中国儿童过敏原检测临床应用专家共识(2021版)

儿童过敏性疾病发病率呈逐年上升趋势,罹患哮喘、过敏性鼻炎和湿疹等过敏性疾病不仅降低了儿童生活质量,而且增加家庭与社会的经济负担。过敏原检测可以明确致敏变应原,为个体化管理过敏性疾病提供依据。常用的过敏原检测方法包括过敏原皮肤点刺试验和血清特异性IgE检测。不同过敏原检测方法的适应证及其结果判断在儿科临床亟待规范。本共识以儿童过敏原检测相关的临床常见问题为导向,查阅相关文献,经多学科临床专家通过德尔菲投票方法达成共识,形成10个临床问题的推荐建议。     

温州地区儿童血清特异性过敏原检测的临床意义

目的了解温州地区不同年龄组儿童哮喘及过敏性疾病的过敏原状况,以指导临床防治。方法采用体外过敏原检测系统(法玛西亚CAP系统)对我院呼吸科门诊及住院患儿468例进行过敏原特异性IgE(sIgE)抗体检测,将所有受检儿童分为婴幼儿、学龄前、学龄期3组,对过敏原状况进行分析比较。结果哮喘发病主要集中于学龄前和婴幼儿期,过敏性鼻炎主要发生于学龄儿童;各种过敏性疾病中过敏性鼻炎sIgE阳性检出率最高,其次是哮喘和过敏性咳嗽;婴幼儿以食物过敏为主,较大年龄儿童以吸入性过敏为主,学龄前儿童两者均可发生;温州地区吸入性过敏原以尘螨为主,食入性以虾为主;在螨sIgE阳性者中哮喘比率最高,其次是过敏性鼻炎和过敏性咳嗽。结论螨及虾是温州地区儿童最常见过敏原。哮喘应在婴幼儿及学龄前期及早进行针对性防治,体外血清过敏原特异性抗体检测CAP系统是婴幼儿及学龄前儿童过敏原检测的方法之一。     

Local allergic rhinitis: A critical reappraisal from a paediatric perspective

The so‐called local allergic rhinitis (LAR) has been proposed as a phenotype of rhinitis with Th2‐driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of ‘systemic’ atopy (negative skin prick test and serum allergen‐specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this ‘Rostrum’ was to critically discuss data and implications of the ‘LAR concept’ in paediatrics. In the natural history of rhinitis due to IgE‐mediated reactions triggered by exposure to allergens, a ‘LAR’ can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to ‘systemic’ IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term ‘local allergic rhinitis’ may be inappropriate, as rhinitis is always ‘local’, while IgE sensitization can be either ‘local’ or ‘systemic’.     

Paediatric allergy diagnosis in primary care is improved by in vitro allergen-specific IgE testing

Allergy testing is an important pre‐requisite for both early identification of infants at increased risk for later development of allergic diseases and for specific allergy treatment including specific allergen avoidance measures, pharmacotherapy and specific immunotherapy. The aim of this study was to investigate the influence of in vitro allergen‐specific immunoglobulin E (IgE) testing on the primary care physician’s diagnosis and clinical management of children with symptoms of eczema, wheezing/asthma and rhinitis. The trial was a prospective study performed at 14 paediatric primary care practices in Germany, covering 380 children below 6 yr of age. For one group of children the physician received the IgE test results as soon as possible and used them as an additional tool when diagnosing and giving clinical management advice. For the other group of children the IgE test results were not made available to the physician until the children were brought to a second visit, about 7 wk later. When diagnosis was made without access to allergen‐specific IgE results, 8% of the children were diagnosed as allergic, 6% as non‐allergic and in 86% of the cases the physician was uncertain. With access to allergen‐specific IgE results the figures were 13%, 65% and 22%, respectively. Concerning clinical management advice no statistically significant differences between the two study groups were observed. When comparing the first and second visits of the patients coming for a second visit advice to reduce aeroallergen exposure was given to 27% of the patients at visit 1 and to 36% of the patients at visit 2 (p = 0.002). The difference between the first and second visits of the other clinical management advice studied did not reach statistical significance. In this study the availability of IgE test results to the primary care physician had an impact on the decision‐making process of the diagnosis but not on the pharmaceutical or avoidance advice given. The reason why IgE test results were not fully exploited needs to be further scrutinized.     

