五、食品敏感性

Food Sensitivities, Allergic Reactions, and Food Intolerances食品敏感性、过敏性反应和食品不耐性,CONTENTS 主要内容,DEFINITION AND MECHANISMS OF ADVERSE FOOD REACTION第一节 食品不良反应的定义和机理SYMPTOMS OF ADVERSE FOOD REACTIONS第二节 食品不良反应的症状DIAGNOSIS OF ADVERSE FOOD REACTIONS第三节 食品不良反应的诊断法,PREVALENCE第四节 发病率FOOD ALLERGENS第五节 食品过敏原FOOD ADDITIVES第六节 食品添加剂FOOD LABELING IN RELATION TO FOOD SENSITIVITIES 第七节 与食品过敏性有关的食品标签,DEFINITION AND MECHANISMS OF ADVERSE FOOD REACTION第一节 食品不良反应的定义和机理,Fig.1 Classification of foods proposed by EAACI图1 EAACI对食品的分级,toxic food reactions 食品毒性反应,A classical toxic food reaction is scombroid fish poisoning, due to large amounts of histamine 鲭亚目鱼组胺中毒是典型的食品毒性反应。,Food intolerance 食品不耐性,enzymatic (resulting from an enzymatic defect, e.g., lactase deficiency), “ 酶促性的”（因酶缺陷造成，如乳糖酶缺乏症） pharmacological (depending on the direct effect of, e.g., vaso-active amines naturally found in foods) “药理学的”（取决于直接效应，如食品中天然存在的血管活性胺）“Undefined不明确的”,SYMPTOMS OF ADVERSE FOOD REACTIONS第二节 食品不良反应的症状,IgE-Mediated Food Allergy一、以IgE-为媒介的食品敏感症,Characteristic 特征,Clinical manifestations of IgE-mediated food allergy can remain localized at the site of the primary direct contact, i.e., 一直保持在最初的直接接触部位 the mouth 嘴throat (oral allergy syndrome)咽喉（口腔敏感综合症）the gastroiniesrinal tract (isolated gastrointestinal food allergy)胃肠道（单独的胃肠道食品敏感症）,Skin Respiratory tract GI tract Cardievascular S.皮肤 呼吸道 胃肠道 心脏血管系统45% 25% 20% 10%,Figure 2 Classical symptoms of IgE-mediated food ailergy图2 以IgE为媒介的食品敏感综合症分布,Oral Allergy Syndrome （一）口腔敏感综合病症,Allergen: fresh foods( fruits and vegetables) 过敏原：新鲜食品（如水果和蔬菜）,Symptom 症状：Itching of the lips, mouth, palate， throat 嘴唇、嘴、上腭咽喉等处立即发痒Hoarseness and/or swelling of the lips, tongue, uvula, and larynx 嗓音嘶哑，嘴唇、舌头、小舌、喉等肿胀,Allergic Reactions After Ingestion of Food （二）摄入食品后的过敏反应,Symptom 症状：1）The main symptoms of gastrointestinal food allergy are vomiting, nausea, diarrhea, and abdominal pains (colics or cramps).胃肠道主要症状:呕吐、反胃、腹泻以及腹部疼痛（绞痛或痛性痉挛）；,2) Skin reactions include local or generalized pruritus, flush, urticaria, angioedema. morbilliform exanthema, and flare-up of atopic dermatitis 皮肤反应：局部的或无显著特点的搔痒症、面部潮红、风疹、血管性水肿、麻疹样疹病、突发特异性皮炎；,3) The symptoms of the upper and the lower respiratory tract are rhinitis (sneezing, pruritus of the nose, nasal stuffiness, and nasal obstruction), larynx edema, cough, wheezing, and bronchial asthma. 上呼吸道或稍低些的呼吸道症状： 鼻炎（打喷嚏、鼻搔痒症、鼻子不通气、鼻塞）、喉肿、咳嗽、喘息以及支气管哮喘；,4) Itching, redness, and watering eyes (conjunctivitis) 发痒、充血以及眼睛流泪（结膜炎）.,Allergic Reactions After Inhalation of Food （三）吸入食品后的过敏反应,Symptom 症状：respiratory symptoms 呼吸道综合症,Allergen: flour, n-amylase, green coffee, castor and soy beans, spices. egg white, and crustaceans 过敏原：面粉、-淀粉酶、绿咖啡、海狸香和大豆、调味品、鸡蛋白以及甲壳动物,Allergic Reactions Following Skin Contact With Food（四）皮肤接触食品后的过敏反应,Allergen: fish, shrimp, flour, and pork 过敏原：鱼、小虾、面粉和猪肉,Symptom 症状： Urticarial lesion 风疹Chronic contact with a food may induce protein contact, dermatitis in food handlers 食品操作工人长期接触某种食品会诱导蛋白接触性皮炎。