1. Chapter 20 Allergy

4. 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 TH2 cells, immunoglobulin E (IgE), mast cells, and eosinophils Allergy is the most common disorder of immunity and affects 20% of all individuals in the United States

5. General Features of Immediate Hypersensitivity Reaction Hallmarks of allergic diseases are the activation of Th2 cells and the production of IgE antibody Strong genetic predisposition Allergens, are usually common environmental proteins and chemicals Cytokines produced by Th2 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

6. 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)

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

8. 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 TH1- and TH17-inducing cytokines Chronic or repeated T cell activation in the absence of strong innate immunity may drive CD4+ T cells toward the TH2 pathway, as the T cells themselves make IL-4,

9. These features include low to medium molecular weight (5 to 70 kD), stability, glycosylation, and high solubility in body fluids Many allergens, such as the cysteine protease of the house dust mite Dermatophagoides pteronyssinus and phospholipase A2 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 hapten- carrier conjugates Specific IgE antibodies

10. Aero-allergens

11. Food allergens

12. Allergic Reaction

21. Skin Prick Test (SPT)

23. THE PROTECTIVE ROLES OF IgE- AND MAST CELL– MEDIATED IMMUNE REACTIONS

24. Immunotherapy for Allergic Diseases Several empirical protocols have been developed to diminish specific IgE synthesis called desensitization, small quantities of antigen are repeatedly administered subcutaneously IgG titers often rise, perhaps further inhibiting IgE 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 TH2 to TH1 Other approaches being used to reduce IgE levels include systemic administration of humanized monoclonal anti-IgE antibodies mentioned earlier

25. Allergic Diseases

26. Allergic Rhinitis

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

28. Risk factors 1 - positive family history of AR 2 – high socio-economic class 3 – total IgE > 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 ) ?

29. AR classification Allergic Rhinitis & & seasonalperennial intermittentpersistent

30. 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 &…

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

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

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

34. ASTHMA

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

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

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

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

40. Hygiene – hypothesis

41. Pathogenesis

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

43. Treatment

45. Atopic dermatitis (atopic eczema)

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

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

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

49. Triggers of atopic dermatitis

50. treatment Local treatment Environment control Systemic treatment

51. Anaphylaxis

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

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

54. 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%

55. Treatment Epinephrine ( Adrenaline ) H1 blocker ( Diphenhydramine ) H2 blocker ( Ranitidine ) Corticosteroid ( Hydrocortisone ) B2 agonist ( Ventolin )

56. Urticaria / Angioedema

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

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

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

60. Acute urticaria

61. Cold urticaria

62. Dermatographism

63. Solar Urticaria

64. 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 Chronic urticaria

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

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

67. Antihistamines & urticaria

68. Classification of angioedema without urticaria

69. ACE - inhibitor angioedema

70. Treatment of HAE is difficult For acute attacks, C1 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 HAE ( treatment )