Practical aspects of allergy-testing

Allergy-testing is a prerequisite for specific allergy treatment, including specific allergen avoidance measures, relevant pharmacotherapy and specific allergy vaccination. All children with persisting, recurrent or severe possible "allergic symptoms" or those with a need for continuous treatment should be tested, irrespective of the child's age. Allergy-testing includes a careful case history and a determination of IgE sensitisation by skin prick test or the measurement of allergen-specific IgE in serum by standardised and validated methods. The diagnosis of food allergy cannot usually be based solely on the case history and IgE sensitisation; the diagnosis has to be confirmed by controlled food elimination and food challenge procedures. The diagnosis of inhalant allergic disease requires only confirmatory nasal, conjunctival or bronchial challenges in equivocal cases or before specific allergy treatment such as extensive allergen avoidance measures or allergy vaccination.     

Analysis of basophil activation by flow cytometry in pediatric house dust mite allergy

Detection of allergen‐induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. The aim of this study was to assess the potential of this technique for the diagnosis of pediatric house dust mite allergy. Quantification of total and specific IgE and basophil activation test were performed to evaluate mite allergic (n = 24), atopic (n = 23), and non‐allergic children (n = 9). Allergen‐induced basophil activation was detected as a CD63‐upregulation. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut‐off value of activated basophils discriminating mite allergic and non‐allergic children. ROC curve analysis yielded a threshold value of 18% activated basophils when mite‐sensitized and atopic children were studied [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.97–1.01, p < 0.001] with a sensitivity and specificity of 96% for 16 μg/ml mite extract. Analysis of the data obtained with 1.6 μg/ml mite extract defined a cut‐off value of 8% activated basophils (AUC = 0.96, 95% CI = 0.91–1.01; p < 0.001) with a sensitivity of 82% and specificity of 100%. Comparison between mite allergic and non‐allergic children produced a cut‐off of 8% activated basophils (AUC = 1.0) with 16 μg/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 μg/ml extract (AUC = 97%, 95% CI = 0.92–1.02; p < 0.001) but sensitivity decreased to 83%. Two atopic children showed negative skin prick and basophil activation tests and high specific IgE (>43 kU/l) values for Dermatophagoides pteronyssinus allergen. They also showed positive prick (wheal diameter >1.0 cm) and basophil activation (>87%) tests and high specific IgE (>100 kU/l) with shrimp allergen. Shrimp sensitization was demonstrated by high levels of Pen a 1‐specific IgE (>100 kU/l). Cross‐reactivity between mite and shrimp was confirmed by fluorescence enzyme immunoassay (FEIA‐CAP) inhibition study in these two cases. This study demonstrated that the analysis of allergen‐induced CD63 upregulation by flow cytometry is a reliable tool for diagnosis of mite allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity. Furthermore, this method can provide additional information in case of disagreement between in vivo and in vitro test results.     

变态反应性疾病患儿血清特异性IgE检测的临床意义

目的　探讨血清特异性IgE(sIgE)与儿童变态反应病发病的关系 ,为临床防治提供依据。 方法　采用法玛西亚公司的免疫CAP诊断系统 ,以荧光酶联免疫法测定sIgE。 结果　 71例患儿中可查到 5 4例 4 8种变应原阳性的sIgE ,有些患儿对多种变应原呈阳性反应。支气管哮喘患儿阳性检出率为 74 % (37∶5 0 ) ;变应性鼻炎患儿阳性检出率为 6 4 % (7∶11) ;特应性皮炎及湿疹患儿阳性检出率为 80 % (8∶10 )。主要阳性变应原为户尘螨、屋尘、蒿草、烟曲霉等吸入性变应原和鸡蛋白、牛奶、花生、黄豆等食物性变应原。年幼儿组 (3～ 6岁 )以食物性变应原为主 ;年长儿组 (7～ 15岁 )以吸入性变应原为主。对上述 8种变应原的sIgE两组之间定量比较 ,经秩和检验发现吸入性变应原蒿草的sIgE在组间有明显差异 ,年长儿组高于年幼儿组 (P <0 0 5 ) ;食物性变应原牛奶的sIgE在组间有明显差异 ,年幼儿组高于年长儿组 (P <0 0 5 )。结论　上述 8种变应原是引起太原地区儿童变态反应病的主要变应原 ,随年龄增长血清中吸入性变应原的sIgE的阳性率增多 ,食物性变应原的sIgE的阳性率减少 ;sIgE对外源性变态反应病阳性检出率高。     