,Non-lgE-Mediated Immune Reactions二、不以IgE为媒介的免疫反应,Heiners Syndrome, Allergic Alveolitis, and Hemorrhagic Gastroenteritis in Childhood（一）儿童Heiner综合症、过敏性齿槽炎、出血性肠胃炎,DEFINITION：The term Heiners syndrome characterizes a milk-induced syndrome with pulmonary disease in infants. Heiner综合症：婴儿因牛奶诱导的肺病,Symptom 症状：chronic or recurrent pulmonary intiltrates 慢性或周期性发生的肺渗透allergic alveolitis 过敏性齿槽炎a chronic rhinitis 慢性鼻炎gastrointestinal blood loss 肠胃失血症iron deficiency anemia 缺铁性贫血chronic cough 慢性咳嗽recurrent fever 周期性发烧Anorexia 厌食Vomiting 呕吐Colic 绞痛Diarrhea 腹泻Hemoptysis 咳血,Control 控制措施：institution of a milk-free diet饮食中去除牛奶,Gluten-Sensitive Enteropathy (Celiac Disease)（二）谷蛋白敏感性肠病（乳糜泻）,Definition：damage to the small intestinal mucosa and symptoms of malabsorption定义：小肠黏膜损伤和吸收不良症状小肠黏膜损伤和吸收不良症状,Allergen 过敏原：Gliadin 麦醇溶蛋白present in wheat, rye, barley, and oat 广泛存在于小麦、燕麦、大麦和黑麦中,The peak incidence of symptoms is in infancy after the introduction of cereals; 婴儿开始添加谷物类食物时最容易发生这类症状，为第一高峰期；A second peak occurs during the third decade. 第二高峰期发生在三十岁。,Symptom 症状：abdominal pain周期性腹部疼痛loose stools便溏anorexia厌食short stature体态短小delayed puberty青春期滞缓nutritional deficiencies吸收不良Dental enamel hypoplasia 牙科瓷发育不全recurrent aphthae周期性口疮,Control 控制措施：Patients with celiac disease must avoid gliadins and related proteins permanently远离麦醇溶蛋白以及相关蛋白质,Dermatitis Herpetiformis （三）疱疹样皮炎,Definition 定义： chronic blistering disease 一种慢性起疱疾病,Symptom 症状：itchy 发痒sometimes burning 有时有灼伤感eruption of grouped vesicles on an erythematous ground 在红斑状范围内出现成群泡样出疹,Some DH patients, even without gastrointestinal symptoms, may have villous atrophy similar to that seen in celiac disease有些DH病人甚至在没有出现胃肠道综合症的情况下，也会出现与乳糜泻类似的绒毛状萎缩症，也就是说DH与CD之间有关连。The cutaneous manifestations may or may not respond to a gluten-free diet饮食中排除麦醇溶蛋白可能会、也有可能不会改善皮肤症状。,Eosinophilic Gastroenteritis （四）嗜酸性胃肠炎,Definition 定义：elevated eosinophil counts in blood and tissue eosinophilia with release of eosinophii major basic protein 释放嗜曙红细胞主要基本蛋白质后，血液中嗜曙红细胞和嗜曙红血球增多的间质组织内嗜曙红细胞计数值升高,Clinical manifestations 临床症状： vomiting 呕吐abdominal pain 腹部疼痛Diarrhea 腹泻 malabsorption 吸收不良bowel obstruction 肠阻塞Ascites 腹水,The cause of EG is unknown 起因还不清楚food hypersensitivity has been suggested EG可能由食品超敏性引起,Utcerative Colitis （五）溃疡性结肠炎,Definition 定义： an inflammatory bowel disease of unknown origin 一种不明起因的炎症性肠病,No adverse food reactions have been shown as causative of UC 还不能证明食品不良反应会造成UC,Allergic Vasculitis（六）变应性脉管炎,Cause 起因：foods and food additives 食品及其添加剂,Symptom 症状：allergic purpura (widespread hemorrhagic macules and papules, mainly on the lower legs) demonstrated by single challenges变应性紫癜（分布广泛的出血性斑丘疹，主要出现在腿的下部）,Food Intolerance三、食品不耐性,Lactase Deficiency乳糖酶缺乏综合征,Definition 定义：Lack of the enzyme that cleaves milk sugar, lactose, gives rise to adverse reactions when lactose is consumed.