Portier and Richet first coined the term anaphylaxis.

1. Portier and Richet first coined the term anaphylaxis. In 1902 when a second vaccinating dose of sea anemone toxin caused a dog's death. The response was the opposite of prophylaxis and thus was referred to as anaphylaxis, meaning without protection. Phylaxis= protection

2. Anaphylaxis- is an acute life-threatening reaction caused by an IgE-mediated reaction and results from the sudden systemic release of mast cells and basophil mediators .

3. Anaphylactoid reaction- reaction that produce the same clinical picture as anaphylaxis but are not IgE mediated. Anaphylactic – this term has been used to describe the clinical reaction (not the mechanism).

4. IMMUNOLOGY OF ANAPHYLAXIS

6. PATHOPHYSIOLOGY OF ANAPHYLAXIS Allergen crosses an epithelial and/or endothelial barrier Access to the reactive, sensitized cells –mast cells, basophils Release of cellular mediators leads to end-organ response in the skin, respiratory tract , cardiovascular system , gastrointestinal tract, nervous system.

7. Histamine H3 receptor H1 receptor H1,H2 receptors Pruritus Rhinorrhea Tachycardia Bronchospasm Headache Flushing Hypotension Left ventricular function

8. Effects of histamine on airways Histamine Bronchoconstriction by stimulation of H1 receptors on smooth muscles. Mucosal edema from increased microvascular permeability (H1) leading to transudation of fluid and macromolecules through wide intercellular gaps (> 12 nm). Direct stimulation of vagal (cholinergic) nerves can induce airway smooth muscle contraction Stimulation of H1 receptors increases mucus secretions, and stimulation of H2 receptors increases mucus viscosity.

9. Effects of histamine on the heart H1 receptors mediate coronary artery vasoconstriction and increased vascular permeability. H2 receptors mediate atrial and ventricular contractile forces, atrial rate, and coronary artery vasodilation. Decreased diastolic pressure and increased pulse pressure

10. Histamine H1 receptor on endothelial cell L-arginine Nitric oxide Decreases venous return

11. Pathologic features of anaphylaxis Laryngeal edema Pulmonary hyperinflation Myocardial edema Visceral congestion or hemorrhage Eosinophilic infiltration Elevated tryptase levels Death from cardiovascular collapse or respiratory obstruction

14. The more rapidly anaphylaxis occurs after exposure to an offending stimulus the more likely the reaction is to be severe and potentially life-threatening. Anaphylaxis often produces signs and symptoms within minutes typically 5-30 minutes , but some reaction , such as aspirin, might develop after 30 minutes . Late-phase or biphasic reactions, which occur 8-12 hours after the initial attack.

16. The average annual incidence of anaphylaxis is 10-20 cases per 100,000 person-years. Fatalities from anaphylaxis range from 0.65-2% of patients with anaphylaxis The annual incidence of fatal anaphylaxis among hospitalized subjects is estimated to be 154 per 1,000,000. ß-lactam antibiotics are tought to cause 400-800 fatal anaphylactic episodes per year. An estimated 150 fatalities from food-induced anaphylaxis occur each year in the united states. Allergen immunotherapy 1 per 2,000,000 injections. Insect stings probably cause at least 50 fatalities annually in USA .

17. Risk factors Atopy Route and timing of administration The longer the interval between exposures, the less likely an anaphylactic (IgE-mediated) reaction will recur. Asthma Delay in administration of epinephrine

19. DIAGNOSIS

20. DIAGNOSIS OF SPECIFIC CAUSE OF ANAPHYLAXIS Skin tests

21. IgE specific - RAST Radio-AllergoSorbent Test

22. Challenge test ( double-blind)

23. Tryptase

27. The first documented case of a food fatal reaction was described in 1926 by a pediatrician. A 1 -year-old boy with atopic eczema experienced three episodes of generalized allergic reactions at home after intake of a few spoons of mashed peas. In the hospital setting an oral challenge with carrots/mashed peas was performed under the supervision of a chief nurse. Immediately after the intake of the test meal the child developed angioedema, cyanosis and collapsed. He died despite emergency treatment.

28. Food and Anaphylaxis

29. Clinical aspects and allergenic foods in life-threatening food anaphylaxis Moneret-Vautrin, D. A., Morisset, M., Flabbee, J., Beaudouin, E. & Kanny, G.Epidemiology of life-threatening and lethal anaphylaxis: a review.Allergy60 (4), 443-451.

