atopic dermatitis
Introduction
Introduction to genetic allergic dermatitis Atopic Dermatitis (AD), also known as atopic dermatitis, atopic dermatitis or atopic eczema (Atopiceczema), is a chronic, recurrent, itching associated with atopic (genetic allergic) quality. Sexual, inflammatory skin disease. If the patient's serum IgE is high, it can be associated with asthma and allergic rhinitis. The "milk mites" and "pregnancy sores" of Chinese medicine are the manifestations of the disease in infancy. basic knowledge The proportion of sickness: 0.002%-0.003% Susceptible people: no special people Mode of infection: non-infectious Complications: ichthyosis, alopecia areata, human papillomavirus infection, herpes simplex, infectious soft palate
Cause
Cause of genetic allergic dermatitis
(1) Causes of the disease
The cause of this disease is very complicated. It is generally believed that the occurrence of this disease is related to genetic, immune and physiological and pharmacological mediators. At present, it seems that these three are closely related, and it is likely that some basic defects and obstacles of genetic control are manifested in many aspects.
1. About 70 patients with genetics have a history of family genetic allergy. In the parental survey, it was found that children with genetic allergies in both parents had a higher incidence of hereditary allergic diseases than those with only one parent, with 81% to 59%. The study of neonatal studies found that the incidence of morbidity in monozygotic twins was up to three times higher than that of twins. There is still disagreement about the way of inheritance, and there have been no consensus opinions on autosomal dominant or recessive inheritance. Studies suggest that the AD-related mast cell chymase gene on chromosomes 14q11, 2 and genes associated with respiratory allergy on chromosome 11q13 dominates the large-scale synthesis of IgE, but has not been confirmed. It is currently believed that the emergence of various clinical symptoms of AD plays an important role in the influence of polygenic genetic factors and environmental factors.
2. Immunological abnormalities in immune response are manifested in two aspects of allergic reactions and cellular immune defects.
(1) Allergic reaction:
1 is closely related to allergic diseases: about 70 patients have bronchial asthma and/or allergic rhinitis. Usually the earliest lesions appear, followed by asthma, and the latest is allergic rhinitis. There is often a tendency for skin lesions and asthma to alternate, that is, when asthma is relieved at the onset of skin lesions, or asthma attacks after skin lesions are relieved, the mechanism of this so-called organ metastasis is unclear. There are also many cases where asthma is parallel with the onset of skin lesions. There are reports of allergic urticaria, angioedema, conjunctivitis, and allergic drug reactions in patients with AD, but the results are not consistent.
2 food allergies: mainly occurs in children with AD, foods that often cause allergies are eggs, milk, seafood, but also allergic to juice, nuts and so on. Skin tests (such as provocation tests) and radiosensitivity adsorption tests (RAST) are not reliable. The re-exposure test has a certain degree of reliability, especially after repeated results. The reaction included itching 15 minutes after exposure, and the rash increased or new lesions appeared 1 to 2 days later. Contact allergies that can occur in food allergens are urticaria reactions, but do not trigger lesions in AD.
3 Inhalation allergy: It can be the cause of deterioration of skin lesions in AD patients, including pollen, animal hair, fungi, house dust, dust mites, etc., which has attracted sufficient attention in recent years. With these inhaled allergens, about 80% of patients can produce a positive reaction of type I allergy skin test, and those with severe skin lesions are more obvious, but the positive rate of exposure test is not high, so the reliability of skin test positive Caused doubt. The reason for the high positive rate of skin test is not clear enough.
