Keynote speech

過敏疾病之介紹與預防

台中榮民總醫院過敏科

蔡肇基 主任

過敏疾病介紹與預防

台中榮總教學研究部

蔡肇基主任

食物過敏是國人最常見的疾病之一，有 20%的國人認為自己有食物過敏之經驗，但真正的食物過敏只有 6-8%，大多數的反應是由於食物耐受不良所引起。食物過敏引起的疾病主要包括蕁麻疹、異位性皮膚炎、急性腸胃炎、急性呼吸道阻塞等，雖然大多數的過敏

症狀僅限於皮膚紅腫，但有些病人會引起急性呼吸道阻塞，甚至呼吹困難而有致命的危

險，因此不可不小心防患。

過敏疾病之致病機轉：大多數的科學家認為造成過敏的主要原因除了過敏體質之外，

環境中之過敏原與空氣汙染都扮演重要之角色。長時間暴露在過多的過敏原尤其是室內之

塵　與食物與室外汙染的空氣，包括汽車的廢氣、工業之廢氣如二氧化碳、一氧化氮、二氧化硫、臭氧都是導致過敏疾病之誘因。最近的流行病學者研究發現，已開發國家之民眾，

生活水準高，公共衛生良好，環境中之致病菌少，家庭成員少、小家庭長大的孩子很少有

機會被病菌感染，但是，這些家庭的小孩過敏盛行率高。相反的，開發中國家之民眾，生

活水準差、公共衛生不佳，環境中之致病菌多、家畜多、家庭成員多，相互之間的傳染機

會高，但是，這些家庭的小孩過敏盛行率反而低。這種環境衛生與過敏疾病相互因果關係

就是”衛生理論”的基礎。也就是環境愈衛生，過敏疾病盛行率反而愈低的理論。

過敏疾病發展的三個階段：過敏疾病的第一階段：身體接觸到過敏原而被導致過敏，

亦即過敏原導致身體產生特異型 B 及 T 淋巴細胞增生並製造 IgE 抗體。這階段通常發生在新生兒 6 個月之內，或者是身體營養狀況差及受疾病侵犯而免疫功能不全之期間最容易產生。環境中過敏原之含量並不需要很多才能導致過敏，此階段身體沒有任何過敏之臨床症

狀。過敏疾病的第二階段：被致敏過的身體再次接觸到過敏原，身體的特異型細胞和 IgE抗體就會引起反應，釋放出多種發炎激素及發炎介質，使身體產生立即型過敏反應及遲緩

型過敏反應。立即型過敏反應發生在 5 至 15 分鐘內，血管會急速擴張使組織液外滲而水腫，平滑肌收縮而有呼吸困難之現象。遲緩型過敏反應發生在 6-8 小時，嚴重者可持續 3天，此期間不但特異型細胞增生，發炎細胞也會聚集。此階段之反應與過敏原的濃度有關，

濃度愈高反應愈強，引起遲緩型反應的時間也愈久。過敏疾病的第三階段：被致敏過的組

織經過重複多次的發炎反應，會形成組織血管增生與纖維化等永久性破壞，此時的臨床症

狀會變成慢性持續性且無法恢復正常功能。此階段之反應與過敏原之含量濃度無關，並且

除過敏原之外，其他任何病毒及細菌都可以誘發反應。

過敏原與過敏相關之疾病：過敏疾病可依接觸的器官來分為呼吸道過敏：過敏性鼻

炎、過敏性結膜炎、呼吸道過敏與氣喘。皮膚過敏：蕁麻疹，異位性皮膚炎、過敏性血管

炎。消化道過敏：過敏性腸胃炎。全身性過敏：全身血管性水腫、過敏性休克。引起過敏

的食物，在小孩以牛乳蛋為主而大人以海鮮、水果為主，通常這些對食物過敏原過敏者也

會對室內中之塵　過敏。這些過敏很多是共通性抗原所引起。根據衛生署調查台灣地區食物常見之過敏原小孩過敏之食物以牛乳、蛋(花生)豆漿、小麥、魚、核果為主，我們調查也發現成人過敏之食物以核果、魚、蝦、有殼貝類為主。由於小孩的牛乳及蛋過敏於長大

