Tài liệu THE STUDY OF STAPHYLOCOCCUS AUREUS’S SUPERANTIGENS AND TREATMENT FOR PATIENT WITH ATOPIC DERMATITIS BY CEFUROXIM

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY CHAU VAN TRO THE STUDY OF STAPHYLOCOCCUS AUREUS’S SUPERANTIGENS AND TREATMENT FOR PATIENT WITH ATOPIC DERMATITIS BY CEFUROXIM Specialist: Dermatology Code: 62 72 01 52 SUMMARY OF THESIS HANOI - 2013 This thesis was completed at: HANOI MEDICAL UNIVERSITY Academic Advisor: Ass.Prof TRAN LAN ANH, PhD Ass.Prof NGUYEN TAT THANG, PhD Opponent 1:……………………………………………………… …………………………………………………………………….. Opponent 2: …… …………………………...…………………… …………………………………………………………………….. Opponent 3: …… …………………………...…………………… …………………………………………………………………….. The thesis was presented to Dissertation Committee of HaNoi medical university Place: …………………………………………………………… Time: ………………………………………………………….... May find the thesis in library: STUDIES RELATING TO THESIS WERE PUBLISHED 1. Chau Van Tro, Nguyen Tat Thang, Tran Lan Anh (2011) "Study of Staphylococcus aureus’s superantigens in adult patient with atopic dermatitis", Journal of practical medicine, 4 (760), pp. 122-126. 2. Chau Van Tro, Nguyen Tat Thang, Tran Lan Anh (2012), "Evaluation of treatment adult patient with subacute atopic dermatitis by cefuroxim combined with topical corticosteroids ", Journal of practical medicine, 5 (821), pp. 108 - 112. INTRODUCTION Atopic Dermatitis (AD) or atopic eczema (AE) is a common chronic inflammatory skin disease. The prevalence is from 10 to 20% of the children population. So far the causes and mechanisms of pathogenesis of AD still has not completely understood. The treatment of AD has a lot of difficulties. The disease is recurrences, so the prevalence diseases tend to be on the increase. In the late 20th century, Michael J. Cork, Abeck. D et al, Shuichi Higaki has found that Staphylococcus aureus played a very important role in the mechanism of pathogenesis of the disease. The studies of Adachi. Y et al, Strange. P et al, Yudate. T et al have shown that Staphylococcus aureus secretes the enterotoxines serves as an superantigen in the mechanism of pathogenesis of AD. According to Gong. J. Q et al, Breuer. K et al, superantigens of Staphylococcus aureus may penetrate the skin barrier and contribute to the persistence and exacerbation of allergic skin inflamation in AD through the stimulation of massive T cells. Until now, the treatment of AD is primarily used antihistamine, topical corticosteroids, topical tacrolimus, pimecrolimus and skincare with moistures. The use of antibiotics when there are bacterial superinfections so that effect of treatment is not good. Study of Gong. J. Q et al also shows a new strategy in the treatment of AD is the use of antibiotics as important component of the overall management of AD. RESEARCH OBJECTIVES 1. Survey clinical characteristics and related factors to adult AD in hospital of Dermato-Venereology of Ho Chi Minh City from 08/2010 to 08/2012. 2. Determinate Staphylococcus aureus infection and Staphylococcus aureus 's superantigens genes on the atopic dermatitis adult patients. 3. Evaluate the effectiveness of treatment of subacute phase adult atopic dermatitis by cefuroxim combine with topical betamethasone dipropionate 0.05%. NEW CONTRIBUTIONS OF DISSERTATION The dissertation proved Staphylococcus aureus has very important role in the mechanism of pathogenesis of atopic dermatitis, making the onset or affect the degree of severity of the disease. The dissertation also proved the effectiveness of the use of oral antibiotics anti – Staphylococcus aureus as a measure of the combined in the treatment of atopic dermatitis. STRUCTURE OF DISSERTATION Dissertation consists of 111 pages, excluding appendices and reference , including 4 chapters , 32 tables, 2 charts, 5 pictures, 6 diagrams, 157 references (17 Vietnamese references, 140 English references) and addendum. The layout of the thesis consists of introduction (2 pages), overview (33 pages), subjects and methods (17 pages), results (29 pages), discussion (27 pages), conclusion (2 pages) and recommendation (1 page), and there are 2 articles related to the thesis has been published. CHAPTER 1: OVERVIEW 1.1 Atopic dermatitis Atopic dermatitis is a