4 abnormal serum immunoglobulin (Ig): mainly expressed as high IgE levels. IgE has been known as a responsive element, and it is more than 80% elevated in AD patients, especially those with respiratory allergies. Elevated IgE in respiratory allergies alone is often less pronounced than in AD alone. Elevated IgE is not only associated with increased serum total IgE, increased specific IgE for inhaled or ingested antigens, but also with increased number of IgE receptors on antigen-presenting cells (APC) and eosinophils (EOS). . The extent of IgE elevation is roughly parallel to the severity and extent of the lesion. IgE gradually decreased with the lesion, and IgE usually fell to normal level after the skin lesion recovered for 1 year. The pathogenic significance of IgE in AD is not clear. In some cases, there is no direct connection between IgE and AD performance, such as:
A. IgE elevation is not always seen in patients with eczema lesions;
B. AD can be elevated without IgE, and can occur in patients without gamma globulinemia;
The level of C.IgE is not always consistent with the severity and breadth of AD;
D.IgE mediates wheal damage rather than eczema lesions. Therefore, IgE is a non-specific manifestation of AD, reflecting the abnormality of immune regulation.
It has been reported that complex IgE circulators with high sedimentation coefficient can be measured in peripheral blood of AD patients with high IgE or even normal IgE, which may be complexed with antigen or antiglobulin, such as IgE to form immune complexes with IgG and C3. IgE anti-IgE complex can also be formed, which is then deposited in the skin to cause mast cells and basophils to release histamine and other mediators to produce lesions. The relationship between IgE complex and this disease needs further study.
Regarding the levels of other immunoglobulins, it is generally considered that IgG, IgM, IgD may be slightly elevated or normal. In patients with severe eczema, IgG may be increased by skin infections, and an increase in IgG4 in children with AD is associated with a small amount of IgE anti-oval protein. The incidence of IgA reduction in AD patients is higher, especially in infants within 3 months, and the reduction in IgA is more likely to occur in AD. It is generally believed that the lack of IgA weakens the barrier function of the intestinal mucosa. At this time, infants fed with foods with strong allergenics such as milk and eggs may introduce allergens and stimulate the body to produce AD. However, the fact that infants with no transient IgA deficiency can still produce AD, suggesting that other mechanisms are involved in the process of allergic sensitization in infants.
(2) Cellular immunodeficiency:
1 lymphocyte immune function defects:
A. Peripheral blood T lymphocyte hypoplasia: In recent years, monoclonal antibodies against T cell antigen have been used to further identify whole T cells (CD3), T helper cells (CD4), and T suppressor cells (CD8), regardless of pediatric The absolute number and relative percentage of CD8 T cells can be seen in adults or adults, resulting in a decrease in the total number of T cells. Previous authors have also measured lymphocytopenia in normal neonates with patients with atopic dermatitis, suggesting the presence of genetically defined primary T lymphocyte defects in AD patients.
B. Peripheral blood lymphocytes reduce the stimulatory response to mitogens such as plant lectin (PHA), concanavalin A (Con A) and Pokeweed (PWM), and respond to some antigens such as candida, tuberculosis The hormone and herpes simplex antigen, streptococcal toxin, and house dust mite antigen are also reduced. As the lesions subsided, the reaction increased. The functional deficit of lymphocytes in response to PHA is reversed after 2 to 4 days of in vitro culture. Therefore, it is speculated that the defect in cell function may be due to immature cell development or incomplete differentiation.
C. Delayed allergic reaction defects: AD patients have reduced or lack of response to a series of antigens such as tuberculin, double-stranded enzyme, and candida. The incidence of allergic contact dermatitis in patients with AD is lower than normal or near normal, and the response to dinitrochlorobenzene (DNCB) patch test is significantly lower, especially in severe AD.
2 neutrophil and monocyte function defects:
A. Low chemotaxis: In the onset of AD patients, the recovery period is rapidly increased. Often in patients with severe AD, the performance is outstanding. This chemotaxis is only partial or mild, so when staphylococci invade the skin, there is no obvious reaction in the early stage, and pustules or abscesses are formed until the slow chemotactic white blood cells accumulate. Xue et al (1993) and other studies suggest that patients with myelin granules (AG) myeloperoxidase (MPO) and lysosomal enzyme defects in hereditary neutrophils, degraded by phagocytic substances, leading to Accumulation of antigenic substances has become an important cause of genetic allergic diseases.