後會逐漸減輕，但大人的海鮮過敏卻不易減輕，因此很難痊癒。

過敏之處理原則：預防勝於治療，處理過敏的最佳方法就是避免接觸過敏原。尤其是

有過敏病史且曾發生休克者應特別注意。因為重複過敏容易引起嚴重之休克反應。這些人

應隨時攜帶有緊急救命藥物。

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教學研究部 蔡肇基主任

List of content1. Pathogenesis of asthma and allergy2. Mite allergy in Taiwan

3 airway and food allergy3. airway and food allergy

4. Allergy prevention

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近三十年來台北地區

過敏疾病盛行率之變化

1974 1985 1994氣喘 1.3% 5.1% 10.8%過敏性鼻炎 7.8% 33.5%異位性皮膚炎 1.4% 1.2% 5.8%蕁麻疹 2.3% 2.3% 6.9%

Asthma 2004, 13.5% in children, 8.6% in adult

First theory:Ventilation system in modern buildings

Rise in Allergy Prevalence Is Not Clear

Tendency for spending more time indoors

Increased exposures to

dust mites & other indoor allergens

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Second theory:Increased exposure to:

Rise in Allergy Prevalence Is Not Clear

Diesel ExhaustCO2 5

Rise in Allergy Prevalence Is Not Clear

Third theory: The Hygiene Hypothesis

DEVELOPING COUNTRIES WESTERNIZED COUNTRIESLarge Family Small Familyg yRural HomesLive Stocks

Intestinal flora - VariableLow Antibiotic Use

High Helminth BurdenPoor Sanitation

Small FamilyModern Home

AffluentIntestinal flora - Stable

High Antibiotic UseLow or -0- Helminth Burden

Good Sanitation

Non-Allergic

Allergic: Asthma, rhinitis, eczema6

2

Reactions of Allergen and Allergen-Specific IgE

Unbound IgEIL-4 & IL-13

T-Cell B-lymphocyte Plasma CellAllergen

IgE antibodies are bound to mast cells in tissue and to basophils in circulation. Once these cells come into contact with an allergen, chemicals (histamine) are released. These chemicals are responsible for injury to surrounding tissues and other visible signs of an allergy such as sneezing, watery, itchy eyes, rashes, hives and runny nose.

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Allergic CascadeAllergic CascadeAllergic CascadeAllergic Cascade consists of 3 phases:consists of 3 phases:

1.1. SENSITIZATION SENSITIZATION 2.2. EARLYEARLY--PHASE REACTIONPHASE REACTION33 LATELATE PHASE REACTIONPHASE REACTION3.3. LATELATE--PHASE REACTIONPHASE REACTION

Allergic Cascade Allergic Cascade is like a domino reaction. Once the first is like a domino reaction. Once the first domino falls, a chain reaction takes place.domino falls, a chain reaction takes place.

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Allergic Cascade, Sensitization

– Initial exposure to allergen leads to production of allergen-specific IgE

Exposure can take place by:– Exposure can take place by:• Ingestion (food, medication)• Inhalation (pollen, mold, dust-mite)• Touch (latex)• Injection (insect venoms, drugs)

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Allergic Cascade,Early-Phase Reaction

– Re-exposure to allergen occurs– The IgE of mast cell binds to the allergen,

cross- linking the IgEg g– Upon completion of cross-linking, the mast

cell detonates and releases chemicals called mediators such as histamine

– Mediators circulate in the body causing typical allergic symptoms such as: Sneezing; coughing; watery, itchy eyes and difficulty breathing

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Allergic Cascade,Late-Phase Reaction

– Takes place at the same time as the early-phase, but it takes longer to reach full cycle

– Sometimes this phase takes place within 3 to 10 hours after the early-phase reaction and can last up to 24 hours

– Late-phase reactions involve immune cells known as eosinophils

– In this phase, typical allergy symptoms are more severe

– In some cases Anaphylactic Shock will be produced 11

Response to inert, inhaled, antigenic particles

GenesEnvironmentRegulation

T regulatory cellsT regulatory cells normal T regulatory cells “ deficient “

T regulatory cells normal ( IL-10/TGF-β secreting ? CD4+CD25+)