very common disease in dermatology. The prevalence is increasing especially in the industrialized countries. The prevalence is from 10 to 20% of the children population. Causes and mechanisms of pathogenesis remains unclear, related to multi factors such as: genes, allergens, nerve, endocrine, immune changes, climate, infection ...Clinical symptoms are plentiful such as: itching, insomnia, erythema, papules, oozing, crusts, lichenfication… There are three phases of atopic dermatitis: acute phase, subacute phase, and chronic phase. Currently there are many measures for treatment the AD but the effectiveness of the treatment is not high. The disease often relapse and influence on the quality of life of the patient. AD becomes the burden on the family and society. 1.2 The role of Staphylococcus aureus in AD On the skin of healthy people, the ratio of Staphylococcus aureus is about 5%. On the AD patients, the ratio of Staphylococcus aureus from 55-75% on the non - lesion skin, 85-90% on the chronic lesions, 80-100% of the acute lesions. It also found that the density of the Staphylococcus aureus on acute inflammatory lesions 1,000 times higher than on the non – lesion skin in AD patients. So the skin of the AD patients is a favorable environment for development of Staphylococcus aureus. The exact mechanism of the increase the ratio and the number of Staphylococcus aureus on skin of AD patients still is unknown. It may be a combination of the following mechanisms: Skin barrier dysfunction, reducing the production of antibacterial peptids in the skin (such as beta defensins and LL-37), reducing the antimicrobial immune response of the skin, change the skin pH...That increase the adhesive of the Staphylococcus aureus on skin of AD patients. When Staphylococcus aureus adhesive on the skin they will produce enterotoxins that act as a superantigen enabled to differentiate a large number of T cells into Th1 and Th2. The differentiation that will produce cytokins such as IL4, IL5, IL10, TNF-γ, ... Cytokins activate the inflammatory response to cause the onset of AD. 1.3 Treatment of Staphylococcus aureus in patients with AD So far, the scientists studied a lot of measures treatment of Staphylococcus aureus in patients with AD. Methods do not take antibiotics such as repair skin barrier by moisturizing, use topical anti-inflammatory substances (corticosteroids, calcineurin inhibitors ...) to reduce adhesive of Staphylococcus aureus on skin of AD patients. The antiseptics: Bactericidal soap, KMnO4, povidone-iodine 10% … reduce the number of Staphylococcus aureus on the skin of patients with AD, improve the clinical symptoms. However, these substances may to irritate the skin. Topical antibiotics: Topical antibiotics alone or in combination with corticosteroids have effective in the treatment of AD. However, using topical antibiotics have some disadvantages such as have only effective at the location of the treatment, cause allergic contact dermatitis, increase bacterial resistant. Therefore, the new trend is the combination of oral antibiotics in the treatment of AD. However, so far there is very little research on this issue. CHAPTER 2: SUBJECTS AND METHODS 2.1 Subjects 128 AD patients, > 12 years old, visit to hospital of Dermato-Venereology of Ho Chi Minh City from 08/2010 to 08/2012 and 40 healthy subjects, > 12 years old, does not have AD or other skin diseases. 2.1.1 Diagnosis of AD: AD was diagnosed following the criteria of Hanifin and Rajka. 2.1.2 Criteria of patient selection Criteria of patient selection for clinical research, the ratio of Staphylococcus aureus and genes encoding superantigens: AD patients > 12 years old, no infected lesions, agreemen participant. Criteria of patient selection for evaluating the effectiveness of treatment AD by taking topical betamethasone dipropionate 5% plus oral cefuroxim: sub – acute AD patients, ages from 12 to 60, positive Staphylococcus aureus on lesions, agreemen participant. 