Atopy and Allergic diseases Prof Mohamed Osman Gad

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 ﺍﺳﺘﻌﺪﺍﺩ - ﺍﻫﺒﻪ for development of immediate hypersensitivity reactions in certain individuals.

The genetics of allergy are complex , involving interactions between several genes. studies of atopic families have identified regions on chromosomes 11 q and 5 q ﻫﺬﻩ ﺍﻟﻜﺮﻭﻣﻮﺳﻮﻣﺎﺕ . ﺍﻟﻤﺴﺒﺒﻪ ﻟﻔﺮﻁ ﺍﻟﺤﺴﺎﺳﻴﻪ : ﻭﻇﻴﻔﻪ ﻛﻞ ﻛﺮﻭﻣﻮﺳﻮﻡ ﻭﻋﻼﻗﺘﻪ ﺑﺘﻜﻮﻳﻦ ﻓﺮﻁ ﺍﻟﺤﺴﺎﺳﻴﻪ chromosome 11 q : encodes the b subunit of the high affinity Ig. E receptor. chromosome 5 q : contain many cytokine genes that increase susceptibility . ﺣﺴﺎﺳﻴﻪ

. The high- affinity Ig. E receptor encoded by chromosome 11 q ﻓﻲ ﺍﻻﺷﺨﺎﺹ ﻏﻴﺮ ﺍﻟﺤﺴﺎﺳﻴﻦ ﻳﻮﺟﺪ ) ﺍﻱ ﺟﻲ ﺍﻱ ( ﻭﻟﻜﻨﻪ ﻟﻴﺲ ﻋﺎﻟﻲ ﺍﻟﺠﺎﺫﺑﻴﻪ ﻭﻛﺜﻴﺮ ﺍﻟﻌﺪﺩ ﻣﺜﻞ ﺍﻻﺷﺨﺎﺹ ﺍﻟﺤﺴﺎﺳﻴﻦ ﻣﺴﺒﺐ ﺍﻟﺤﺴﺎﺳﻴﻪ ﻳﺮﺗﺒﻂ ﺏ 2 ) ﺍﻱ ﺟﻲ ﺍﻱ (

: contain genes for ﻣﻮﻗﻊ The 5 q locus . 31 & 9 , 5 , 4, 3 - - IL ﺗﺬﻛﻴﺮ ) ﻣﻦ ﺍﻟﺒﻠﻮﻙ ﺍﻻﻭﻝ ( – ﺍﻻﻧﺘﺮﻟﻮﻛﻴﻦ ﻫﻮ ﻣﺎﺩﻩ ﻛﻤﻴﺎﺋﻴﻪ ﺗﻨﺘﺞ ﻣﻦ ﺍﻟﺨﻼﻳﺎ ﺍﻟﺒﻴﻀﺎﺀ ﻭﺗﺆﺜﺮ ﻋﻠﻰ ﻋﺪﻩ ﺍﻫﺪﺍﻑ ﻫﺬﻩ ﺍﻻﻫﺪﺍﻑ ﻫﻲ ﺧﻼﻳ ﺗﺮﺗﺒﻂ- ﻟﻬﺎ ﻋﻼﻗﻪ ﺑﺎﻟﺠﻬﺎﺯ ﺍﻟﻤﻨﺎﻋﻲ ﻭﺗﺆﺜﺮ ﻋﻠﻴﻬﺎ ﺍﻣﺎ ﺑﻨﺘﺸﻴﻄﻬﺎ ﻟﻼﻧﻘﺴﺎﻡ ﺍﻭ ﺗﻨﺸﻴﻄﻬﺎ ﻟﻠﺘﺤﻮﻝ ﻟﻠﺸﻜﻞ ﺍﻟﻨﺸﻂ ﺍﻭ ﺗﺤﻮﻳﻠﻬﺎ ﻟﺸﻜﻞ ﺍﺧﺮ ﻭﻫﻲ ﺑﺮﻳﺴﻴﺒﺘﻮﺭ ﺧﺎﺹ ﻋﻠﻰ ﺟﺴﻢ ﺍﻟﺨﻠﻴﻪ ﺍﻟﻬﺪﻑ. ﻭﺑﺬﻟﻚ ﻳﻜﻮﻥ ﻟﻬﺎ ﻋﻼﻗﻪ ﺑﺎﺛﺎﺭﻩ ﺍﻟﺠﻬﺎﺯ ﺍﻟﻤﻨﺎﻋﻲ ﺍﺫﺍ ﻛﺜﺮﺕ : -These cytokines responses by ﺗﻲ ﻫﻠﺒﺮ ﺳﻴﻠﺰ 2 TH ﺗﻌﺰﺯ - promote : ﺗﻨﻤﻴﻪ enhancing . * Ig. E isotype switching in B cells . * eosinophils survival . * mast cell proliferation - variation in the IL-4 gene has been associated . with high levels of Ig. E in atopic individuals

Allergy is a systemic disorder ﺷﻐﻞ ﺍﻟﻌﺮﺽ Respiratory system Nose Esophagus Pharynx Lungs GIT Food allergy Allergic rhinitis Asthma Stomach Skin skin Eczema Urticaria Allergic dermatitis

Clinical presentation : ﺍﻻﻋﺮﺍﺽ atopic individuals may present with one or more of the following conditions : - allergic rhinitis. - allergic conjunctivitis ﺍﻟﺘﻬﺎﺏ ﺍﻟﻌﻴﻦ ﻭﻫﻮ . ﺩﺍﺋﻤﺎ ﺑﺴﺒﺐ ﻣﻨﺎﻋﻲ - 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 ﺍﻻﻧﺘﺸﺎﺭ 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. Gad. El. Rab. Annal of Allergy, Asthma &Immunology, 2001, 86: 292 -296.