Non-atopic response( Harmless)

Atopic response(IgE-mediated hypersensitivity )

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A pathogenesis schema for childhood asthma

Environment•Allergens•Microbes•Pollutants

•Stress

Aberrant immune development & responses

Age

Biological &Genetic Risk

•Immune•Lung

•Repair1°

Prevention

Airways Injury

Aberrant Repair

•Viral infections•Aeroallergens•Pollutants/toxicants

•Persistent inflammation•BHR•Tissue remodeling•Lung growth/differentiation

Aberrant immune development & responses

Atopy2°

Prevention

EarlyIntervention

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Primary prevention

• Lactobacilli• Fish oil• Fish oil• Allergen reduction• Allergen tolerance

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Secondary prevention

• Antihistamine.• Calcineurin inhibitor• Calcineurin inhibitor

(tacrolimus).• Allergen immunotherapy.

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Early intervention

• Close monitoring of allergen marching.

• Immunotherapy for symptomaticImmunotherapy for symptomatic allergic rhinitis to prevention asthma.

• Peak flow meter (close monitor of lung function).

• Drug monitor.

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台灣食物過敏現況

台中榮民總醫院過敏免疫風濕科 陳怡行醫師

台灣食物過敏現況

台中榮民總醫院過敏免疫風濕科

陳怡行醫師

Food Allergy in Taiwan Abstract

Food allergy has been increasing in Taiwan as well as world-wide. Adverse reactions to food and drink have been observed in the human life for centuries. Food allergy is an abnormal reaction resulting from overreaction of immunologic responses to proteins or glycoproteins in food.

Almost every major food allergen identified is a protein or glycoprotein with a molecular weight between 10 and 40 kDa. Most food allergens resist denature to heat, acid and degradation by proteases. In the western countries, the most common food allergens causing systemic reaction in adults are peanuts, tree nuts, crustaceae, fish and egg, while in Taiwan, crustaceae are the most common causative food allergens among adults.

Immediate reaction food allergy including oropharyngeal reactions, which are often observed first, GI manifestations, urticaria, angioedema and systemic anaphylaxis. Atopic dermatitis is another presentation of food hypersensitivity. Besides, delayed reactions to foods, such as allergic eosinophilic gastroenteritis, gluten-sensitive enteropathy and dermatitis herpetiformis represent another form of food allergy. The diagnosis of food allergy is dependent on the history, an appropriate exclusion diet, skin testing or allergen-specific IgE in vitro tests and double-blind-placebo-control- food-challenge test.

This talk will give an overview of clinical manifestations and diagnostic methods for food allergy. Common misunderstanding to food allergy in Taiwan from the observation of an allergist will be addressed in this talk as well.

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台灣食物過敏現況

陳怡行醫師台中榮民總醫院

內科部過敏免疫風濕科主治醫師國防醫學院內科臨床副教授

陽明大學內科助理教授

加拿大少女吻吃過花生醬男友後因花生過敏死亡 !

2005-11-30加拿大一名對花生過敏的女孩，在與剛吃過花生醬的男朋友親嘴後，休克死亡。這名15歲少女來自加拿大東部的魁北克省。上星期一個晚上，她與16歲的男友租了一些電影準備在家看，兩人開始親嘴。但是女孩隨即出現過敏反應，並且呼吸困難。送抵醫院後，醫生立刻給她注射用來治療花生過敏的腎上腺素。可是這種治療方她注射用來治療花生過敏的腎上腺素。可是這種治療方法並沒有起作用，她在經過多天治療後不治死亡。據悉，死者男友在與她親嘴前9個小時，曾經吃了幾片抹了花生醬的面包。當地一名記者說：“她對花生異常敏感，但是她的男朋友卻並不知情。＂研究花生過敏症的專家卡根指出，這宗意外十分罕見，而且令人憂慮。她說，每個人對敏原的反應都不一樣，有些人特別敏感，因此很難預測。花生過敏的症狀包括：血壓降低、面部和喉嚨腫脹，這些都會阻礙呼吸，從而導致休克。

Rémy Legaludec是怎麼死的?