Hyposensibilisierungstherapie bei allergischen Erkrankungen unter besonderer Berücksichtigung des atopischen Ekzems

According to modern concepts allergen immunotherapy influences the capacity of allergen specific T cells to react to allergen presentation. Subcutaneous immunotherapy with allergen extracts has been shown to be superior to placebo in the treatment of allergic rhinoconjunctivitis and allergic asthma. Because the treatment does not interfere with other antiinflammatory and symptomatic treatments of asthma and rhinoconjunctivitis it is an additional treatment option in children aged 5 years and older in whom allergen exposure is an important determinant of the course of the disease. As yet, there is no sufficient data to recommend allergen immunotherapy in the treatment of atopic eczema. However, allergen immunotherapy for rhinoconjunctivitis or asthma is not contraindicated if atopic eczema is present. If allergy to hymenoptera venom leads to life-threatening symptoms, specific immunotherapy is indicated absolutely even in children below the age of 5 years     

具有喘息症状或过敏性疾病的年幼儿皮肤点刺试验结果分析

目的：通过分析0~5岁儿童变应原皮肤点刺试验结果,了解具有喘息症状的可疑哮喘及过敏性疾病症状的患儿对吸入变应原过敏反应的特点,为儿童哮喘及过敏性疾病的早期诊断提供依据。方法：选择2010年9月1日至12月31日长沙市某社区0~5岁具有喘息症状或过敏性疾病症状的患儿共102例为变应原筛查组;对照组选择同年龄组无喘息及过敏性疾病史的儿童94例。两组均进行变应原皮肤点刺试验。结果：变应原筛查组皮肤点刺试验阳性率61.8%（63/102）明显高于对照组的9.6%（9/94）,差异有统计学意义（P<0.05）;反复喘息合并过敏性鼻炎者的皮肤点刺试验阳性率明显高于单纯喘息组（P<0.05）;喘息次数与皮肤点刺试验阳性率呈正相关（r=0.91,P<0.05）;对螨虫的皮肤点刺试验阳性率（24.2%）明显高于其他过敏原（3.5%）,差异有统计学意义（P<0.05）;粉尘螨的皮肤点刺阳性率（50.0%）明显高于屋尘螨（14.7%）,差异有统计学意义（P<0.05）。结论：早期儿童喘息可能是发生过敏性哮喘的重要因素;变应原皮肤点刺试验是诊断过敏性疾病的重要依据,并有助于评估喘息患儿对吸入性变应原的过敏反应特点。     

标准化屋尘螨变应原特异性免疫治疗对儿童变应性鼻炎合并哮喘的临床疗效

目的 评估标准化屋尘螨变应原特异性免疫治疗(specific immunotherapy,SIT)对儿童变应性鼻炎合并哮喘的临床疗效.方法 选择我院42例接受标准化屋尘螨SIT的变应性鼻炎合并哮喘儿童为研究对象.所有患儿治疗前、治疗1年后均进行变应原皮肤点刺试验、测定血清屋尘螨和粉尘螨特异性IgE水平、进行肺功能测定和自觉症状评分.结果 治疗1年后屋尘螨和粉尘螨的皮肤指数和自觉症状评分均较治疗前显著降低(P＜0.01,P＜0.05),而治疗前后屋尘螨和粉尘螨特异性IgE水平、肺功能(肺活量、第1秒用力呼气量、最大呼气中段流量)均无明显变化(P＞0.05).结论 变应性鼻炎合并哮喘儿童给予SIT1年后其皮肤敏感性显著改善,临床症状明显好转,但对气道炎症的影响有待于进一步的观察.     