当摄入乳糖时，由于体内缺乏一种能将牛奶糖质-乳糖水解的酶，从而产生不良反应,The only food of which lactose is a natural constituent is milk (3.7 g/100 ml cows milk). 天然含乳糖的唯一食品是牛奶（3.7g/ml牛奶）,Classification 分类：1） congenital lactase deficiency先天性乳糖酶缺乏综合征2） primary lactase deficiency初级的乳糖酶缺乏综合征3） secondary lactase deficiency二级乳糖酶缺乏综合征,1） congenital lactase deficiency先天性乳糖酶缺乏综合征lactase is not present and symptoms will appear when the patient is breast-fed. 人体内不存在乳糖酶，当进行人乳哺育时会出现综合征The congenital form is very rare 这种症状极少见,2） primary lactase deficiency初级的乳糖酶缺乏综合征seen in most of the worlds population where the production of lactase decreases or disappears from the age of 2 to the teenage years在2-10岁时，乳糖酶分泌下降或消失,Persistent high lactase activity in adult life occurs among relatively few ethnic groups:成年人体内乳糖酶活性一直处于高峰的人群： northern Europeans and their overseas descendants北欧以及沿海后代a few African groups of pastoral tradition Bedouins and other Saudi Arabs一些源于牧人的非洲人、贝都因人和沙特阿拉伯人 certain groups from west India and Pakistan西印度和巴基斯坦部分人群,3） secondary lactase deficiency二级乳糖酶缺乏综合征a consequence of pathological changes in the gut mucosa, as seen in celiac disease or inflammations. 乳糜泻或炎症引起内脏黏膜病变的结果 When the gut mucosa has regained its normal appearance the lactase production reappears 当内脏黏膜恢复正常，乳糖酶也开始重新分泌。,The symptoms 症状：Diarrhea 腹泻gas production 产气Colic 绞痛,Control 控制措施：avoid all products containing even small amounts of lactose 避免食用任何含乳糖的食品,PREVALENCE第四节 发病率,The total prevalence of food allergy/food intolerance is not known. 总发病率未知Estimates based on data from one country do not necessarily reflect the prevalence of another country 在某个国家统计得到的数据并不能用到另一个国家，因为：1） frequency and duration of breast feeding 母乳喂养的频率和持续时间2）eating habits饮食习惯3） flora植物群,Children一、儿童,Food（一）食品,allergy to cows milk, egg, and fish predominantly begins before the second year of age 对牛奶、鸡蛋和鱼的过敏性主要发生2岁以前allergy to fruit, legumes, and vegetables predominantly begins after the second year. 对水果、豆类和蔬菜的过敏性主要发生在2岁以后,Table 1 Prevalence of Rhinitis and Oral Itch in Danish School Children 丹麦学龄儿童中鼻炎和口腔发痒的发病率 Age (yr) Rhinitis (%) Oral itch（%) boys/girls boys/girls 5-7 9.0/5.7 0/0.38-10 8.5/7.1 0.8/1.111-13 14.0/8-5 1.9/1.514-16 17.3/13.0 2.9/2.0,Food Additives （二）食品添加剂,Adverse reactions to food additives are found in 1-2% of school children 1-2%学龄儿童对食品添加剂有不良反应The prevalence in younger children is not known. 至今不知小年龄儿童的发病率,Adults二、成年人,Food （一）食品,In European studies the majority of allergic food reactions in adults are caused by fruits. vegetables, and nuts and are related to pollen allergy 在欧洲，大部分成年人食品过敏性反应是由水果、蔬菜和坚果引起的，且与花粉过敏症有关The prevalence is around 5% 发病率在5%左右,probably only 0,5% have symptoms other than oral itch. 