當黑密管家喝下那杯掺了花生粉的威士忌……

台中榮總的實例

46歲蔡女士,有30年過敏性鼻炎及氣喘病史,年輕時吃蝦就會長蕁麻疹某天中午與家人到日本料理店用餐,吃完開胃菜紅燒魚卵十幾分鐘後,開始腹部絞痛部絞痛

約三十分鐘後,身上開始出現蕁麻疹,並感覺呼吸困難

家人將她送到附近醫院急診室,在急診室因嚴重呼吸困難且血壓下降,緊及插管急救後,轉送至本院並住進加護病房

台中榮總的實例

李小弟

在美國出生,baby時因常血便,嚴重嘔吐, 發現對牛奶及花生過敏

幼稚園點心是花生湯

老師好心把花生都撈走只給李小弟喝花老師好心把花生都撈走只給李小弟喝花生湯

結果….

什麼是過敏Allergy?

根據2003年WHO對過敏之定義Hypersensitivity敏感

Objectively reproducible stimulus at a dose tolerated by normal persons, could be immune or non-immune

Intolerance耐受不良non-immune

Allergy過敏A hypersensitivity reaction initiated by specific immunologic mechanisms

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Gell and Coomb’s Classification of Allergic Reactions 食物過敏

A group of disorders characterized by an abnormal exaggerated immunological response to specific food proteins

IgE mediated or non-IgE mediated

T cellseosinophils

食物過敏有多常見?

Children

異位性皮膚炎與食物過敏

光田綜合醫院風濕免疫科

洪國棟 醫師

異位性皮膚炎與食物過敏

光田綜合醫院風濕免疫科

洪國棟 醫師 Atopic dermatitis is a pruritic disease of unknown origin that usually starts in early

infancy and is typified by pruritus, eczematous lesions, xerosis (dry skin), and lichenification on the skin (thickening of the skin and increase in skin markings). Atopic dermatitis is associated with other atopic diseases (eg, asthma, allergic rhinitis, urticaria, acute allergic reactions to foods, increased IgE production) in many patients. It is a disease of great morbidity, and the incidence appears to be increasing. The prevalence rate is as high as 18% and is rising, especially in developed countries. It often begins in early infancy and follows a course of remission and exacerbations. The pathophysiology of atopic dermatitis is poorly understood. Several cell types seem to be involved, including T lymphocytes, eosinophils, Langerhans cells, and keratinocytes. Other factors, including cytokines and IgE, are also implicated. There is increasing evidence that T cell responses to environment allergens are important for the pathogenesis of atopic dermatitis. In 80% of patients with atopic dermatitis, the skin disease is more often associated with existence of environmental allergen-specific IgE.(the “extrinsic” form of atopic dermatitis). In 20% of patients with the typical clinical appearance of atopic dermatitis, no specific IgE was found (the “intrinsic” form of atopic dermatitis). The role of food antigens as trigger factors of atopic dermatitis has been discussed for more than 60 years. It is possible that intestinal permeability is enhanced in atopic individuals and this may fascitate the resorption of food proteins. The incidence of atopic dermatitis and IgE-mediated food allergies peaks in early childhood, which suggests that these 2 clinical entities may be associated. However, IgE-mediated food allergy is not the whole story as food intolerance is concerned. A lack of correlation between specific IgE and the clinical response to food has been reported for food-responsive atopic dermatitis in several studies and this may point to the relative importance of allergen-specific T lymphocytes in these reactions. Both food allergy and food intolerance due to non-immunological mechanisms are complicating factors in atopic dermatitis. The preventive dietary approach involves the delayed introduction of mixed feeding, and the exclusive breastfeeding of infants known to be at high risk. A lower incidence of atopic dermatitis was found in children who gave been breastfed, or fed with hypoallergenic milk formula for at least 6 months. However, at 4 years, no difference was noted in the incidence of atopic dermatitis between the group that had not been exclusively breastfed and the group that had. The curative dietary approach may be done either by exclusion of an item of food that the patient or parent has noticed specifically exacerbates the disease or by nonspecific exclusion of foods. A very small number of patients with severe and intractable disease derive benefit from an elemental diet.