Atopy patch testing in children with asthma and rhinitis symptoms allergic to house dust mite

The atopy patch test (APT) is generally used to assess immunoglobulin E (IgE) mediated sensitization to allergens in patients with atopic dermatitis, but its diagnostic role in children with respiratory allergy is still controversial. The aim of the study was to evaluate APT with house dust mite (HDM) in children with asthma and rhinitis symptoms allergic to HDM and its relevance to skin prick test (SPT) diameters and specific IgE levels. The study population consisted of 33 children, aged 8-16 yr (median: 12 yr) with asthma and 30 children with allergic rhinitis in the same age range (median: 11 yr). All patients had positive SPT results and high serum specific IgE levels for Dermatophagoides pteronyssinus APT was performed on back skin of all patients with 200 index of reactivity (IR)/ml of D. pteronyssinus allergen extracts in petrolatum (Stallerpatch) and evaluated at 72 h. Of 63 patients, 16 (25%) showed a positive patch test result. APT with HDM showed 30% (10/33) positivity among the patients with asthma and 20% (6/30) positivity among the patients with allergic rhinitis. APT presented no significant correlation with age, SPT diameter, serum total and specific IgE levels for D. pteronyssinus, nasal provocation test or pulmonary function test results. Patch testing with HDM may partly identify mite sensitive children with respiratory allergy. Positive APT results may imply that delayed hypersensitivity reactions play a role in children with asthma and rhinitis allergic to HDM.     

Marche allergique chez l’enfant,de la rhinite à l’asthme : prise en charge,place de la désensibilisation

Allergic rhinitis (AR) is a common IgE dependent disorder. AR is maybe one of the steps of the allergic march, which starts with atopic dermatitis and food allergy and includes atopic asthma. AR and asthma are frequently associated. AR is frequently under-diagnosed and undertreated although it affects quality of life and school performance. Management of AR depends on its severity and will associate environmental control (best guided by environmental investigation and skin testing of specific IgE antibodies), pharmacotherapy (with antihistamines and intranasal corticosteroids as first line drugs). At present allergen immunotherapy is considered in patients with severe AR, insufficiently controlled by pharmacotherapy and who demonstrate specific IgE antibodies to relevant allergens. Sublingual immunotherapy is well tolerated. Only immunotherapy with the right allergens has the potential to alter the natural history of the allergic march, by preventing the development of new allergen sensitizations and reducing the risk for the subsequent development of asthma. This fact might extend the indications of specific allergen immunotherapy. Patients (and parents) education is of utmost importance in the management of allergic disorders.     

Immunological Aspects of Asthma (Prophylaxis)

A long follow-up study revealed that convalescent stage children still have the potency to have an immediate type hypersensitivity reaction on exposure to mite antigen, with a high titer of mite specific IgE in their sera, but they are free from asthmatic attacks because of the reduction in the amount of mite antigen in the body, as shown by the reduction in the amount of mite specific IgG. We also made a prospective study to see whether early elimination of the allergen has any beneficial effect on the cessation of the development of allergic diathesis thereafter. Our study suggested that early elimination of food allergen in infancy not only improved clinical manifestations but also had a protective effect on the progression of the allergic march so far as production of reaginic antibodies was concerned: production of total IgE and mite specific IgE was kept to a minimum.     