2.1.3 Criteria of patient exclution: Patients used topical antibiotics within 2 weeks and oral antibiotics within 1 month. Patients has signs of heart, liver or lung severe diseases. Patients with immunodeficiency (HIV/AIDS, diabetes, immune suppressant medication...). Patients who are pregnant or are breastfeeding. Patients suffering the side effects of corticosteroids such as skin atrophy, vasodilation, hirsutisum .... Patients allergic to either medication use (betamethasone dipropionate 0.05%) or cefuroxim. 2.2 Materials Beprosone®: Betamethasone dipropionate 0.05% is average topical corticosteroids, produced by HOE Pharmaceuticals Sdn Bhd, Malaysia. Licensed in VietNam by decision No VN-0421-6, 17/QDQLD of Ministry of health. Zinnat®: Cefuroxim is bactericidal antibiotic belong to two generation Cefalosporin, tablets 500mg, produced by Glaxo Operations UK Ltd, licensed in Viet Nam VN-8475-04 by decision No. 85/QD-QLD of Ministry of health. 2.3 Methods 2.3.1 Study design: Cross-section, case - control and clinical trial. 2.3.2 Sample size - Cross - sectional study (for object 1): Convenient sampling, select all of the patients eligible for the study from August, 2010 to August, 2012. - Case – control study (for object 2): sample size is estimated according to the following sample size calculator: Z N 1  / 2 2 P2 (1  P2 )  Z1  P1 (1  P1 )  P2 (1  P2 ) ( P1  P2 ) 2 P1: Ratio of the positive Staphylococcus aureus in AD patients (8095%, depending on the study). P2: Ratio of the positive Staphylococcus aureus in healthy subjects (35-45%, depending on the study). α: Probability of type 1 error (α = 0.05) → Z 1-α/2 = 1.96. β: Probability of type 2 error → Z 1-β = 1.28. We select P1 = 80%, P2 = 45% instead of the sample size calculator  N = 40  The minimum sample size of each group is 40.  2 - Clinical trial (for object 3): Convenient sampling, select all of the sub – acute AD patients during the period from 08/2010 to 08/2012, eligible for the clinical trial stage and each group must be > 30 patients. 2.3.3 Steps to study - Clinical examination to identify AD. - Data collection - Assess the severity of the disease by SCORAD: Mild: SCORAD < 25 Moderate: SCORAD from 25 to 50 Severe: SCORAD > 50 - Assess the stage of the disease: acute, sub-acute and chronic - Culture to identify Staphylococcus aureus: In AD patients, we Culture and determine the Staphylococcus aureus on new lesions. In healthy subjects, we culture and determines the Staphylococcus aureus in the skin around the nostrils. - Identify of the genes encoding superantigens: By multiplex PCR (Polymerase Chain Reaction). - Clinical trials: We Split AD patients randomly into two groups: + Group 1: Will be treated with a regimen including shower by KMnO4 1/10,000, fexofenadin 60 mg (1 tablet /morning and 1 tablet / evening), cefuroxim 500 mg (1 tablet / morning and 1 tablet / evening), beprosone ® apply twice /day. + Group 2: Will be treated with a regimen including shower by KMnO4 1/10,000, fexofenadin 60 mg (1 tablet /morning and 1 tablet / evening), beprosone ® apply twice /day. + Duration of treatment: 2 weeks + Assess the result: Assess the clinical symptoms and SCORAD score after a week of treatment, culture Staphylococcus aureus at the end of week two. 2.4 Data processing: The data are processed and analysed by using EpiInfo software in 2002. - Descriptive statistics: Frequency, percentage is presented in the form of table and diagram. - Statistical analysis: Use χ ² and RR at 5% significance, confidence intervals (CI) 95% to measure differences in the relationship of results. - Use One-Way-ANOVA to compare average scores of clinical symptoms, SCORAD score of two groups before treatment, after 1 week of treatment, after 2 weeks of treatment. 2.5 Place and time of study: Place of study in hospital of DermatoVenereology of Ho Chi Minh City and NamKhoa Biotek company (ISO 9001: 2000 and GMP/GLP of the WHO). Duration of study from 08/2010 to 08/2012 2.6 Research ethics: Proposal of the research was through by the Council of PhD proposal of Hanoi Medical University. The objects of the study was announced, explained and agreed to voluntarily participate in the study. All object information are kept secret through the computerized. All Patients are paid for tests. 