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異位性皮膚炎與食物過敏

光田綜合醫院

內科部 過敏免疫風濕科

洪國棟醫師

Atopy versus Allergy • Atopy refers to a tendency for exaggerated IgE

antibody responses, defined clinically by the presence of one or more positive skin prick tests( or caused serum allergen-specific IgElevels) to common allergens.i.e. a predisposition to develop allergy.

• Allergy refers to the clinical expression of atopic IgE-mediated disease, including asthma, rhinitis, eczema and food allergy.

Atopic dermatitis

• a common inflammatory skin disorder,• characterized by

a. severe pruritispb. chronic relapsing coursec. a distinctive distribution of eczematous skin lesionsd. a personal or family history of atopic diseases.

Atopic dermatitis

• Prevalence in children: 10-20%• Prevalence in adults: 1-3%• Prevalence of atopic dermatitis increased

b 2 3 f ld d i th t 30by 2-3 fold during the past 30 years.• Higher prevalence in urban regions than in

rural regions of developed countries.• More common in higher social class

groups.

Two types of atopic dermatitis

• Extrinsic type with IgE mediated sensitization: 70-80% of patients

• Intrinsic type without IgE mediated sensitization of patientssensitization of patients

Clinical features of atopic dermatitis

Essential features• Pruritis• Facial and extensor eczema in infants and

hildchildren• Flexural eczema in adult• Chronic or relaping dermatitis

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Pruritis in atopic dermatitis

• can occur throughout the day• usually worse in the early evening and

nightlt i t hi li h ifi ti d• result in scratching, lichenification, and

prurigo papules• reduced humidity, excessive sweating and

low concentrations of irritants can exacerbate pruritis and scratching

Facial eczema in infants

Facial eczema in infants Facial eczema in children

Flexual eczema in adults

popliteal fossaeantecubital fossae

Dennie-Morgan folds

食物過敏者飲食治療原則

慈愛綜合醫院營養室

林旻樺主任

食物過敏者飲食治療原則

慈愛綜合醫院營養室

林旻樺主任

食物過敏最常發生在 3 歲以下的幼兒佔 6-8%，成人發生率佔 4%。食物過敏是食物對身體產生 IgE 反應或抗體造成免疫系統反應，來自免疫系統機制反應稱食物過敏，非免疫造成稱食物不耐。食物過敏會產生呼吸、胃腸、皮膚和心臟方面的症狀，有時嚴重時會導致對

生命威脅的過敏性休克，診斷時要詢問醫藥史和皮膚試驗，雙盲控制食物質疑必需執行。

最常見的有 8 種食物容易導致食物過敏(花生、樹堅果、蛋、牛奶、小麥、黃豆、魚和甲殻魚類)，造成呼吸症狀關聯的食物過敏原有奇異果、樹堅果等，(榛果、腰果)等香料，黃金奇異果會引起食物過敏綠色奇異果雖造成過敏機率低但也不可忽視。食品添加劑如二氧

化硫或硫化物引起 40%孩子哮喘,在乾果,飲料裡普遍會噴灑二氧化硫氣體,導致刺激喉頭引起氣喘，因二氧化硫氣體進入胃導致刺激喉嚨引起氣喘。有些人會對黃色食物染料酒石

磺產生敏感，但個案相當罕見,只影響 0.1%人口。花生過敏在美國影響大約 1.5 百萬人民。花生過敏每年佔致命或近致命過敏反應的 80%。要降低花生過敏風險，必需知道花生相關產品及如何避免。

新鮮水果、堅果、菜和香料也會導致反應在嘴唇的局部組織,在嘴和在喉頭這是所謂的口頭過敏綜合症狀 (OAS)。口頭過敏傾向於通常發生在對樺樹和草花粉過敏的個體。如果沒有找到明顯的過敏食物,可使用麼簡單的無過敏飲食二個到四個星期。包括低過敏食物譬如:小羊肉或雞、精白米、米糕、梨、香蕉、水和葵花油或橄欖油。食物過敏常見發生在幼兒，常發生皮膚炎、氣喘或鼻炎可能造成營養不良，貧血和吸收不良，特別是長期腹