B. Antibody-dependent cell-mediated cytotoxicity (ADCC) is inferior: experimental results show that neutrophils and monocytes have normal ability to bind to target cells, but phagocytosis, release of lysozyme, and ability to produce reducing oxy groups in cells. Reduced and activated cytotoxicity is defective. The number of natural killer cells (NK) in AD is reduced, and the activity of NK is decreased. These may be related to the inhibitory effects of PDE and prostaglandin E (PGE2) produced by AD patients.
Due to the above-mentioned immunodeficiency, it is not difficult to understand that there are many infections in the clinical manifestations of AD, such as viruses (herpes, sputum), fungi (chronic rickets), and bacteria (septicococcus).
(two) pathogenesis
In the pathogenesis, the abnormal expression of Langerhans cell (LC) surface molecules and its increased activity of T lymphocytes, the regulation of immune cytokines and the imbalance of T lymphocyte subsets, and the excessive synthesis of IgE.
1. LC and T lymphocytes were used to detect the number of immunoglobulin-positive lymphocytes in the skin of our patients by direct immunofluorescence technique. It was found that there were more than half of the patients with AD with or without skin lesions in the dermal papilla layer. IgE positive lymphocytes. AD lesions showed an increase in the number of LC in the dermis, an abnormal phenotype of LC in the epidermis (ie, the phenotype with the same expression in the dermis: high concentrations of CDla and CDlb, CD36), and aberrantly expressed reticular cell marker RFD-1. Hypersensitivity state with self-activated T cells. There are three IgE receptors in normal skin LC: FcRI, FcRII (CD23) and IgE conjugated proteins. The expression of FcRI with high affinity on AD and LC is significantly enhanced, and an important interaction between the allergen carried by binding to specific IgE and antigen-specific T cells. We and other authors have reported that soluble interleukin-2 receptor (SIL-2R) is elevated in AD serum, suggesting that AD, T cells are activated in AD. These above demonstrate that there is a hypersensitive cellular basis for both the primary antigen presenting cells (LC) and immunocompetent cells (T lymphocytes) of AD.
2. Immune Cytokine Regulatory Disorders and T Lymphocyte Subpopulation Imbalance AD monocytes may have abnormal cytokine effects such as IL-10 production that affect T cell differentiation due to dysregulation of the following cyclic nucleotide linkages. At the same time, the LC of AD is in a hypersensitivity state, and the treated heterologous antigen is presented, and the superantigen, such as the most common type of Staphylococcus aureus enterotoxin, is combined to stimulate T cells in the lesion. After repeated stimulation by activated LC, T lymphocytes tend to differentiate into antigen-induced antigen-specific THz cells and produce large amounts of IL-4, IL-5 and IL-13 and a very small amount of IFN-. IL-4 and IL-13 can stimulate the proliferation of B cells and induce the expression of IgE receptors on the surface of IgE and LC cells, further promoting the formation of IgE. IL-5-induced EOS, activated at the lesion, partially degranulated, releases cationic proteins and major base proteins (MBP), contributes to tissue damage and exacerbates lesions. Excess PGE2 produced by monocytes of AD also inhibits the release of IFN- by Th1 and directly acts on B cells to increase the synthesis of IgE. Tumor necrosis factor (TNF) released by activated mast cells also inhibits Th1. Therefore, the regulation of AD cytokines is abnormal, and the response to the antigen is that the activity of TH2 is greater than TH1, resulting in a serious imbalance of Th1 and Th2.
3. IgE over-synthesis Animal and human experimental studies have shown that IgE is mainly produced in the periphery of AD by B lymphocytes carrying IgE on the surface. It is controlled by T cells and is controlled by IgE-regulated cytokines such as IL-4 and IL-13 produced by TH2 cells.
