Atopy and Allergic diseases .

Prof. Mohamed Osman Gad El Rab.College of Medicine & KKUH.

Terminology التعريف :

Human disease caused by immune responses to

environmental antigens that lead to :

immediate reactions in the target tissues & rapid onset of symptoms

are called :

allergic diseases .

With reference to Coombs & Gell classification of hypersensitivity these are :

Immediate ( type I )hypersensitivity reactions .

In clinical practice these reactions are commonly called :

allergy or atopy .

atopy : is derived from a Greek term (atopos ) which mean : out of place .

The term refer to :

a strong genetic predisposition - استعدادfor development of immediate hypersensitivity اهبه

reactions in certain individuals.

The genetics of allergy are complex , involving interactions between several genes .

studies of atopic families have identified regions

on chromosomes 11q and 5q هذهالحساسيه لفرط المسببه .الكروموسومات

فرط بتكوين وعالقته كروموسوم كل وظيفه:الحساسيه

chromosome 11q : encodes the b subunit of

the high affinity IgE receptor.

chromosome 5q : contain many cytokine genes that

increase susceptibility حساسيه .

The high- affinity IgE receptor encoded by chromosome 11q .الجاذبيه ) ) عالي ليس ولكنه اي جي اي يوجد الحساسين غير االشخاص في

الحساسين االشخاص مثل العدد وكثير

مسبب الحساسيه

2يرتبطب اي) ) جي اي

The 5q locus موقع contain genes for : - IL-3 ,4, 5 , 9 & 13 .

-These cytokines : - promote تعزز TH2 سيلز هلبر responses by تي

enhancing تنميه : * IgE isotype switching in B cells. * eosinophils survival . * mast cell proliferation .

- variation in the IL-4 gene has been associated with high levels of IgE in atopic individuals.

عده ) ) – \ على وتؤثر البيضاء الخاليا من تنتج كميائيه ماده هو االنترلوكين االول البلوك من تذكيراو لالنقسام بنتشيطها اما عليها وتؤثر المناعي بالجهاز عالقه لها خاليا هي االهداف هذه اهداف

وهي اخر لشكل تحويلها او النشط للشكل للتحول جسم- تنشيطها على خاص بريسيبتور ترتبطكثرت . اذا المناعي الجهاز باثاره عالقه لها يكون وبذلك الهدف الخليه

Allergy is a systemic disorderالعرض شغل

NosePharynx

Stomach

EsophagusLungs

SkinFood allergyFood allergy

Allergic rhinitisAllergic rhinitisAsthmaAsthma

EczemaEczemaUrticariaUrticariaAllergic dermatitisAllergic dermatitis

skin

Respiratory system

GIT

Clinical presentation االعراض:

atopic individuals may present with one or more of the following conditions :

- allergic rhinitis.

- allergic conjunctivitis وهو العين التهابمناعي بسبب . دائما

- allergic asthma.

- atopic dermatitis ( eczema (.

A newborn approximate risk of developing symptoms according to family history of allergic disease :

1. no family member allergic 5-15 %.

2. one sibling allergic 25-35 %.

3. one parent allergic 20-40 %.

4. both parents allergic 40-60 %.

5. both parents allergic ,

( same symptom ( 50- 70 %.

Epidemiology الوبائيات :

The prevalence االنتشار of allergic disease worldwide ranges

from 30% to 40%.

There is substantial قطعي evidence برهان that the incidence حدوث of allergy is steadily ببانتظام increasing all over the world .

A study in U.K. between 2001-2005 showed that the

incidence of patients with at least one allergic disease

increased from 18.9% to 24.2 %.

J R Soc Med. 2008, 101(11(:558-563.

A study in Saudi Arabia documented a significant increase in incidence :

Allergic asthma:

From 8% (in 1986 ( to 23% (in 1995(. ( p <.0001 (.

Allergic rhinitis: From 20% (in 1986 ) to 25% ( in 1995). (p < .003).

A.R.Al-Frayh,Z.S hakoor,M.O.GadElRab.Annal of Allergy, Asthma &Immunology, 2001,86:292-296.

* Allergic disease is the 5 th leading chronic disease

among all ages .

* And the 3rd chronic disease among children under

18 years old ; up to one child in three is affected .

* Trend انه الى يشير indicate that by 2015 half of الميلall Europeans

may be suffering from an allergy ( مسوي مساكييينمنها ) . طالع

Antigens that elicit تثير allergic reactions are called allergens

because they have the following features :

1. low molecular weight.

2. glycosylation القاموس the formation of : منlinkages with glycosyl groups.

3. high solubility in body fluids .

4. proteins, in nature ,or chemicals bound

to proteins , and some have enzyme

activity .

Common allergens associated with type 1 hypersensitivity :

اللقاح حبوبللفطريات

Fungal spores (aspergillus ( common indoor & outdoor allergens ( ( ورانا ورانا البيت وخارج .بالبيت

tree pollens ( mesquite ( common outdoor allergens in Saudi Arabia ..

Ragweed & ragweed pollens : common outdoor allergen .

House dust mite &Cockroach صرصور insects :

Common indoor allergens that may cause allergy symptoms All through the year . ( perennial ( .

Honey-bee black( fire ( ant . Common causes of anaphylaxis وفوري شديد ظهورالحقا ) ) تفصل .. للحساسيه

Manifestations ظهور of allergic disease require two steps .

1. sensitization phase : االولى االصابه first exposure to allergen.