Cockroach allergy in a group of Turkish children with respiratory allergies

Exposure to cockroach may lead to exacerbations of bronchial asthma and/or allergic rhinitis in sensitized patients. Although there is a widespread belief that cockroach allergy is a common problem in patients with respiratory allergies, little is known in Turkish children. In order to investigate the prevalence and characteristics of cockroach allergy in respiratory allergic children, we performed a study in newly referred children with respiratory allergies. All patients underwent questionnaire-interview and skin prick tested with common inhalant allergens in addition to two cockroach allergens: Blatella germanica (Bg) and Periplaneta americana (Pa). A subgroup of patients was also serologically investigated for specific IgE against Bg and house dust mite. Three hundred- and thirty-seven children aged 2-16 years were recruited for the study and 77.7% of these were atopic, with the most common indoor and outdoor allergens of house dust mite (47.5%) and grass pollens (45.1%), respectively. According to the prick test results, allergies to Bg and Pa were 11.9% and 7.4%, respectively, and there was a weak correlation between size of the prick test and specific IgE levels for Bg allergen. Almost 30% of the cockroach-sensitive patients were allergic to both cockroach antigens. Seventy percent of cockroach-sensitive patients were also sensitive to house dust mite, and only 1% were monosensitive. Dwellings in the Middle Anatolia and Black Sea regions were less commonly infested by cockroach compared to the dwellings in other regions. In conclusion, our preliminary study showed that cockroach sensitization is common among children with respiratory allergies irrespective of infestation history, suggesting that addition of cockroach allergen to the routine allergy screening panel is critical.     

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目的比较3~14岁哮喘和变应性鼻炎患儿吸入性致敏原分布特征的异同。方法2004-10—2005-10,北京儿童医院对527例哮喘和620例变应性鼻炎患儿进行吸入性致敏原皮肤点刺试验(skin prick test,SPT),分析比较检出阳性的致敏原在两组病例中的分布特征。结果哮喘和变应性鼻炎患儿SPT阳性检出率分别为77·8%和78·9%(χ2=0·823,P>0·05)。户尘螨、粉尘螨、交链孢霉、猫上皮、艾蒿是两种疾病主要致敏原。哮喘患儿户尘螨、粉尘螨、混合霉菌的阳性率分别为64·6%、59·8%、8·8%,均高于变应性鼻炎患儿(49·5%、47·9%、3·9%,均P<0·05)。变应性鼻炎患儿杂草花粉和艾蒿的阳性率分别为25·6%、26·0%,均高于哮喘患儿(19·3%、19·3%,均P<0·05)。40·2%的哮喘和46·2%的变应性鼻炎为单致敏原阳性。尘螨霉菌混合致敏及尘螨宠物混合致敏在哮喘和变应性鼻炎中最为常见。结论尘螨、霉菌、夏秋季花粉和宠物是3~14岁哮喘和变应性鼻炎患儿主要吸入性致敏原,两病具有相似的致敏原分布特征,但尘螨及霉菌过敏多见于哮喘,夏秋季花粉过敏多见于变应性鼻炎。     

Allergenspezifische Immuntherapie/Hyposensibilisierung

Immunologic desensitization

Hyposensitization/allergen-specific immunotherapy represents the only disease-modifying treatment of IgE-mediated allergic disorders. According to test results relevant allergens are administered in increasing doses by subcutaneous or sublingual route. The most promising results in allergen immunotherapy are obtained in subcutaneous hyposensitization in insect venom allergy, allergic rhinoconjunctivitis and mild persistent bronchial asthma.

Possible adverse effects and their treatment

To prevent adverse effects of allergen-specific immunotherapy it is important to identify patient-related risk factors having a negative impact on the tolerance to treatment; these risk factors include acute infectious diseases, current allergic symptoms and individually excessive dose of allergen. Monitoring the patient by trained personnel during the first 30 min after subcutaneous allergen administration is mandatory. Systemic allergic reactions are treated immediately according to the prevailing symptoms, including prompt administration of epinephrine for anaphylaxis.

Conclusion

Hyposensitization treatment provided by allergy-experienced medical staff is a safe and sustainable therapy.     

Associations between cat keeping, allergen exposure, allergic sensitization and atopic diseases: Results from the Children of Lübeck Allergy and Environment Study (KLAUS)

