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 adult-onset patients. 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, with a total prevalence of 0.70% among school-age adolescents (6-20 years old) in 1998 and 2.78% among preschool children (1-7 years old) in 10 cities in 2002, while an epidemiological survey in Shanghai in 2012 showed that the prevalence among children aged 3-6 years reached 8.3% (8.5% for males and 8.2% for females ), which is significantly higher in urban than in rural areas (10.2% vs. 4.6%).
1, etiology and pathogenesis 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., mental 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 generally believed to be based on genetic factors, due to allergen entry and microbial colonization (e.g., Staphylococcus aureus and Malassezia), resulting in an abnormal immune response and inflammation of the skin, triggering 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, etc. Non-immune factors such as abnormal neuro-endocrine factors can also be involved in the occurrence and development of skin inflammation.
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 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): manifests as infantile eczema, mostly on both cheeks, forehead and scalp, and the rash may be dry or oozing. Childhood (2 to 12 years old): Mostly evolved from infancy, or may not occur through infancy. The rash tends to be dry and hypertrophic, with obvious mossy changes. Young people and adults (12 years old and above): the lesions are similar to those of children, and are also mainly subacute and chronic dermatitis, mainly occurring in the elbow fossa, rouge fossa, front of the neck, etc., but also on the trunk, extremities, face, back of the hands, mostly dry, hypertrophic dermatitis damage, some patients may also manifest as itchy rash-like rash.
Patients with atopic dermatitis have a number of characteristic manifestations that 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 in the subnasal and ear folds, white skin scratching, pruritus during sweating, and sensitivity to wool. In addition, some patients also have other atopic diseases at the same time, such as allergic asthma and allergic rhinitis, and some have significant allergic protein allergies, such as allergy to some food proteins (meat, eggs, milk, nuts, etc.) or inhalants (dust mites, house dust mites, etc.). All these features are of great value for the diagnosis of atopic diseases.
About 40% to 80% of patients have a family history of allergy, such as family members with atopic dermatitis, allergic asthma, allergic rhinitis, allergic conjunctivitis, etc. The inquiry of 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. Elevated eosinophils are often associated with disease activity, and elevated disease activity can be rapidly normalized 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, whereas 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.
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.
History of flexural dermatitis eczema, including elbow fossa, rouge fossa, anterior ankle, and neck (including cheek rash in children under 10 years of age); history of asthma or allergic rhinitis (or history of atopic disease in first-degree relatives of children under 4 years of age); history of generalized dry skin in recent years; presence of flexural eczema (cheek/forehead and extensor eczema of extremities in children under 4 years of age); onset before 2 years of age (for patients over 4 years of age). Determine diagnosis: primary criteria + 3 or more secondary criteria.
The diagnosis of atopic dermatitis is not difficult in those with typical manifestations, but some patients with atypical clinical manifestations should not be easily excluded from the diagnosis of atopic dermatitis, and should be carefully examined and questioned, with long-term follow-up if necessary.
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 dermatitis that is persistent and severe itching that interferes with sleep. The assessment of disease severity can be used as a basis for developing a treatment plan.
4, treatment of atopic dermatitis is a chronic recurrent disease, the purpose of treatment is to relieve or eliminate clinical symptoms, eliminate triggering and/or aggravating factors, reduce and prevent recurrence, and improve the quality of life of patients. Formal and good treatment can lead to complete remission or significant improvement of symptoms of atopic dermatitis, and patients can enjoy normal life.
4.1. 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. The patient’s underwear should be cotton and loose; violent scratching and friction should be avoided; attention should be paid to maintaining appropriate environmental temperature and humidity and minimizing allergens in the living environment, such as changing clothes and bed sheets, not keeping pets, not laying carpets, and keeping fewer flowers and plants; avoiding alcohol and spicy food, avoiding allergenic food, and observing whether dermatitis and pruritus worsen after eating protein-based food. The doctor 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, etc. Good patient education can significantly improve the efficacy of treatment.
4.2. 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 at appropriate water temperature (32~40°C) once a day or once every two days for 10~15 min. hypoallergenic and non-irritating skin cleansers with a pH value preferably close to the normal physiology of the epidermis (pH about 6) are recommended. 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 water evaporation, but also repair damaged skin and diminish the stimulation 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.