2.7 Limits of the study: Superantigens are a relatively new concept. Their mechanism are very complicated. Therefore, we accept the mechanism of pathogenesis of superantigens in AD is explained on the dermatologist journals of the World Health Organization website. (http://www.who.int/hinari/en/). AD is a very complicated disease. The treatment is depending on the stage of the disease. We conducted clinical trial research on sub-acute phase. Because this stage occupy the majority of AD. CHAPTER 3: RESULTS From 8/2010 to 08/2012, we studied 128 AD patients and 40 healthy subjects. 3.1 Clinical characteristics and related factors of AD 3.1.1 Clinical characteristics Ratio of clinical symptoms: Itching 100%, dry skin 78.91%, insomnia 75% , non – pecific hand dermatitis 57.81%, cheilitis 47.56%, anterior neck folds 42.18%, white dermographism 40.62%, orbital darkening 26.56%, Dennie Morgan infraorbital folds 21.09%, pityriasis alba 18.75%, keratosis pilaris 18.75%, ichthyosis vulgaris 7.81%, nipple eczema 3.9%. The stage and the severity: Sub-acute phase 71.87%, chronic phase 17.97%, and acute phase 10.16%. Average SCORAD score is 12.35 ± 40.55. Moderate 44. 53%, severe 28.12%, and mild 27.34%. 3.1.2 Related factors of AD Patient and family history has atopic diseases Table 3.1: Ratio of patient and family history has atopic diseases History AD Asthma Allergic rhinitis n (%) n (%) n (%) Patient (n = 128) 125 (97.65) 63 (49.22) 68 (53.13) Father (n = 128) 75 (58.59) 23 (17.97) 32 (25) Mother (n = 128) 27 (21.1%) 19 (14.84) 12 (9.37) Brothers (n = 83) 42 (50.60) 33 (39.76) 51 (61.44) Children (n = 67)) 29 (43.28) 17 (25.37) 15 (22.3) Onset factors of AD Chart 3.1: The majority of adult AD patients (55.47%) was exacerbated by contact allergens. The age of onset Chart 3.2: The majority of AD patients (51.56%) has the age of onset < 2 years old. Relation between severity of AD with related factors We used 2 x 2 table statistic analysis found that gender, age, history of AD, asthma, allergic rhinitis does not affect the severity of the disease. However, contact allergens and early age onset affects severity of the disease. 3.2 Staphylococcus aureus and genes encoding superantigens of Staphylococcus aureus on AD patients skin. 3.2.1 Ratio of Staphylococcus aureus positive in AD patients and healthy subjects % p < 0.001; RR = 2.17; 95% CI (1.44 – 3.26) Chart 3.3: Ratio of the Staphylococcus aureus positive on the lesions of AD patients is higher than that on peri – notrils of healthy subjects statistical significance p < 0.001; RR = 2.17; 95% CI (1.44 - 3.26). We used 2 x 2 table statistic analysis found that the ratio of Staphylococcus aureus positive in severe patient groups is higher than that in the mild patient group statistical significance p = 0.001, RR = 7.12; 95% CI (1.08-47.04). The ratio of Staphylococcus aureus positive in acute and sub-acute stage is higher than that in chronic stage statistical significance p = 0.015, RR = 1.38; 95% CI (1.006-1.90). 3.2.2 The genes encoding superantigens of Staphylococcus aureus on AD patients skin and on healthy subjects p < 0.001; RR = 8.65 ; 95% CI (1.29 – 57.9) Chart 3.4: Ratio of the genes encoding superantigens of Staphylococcus aureus on the lesions of AD patients is higher than that on peri – notrils of healthy subjects statistical significance p = 0.0006; RR = 8.65; 95% CI (1.29-57.9). We used 2 x 2 table statistic analysis found that the ratio of the genes encoding superantigens of Staphylococcus aureus on the lesions of severe AD patients is higher than that on the lesions of mild AD patients no statistically significant with p = 0.04; RR = 1.58; 95%CI (0.95-2.67) and the ratio of the genes encoding superantigens of Staphylococcus aureus on the lesions at the stage acute, sub-acute and chronic difference not statistically significant with p > 0.05. 3.3 Effective treatment adult AD patients by topical betamethasone dipropionate 0.05% plus oral cefuroxim. During the study period, 74 AD patients were eligible for the clinical trial. We divided all the patients randomly into two groups. Each group has 37 patients. However, during follow-up treatment (2 weeks), group 1 has 1 (2.7%) patient and group 2 has 5 (13.5%) patients did not finish the study. Therefore, We analysis only 68 patients (group 1: 36 patients and group 2: 32 patients). 