2. challenge phase : الالحقه االصابه re-exposure to allergen .

Sequence of events in immediate H/S reactions.

First exposure to allergen.

Activation of TH2 cells & stimulation of IgE class switching in B –cells .

Binding of IgE to FcR1 on mast cells.

sensitization .

Sequence of events in immediate H/S reactions.

Repeated exposure to allergen

Activation of mast cells : release of mediators .

challenge .

primary نفسها سيل الماست من and يصدرsecondary الخارج االنفالميشن mediators من :عوامل

Allergic reactions can be divided into immediate and

late- phase responses .

- the immediate response start within seconds

and is due to preformed mediators.

- the late reaction ,which takes up to 8-12 hours to

develop , is due to induced synthesis and release

of mediators & cytokines .

The immediate response :

due to preformed &rapidly synthesized Mediators .

start within seconds.

The late-phase response :

due to synthesis of new mediators (PG,(LT.,( chemokines& cytokines, withInflux تدفقof eosinophils and T-cells .

takes 8-12 hours to develop.

clinical presentations :

- allergic rhinitis .

- allergic asthma .

- skin allergy .

- food allergy .

- systemic anaphylaxis .

Allergic rhinitis :

inhaled allergens activate mucosal mast cells

beneath the nasal epithelium .

mediators released .

diffuse across the mucous membranes of the nasal

passages .

The immediate reaction in allergic rhinitis is characterized by :

1. intense شديده itching & sneezing .

2. local edema (leading to blocked nasal passages(.

3. nasal discharge سيوله ( typically rich in eosinophils (.

4. irritation تهيج of the nose ( as a result of histamine( .

A similar reaction to airborne allergens deposited تدخل in the conjunctiva of the eye can result in :

allergic conjunctivitis.

Allergic asthma :

inhaled allergens activate submucosal mast cells in the lower airways . mediators released within seconds & lead to :

contraction of bronchial smooth muscles. (bronchial constriction – difficulty in breathing (.

increased secretion of mucus .

increased vascular permeability .

influx تدفق of inflammatory cells ( including eosinophils & TH2 cells (.

An important feature of asthma is chronic inflammation of the airways .

This result from the influx of inflammatory cells .

TH2 cells .IL-9 & IL-13 .

eosinophils .Major basic protein

neutrophils .proteolytic E.

Lung epith. Cells .Rantes & eotaxin .

These cell products act on

1. Airway smooth muscle cells .2. Lung fibroblasts . 3. Mucous glands .

and cause :

airway remodeling .

Airway remodeling :

thickening of the airway walls by hyperplasia & hypertrophy of the smooth muscle layer

Goblet cell metaplasia .

Development of fibrosis .

Increased mucus permanent narrowing of the permanent secretion . airways . tissue damage.

Irreversible lung damage .

mucus plug .

smooth musclecontraction.

Hyperreactive airways react to non- specific

factors:

chemical irritants .

smoke & Strong perfumes .

sulphur dioxide & air pollutants.

viral & bacterial respiratory infections .

Skin allergy :

manifest as : - acute urticaria .

- chronic eczema .

* allergens enter the epidermis or dermis by :

1. a stinging insect .

2. direct contact .

3. through the blood ( ingested food or drug (.

local connective tissue mast cells become

activated & release mediators .

* mediators activate local increase in

local nerve endings. vasc. permeability.

- vasodilatation of extravasation of

blood vessels. fluid from blood.

( redness of the skin. ( ( Swelling of the skin.(

this skin lesion is called :

wheal انتفاخ-and flare حمره reaction .

Acute urticaria : كله الجسم حول تنتشر

a disseminated متبعثر form of the wheal-and- flare

reaction .

sometimes appear when ingested allergens

enter the blood stream and reach the skin .

Histamine released by mast cells in the skin

causes :

large , itchy red swellings of the skin.

( urticaria or hives (.

Acute urticaria :

Swelling of the lipsand eyes may be associated with urticaria . Angioedema :

Food allergy :

A significant مهم health problem especially in children .

In USA food allergy cause approximately 30,000

anaphylactic reactions each year , including 200

deaths .

* food allergens resist مقاوم digestive enzymes & therefore reach the mucosal surface of the small intestine as an intact molecule .

Ingested allergens in food cause activation of mucosal

mast cells in the gastrointestinal tract .

mediators released .

transepithelial fluid loss smooth muscle contraction.

diarrhea . vomiting .

Ingested food allergens may enter the bloodstream

and cause systemic reactions .

activation of connective disseminated mast cell

tissue mast cells in the activation .

skin .

urticaria . generalized anaphylaxis.

Systemic anaphylaxis ( anaphylactic shock).

Allergens may be introduced directly into the

bloodstream as a result of :

- penicillin injection ( مهب المحقون الدواءبنسلين ) . شرط

- honey-bee sting .

disseminated منتشر mast cell activation .

شائعه : اسبابلحدوثها

massive mediator release into the blood result in :

wide spread increase airway swelling of the

in vascular permeability . Constriction. larynx

loss of blood pressure . difficulty in suffocation. (hypotension( . Breathing ( difficulty in breathing (.

this condition can be rapidly fatal but can be controlled by العالج * immediate injection of epinephrine ( adrenaline ( .

Diagnosis : التشخيص

1. skin prick test (SPT(.

2. specific IgE measurement .

3. challenge tests.

4. elimination – provocation tests.

( food allergy (.

skin prick test

skin prick test .