大约只有0.5%不是口腔发痒症状The prevalence of allergy to milk, egg, fish. etc. is around 0.2%，牛奶、鸡蛋、鱼等引起的过敏症发病率大约为0.2%,Food Additives （二）食品添加剂,The estimated frequency was 0.03-0.15% 1982年EEC理论计算值：食品添加剂引起的发病率为0.03-0.15%,In British ：theprevalence 大不列颠人 ：发病率为0.026% Dutch 丹麦 ：0.4%,Contact Allergens （三）接触性过敏原,10 % Danish women have contact allergy caused by nickel. 10%丹麦妇女因镍造成接触性过敏症Up to 10% of these may benefit from a nickel-restricted diet 其中10%以上会因排除镍的饮食而改善,What is contact allergens？In dermally sensitized subjects ingestion of the contact allergen may cause skin flare reactions or other symptoms, e.g., in the gastroinlestinal tract 皮肤敏感症受检者摄入接触性过敏原后会导致皮肤潮间带反应或胃肠道症状等其他症状。,Contact Allergens：fragrances 芳香物质food flavors（natural or synthetic）食品风味物Nickel 镍,Other Adverse Reactions （四）其它不良反应,1）Celiac disease腹部疾病：Cause：wheat gliadin and related proteins起因：小麦麦醇溶蛋白和相关蛋白质The prevalence ： 0.2-0.5%发病率：0.2-0.5%,2） lactase deficiency 乳糖酶缺乏综合征Cause：Lack of lactase起因：缺乏乳糖酶 The prevalence ： varies from a few percent in northern European countries to almost the entire adult population in Asia and Africa 发病率：从北欧国家到亚洲和非洲国家，成年人发病率相差好几个百分点,Conclusion：It is not known whether the prevalence of food allergy or intolerance is increasing 不清楚食品过敏/不耐性的发病率是否有上升趋势 The prevalence of pollen-related food allergies has increased. 与花粉相关食品敏感症的发病率在提高。,FOOD ALLERGENS第五节 食品过敏原,Definition 定义,Allergens are antigens that give rise to allergy . 过敏原是能引起敏感的抗原,Where is food allergens from？,Pollen花粉Mammals哺乳动物 mites螨other insects其他昆虫 foods食品,Component：过敏原成分： Proteins or glycoproteins with a molecular weight from 3 to 90 kDa, the majority ranging from 10 to 40 kDa 已知结构的过敏原都是蛋白质或糖蛋白，分子量从3kDa到90kDa，大部分在10kDa到40kDa之间,The identified allergens：,the first three letters of the genus, space, the first letter of the species, space, and an Arabic number. XXX X X 属 种 阿拉伯数字For example： Lol p 1 refers to the first pollen allergen identified from Lolium perennc, or rye grass Lol p 1表示第一个花粉过敏原，来自Lolium perenne 或黑麦草,Classification 分类,major： proteins for which 50% or more of the allergic patients studied have specific IgE“主要的”：能使50%或以上被研究病人具有特异性IgE的蛋白质minor“：the remaining allergens are considered minor“次要的”：能使50%以下的被研究病人具有特异性IgE的蛋白质,The Nature of Food Allergens一、过敏原的种类,To make a complete list of allergenic foods on a global basis is virtually impossible. 我们不可能列出一张食品过敏原清单Whether a food allergen causes significant problems in a population is dependent on several factors：某种食品过敏原是否会在消费者中引起明显的问题取决于以下几个方面：,（a）the potency of the allergen过敏原的效能,some are much more frequent sensitizers lhan others有些抗体比其他抗体造成敏感症的次数更多，e.g., -lactoglobulin in milk or ovomucoid from egg white如：牛奶中的-乳球蛋白或鸡蛋蛋白中的卵类粘蛋白,（b）the physiochemical properties物化性质：,1）The chemical structure, i.e., the amino acid sequence, and the tertiary structure 化学结构如氨基酸序列，蛋白质三级结构2）heat stability 热稳定性3）digestibility 可消化性4）Structural relationship with epitopes from nonfood allergens 非食品过敏原与抗原决定族之间的结构关系,（c） the frequency of exposure暴露的频率：,In Europe allergy to rice and buckwheat is uncommon.