4. Other
(1) Neurological aspects: AD manifests as an abnormality in the distribution of some nerve fibers and an increase in the activity of neuropeptides. Neuropeptide substance P can induce mastoid degranulation, release histamine, produce wheal, and may be associated with leukocyte infiltration and itching, which may explain the skin inflammation that exacerbates AD. AD lesions showed an increase in vasoactive intestinal peptide (VIP) levels and a decrease in substance P levels, which differed in immunomodulatory effects and performance. Substance P stimulates lymphocyte proliferation and monocytes produce cytokines, while VIP inhibits lymphocyte proliferation and NK cell activity. The imbalance between the two may also be one of the factors that impair the AD skin immune response.
(2) Abnormal metabolism of essential fatty acids (EFA): EFA can control the proliferation of epidermis and regulate cellular immunity to maintain the barrier function of the skin. The clinical manifestations of AD are dry skin disease, which may be related to the reduction of ceramide found in the skin, the change of epidermal cell function and the promotion of inflammation.
In short, the etiology and pathogenesis of AD are complex, and future research trends must be closely related to the above various mechanisms.
Prevention
Genetic allergic dermatitis prevention
It mainly prevents the occurrence, aggravation and deterioration of atopic dermatitis from alleviating or improving the already existing disease. Some of the content is mentioned in the treatment section.
1. Try to avoid local irritation, such as not using irritating medicines, hot water soap and so on.
2. The clothes and diapers used by infants and young children should be soft, and wash the soap as much as possible. It is not advisable to use plastic products for diapers. The patient wears cotton on the clothes, making the artificial fibers and wool directly stimulate the skin as little as possible.
3. It is not advisable to overwork to avoid excessive emotional excitement and excessive sweating.
4. Do not take penicillin and serum preparations casually.
5. To prevent viral infections, such as colds, especially in infants and young children should be prevented from contact with herpes simplex and acne.
Complication
Genetic allergic dermatitis complications Complications, ichthyosis, alopecia, papillomavirus infection, herpes simplex, soft palate
In addition to the above clinical manifestations, some patients may also have the following complications, which will help the diagnosis of this disease. Patients are often accompanied by dry skin, mild ichthyosis-like changes, rough palm texture called palm plaque, upper lip and cheekitis, non-specific hand dermatitis, pigmentation around the eyelids, wrinkles around the eyelids called underarm folds Conjunctivitis, pale complexion, white pityriasis, keratosis, conical cornea, albinism, alopecia areata, etc. Repeated skin infections, including herpes simplex, infectious soft palate, and human papillomavirus infections, are common with herpes simplex, and Kaposi varicella-like rash can occur, which is associated with T cell defects in AD patients. Other infections such as Trichophyton rubrum, AD patients are three times as many as non-AD patients, S. aureus infection rate is about 90%, and non-AD patients only 3%.
Symptom
Genetic allergic dermatitis symptoms common symptoms dermatitis itching skin dry eczema pimples special body scaly edema pustule blood stasis
AD is a common skin disease. In China's children's skin diseases, AD accounts for about 30% of the number of dermatological children. AD often fluctuates with seasonal changes (especially in spring and autumn).
Rash: The clinical features of this disease are various, but the most basic are chronic recurrent episodes, severe itching, age-related rash manifestations and certain predilection sites. According to the characteristics of the occurrence and development of rash, it can be divided into three stages, namely, infancy, childhood and adolescent, which can be developed one after another or only one or two stages. Generally, the age of onset is early, 60% of patients are ill within 1 to 6 months, and there are cases as early as 1 week. About 90% of the cases occur within 5 years of age. The number of people over the age of 35 is no more than 5%.
1. Infancy This disease occurs on the face at least one month or more after birth, especially on the cheeks and forehead. Beginning with acute erythema and papules, when the climax is reached, the cheek damage can be fused into a large edematous epithelium that is significantly higher than the skin, with papules, blisters, pustules, serum or pus and jaundice. Spilling serous or pus in the cracks of the sputum, sometimes dropping into beads. When the liquid is leaking for a long time, part of the scutellaria can be washed away, and the smashed surface is exposed. Forehead damage is similar to cheek damage, but it is often lighter. Sometimes the entire face is involved except for the wrinkles of the nose and the nose. There are scattered small yellow sputum attached to the hair root between the hair, and some may be characterized by seborrheic dermatitis. There are secondary infections that can be associated with fever and localized lymphadenopathy. In addition to paroxysmal itching causes the baby to cry and cry, its health is generally normal.