The role of cat keeping on the promotion of allergies is discussed controversially. We investigated the associations between cat keeping, allergen exposure, allergic sensitization and atopic diseases in pre-school children. A total of 606 children (5- to 6-yr old) were studied in the course of the mandatory school entrance examination. Information on doctor diagnosed asthma and allergic rhinitis, pet keeping and confounders was obtained by questionnaire. The prevalence of atopic eczema was determined by dermatological examination, allergic sensitization was assessed by skin prick test, and the allergen exposure to cat allergen Fel d 1 was measured by a commercial wipe test. Cats were present in 16% of the households and results of the exposure categories (0–III) on cat allergen were 47.2%, 25.5%, 24.3% and 3.0% respectively. The prevalence of cat keeping increased significantly with exposure categories from 0.5% to 61.5% (p_trend < 0.001). Children (6.3%) were sensitized to cat allergen and sensitization rates increased also significantly with exposure categories from 3.0% to 15.4% (p_trend < 0.001). Children (9.3%) were diagnosed with atopic eczema and a positive history of asthma/rhinitis was given in 3.6% and 3.9% respectively. Sensitization to cat was associated with atopic eczema (23.3% vs. 7.4%; OR_adj.= 3.8, CI: 1.4–10.8), asthma (12.5% vs. 3.7%; OR_adj.= 4.9, CI: 1.1–21.2), allergic rhinitis (6.9% vs. 2.7%; OR_adj.= 3.1, CI: 0.7–15.2) and any atopic disease (43.5% vs. 16.3%; OR_adj.= 3.8, CI: 1.5–9.5). The data suggest a promoting effect of cat keeping for atopic diseases.     

Urinary N-methylhistamine excretion. Following exogenous histamine administration and allergy/exercise-induced bronchoconstriction]

Histamine is partly metabolized to a stabile metabolite N-methyl-histamine and excreted in the urine. We analysed the degradation of infused histamine and the N-methyl-histamine-excretion in atopic and normal individuals as in patients with a bronchoconstriction due to allergen/exercise challenge. N-methyl-histamine was determined by a newly developed radioimmunoassay. 60 controls and 38 atopic individuals were investigated. There is a proportional increase of N-methyl-histamine in the urine in young children. However, no significant difference between allergic and non-allergic individuals was found. After parenteral administration of a standardized amount of histamine 12% of the applied amount was secreted in the urine as N-methylhistamine. The most significant increase of N-methylhistamine-excretion was observed in the first hour after application. Only an 0.1% rise of N-methyl-histamine was observed following an oral administration of histamine. Neither bronchial challenge with specific allergen nor physical exercise elicited significant changes of N-methylhistamine excretion. The secretion of N-methyl-histamine demonstrates the degradation of histamine in the circulation, the measurement oft this metabolite in the urine should be considered when analysing the cause of severe systemic allergic reaction as anaphylaxis but not asthma or atopic disposition.     

Food-dependent exercise-induced anaphylaxis in childhood

The clinical syndrome of food-dependent exercise-induced anaphylaxis (FDEIA) is typified by the onset of anaphylaxis during (or soon after) exercise which was preceded by the ingestion of the causal food allergen/s. In FDEIA, both the food allergen/s and exercise are independently tolerated. FDEIA is an uncommon allergic condition in childhood, but nonetheless is an important differential diagnosis to be considered when faced by a child who has experienced exercise-associated anaphylaxis. The diagnosis of FDEIA is heavily dependent on the clinical history. Allergy tests may need to be performed to a broad panel of food and food additives. Modified exercise challenges (performed with and without prior ingestion of food) are frequently required as allergy test results frequently return low-positive results. A diagnosis of FDEIA facilitates the safe independent return to exercise and reintroduction of foods for patients who otherwise may unnecessarily avoid exercise and/or restrict their diet. The natural history of FDEIA is unknown; however, a safe return is usually achieved when the ingestion of the causal food allergen/s and exercise are separated.     

Gastrointestinal allergy

One of the more frequent problems in medicine is the question of a possible association between ingestion of a particular food or drug, and symptoms experienced by a patient. Food allergens are mainly cow's milk, egg, fish, nuts and fruits. Ingested antigen/allergen may induce antibody production and thus sensitization. But the presence of specific antibodies or a positive skin test are not synonymous with allergic symptoms. The convincing diagnostic procedure in adverse reactions to foods or drugs is a controlled exposition. The thrombocytopenia test is a useful addition. Intestinal biopsy is helpful in excluding celiac disease. Younger children are more likely to lose food sensitivity than older ones. At present, the optimal therapy of food sensitivity is to avoid the offending food or drug.