times a day.
3. Topical medication mainly uses topical glucocorticoids and calcium-regulated neurophosphatase inhibitors to control the inflammatory skin reaction. Among them, topical glucocorticoids are the first-line drugs for AD treatment, and topical glucocorticoids combined with calcium-modulated neurophosphatase inhibitors are the first choice for long-term treatment of AD. Different treatment plans should be formulated according to the age of the child, the nature and location of the lesions and the severity of the disease. When the skin is infected with secondary bacteria, fungi or viruses, the corresponding topical medication can be selected according to the condition.
Topical glucocorticosteroids: The initial treatment should be selected with preparations of sufficient strength for rapid control of inflammation, after which the strength of topical preparations should be gradually reduced or calcium-modulated neurophosphatase inhibitors should be used. Maintenance treatment should be given once or twice a day, with a minimum of 2 weeks and a maximum of 6 weeks of continuous application depending on the recovery of the skin lesions. Moderate and weak hormones are recommended for infants and children. Weak hormones should be used on eyelids, face and skin folds to avoid causing skin atrophy, capillary dilation, hormonal acne and local hirsutism. When the skin inflammation is completely controlled, it is recommended to continue topical hormone preparations or calcium-regulated neurophosphatase inhibitors twice a week along with the application of emollients for maintenance treatment to keep the lesions in long-term remission. Commonly used pediatric preparations include 0.1% mometasone furoate ointment (moderately effective), hydrocortisone butyrate ointment (moderately effective), dexedrine ointment, and dexamethasone cream (weakly effective).
Calcium-regulated neurophosphatase inhibitors have a selective inhibitory effect on T lymphocytes and have strong anti-inflammatory effects. The main ones commonly used are 1% pimecrolimus cream and 0.03% or 0.1% tacrolimus ointment. As a second-line drug, it can be used to treat AD patients who do not respond well to hormone or other therapies or who are not suitable for hormone application, twice daily for 3-4 weeks. It can also be used in combination with hormone or sequential and long-term intermittent maintenance treatment (twice a week). 0.1% tacrolimus ointment is suitable for children over 2 years old with AD.
4.Systemic treatment systemic drugs include antihistamines, antibiotics, immunomodulators, glucocorticoids and immunosuppressants, which can be used according to the condition as appropriate. In principle, systemic glucocorticoids should not be used or used sparingly, but for those with severe disease and cannot be controlled by general treatment, short-term use can be considered. Patients with recurrent refractory AD whose disease is severe and not easily controlled by conventional therapy may use immunosuppressants such as cyclosporine and azathioprine as appropriate, but close monitoring of adverse effects is required. The starting dose of cyclosporine is 2.5-3.5mg/(kg.d), divided into two daily doses, generally not more than 5mg/(kg.d), and can be gradually reduced to the minimum amount for maintenance after the disease is controlled. However, the disease is prone to recurrence after stopping the drug. Interferon γ has certain efficacy in the treatment of AD. Use recombinant human interferon γ, 100ug subcutaneously once a day in the first week, and 100ug subcutaneously once every other day for 12 weeks. Glycopyrrolate preparation, calcium, probiotics and immunomodulators such as transfer factor and BCG polysaccharide nucleic acid injection can be used as adjuvant therapy.
5.Ultraviolet ray therapy is an effective method for treating AD. narrow spectrum medium wave ultraviolet (NB-UVB) and UVA1 are safe and effective, attention should be paid to side effects, and emollients should be used after phototherapy. children under 6 years old should avoid using UV therapy for the whole body.
6. Specific immunotherapy (SIT) is suitable for children over 4 years old. Studies have shown that SIT can not only improve AD symptoms, but also reduce the use of allopathic drugs and effectively prevent the recurrence of allergen-induced dermatitis and the possibility of asthma or allergic rhinitis. Allergy to inhaled allergens (e.g., dust mites and pollen) must be identified prior to treatment. Currently, subcutaneous injections and sublingual specific immunotherapy are available for 3-5 years, especially for children with AD with asthma or allergic rhinitis.
V. Patient education, management and follow-up
Patient health education and skin care is one of the most important measures in the treatment of AD. Physicians should explain in detail to the children and their parents the etiology, pathogenesis, clinical characteristics, changes and treatment plan, and physicians and patients should establish a long-term and good doctor-patient relationship and cooperate with each other to obtain the best possible results. Patient education is the basis for good long-term treatment management of AD.
Triggers or stimulating aggravating factors should be sought and avoided as much as possible in life, such as avoiding dry skin, hot water washing, reducing sweat stimulation, avoiding scratching and tension, avoiding passive smoking, keeping a happy spirit, and not overworking. Clothing should be slightly thin, cotton, loose and soft; the living environment should be cool, ventilated and clean, change clothes and bed sheets regularly, no pets, no carpets, less flowers and plants, and minimize allergens in the living environment. Encourage the child to swim and use emollients on the whole body after swimming. Pay attention to the presence of allergies to food (eggs, milk, peanuts, soybeans, nuts, shrimp, wheat, etc.) and environmental allergens (house dust, dust mites, pollen, animal fur, mold, etc.) Food allergies often appear within half a year of age, and allergies to eggs and/or milk are common, while environmental allergies are often seen in older children. If food allergy is clearly present, dietary management should be carried out. Breastfeeding should be promoted, the child and the nursing mother should avoid allergic foods, and attention should be paid to digestive function. However, blind fasting of food groups should be avoided. Complementary foods can be added as in normal infants, but should be added in small amounts, one by one, and with adequate steaming. Avoid contact with patients with simple scars, which may cause 2 rash eczema. Follow up regularly, usually every 2-3 months, and older children may be followed up once every 3-4 months.