在欧洲，稻米和荞麦一般不引起敏感症In Japan rice and buckwheat are common food allergens 在日本，稻米和荞麦通常是食品过敏原。,(d) the route of exposure 暴露途径,1）aero-allergens：grasses, pollen of trees and herbs ， house dust mites ，o cat dander 飞散过敏原：草、树或药草的花粉、屋尘螨、猫毛发皮屑 2）work environment：baker工作环境：面包工人3）via the skin：Natural rubber (latex) 通过皮肤：天然橡胶,（e） cross-reactions to aero-allergens飞散过敏原的交叉反应,1) local species of grass, trees, and herbs and pollution 当地生长的草、树以及药草种类e.g., Allergy to hazelnuts is common in areas with many birch trees, where birch pollen hay lever is frequent榛实敏感症一般发生在有许多桦树的地区，在这些地区经常发生桦树花粉热2) air pollution空气污染,(f) the age at which the allergen is introduced受过敏原入侵的个体年龄,In early infancy an increased uptake of antigen takes place at a time when the gut-associated lymphoid tissue is still incompletely developed 在幼年早期，在与消化道相关淋巴组织还没有发育好的时候，抗原的摄入量相对较高。,Allergens of Animal Origin二、来源于动物的过敏原,Milk （一）牛奶,1）Albumin, -lactoglobulin, and immunoglobulins of milk are the most important allergens in infants婴儿：清蛋白、-乳球蛋白和免疫球蛋白2） In older children -lactoglobulin, caseins, and I-lactalbumin may be more reactive.大孩子：-乳球蛋白、酪蛋白和-乳白蛋白 3）in adulthood： casein to be the most frequent allergen 成人期：酪蛋白,cross-reactions交叉反应The majority of patients with allergy to cows milk proteins will also react to proteins from sheeps and goats milk 大部分对牛奶蛋白质有敏感症的病人同样对绵羊奶和山羊奶有敏感症 Cross-reactions between milk from these species is not always present.各种奶之间的交叉反应并不一直存在,Eggs（二）鸡蛋,the second most frequent food allergen in small children after cows milk 在小孩子中大概是仅次于牛奶的食品过敏原 Egg white proteins are reported to elicit allergic reactions more frequently than egg yolk. 鸡蛋蛋白比蛋黄更易引起过敏反应,蛋黄中的主要过敏原,cross-reactions交叉反应: allergy to egg can be correlated to allergy to bird feathers 鸡蛋敏感症与鸟类羽毛敏感症之间有相关性 the major cross-reacting determinants are the livetins from egg yolk. 主要交叉反应的决定因素是蛋黄中的卵黄蛋白,Allergens of Plant Origin三、来源于植物的过敏原,The vegetable foods that most commonly cause hypersensitivity symptoms致敏性蔬菜种类,hazelnut 榛实Walnut 胡桃Brazil nut 巴西坚果Apple 苹果Almond 杏仁Peach 桃子Plum 李子Cherry 樱桃,Peanut 花生Peas 豌豆Carrot 胡萝卜parsley 欧芹Celery 芹菜Orange 橘子Strawberry 草莓Cereals 谷物,The ranking lists vary depending on各种蔬菜致敏程度的影响因素,1）the age of the patients 病人的年龄2）the methods of diagnosis 诊断方法以及3）the geographic location of the population 地理环境,Fruits, Nuts, and Vegetables （一）水果、坚果和蔬菜,More than 90% of patients with sensitization to vegetable foods had concomitant sensitization to pollen 90% 以上的蔬菜敏感症总是伴随着花粉敏感症而来,In a group of birch pollen allergies the patients with additional hypersensitivity to nuts and apples had： 在一组同时有另外的坚果和苹果超敏性的桦树花粉敏感症病人中 (1) more severe symptoms during the pollen season 在花粉季节症状严重加重(2) higher values of IgE to birch and hazel pollen, 桦树和榛子花粉的IgE值较高(3) a larger area of the skin prick test reactive to birch and hazel pollen compared to the group without apple and nut allergy 与那些没有坚果和苹果超敏性病人相比，桦树和榛子花粉的皮肤穿刺试验反应区域要大得多。