China's dermatologist Chen Shigong said in his book "Surgical Authentic" in 1617 that he said: "Children are in the fetus, the mother food is five sin... The heat and the child are born. The flow of fat into tablets, sleeplessness, and itching are endless. It is believed that this disease is related to its maternal protein food. Its clinical narrative, although only a few words, is also very appropriate.
The course of the disease is chronic, and the light gradually relieves after half a year. The redness and swelling disappear, the discharge is reduced, the damage is gradually dry, and there is no thick sputum. Only thin sputum and scales, or only scales, can be cured by the age of one. The heavier ones healed by the age of 2, and the heavier ones continue to develop into childhood.
2. Childhood AD can be divided into three types, which can be the continuation of infancy and also begin in childhood.
(1) Four-bend type: facial damage gradually subsides, and subacute red patches appear in the elbow fossa and nest (China's four-bend wind), with needle-sized papule blisters, scales or thin suede, margin With limitations, the red color subsides and the lesions are dry. As a result of constant scratching, the damage gradually thickens and the moss changes, and the time is good and bad. The long-term unhealed, the distribution is symmetrical, and the two calves are stretched sideways, and both hands and lips can sometimes be involved. Cracks can still occur in the latter two locations. When injecting vaccinations, colds, and teething, the condition often worsens.
(2) Chronic eczema type under the knee: common in children 4 to 6 years old, less common. The lesion is an irregular elliptical patch, located a few centimeters below the knees, with marginal limitations, no significant inflammatory response, only thickening and mossy changes, with small scales attached. There are varying degrees of itching. The course of the disease is chronic, light and heavy, and it seems that the other two types are stubborn and have a tendency to heal themselves.
(3) pruritus type: the disease occurs in school-age children. The limbs can be spread to the sides, the back or the whole body. The size of the rice grains to the soybeans can be discolored, brown or brown. It is not regular. The dry and rough papules are evenly distributed and symmetrical. The new rash can be large and red, and the old ones are irregular hard papules, often accompanied by many scratches or blood stasis. The inguinal lymph nodes are often symmetrical, but there is no inflammation or suppuration. The damage has not healed for many years, so that the child is thin.
3. Adolescents and adults refer to the stage of adolescents and adults after the age of 12, which can develop from childhood or directly, similar to late childhood damage, mainly in the elbow fossa and fossa, but in a wider range, sometimes involving Neck and hands. Distribution is symmetrical. The skin is dry and thick, accompanied by mossy changes. Some patients may have subacute eczema-like patches on the extremities of the limbs. The base is reddish and has a large amount of scales and crusting attached to it. The skin lesions are changed by disseminated neurodermatitis. The course of the disease is chronic, repeated attacks, can spread the whole body, consciously itchy, and can also have a longer period of remission, and individual patients can be extended to the elderly.
4. The patient's small blood vessels react abnormally to various stimuli
(1) White scratches: After rubbing the skin with a thin stick, the normal person often turns red on the rubbing part, while the patient is pale in the rubbing part.
(2) Delaying the pale phenomenon: 15 minutes after intradermal injection of 10,000: 10,000 acetylcholine 0.1ml, localized flushing, hyperhidrosis and chicken skin disease in normal people, subsided after 4 to 5 minutes, and 3 to 5 minutes after skin test. A pale area appears around the injection site and lasts for 15 to 30 minutes.
5. Patients may be associated with allergic diseases such as hay fever, allergic rhinitis, asthma, urticaria, in addition to ichthyosis, cataract, map tongue and so on.