3.3.1 Comparison of therapeutic effect between two groups Table 3.2 Comparison of therapeutic effect based on the mean of SCORAD. SCORAD Group 1 Group 2 Baseline 44.61 ± 8.34 43.03 ± 12.98 After 7 days treatment 26.69 ± 6.05 32.53 ± 9.31 After 14 days treatment 16.61 ± 3.85 23.41 ± 7.49 P value (Mean ± SD) 0.55 REDUCE SCORAD AFTER TREATMENT After 7 days treatment -17.92 -10.5 0.003 After 14 days treatment -28 -19.62 < 0.001 Comments of the table 3.2 - Before treatment: Mean of SCORAD of group 1 was 44.61 ± 8.34, group 2 was 43.03 ± 12.98, the difference between the two groups was not statistically significant with p = 0.55. - After 7 days treatment: Mean of SCORAD of group 1 was 6.05 ± 26.69, group 2 was 9.31 ± 32.53, mean SCORAD of group 1 reduces 17.92 and mean SCORAD of group 2 reduced 10.05. Mean SCORAD of group 1 reduced more than group 2 statistically significant with p = 0.003. - After 14 days treatment: Mean of SCORAD of group 1 was 3.85 ± 16.61, group 2 was 7.49 ± 23.41, mean SCORAD of group 1 reduced 28 and mean SCORAD of group 2 reduced 19.62. Mean SCORAD of group 1 reduced more than group 2 statistically significant with p < 0.001. Table 3.3 Comparison of therapeutic effect based on clinical symptoms Clinical signs Group 1 Group 2 P value (Mean±SD) (Mean±SD) - Baseline 8.11±3.23 8.81±3.35 0.38 - After 7 days treatment 3.44±1.98 4.75±2.37 0.016 - After 14 days treatment 1.55±0.87 2.62±1.36 0.0002 C = Itching + Insomnia B = Erythema + edema/papules + oozing/crusts + excoriations + lichenification + dryness - Baseline 9.80±2.02 9.09±2.99 0.25 - After 7 days treatment 6.36±2.93 7.15±2.31 0.22 - After 14 days treatment 3.6 ±1.10 5.22±1.91 0.0001 - Baseline 13.50±5.22 11.72±3.72 0.11 - After 7 days treatment 13.19±5.05 11.25±3.29 0.075 - After 14 days treatment 12.64±4.90 11.20±3.64 0.25 A = Area of lesions Comments of the table 3.3 C = Itching + insomnia - Before treatment: Mean of C of group 1 was 8.11 ± 3.23, group 2 was 3.35 ± 8.81, the difference between the two groups was not statistically significant with p = 0.38. - After 7 days treatment: Mean of C of group 1 was 3.44 ± 1.98, group 2 was 4.75 ± 2.37. Mean C of group 1 reduced much more than mean C of group 2 statistically significant with p = 0.016. - After 14 days treatment: Mean of C of group 1 was 1.55 ± 0.87, group 2 was 1.36 ± 2.62. Mean C of group 1 reduced much more than mean C of group 2 statistically significant with p < 0.0002. B = Erythema + edema/papules + oozing/crusts + excoriations + lichenification + dryness - Before treatment: Mean of B of group 1 was 9.80 ± 2.02, group 2 was 9.09 ± 2.99, the difference between the two groups was not statistically significant with p = 0.25. - After 7 days treatment: Mean of B of group 1 was 6.36 ± 2.93, group 2 was 7.15 ± 2.31. Mean B of group 1 reduced much more than mean B of group 2 but the difference was not statistically significant with p = 0.22. - After 14 days treatment: Mean of B of group 1 was 3.61 ± 1.10, group 2 was 5.22 ± 1.91. Mean B of group 1 reduced much more than mean B of group 2 statistically significant with p = 0.0002. A = Area of the lesions - Before treatment: Mean of A of group 1 was 13.50 ± 5.22, group 2 was 11.72 ± 3.72, the difference between the two groups was not statistically significant with p = 0.11. - After 7 days treatment: Mean of A of group 1 was 13.19 ± 5.05, group 2 was 11.25 ± 3.29. Mean B of group 1 reduced much more than mean B of group 2 but the difference was not statistically significant with p = 0.075. - After 14 days treatment: Mean of A of group 1 was 12.64 ± 4.90, group 2 was 11.20 ± 3.64. Mean A of group 1 reduced much more than mean A of group 2 but the difference was not statistically significant with p = 0.25. Table 3.4: Results of Staphylococcus aureus cultured of 2 groups after the 14 days treatment Staphylococcus aureus Group 1 Group 2 P value Positive 3 (8.33%) 25 (78.12%) P < 0.001 Negative 33 (91.67%) 7 (21.88%) Total 36 (100%) 32 (100%) 95% CI (2.5710.12) Comments of the table 3.4: After the 14 days treatment, 91.7% of the patients in Group 1 had resulted Staphylococcus aureus negative; 21.88% of the patients in Group 2 had resulted Staphylococcus aureus negative. Ratio of Staphylococcus aureus negative in Group 1 was more than that of group 2 statistically significant with p < 0.001; RR = 5.1; 95% CI (2.57-10.12). 