,The symptoms 主要症状：Mainly from the mouth and pharynx, with itching, swelling of the lips, tongue, and throat. syndrome. 从嘴到咽发痒，嘴唇、舌头以及咽喉肿胀These symptoms are called the “oral allergy” “口腔敏感综合症”,cross-reactions交叉反应:1）A sensitization to mugwort pollens and different spices, the so-called mugwort-celery-spices syndrome, has been reported 艾蒿及其不同种艾属植物的花粉有致敏性，又称艾蒿-芹菜-香料综合症。,2） It was shown by prick, RAST studies, and RAST inhibition experiments 皮肤穿刺、RSAT研究以及RSAT抑制实验证明：a celery-thermolabile allergen seems to be involved in celery-birch-pollen-allergic patients 一种不耐热芹菜过敏原会导致芹菜-桦树-花粉敏感症 a thermostable allergen is involved in celery -mug wort-allergic patients. 一种耐热过敏原会导致芹菜-艾蒿敏感症,Pollen-related food allergies are thought to be caused by cross-reactions of pollen-specific IgE antibodies with epitopes of food proteins.花粉特异IgE抗体与食品蛋白质的抗原决定族发生交叉反应，导致了花粉相关食品敏感症,Three distinct cross-reactive structures in pollen and vegetable foods花粉和蔬菜中的3个明显交叉反应结构,1） Bet v l is the major birch pollen allergen Bet v 1是主要的桦树花粉过敏原Allergens with cross-reactivity to Bet v 1 ： 与Bet v 1有交叉反应的过敏原有：Apples 苹果Hazelnuts 榛实 cherries 樱桃,Pears 梨子Celery 艾蒿 carrots 胡萝卜,2）Profilins are widely distributed in the plant kingdom and have been identified as plant pan Allergens. Profilin广泛分布在植物王国，被称为“植物pan过敏原” 10 to 20% of the pollen-allergic patients are sensitized to pronlins. 10-20%花粉敏感病人对profilins敏感,3） Cross-reactions of allergen-specific IgE antibodies can be caused by so-called cross-reactive carbohydrate determinants of food and pollen glycoproteins. 食品和花粉糖蛋白，又称为 “交叉反应碳水化合物决定物”会引起过敏原与特异性IgE抗体的交叉反应。,Cereals （二）谷物,two major allergens ： 两个主要过敏原IgE： one at 47 kDa one at 20 kDa,When challenged with double-blind, placebo-controlled food challenge DBPCFC实验证实21% of the patients with suspected allergy to cereals had symptoms 21%谷物过敏儿童有综合症状8% had clinical reactions to only one cereal 8%儿童只对一种谷物有临床反应The majority of the children had clinical reactions to wheat (76%) 大部分儿童（76%）对谷物有临床反应,Legumes （三）豆类,Peanut allergy may be the most common food allergy in the United States 在美国，花生敏感症是最常见的食品敏感症 Allergic reactions are often acute and severe 过敏反应经常是急性和严重的,The major peanut allergen： 主要的花生过敏原：,glycoprotein糖蛋白,Ara h 1， molecular weight of 66 kDa,Ara h 2, molecular weight of 17 kDa,The characteristic特征：heat stable 热稳定性a potential source of hidden food allergens 一种“隐藏性食品过敏原”的潜在资源,Natural Rubber (Latex)-Related Food Allergens（四）与天然橡胶（乳胶）有关食品过敏原,The latex allergens are proteins from the rubber tree 乳汁过敏原是来自橡胶树的蛋白质 Common antigenic determinants demonstrated between latex and avocado, chestnut, and banana 乳汁与鳄梨、栗子和香蕉之间存在共同的抗原定子,Allergy to natural rubber (latex) has become increasingly problematic天然橡胶（乳汁）敏感症有上升趋势 These reactions are severe, e.g., anaphylactic shock 许多反应是