Examine
Examination of genetic allergic dermatitis
1. Peripheral blood eosinophils are often significantly increased. The number of T lymphocytes was reduced, with CD8 being significantly lower. The number of B lymphocytes is usually increased. Most of the serum IgE was significantly increased. IgG, IgM may have a slight increase, and most may have a low IgA.
2. Skin test
(1) Type I: The quick-acting skin test reaction is often positive. Nowadays, the provocative or scratch method is commonly used, and the commonly used original fungi, pollen, house dust, dust mites, and dander are used. However, it should be noted that positivity is not necessarily a sensitizer for AD.
(2) Type IV: delayed type allergy test, often low. Intradermal testing is generally performed on the forearm flexion. Commonly used antigens include tuberculin, Mycobacterium tuberculosis pure protein derivative (PPD), double-stranded enzyme (SD-SK), chymectin, candida, mumps vaccine, and the like. There are also phytohemagglutinin (PHA) for intradermal testing. In addition, there is a DNCB patch test. Patients with AD are often negative or weakly positive.
3. Pathophysiological skin test
(1) Skin white scratch test: The scratch was pressed at the normal or skin lesion with a blunt stick, and a white line was formed after 15 s instead of the red line.
(2) Delayed whitening reaction of acetylcholine: The concentration of acetylcholine is in the range of 1:100 to 1:100, and the usual concentration is 1:10000. After intradermal injection of 0.1 ml, local flushing, sweating and chicken skin disease occurred in normal people for 15 s, and disappeared after 3 to 4 minutes. The patient usually has a white reaction 3 to 5 minutes after the skin test, and the elderly can last for 15 to 30 minutes.
(3) Histamine test: the commonly used concentration is 1:10000, 30s after intradermal injection of 0.1ml, the redness is not obvious or the lack is negative.
All of the above tests are prone to abnormal reactions in the skin lesions and normal skin of AD patients, especially in the skin lesions, but the significance of abnormal reactions on normal skin is large.
Histopathology: no specificity. In the acute phase, acanthosis can be seen in the epidermis, intercellular edema or sponge formation, lymphocyte and histiocyte infiltration in the epidermal sponge formation zone and upper dermis, neutrophils and eosinophils, and dermal edema. As the eczema inflammation subsides, the mossy lesions appear, and the tissue image also changes accordingly, showing a marked epidermal hyperplasia with little or no sponge formation. The dermal papillary thickening is accompanied by moderately intensive inflammatory cell infiltration, with an increased number of LCs, sometimes accompanied by more EOS. Staining with anti-lymphocyte surface antigen monoclonal immunoenzyme labeling confirmed that the dermal infiltrate was mainly T lymphocytes (CD4) and had HLA-DR antigen, suggesting activation characteristics. In addition, there have been reports of a large number of mast cells and phagocytic cells. The LC in the epidermis of the mossy lesions increased significantly.
Diagnosis
Diagnosis and diagnosis of genetic allergic dermatitis
diagnosis
1. History of genetic allergies in individuals or families (asthma, allergic rhinitis, hereditary atopic dermatitis).
2. Characteristics of various rashes and predilection sites, except for infancy, the rash is mostly dry, prone to papules, pruritus, and mossy damage, and the winter and spring are heavier and the course of disease is longer.
3. Intense itching, severe itching when sweating and nervousness.
4. Laboratory tests may have elevated eosinophils, elevated serum IgE, and decreased T suppressor cells.
5. Inhalation or food allergies, skin test is often positive.
6. White scratches and delayed pale reactions.
Differential diagnosis
1. Eczema skin damage is similar to this disease, but there is no certain predilection site, and there is no history of "ectopic" in the family.
2. Pediatric pruritus has no history of hereditary atopic dermatitis and allergic disease in the family. There is no specific antibody in serum, only found in children.
3. There is no history of "ectopic" in the disseminated neurodermatitis family. There is no specific antibody in the serum. The eosinophils in the blood are not high, mostly adults. There is no history of infants and children with eczema.
