Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease that is often intensely pruritic and seriously affects the quality of life of patients. The disease usually begins in infancy and accounts for about 50% of all patients before the age of 1. The disease has a chronic course and can extend into adulthood in some patients, but there are also adults with the disease. In developed countries, the prevalence of this disease in children can be as high as 10% to 20%. In China, the prevalence of atopic dermatitis has been gradually increasing over the past 20 years. In 1998, the total prevalence rate of school-age adolescents (6-20 years old) was 0.70%; in 2002, the prevalence rate of preschool children (1-7 years old) in 10 cities was 2.78%; and in 2012, the epidemiological survey in Shanghai showed that the prevalence rate of children aged 3-6 years old reached 8.3% (8.5% for males and 8.2% for females). ), which is significantly higher in urban than in rural areas (10.2% compared to 4.6%).
I. Etiology and pathogenesis
The development of atopic dermatitis is closely related to genetic and environmental factors. Family members with a history of allergic diseases, such as parents, are significantly more likely to develop the disease, and genetic factors mainly affect skin barrier function and immune balance. Environmental factors include environmental changes, lifestyle changes, excessive washing, infectious agents and allergens. In addition, psychological factors (e.g., stress, anxiety, depression, etc.) also play a role in the development of atopic dermatitis.
The exact pathogenesis of atopic dermatitis is not known. It is believed that the genetic basis of atopic dermatitis is due to the entry of allergens and microbial colonization (e.g., Staphylococcus aureus and Malassezia), resulting in an abnormal immune response and inflammation of the skin, leading to rash and pruritus, which can be further aggravated by adverse stimuli such as scratching and excessive washing. The abnormal immune response in atopic dermatitis involves multiple components, such as allergen presentation by Langerhans cells and skin dendritic cells, Th2-dominant abnormal immune response, regulatory T cell dysfunction, IgE overproduction, and elevated eosinophils. In addition, the production of cytokines and inflammatory mediators by keratinocytes is also involved in the inflammatory response. Non-immune factors such as abnormal neuro-endocrine factors can also be involved in the development of skin inflammation.
II. Clinical manifestations
The clinical manifestations of atopic dermatitis are varied, but the most basic features are dry skin, chronic eczema-like dermatitis and intense pruritus. The vast majority of this disease first occurs in infancy and childhood, and some can occur in childhood and adulthood. Depending on the age of presentation, it is divided into three stages: infancy, childhood, and youth and adulthood. Infancy (birth to 2 years old): The rash may be dry or oozing, mostly on both cheeks, forehead and scalp. Childhood (2 to 12 years old): Mostly evolved from infancy, but may or may not occur through infancy. The rash tends to be dry and hypertrophic, with obvious moss-like changes. Young people and adults (12 years old and above): the lesions are similar to those of children, with subacute and chronic dermatitis mainly occurring in the elbow fossa, N fossa, and anterior neck, but also on the trunk, extremities, face, and dorsum of the hands, mostly with dry, hypertrophic dermatitis.
Patients with atopic dermatitis have a number of characteristic features that may help in the diagnosis of the disease, including dry skin, ichthyosis, periorbital keratosis, palmaris, eyelid eczema, hand eczema, nipple eczema, discoid eczema, sweat pimples, labyrinthitis, recurrent conjunctivitis, infraorbital folds, periorbital dark halo, pale face, anterior cervical folds, eczema under the nose and ear folds, white skin scars, itching during sweating, and sensitivity to wool. In addition, some patients also have other atopic diseases such as allergic asthma, allergic rhinitis, and some patients have significant allergic allergies to xenoproteins, such as to some food proteins (meat, eggs, milk, nuts, etc.) or inhalants (dust mites, house dust mites, etc.). These features are of great value in the diagnosis of atopic diseases.
About 40% to 80% of patients have a family history of allergy, such as atopic dermatitis, allergic asthma, allergic rhinitis, allergic conjunctivitis, etc. in the family. The family history is very important for the diagnosis of atopic dermatitis. Some patients, especially those with severe atopic dermatitis, may have elevated total serum IgE, and about 40% to 60% of patients have elevated peripheral blood eosinophils, which often correlate with the activity of the disease and can rapidly return to normal with effective treatment.
Atopic dermatitis can be divided into simple and mixed types according to the combination of other allergic diseases, with the former manifesting only as dermatitis and the latter also combining allergic asthma, allergic rhinitis and allergic conjunctivitis. The exogenous type has elevated total serum IgE levels, elevated specific IgE levels and elevated peripheral blood eosinophils, while the endogenous type has no significant or absent changes as described above. The endogenous type of atopic dermatitis is easily missed and should be taken seriously.
