This document provides an overview of the different types of hypersensitivity reactions. It describes the pathophysiology, clinical manifestations, treatments, and examples for each of the 5 types of hypersensitivity reactions: Type I (immediate/anaphylactic), Type II (cytotoxic antibody), Type III (immune complex), Type IV (delayed-type), and Type V (stimulatory). It also provides details on the diagnosis and management of anaphylaxis, including the use of epinephrine as first-line treatment.

1. Hypersensitivity Josyann Abisaab, MD Department of Emergency Medicine New York Presbyterian Hospital- Weill Cornell Medical Center

2. Outline Types of Hypersensitivity Anaphylaxis Disposition Prevention

3. Definition of Hypersensitivity Undesirable reactions produced by the normal immune system.

4. Classification of Hypersensitivity Type I: Immediate/ A naphylactic Type II: C ytotoxic Antibody Reaction Type III: I mmune Complex Reaction Type IV: D elayed-Type Hypersensitivity Type V: S timulatory Hypersensitivity

5. Type I- Immediate hypersensitivity Provoked by reexposure to a specific antigen. IgE mediated Mast cells and Basophils stimulation Release of Histamine and other chemicals Vasodilation, mucous secretion, bronchospasm

6. Type I- Immediate Acute response within 1 hour Late-phase response 4-6 hours after original reaction, can last 1-2 days Local vs. systemic

7. Type I- Immediate Urticaria (hives) Angioedema Allergic conjunctivitis Allergic Rhinitis Allergic Asthma Anaphylaxis

8. Type II- Cytotoxic Antibody Reaction Antigen is on the patient’s own cell surfaces Mediated by IgG and IgM Complement activation Cell lysis and death Reaction takes hours to a day

9. Type II- Cytotoxic Transfusion reactions Rh incompatibility Autoimmune hemolytic anemia Goodpasture’s syndrome Pemphigus ITP Rx: anti-inflammatory + immunosuppressive agents

10. Type III- Immune Complex Hypersensitivity Antigen-antibody complexes deposit in tissue Antigen is soluble- not attached to organ involved Classical pathway of complement activation Takes hours to days to develop

11. Type III- Immune Complex Serum sickness SLE Rheumatoid arthritis Erythema nodosum Arthus reaction (Farmer’s Lung) Immune complex glomerulonephritis Rx: anti-inflammatory agents

12. Type IV- Delayed-Type Hypersensitivity Mediated by T-Lymphocytes Takes 2-3 days Contact dermatitis (poison ivy, nickel) PPD Transplant rejection (GVHD) Rx: corticosteroids + other immunosuppressive agents

13. Contact Dermatitis

14. Delayed Hypersensitivity Reactions TB, leprosy Foreign body presence Hardening 21-28 days Granuloma Tuberculin Intradermal Local induration 48-72 hr PPD Poison ivy, heavy metals Epidermal Eczema 48-72 hr Contact Antigen Site Clinical Appearance Reaction time Type

15. Type V- Stimulatory Hypersensitivity IgG stimulate their target Graves Disease Myasthenia Gravis Ligand induced apoptosis Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (TENS)

16. Type V- Stimulatory Stevens Johnson Syndrome TENS

17. Anaphylaxis Case Presentation: 39 y.o male BIBA in respiratory distress with agonal pulse. Paramedics report patient was helping a friend paint when he was stung by a bee. He walked into the house, saying:”I don’t feel good” and collapsed. Intubated at scene, en route given endotracheal and IV Epi, IV Benadryl

18. Anaphylaxis Case Presentation: On arrival in ED, patient intubated, cyanotic from neck up, CPR in progress 2 nd Large bore IV, wide open fluids Dopamine drip Epnephrine drip Central line Isuprel drip, Levophed drip Monitor: agonal wide-complex

19. Anaphylaxis Case presentation: TVP failed to capture After 20 min prehospital and 30 min hospital resuscitation, no response. Patient died. Cause: “Fatal Anaphylactic Reaction”

20. What is Anaphylaxis? “ A systemic reaction of multiple organ systems to an antigen-induced IgE-mediated immunologic mediator release in a previously sensitized individual”

21. What does the word mean? “ ana” means against or backwards “ phylaxis” means guard or protect Anaphylaxis= “without protection” Prophylaxis= “for protection”

22. What is Anaphylactoid? A nonimmunologic reaction Not mediated by IgE Direct histamine release Same manifestations & treatment as anaphylaxis Causes: RCM, opiates, ACEI, exercise, blood products, gammaglobulin, NSAIDs, ASA

23. Anaphylaxis: How does it manifest? Clinical severity varies from mild to fatal Majority of reactions are respiratory and dermatologic Innocent early findings may progress to lethal over a short time

24. What causes the deaths? Laryngeal edema and acute bronchospasm >70% Circulatory collapse >25% other <5% - ?brain ?MI

25. In USA 30,000 emergency room visits each year 400 to 800 deaths/year IV penicillin accounts for 100 to 500 deaths per year Hymenoptera stings account for 40 to 100 deaths per year Risk factors: protracted course, betablockers, adrenal insufficiency

26. Histamine Prime mediator of both local and systemic effects H1: smooth muscle contraction,  vascular permeablility H2: gastric acid secretion, release of more histamine,  vascular permeability H3: inhibition of central and peripheral neurotransmitter release, inhibition of further histamine

27. Clinical expression depends on: Degree of hypersensitivity Quantity, route, rate of antigen exposure Pattern of mediator release Target organ sensitivity and responsiveness

28. Timing Uniphasic Biphasic Protracted Laryngeal edema more common in biphasic (40%) or protracted (57%) cases

29. Usual culprits

30. Clinical manifestations Skin: urticaria and angioedema Respiratory: cough, dyspnea, wheezing, hoarseness

31. Clinical manifestations Lightheadedness or syncope Nasal congestion and sneezing Ocular itching and tearing Cramping abdominal pain with N/V/D Headache Sense of impending doom ↓ level of consciousness

32. Examination Urticaria

33. Examination Angioedema

34. Examination Angioedema of oropharynx

35. Examination Conjunctivitis, rhinitis Tachypnea, tachycardia, hypotension Laryngeal stridor, hoarseness Wheezing, ronchi, diminished air flow

36. Optimal Management High index of suspicion Early diagnosis Pharmaceutical intervention Observation Disposition

37. Index of suspicion The motto of Emergency Medicine: TREAT FIRST ASK QUESTIONS LATER

38. Treating mild anaphylaxis Urticaria, rhinitis, conjunctivitis, mild bronchospasm Epinephrine 1:1000 0.3cc IM may repeat every 5-20min prn 0.01mg per kg in children Benadryl 50 mg po or IM Consider: H2-blocker, prednisone, inhaled beta-agonists

39. Steroids Benefit 6-12 hrs after administration May prevent biphasic or protracted reaction

40. