Allergy Chapter 20 Immediate hypersensitivity because

Allergy Chapter 20

Immediate hypersensitivity because it begins rapidly, within minutes of antigen challenge (immediate), and has major pathologic consequences (hypersensitivity) In clinical medicine, these reactions are called allergy or atopy, and the associated diseases are called allergic, atopic, or immediate hypersensitivity diseases A variety of human diseases are caused by immune responses to nonmicrobial environmental antigens that involve TH 2 cells, immunoglobulin E (Ig. E), mast cells, and eosinophils Allergy is the most common disorder of immunity and affects 20% of all individuals in the United States

General Features of Immediate Hypersensitivity Reaction Hallmarks of allergic diseases are the activation of Th 2 cells and the production of Ig. E antibody Strong genetic predisposition Allergens, are usually common environmental proteins and chemicals Cytokines produced by Th 2 cells Clinical and pathologic manifestations consist of the vascular and smooth muscle reaction that develops rapidly after repeated exposure to the allergen (the immediate reaction) and a delayed late-phase reaction consisting mainly of inflammation

Allergic reactions are manifested in different ways, depending on the tissues affected, including skin rashes, sinus congestion, bronchial constriction, abdominal pain, diarrhea, and systemic shock (Anaphylaxis)

PRODUCTION OF IGE Ig. E antibody is responsible for sensitizing mast cells and provides recognition of antigen for immediate hypersensitivity reactions Atopic individuals produce high levels of Ig. E in response to environmental allergens, whereas normal individuals generally synthesize other Ig isotypes, such as Ig. M and Ig. G, and only small amounts of lg. E

The Nature of Allergens Antigens that elicit immediate hypersensitivity reactions (allergens) are proteins or chemicals bound to proteins to which the atopic individual is chronically exposed Typical allergens include proteins in pollen, house dust mites, animal dander, foods, and chemicals like the antibiotic penicillin Two important characteristics of allergens are that individuals are exposed to them repeatedly and, unlike microbes, they do not generally stimulate the innate immune responses that are associated with macrophage and dendritic cell secretion of TH 1 - and TH 17 -inducing cytokines Chronic or repeated T cell activation in the absence of strong innate immunity may drive CD 4+ T cells toward the TH 2 pathway, as the T cells themselves make IL-4,

These features include low to medium molecular weight (5 to 70 k. D), stability, glycosylation, and high solubility in body fluids Many allergens, such as the cysteine protease of the house dust mite Dermatophagoides pteronyssinus and phospholipase A 2 in bee venom, are enzymes, but the importance of the enzymatic activity Polysaccharides cannot elicit these reactions unless they become attached to proteins, and penicillin react chemically with amino acid residues in self proteins to form haptencarrier conjugates Specific Ig. E antibodies

Aero-allergens

Food allergens

Allergic Reaction

Skin Prick Test (SPT)

THE PROTECTIVE ROLES OF Ig. E- AND MAST CELL– MEDIATED IMMUNE REACTIONS

Immunotherapy for Allergic Diseases Several empirical protocols have been developed to diminish specific Ig. E synthesis called desensitization, small quantities of antigen are repeatedly administered subcutaneously Ig. G titers often rise, perhaps further inhibiting Ig. E production by neutralizing the antigen and by antibody feedback, and induction of Treg to iduce tolerance Changing the predominant phenotype of antigen-specific T cells from TH 2 to TH 1 Other approaches being used to reduce Ig. E levels include systemic administration of humanized monoclonal anti-Ig. E antibodies mentioned earlier

Allergic Diseases

Allergic Rhinitis

Allergic Rhinitis : AR is the most common form of perennial rhinitis ( % 43 – 77 ) AR is the most common form of allergy ( 500, 000 )

Risk factors 1 - positive family history of AR 2 – high socio-economic class 3 – total Ig. E > 100 before 6 year 4 – passive smoking especially before 1 yr 5 – feeding start before 6 month 6 – heavy contact with indoor allergens (esp. mite) 7 – male gender ? 8 – birth in pollination season ? 9 – first baby ( single baby ) ?

AR classification Allergic Rhinitis & seasonal perennial & intermittent persistent

AR classification 1 – seasonal allergic rhinitis ( SAR ) : - often related with outdoor allergens - tree pollens in early spring - grass pollens in spring & summer - weed pollens in summer & autumn 2 – perennial allergic rhinitis ( PAR ) : - often related with indoor allergens - mite , cockroach , danders , mold &…

Inflammatory cells in allergic rhinitis 1 – mast cell 2 – eosinophils 3 – T lymphocyte 4 – dendritic cells & macrophages 5 – epithelial cell

Clinical manifestations : Classic symptoms of allergic rhinitis are : 1 – sneezing 2 – itching ( itchy nose ) 3 – rhinorrhea ( runny nose ) 4 – blockade ( congestion )

Treatment : 1 – Environment control : aeroallergen & food allergen irritants 2 – pharmacotherapy : intermittent ----- anti-H +/- decongestant persistent ------- INCS 3 – Immunotherapy