Diagnosis and severity assessment of atopic dermatitis
If a patient presents with chronic symmetrical eczema-like dermatitis, the possibility of atopic dermatitis should be suspected and testing of peripheral blood eosinophil count, total serum IgE, eosinophil cationic protein, inhaled allergens, ingested allergens and patch test is recommended. The diagnosis of atopic dermatitis should be considered by integrating all aspects of evidence from medical history, clinical presentation, family history and laboratory tests. Atopic dermatitis is a heterogeneous disease with a variety of manifestations and requires certain criteria for diagnosis. At present, the commonly used diagnostic criteria abroad include Hanifin and Rajka criteria, Williams criteria, and Kang Kefei and others in China have also proposed diagnostic criteria. Comprehensive analysis, Williams diagnostic criteria are simple and easy to use, and the specificity and sensitivity are similar to Hanifin and Rajka criteria, which are applicable to the current clinical practice needs in China, so this guideline is recommended.
Williams diagnostic criteria for atopic dermatitis: primary criterion: pruritus of the skin. Secondary criteria.
(i) history of flexural dermatitis eczema, including elbow fossa, N fossa, anterior ankle, and neck (including cheek rash in children under 10 years of age).
(ii) History of asthma or allergic rhinitis (or a history of atopic disease in a first-degree relative of a child younger than 4 years of age).
(iii) History of generalized dry skin in recent years.
④ presence of flexural eczema (cheek/forehead and extensor eczema of the extremities in children under 4 years of age)
⑤ onset before 2 years of age (for patients over 4 years of age). To determine the diagnosis: primary criteria + 3 or more secondary criteria
The diagnosis of atopic dermatitis is not difficult for those with typical manifestations, but some patients with atypical clinical manifestations should not be easily excluded from the diagnosis of atopic dermatitis, but should be carefully examined and questioned, and if necessary, followed up for a long time.
The differential diagnosis of atopic dermatitis includes seborrheic dermatitis, non-atopic eczema, pityriasis simplex, ichthyosis, scabies, parapsoriasis, eosinophilic dermatitis, cutaneous T-cell lymphoma, Netherton syndrome, hyper IgE syndrome, Wiskott-Aldrick syndrome, and atopic dermatitis-like graft-versus-host disease.
The severity of atopic dermatitis is evaluated by a variety of methods, commonly used are the Score of Atopic Dermatitis (SCORAD), the Eczema Area and Severity Index score (EASI), the Investigator’s Overall Score (IGA), and the Visual Analogue Scale Score (VAS) of pruritus. Clinical judgments can also be made using simple and easy-to-use indicators, such as: mild as a rash area of less than 5%; moderate as 5% to 10%, or recurrent rash; severe as lesions exceeding 10% of body surface area, or persistent dermatitis with intense itching that interferes with sleep. The assessment of disease severity can be used as a basis for treatment planning.
IV. Treatment
Atopic dermatitis is a chronic recurrent disease, and the goal of treatment is to relieve or eliminate clinical symptoms, eliminate triggering and/or aggravating factors, reduce and prevent recurrence, and improve the patient’s quality of life. Formal and good treatment can lead to complete remission or significant improvement of symptoms of atopic dermatitis and patients can enjoy normal life.
(i) Patient education: Patient education is very important and physicians should explain the nature, clinical features and precautions of the disease to patients and families. Doctors and patients should establish a long-term and good doctor-patient relationship and cooperate with each other in order to obtain the best possible results. Patients should avoid violent scratching and friction; pay attention to maintaining appropriate environmental temperature and humidity, and minimize allergens in the living environment, such as changing clothes and bed sheets, not keeping pets, not laying carpets, and keeping fewer flowers and plants; avoid alcohol and spicy food, avoiding allergenic food, and observing whether dermatitis and pruritus worsen after eating protein-based food. The physician should also explain to the patient how to use the medication, the expected efficacy and possible side effects, and remind the patient to follow up regularly. Good patient education can significantly improve the efficacy of treatment.
(ii) Basic treatment.
1. Bathing: Basic skin care is very important for the treatment of atopic dermatitis. bathing helps to remove or reduce epidermal dirt and microorganisms. bathing should be done at a suitable water temperature (32-40 ℃) once a day or once every two days for 10-15 min. it is recommended to use hypoallergenic and non-irritating skin cleansers whose pH value is preferably close to the normal physiology of the epidermis (pH about 6). Those with significantly dry skin should reduce the number of cleansing products used and try to choose fragrance-free cleansing products. Apply topical moisturizers and emollients immediately after drying the skin after bathing.