* Allergic disease is the 5 th leading chronic disease among all ages. * And the 3 rd chronic disease among children under 18 years old ; up to one child in three is affected. * Trend ﺍﻟﻤﻴﻞ ﻳﺸﻴﺮ ﺍﻟﻰ ﺍﻧﻪ indicate that by 2015 half of all Europeans may be suffering from an allergy ﻣﺴﺎﻛﻴﻴﻴﻦ ) ﻣﺴﻮﻱ ﻃﺎﻟﻊ ﻣﻨﻬﺎ (.

Antigens that elicit ﺗﺜﻴﺮ allergic reactions are called allergens because they have the following features : 1. low molecular weight. 2. glycosylation : ﻣﻦ ﺍﻟﻘﺎﻣﻮﺱ the formation of linkages 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 : ﺣﺒﻮﺏ ﺍﻟﻠﻘﺎﺡ ﻟﻠﻔﻄﺮﻳﺎﺕ

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

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 ﻇﻬﻮﺭ ﺷﺪﻳﺪ ﻭﻓﻮﺭﻱ ( . . ﻟﻠﺤﺴﺎﺳﻴﻪ ) ﺗﻔﺼﻞ ﻻﺣﻘﺎ

Manifestations ﻇﻬﻮﺭ of allergic disease require two steps. 1. sensitization phase : ﺍﻻﺻﺎﺑﻪ ﺍﻻﻭﻟﻰ first exposure to allergen. 2. challenge phase : ﺍﻻﺻﺎﺑﻪ ﺍﻟﻼﺣﻘﻪ re-exposure to allergen.

Sequence of events in immediate H/S reactions. First exposure to allergen. Activation of TH 2 cells & stimulation of Ig. E class switching in B –cells. Binding of Ig. E to Fc. R 1 on mast cells. sensitization.

Sequence of events in immediate H/S reactions. Repeated exposure to allergen Activation of mast cells : release of mediators. challenge.

ﻣﻦ and secondary ﻳﺼﺪﺭ ﻣﻦ ﺍﻟﻤﺎﺳﺖ ﺳﻴﻞ ﻧﻔﺴﻬﺎ primary : ﻋﻮﺍﻣﻞ ﺍﻻﻧﻔﻼﻣﻴﺸﻦ mediators ﺍﻟﺨﺎﺭﺝ

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 late-phase response : The immediate response : due to preformed &rapidly synthesized Mediators. start within seconds. due to synthesis of new mediators (PG, ) LT. , ) chemokines & cytokines, with Influx ﺗﺪﻓﻖ of 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 & TH 2 cells ).

An important feature of asthma is chronic inflammation of the airways. This result from the influx of inflammatory cells. TH 2 cells. IL-9 & IL-13. eosinophils. Major basic protein neutrophils. proteolytic E. These cell products act on 1. Airway smooth muscle cells. 2. Lung fibroblasts. 3. Mucous glands. and cause : airway remodeling. Lung epith. Cells. Rantes & eotaxin.

Airway remodeling : Goblet cell metaplasia. thickening of the airway walls by hyperplasia & hypertrophy of the smooth muscle layer Increased mucus secretion. permanent narrowing of the airways. Irreversible lung damage. Development of fibrosis. permanent tissue damage.

smooth muscle contraction. mucus plug.

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 nerve endings. local increase in vasc. permeability. - vasodilatation of blood vessels. extravasation of fluid from blood. ( redness of the skin. ) ( Swelling of the skin. ) this skin lesion is called : wheal -ﺍﻧﺘﻔﺎﺥ and flare ﺣﻤﺮﻩ reaction.

Acute urticaria : ﺗﻨﺘﺸﺮ ﺣﻮﻝ ﺍﻟﺠﺴﻢ ﻛﻠﻪ 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 lips and 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 diarrhea. smooth muscle contraction. vomiting.

Ingested food allergens may enter the bloodstream and cause systemic reactions. activation of connective tissue mast cells in the skin. urticaria. disseminated mast cell activation. generalized anaphylaxis.

Systemic anaphylaxis ( anaphylactic shock). Allergens may be introduced directly into the bloodstream as a result of : : ﺍﺳﺒﺎﺏ ﺷﺎﺋﻌﻪ ﻟﺤﺪﻭﺛﻬﺎ - penicillin injection ﺍﻟﺪﻭﺍﺀ ﺍﻟﻤﺤﻘﻮﻥ ) ﻣﻬﺐ ﺷﺮﻁ ( . ﺑﻨﺴﻠﻴﻦ - honey-bee sting. disseminated ﻣﻨﺘﺸﺮ mast cell activation.

massive mediator release into the blood result in : wide spread increase in vascular permeability. airway Constriction. loss of blood pressure. difficulty in (hypotension). Breathing swelling of the larynx suffocation. ( difficulty in breathing ). * ﺍﻟﻌﻼﺝ this condition can be rapidly fatal but can be controlled by immediate injection of epinephrine ( adrenaline ).

Diagnosis : ﺍﻟﺘﺸﺨﻴﺺ 1. skin prick test (SPT). 2. specific Ig. E measurement. 3. challenge tests. 4. elimination – provocation tests. ( food allergy ).

skin prick test. skin prick test