4.3. Topical drug treatment.
Glucocorticoids: Topical topical glucocorticoids (hereinafter referred to as hormones) are the first-line therapy for atopic dermatitis. There are many types of topical hormones, which are economical and convenient, and their efficacy is certain, but they 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 degree of the disease, in order to control inflammation and reduce symptoms quickly and effectively. The strength of topical hormones can generally be divided into four levels, such as hydrocortisone cream as weak hormone, hydrocortisone butyrate cream and tretinoin cream as medium-acting hormone, mometasone furoate cream as strong hormone, and halometasone and clobetasol cream as super-acting hormone. Generally, preparations with sufficient strength (strong or super-strong) should be used for initial treatment in order to rapidly control inflammation within a few days, usually twice daily, and gradually transition to medium- and weak-acting hormones or calcium-regulated neurophosphatase inhibitors after inflammation control; medium- and weak-acting hormones are recommended for the face, neck and folds, and long-term use of strong-acting hormones should be avoided. Hormone shampoos or tinctures can be used on the scalp. For pediatric patients, try to use moderate to weak hormones or dilute hormone creams with emollients appropriately. For hypertrophic lesions, encapsulation therapy can be used. After the condition is controlled, the encapsulation should be discontinued and the number and dosage of hormones should be gradually reduced. After the acute phase of the disease is controlled, there should be a gradual transition to maintenance therapy, that is, the use of 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. They should let patients understand that the skin absorption of topical drugs is very small (generally 1%-2%) and the systemic absorption is even smaller, which can make patients eliminate their worries and improve the compliance of treatment.
Calcium-regulated neurophosphatase inhibitors: These drugs have a selective inhibitory effect on T lymphocytes, have a strong anti-inflammatory effect, have a better efficacy in atopic dermatitis, and are mostly used on 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 combined with hormones or used sequentially. These drugs are also a better choice for maintenance therapy and can be used 2-3 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 doses.
Topical anti-microbial agents: Since bacterial and fungal colonization or secondary infection can trigger or aggravate the disease, for heavier patients, especially with exudative lesions, systemic or topical antimicrobial agents are beneficial for disease control, and the use of medication is appropriate for 1~2 weeks, and long-term use should be avoided. If a viral infection is suspected or confirmed, antiviral agents should be used.
Other topical medications: zinc oxide oil (paste), black bean distillate ointment, etc. are also effective for atopic dermatitis, physiological sodium chloride solution, 1% to 3% boric acid solution and other wet dressing drugs have better efficacy for atopic dermatitis acute exudation, Doxepin cream and some non-steroidal anti-inflammatory drugs have antipruritic effect.
4.4. Systemic therapy.
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, and mast cell membrane stabilizers.
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. If herpes virus infection is combined, the corresponding antiviral drugs can be added.
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. For more stubborn cases, hormones can be gradually transitioned to immunosuppressive drugs or ultraviolet therapy. 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.
Immunosuppressants: Suitable for patients with severe disease and not easily controlled by conventional therapy, cyclosporine is the most used, with a starting dose of 2.5~3.5mg?kg-1?d-1, divided into two oral doses, generally not more than 5mg?kg-1?d-1, which can be gradually reduced to the minimum amount after the disease is controlled. Cyclosporine has a rapid onset of action and generally reduces the severity of disease by 55% in 6-8 weeks of treatment [24], but the disease is prone to recur after discontinuation. Blood pressure and renal function should be monitored during administration, and blood levels should be monitored if possible, and no concomitant phototherapy is recommended. Methotrexate is a commonly used immunosuppressant by 10-15 mg per week, either as a single dose or in 2 divided doses. Azathioprine 50~100mg per day can be started in small doses and the blood picture should be closely monitored during administration. The indications and contraindications for the use of immunosuppressive drugs must be noted, and adverse reactions should be closely monitored.
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.
4.5. Traditional Chinese medicine.
Treatment should be based on clinical symptoms and signs and should be evidence-based. The adverse reactions of drugs should also be noted in TCM treatment.
4.6. 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 the most used, and traditional photochemotherapy (PUVA) is also available, but attention should be paid to side effects. Emollients should be used after phototherapy, and whole-body UV therapy should be avoided in children under 6 years of age.
4.7. 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 doctor should pay attention to patient (including the patient’s family) education, when the patient is first seen, the patient’s medical history, disease duration, lesion area and severity should be comprehensively evaluated to determine the treatment plan, and strive to control the disease in the short term; in the subsequent follow-up visits the doctor 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’s treatment and pay attention to the protection in “clothing, food, housing, transportation and washing”, avoid contact with the factors that trigger the aggravation of the disease as much as possible, and learn to observe the changes of the disease and give feedback to the doctor in a timely manner without stopping or reducing the medicine at will. In case of poor efficacy or exacerbation, the doctor should analyze the reasons and take targeted measures in a timely manner. Maintenance treatment should be carried out after remission, and topical hormones or calcium-regulated phosphatase inhibitors can be used 2-3 times a week. Due to increasing advances in diagnosis and treatment, many patients with atopic dermatitis are able to receive timely and correct diagnosis and treatment, and the vast majority of patients are able to achieve good control.