ASTHMA

Ø Asthma is one of the most common chronic diseases, with an estimated 300 million individuals affected worldwide. Its prevalence is increasing, especially among children Ø Asthma is a chronic inflammatory disorder of the airways Ø Asthma is not a cause for shame. Olympic athletes, famous leaders, other celebrities, and ordinary people live successful lives with asthma

Prevalence data for childhood asthma v Male > female ( prepubertal ) v Female > male ( postpubertal ) v Urban > rural v Developed (western) > undeveloped countries v Slack > white ( minimal different ) v School age > preschool age ( prevalence ) v Preschool age > School age ( incidence )

Allergy & asthma ? Childhood asthma Adult asthma % 80 allergic % 50 allergic

Risk factors for asthma ü atopy ü allergy to house dust mite ü allergen exposure ü family history of asthma ü early viral RTI ü passive smoking ü cigarette smoking ü maternal smoking ü prematurity ü male gender ü length of breast feeding ü food intolerance & hypersensitivity ü high dietary intake of sodium ü air pollution ü urban living

Hygiene – hypothesis

Pathogenesis

Clinical manifestation The classic symptoms of asthma cough wheez Chest Thightness chest pain

Treatment

Atopic dermatitis (atopic eczema)

Age-specific lesions of AD - in infants - in older children & adult cheek , scalp , extensors surface flexors (politeal fossa, antecubital fossa )

Environment factors 1 – allergens ( aeroallergen – food allergen ) 2 – irritants ( detergent-soaps-low humidityhigh humidity-hot air-cold air-, … ) 3 – infections ( S. A , HSV , malsseziafurfur ) 4 – emotional stress 5 – endocrine factors

Vicious cycle of skin infection and AD Decreased function Of skin barrier AD Skin infections

Triggers of atopic dermatitis

Local treatment Systemic treatment Environment control

Anaphylaxis

Etiology Foods : 36% Drug : 17% Insect sting : 15% others: 32% ( latex– exercise– cold- idiopathic)

The most common causes of anaphylaxis Foods Drugs Peanut Tree nut Fish Shellfish Egg Cows milk wheat Antibiotics Aspirin NSAIDs Anesthetic agents Opioids RCM

Clinical manifestation Cutaneous : 80 -90% flushing, urticaria angioedema Respiratory : 50 -60% hoarseness, nasal congestion, sneezing, dyspnea, cough, wheezing and laryngeal edema Cardiovascular : 30 -35% hypotension, dysrrhytmia, arrhythmia, myocardial ischemia Gastrointestinal : 20 -25% nausea, abdominal cramping, vomiting, and diarrhea Miscellaneous: headache : 5 -8%, Substernal pain : 4 -6%, Seizure : 1 -2%

Treatment Epinephrine ( Adrenaline ) H 1 blocker ( Diphenhydramine ) H 2 blocker ( Ranitidine ) Corticosteroid ( Hydrocortisone ) B 2 agonist ( Ventolin )

Urticaria / Angioedema

Episodes of hives that continue for < 6 week are considered acute, and Those that persist for > 6 week are designated chronic

Etiology (1) Foods & food additives (2) Drugs (3) Insect bite & insect sting (4) Latex & other contactants (5) Physical agents (6) Infections (7) (8) (9) (10) (11) (12) (13) Transfusion reactions CVD Malignancy Complement disorders Hereditary disease ( HAE , muckle-well , … ) Systemic disease ( PV , systemic mastocytosis , . . ) Idiopathic

Acute urticaria Ig. E - mediated Foods , drugs , insect sting , latex , … Directly: morphine, exercise, cold, sunlight Non-Ig. E-mediated Leukotrienes change: aspirin & NSAIDS Alternative pathway activation: RCM

Acute urticaria

Cold urticaria

Dermatographism

Solar Urticaria

Chronic urticaria is reported to be more common in adults, while acute urticaria is more common in children Both sexes are affected; however, chronic urticaria is more common in women, especially in middle-aged women CIU occurs twice as often in women as in men

Urticaria Ø Male = female Acute urticaria Ø More common in children and adolescent Ø peak : 20 – 30 year Ø Often due to foods & drugs Ø % 15 – 20 of GP Ø female > male chronic urticaria Ø More common in middle age Ø peak : 30 – 50 year Ø Often idiopathic ( CIU ) Ø Approximately % 1

Etiology of Chronic urticaria % 80 Idiopathic ( CIU ) % 15 Physical agents %5 Autoimmunity , malignancy , complement disorder , occult infections , systemic disease , …

Antihistamines & urticaria

Classification of angioedema without urticaria

ACE - inhibitor angioedema

HAE ( treatment ) Treatment of HAE is difficult For acute attacks, C 1 INH concentrate or FFP should be administered Intubation or tracheotomy may be necessary Corticosteroids and antihistamines are not helpful Subcutaneous adrenaline ( 0. 01 ml / kg , epinephrine 1 : 1000, max = 0. 3 ml ) may be tried