30. Anaphylactic reactions to foods almost always occur immediately. The majority of reactions are not fatal. In general, reactions worsen with the development of asthma and as children get older. The most useful diagnostic tests: SPT and food challenges Epinephrine should be available for use

34. Exercise-induced anaphylaxis • This is a rare syndrome that can take one of two forms: • The first form is food-dependent, requiring both exercise and the recent ingestion of particular foods to cause an episode of anaphylaxis ~ 50%. • The second form is characterized by intermittent episodes of anaphylaxis during exercise, independent of any food ingestion. Anaphylaxis will not necessarily occur during every episode of physical exertion

35. Premonitory symptoms can include: diffuse warmth, itching and erythema, urticaria generally ensues and progress to angioedema. Episodes can include gastrointestinal symptoms, laryngeal edema, and/or vascular collapse. Delaying exercise for about 5 hours after eating will prevent reaction in food related exercise-induced anaphylaxis. Carry Epipen, should wear alert identification denoting their condition, have a companion with them when exercising.

36. idiopathic anaphylaxis The diagnosis of idiopathic anaphylaxis a diagnosis of exclusion. Nearly 20% of cases of anaphylaxis are idiopathic. There are no clinically distinguishing features, and it may be fatal. Management often consists of prophylactic corticosteroid and antihistamine therapy.

37. Drug anaphylaxis

39. Etiologies of 100 cases of life-threatening drug anaphylaxis Moneret-Vautrin, D. A., Morisset, M., Flabbee, J., Beaudouin, E. & Kanny, G.Epidemiology of life-threatening and lethal anaphylaxis: a review.Allergy60 (4), 443-451.

40. Penicillin and its metabolites are haptens, small molecules that only elicit an immune response when conjugated with proteins. 95% 5% Benzylpenicilloyl (BPO) Major determinant Pre-Pen Benzylpenicilloate , Benzylpeniloate Minor determinant Most severe allergic reaction

41. Other beta-lactam antibiotics may cross-react with penicillins or may have unique structures that also act as haptens. The incidence rate of anaphylaxis to cephalosporins in penicillin-anaphylactic patients appears to be much less than the 10% frequently quoted. • Patients with less well-defined reactions to penicillin have a very low risk (1-2%) of developing anaphylaxis to cephalosporins. The rate of skin-test reactivity to imipenem in patients with a known penicillin allergy is almost 50%.

42. The use of BPO and Penicillin G 10000 unit ( without minor determinants) can detect 97%-99% of potential life threatening reactions. Skin test positive To BPO and Penicillin G Skin test negative to BPO and Penicillin G 1.Give alternative drug 2. Desensitize to penicillin History of mild reaction History of immediate or severe reaction Graded challenge given 1/100th of dose followed in 30 min by full dose 1.Graded challenge given 1/1000th of dose followed in 30 min by full dose. 2. desensitize

43. NSAIDs ALLERGY Aspirin (ASA), by irreversibly inhibiting platelet cyclooxygenase-1 enzyme (COX-1), prevents platelet aggregation

45. ASA can also cause a hypersensitivity reaction: • respiratory sensitivity (asthma and/or rhinitis)-These patients have marked cross-reactivity between aspirin and most NSAIDs. • Arachidonic acid • cutaneous sensitivity (urticaria and/or angioedema) • systemic sensitivity (anaphylactoid reaction) mechanism that is more consistent with IgE-mediated anaphylaxis. With true anaphylaxis, the different cyclooxygenase inhibitors do not appear to cross-react. cyclo-oxygenase pathway lipoxygenase pathway leukotrienes

46. Latex is the name for the milky sap collected from the rubber tree- hevea brasiliensis

47. The latex has a cross-reactive epitopes of foods: banana, avocado, chestnut.

49. 3 groups are at higher risk: health care workers: 4.5-14.4% sensitivity. , children with spina bifida and genitourinary abnormalities: 34-100% sensitivity. workers with occupational exposure to latex. Dig : SPT better than RAST Patients with spina bifida – regardless of a HISTORY OF LATEX ALLERGY should have all medical-surgical-dental procedures performed in a latex-safe environment.

50. Hymenoptera sting anaphylaxis Yelow jacket Anaphylaxis occur with 0.5-1.5% of stings. Vespa orientalis Wasp