2. Restore and maintain the skin barrier function: Topical emollients are the basic treatment for atopic dermatitis and help restore the skin barrier function. Emollients not only stop the evaporation of water, but also repair damaged skin and diminish the irritation of exogenous adverse factors, thus reducing the number and severity of disease attacks. Emollients with hydrophilic base should be used at least twice a day, and moisturizers and emollients should be used immediately after bathing, and patients are advised to choose the appropriate emollients for themselves.
(iii) Topical drug treatment.
1. Glucocorticoids: Topical topical glucocorticoids (hereinafter referred to as hormones) are the first-line therapy for atopic dermatitis. The topical hormones are economical, convenient and effective, but should be carried out under the guidance of a doctor. Hormone preparations of different dosage forms and strengths are selected according to the patient’s age, the nature and location of the lesions and the extent of the disease, in order to control inflammation and reduce symptoms quickly and effectively. The strength of topical hormones can be generally divided into four levels, such as hydrocortisone cream as a weak hormone, hydrocortisone butyrate cream and tretinoin cream as a medium-acting hormone, mometasone furoate cream as a strong hormone, and halometasone and clobetasol cream as super-acting hormones. Generally, a strong enough preparation (strong or super-strong) should be used for the initial treatment in order to control the inflammation rapidly within a few days, usually twice a day. Hormonal shampoos or tinctures may be used on the scalp. For pediatric patients, try to use moderate to weak hormones or dilute hormone creams with emollients. For hypertrophic lesions, encapsulation therapy can be used. After the condition is controlled, the encapsulation should be discontinued and the number and amount of hormone use should be gradually reduced. After the acute stage of the disease is controlled, the treatment should be gradually transitioned to maintenance therapy, i.e. 2 ~ 3 times a week, which can effectively reduce recurrence. Long-term extensive use of hormones should pay attention to skin and systemic adverse reactions.
As some patients are apprehensive about topical glucocorticoids, they even refuse to use them. Doctors should patiently explain the safety, dosage, method of administration, frequency of administration, course of treatment, and how to adjust the drugs, etc. They should let patients understand that the skin absorption of topical drugs is very small (generally 1% to 2%) and the system absorption is even smaller, which can make patients eliminate their worries and improve the compliance of treatment.
2, calcium-regulated neurophosphatase inhibitors: these drugs have selective inhibition of T lymphocytes, have a strong anti-inflammatory effect, atopic dermatitis has a better efficacy, mostly used in the face and neck and folds. Calcium-regulated neurophosphatase inhibitors include tacrolimus ointment and pimecrolimus cream, pimecrolimus cream is mostly used for mild to moderate atopic dermatitis, and tacrolimus ointment is used for moderate to severe atopic dermatitis, of which 0.03% concentration is recommended for children and 0.1% concentration is recommended for adults. 0.1% tacrolimus ointment is equivalent to moderately potent hormone. Calcium-modulated neurophosphatase inhibitors can be used in combination with hormones or in a sequential manner. These drugs are also a good choice for maintenance therapy and can be used two to three times a week to reduce the recurrence of the disease. Adverse reactions are mainly local burning and irritation, which can gradually disappear with the increase in the number of drugs.
3, topical anti-microbial agents: as bacteria, fungal colonization or secondary infection can induce or aggravate the disease, for heavy patients, especially exudative lesions, systemic or topical antimicrobial agents are beneficial to disease control, the use of 1 to 2 weeks is appropriate, should avoid long-term use. If a viral infection is suspected or diagnosed, antiviral agents should be used.
4, other topical drugs: zinc oxide oil (paste) agent, black bean distillation oil ointment, etc. for atopic dermatitis is also effective, physiological sodium chloride solution, 1% to 3% boric acid solution and other wet dressing drugs for atopic dermatitis in the acute phase of exudation has a better effect, Doxepin cream and some non-steroidal anti-inflammatory drugs with antipruritic effect.
(iv) Systemic treatment.
1. antihistamines and anti-inflammatory mediators: for patients with obvious pruritus or comorbidities such as sleep disorders, urticaria and allergic rhinitis, first- or second-generation antihistamines can be used, among which first-generation antihistamines help patients improve pruritus and sleep because they can pass the blood-brain barrier. Other anti-allergy and anti-inflammatory drugs include thromboxane A2 inhibitors, leukotriene receptor antagonists, mast cell membrane stabilizers, etc.