瀉應該時常檢視生長是否落在正常的生長曲線點上。營養師的忠告應持續叮嚀確定完整排

除和監測飲食營養素成份特別是鈣、鐵和維生素補充，無牛奶飲食的人應補充鈣

(400-800mg/day),和限制麥類食物者需要補充維生素 B。

如果基礎飲食需要從飲食中被排除,應該尋求營養師咨詢以建議如何攝取可保證飲食可以得到充分的營養。

7 July 13

1DISTRIBUTED BY FDA/CFSAN

食物過敏者飲食治療原則

慈愛綜合醫院

營養室主任林旻樺

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What Is Food Allergy?Common Food AllergiesFood Allergy or Food Intolerance?Food Allergy or Food Intolerance?DiagnosisFood Allergy in Infants and ChildrenTreatment

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Prevalence of true food allergies

Infants 4-6%Young children 1-2%Ad lt 1 1 5%Adults 1-1.5%

Recent estimates 11.4 million Americans, or 4% of population, have food allergy10 years ago, less than 1%

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Most common food allergies90% from peanut, tree nuts, milk, egg, soy, fish, shellfish & wheat.

10% from over 160 other foods including fruits (kiwi) and seeds (sesame).

Children 90% from Milk, egg, peanuts, tree nuts,wheat, soy

Adults85% from Peanuts, tree nuts (almonds, walnuts), fish, shellfish (shrimp, lobster, crab), mollusks (oysters, clams, scallops)

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Prevalence of Food Allergies in the U.S.

Food Young Children Adults

Milk 2.5% 0.3%

Egg 1 3% 0 2%Egg 1.3% 0.2%

Peanut 0.8% 0.6%

Tree nuts 0.2% 0.5%

Fish 0.1% 0.4%

Shellfish 0.1% 2.0%

Overall 6% 4%

Sampson, 2004 5

Symptoms

Severe reactions more common in peanuts, tree nuts, shellfish, fish, and eggs.Peanuts and tree nuts are the leading causes of thePeanuts and tree nuts are the leading causes of the potentially deadly food allergy reaction called anaphylaxis. Also more common in those with asthma.Death usually seen in peanuts or tree nuts.

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7 July 13

2DISTRIBUTED BY FDA/CFSAN

What is a food intolerance?

A food intolerance mimics a food allergy but does not cause a reaction by the body’s immune system.

Example:

Lactose intolerance

• not an immune system response• not an immune system response

• unable to digest the sugar in milk

• symptoms similar to allergy

• stomach-ache

• diarrhea7

Food Intolerance

More common than allergiesFood poisoningHistamine toxicity (cheese, wine, fish)Lactose intoleranceFood additives (MSG)Food additives (MSG)Gluten intolerance (small intestine)Corn productsTrue allergy – avoid food (immune system)Intolerance – small amount is ok (digestive system)

Reported food intolerance 12-35%8

What are the symptoms of a food allergic reaction?

Skin Symptoms

GI Symptoms

Respiratory Symptoms

Cardiovascular Neurological

Hives Swelling Itchy red rash Excema

Cramps Nausea Vomiting Diarrhea

Itchy,watery eyesRunny nose Sneezing, cough Itching or swelling of lips tongue

Reduced blood pressure Increased heart rate

Shock

Impendingdoom Weakness

Excema flare

of lips, tongue, throat Change in voice Tightness in chest, wheezing Shortness of breath Repetitive clearing of throat

Shock

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How are food allergies diagnosed?

PhysicianMedical history, physical examSkin testLab testsOral food challengeElimination dietDouble-blind food challenge

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What to do if Child has Food Allergies

Consult with an allergist and dietitianU th h t ft t hild’Use growth charts often to assess child’s growth.

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Food Allergies Linked to Poor Growth

Increased risk for poor nutrient intake.

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Parents may eliminate too many foods from child’s diet or neglect to supplement.In severe cases, children can develop failure to thrive.

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