3.3.2 Adverse effects of 2 medications: During 2 weeks treatment we not recorded any adverse effects of the medicine in both groups Chapter 4: DISCUSSION 4.1 Clinical features and related factors of Atopic Dermatitis 4.1.1 Clinical features Pruritus: Pruritus is the main symptom and one of the main criteria for diagnosing Atopic Dermatitis (AD). According to medical books, 80-100% of patients with AD experience symptoms of pruritus. In our research, 100% of our patients had pruritus. Pruritus causes scratching and rubbing leading to secondary lesions such as infection, hardened skin, scratches, etc. Pruritus also causes insomnia, which impinges on patients’ quality of life. Insomnia: In our research, 75% of our patients developed insomnia. Like other chronic diseases, AD greatly affects patients’ mental health. It progresses chronically, recurs repeatedly, which has bad effects on patients’ quality of life, brings on worry, depression, and insomnia. Dry skin: According to our research results, 78.91% of the patients experienced dry skin. According to medical books, patients with this symptom make up around 50-70% of all AD patients. The causes of dry skin lie in the decreased filaggrin and ceramide production as well as the increased trans-epidermal water loss. Dry skin makes patients feel pruritusy, be prone to stimuli, and worsens the disease process. Therefore, applying moisturizing creams or lotions plays a crutial role in AD treatment. Other symptoms such as: Palmar and plantar dermatitis, cheilitis, skin folds on the anterior aspect of the throat, white dermographism, periocular darkening of the skin, infraorbitary (Dennie-Morgan) skin fold, pityriasis alba, keratosis pilaris, ichthyosis, nipple eczema are also common symptoms in patients with AD. 4.1.2 Related factors In our research on 128 adults with AD, males made up 58.6%, higher than females with 41.4%. The youngest age was 13, the eldest was 78, and the average age was 37.65 ± 14.09 with a high proportion of the group of 21-40 (56.25%). An occupation requiring frequent exposure to allergens plays an important role in the triggering or aggravation of the disease. Proportions of occupations in our research were as follow: of all subjects, 35.16% were office workers, 21.87% were students, 21.09% were farmers, 14.06% were freelancers, and 7.81% were workers. Georaphy is also one of the significant epidemiological characteristics of AD. AD is more common in urban areas than in the rural ones, particularly common in industrialized zones. In our research, 64.8% of the patients lived in Ho Chi Minh City while only 35.2% lived in other provinces. The atopic factor in AD was evident in the patients having concurrent allergic diseases such as asthma and allergic rhinitis. Figures in our research have shown that of all AD patients, 97.65% had a family history of AD, 49.22% had history of asthma, and 53.13% had history of allergic rhinitis. AD is proved to be have a hereditary component. Recently, scientists have indentified a lot of genes related to AD, which lie on chromosomes: 11q13, 5q31-33, and 16p11.2-11.1. As can be seen from our research figures, our AD patients had family history as follow: 58.59% of them had an ADaffected father, 17.97% had an asthma-affected father, and 25% had a allergic-rhinitis-affected father; the percentages of those who had a mother affected by AD, asthma, and allergic rhinitis were 21.1%, 14.84%, and 9.37% respectively; the percentages for having an affected sibling were 50.60%, 39.76%, and 61.44% respectively; and for having an affected child were 43.28%, 25.37%, and 22.39% respectively. Triggering factors play a crucial role in the pathogenesis of AD. They are diverse and plentiful, usually divided into 3 groups: aeroallergens, contact allergens and food allergens. Our research results have shown that of all AD patients, 55.47% had contact allergens as triggering factor, 28.12% had food allergens as triggering factor, 12.5% had aeroallergens as triggering factor, and 3.91% did not show a clear triggering factor. 4.2 S.aureus and the superantigen-encoding genes of S.aureus in AD patients