2. Systemic anti-infective drugs: For patients with severe disease (especially those with exudate) or proven secondary bacterial infection, systemic anti-infective drugs can be given for a short period of time (about 1 week). Erythromycin, tetracycline or quinolone antimicrobials can be used, and allergy-prone antimicrobials such as penicillins and sulfonamides should be used sparingly. When combined with herpes virus infection, the corresponding antiviral drugs can be added.
3. Glucocorticoids: In principle, these drugs should not be used or used sparingly. For patients with severe disease and difficult to control by other drugs, they can be applied for a short period of time, and the dosage should be reduced in time after the condition improves until it is stopped. Long-term application of hormones should be avoided to prevent the side effects of hormones, and the dose should not be reduced too quickly after the disease is controlled, and the reduction or discontinuation of the drug too quickly can lead to rebound.
4. Immunosuppressant: It is suitable for patients with serious disease and not easily controlled by conventional therapy, cyclosporine is the most used, the starting dose is 2,5~3,5 mg?kg-1?d-1, divided into two oral doses, generally not more than 5 mg?kg-1?d-1, after the disease is controlled, it can be gradually reduced to the minimum amount of maintenance. Cyclosporine has a rapid onset of action and can generally reduce the severity of the disease by 55% in 6-8 weeks of treatment, but the disease is likely to recur after discontinuation. Blood pressure and renal function should be monitored during treatment, and blood levels should be monitored if possible. Methotrexate is a commonly used immunosuppressant and is administered at 10-15 mg per week, either as a single dose or in two divided doses. Azathioprine 50-100 mg per day can be started in small doses, and the blood picture should be monitored closely during administration. The indications and contraindications for the use of immunosuppressive drugs must be noted, and adverse reactions should be closely monitored.
5. Others: Glycopyrrolate preparations, calcium and probiotics can be used as adjuvant therapy. Biological agents can be used for patients with severe disease and ineffective conventional treatment.
(E) Traditional Chinese medicine: Treatment should be based on clinical symptoms and signs. The adverse reactions of drugs should also be noted in Chinese herbal medicine treatment.
(6) Ultraviolet therapy: Ultraviolet light is an effective treatment for atopic dermatitis. Narrow-spectrum medium-wave ultraviolet light (NB-UVB) and UVA1 are safe and effective and thus most used, and traditional photochemotherapy (PUVA) is also available, but attention should be paid to side effects. The use of emollients after phototherapy should be noted. whole-body UV therapy should be avoided in children under 6 years of age.
(vii) Doctor-patient cooperation and precautions in the treatment of atopic dermatitis: During the treatment of atopic dermatitis, great attention should be paid to doctor-patient cooperation and a good doctor-patient relationship should be established. The physician should pay attention to patient (including the patient’s family) education, and should make a comprehensive assessment of the patient’s medical history, disease duration, lesion area and severity when first seeing the patient to determine the treatment plan and strive to control the disease within a short period of time; during subsequent follow-up visits the physician should carefully observe the changes in the patient’s condition and adjust the treatment plan in a timely manner. Patients should actively cooperate with the doctor and pay attention to the protection of “clothing, food, housing, transportation, and washing”, avoid contact with factors that may cause aggravation of the disease, have regular follow-ups and long-term follow-ups, learn to observe the changes of the disease, give feedback to the doctor in a timely manner, and do not stop or reduce the medication at will. In case of ineffective treatment or exacerbation, the doctor should analyze the causes and take targeted measures. After remission, maintenance treatment should be carried out with topical hormones or calcium phosphatase inhibitors 2 to 3 times a week. Due to increasing advances in diagnosis and treatment, many patients with atopic dermatitis can be treated promptly and correctly, and the majority of patients can be well controlled.
The SCORAD scale: A/5 + 7B/2 + C. Where A is the area of the lesion: 9% for the head and neck and upper extremities, 13,5% for the front and back of the trunk, and 22,5% for the lower extremities in adults; 9% for the head and neck and upper extremities, 18% for the front and back of the trunk and lower extremities in children under 14 years of age; 17% for the head and neck, 9% for the upper extremities, 18% for the front and back of the trunk, and 12% for the lower extremities in children under 2 years of age B is the severity of the lesions, including six signs: erythema, papules (or) edema, exudation (or) crusting, epidermal peeling, mossiness, and dry skin (evaluation of uninvolved skin). The scale was based on a four-point scale of 0 to 3 according to the severity of the lesions; C was the degree of pruritus and sleep disturbance: the score was averaged over the last 3 days and nights, with a score of 0 to 10 for each item (visual analog scale). The total score range is 0 to 103. In clinical use, the severity of the disease can be determined based on the total score, with 0 to 24 being mild, 25 to 50 being moderate, and 51 to 103 being severe.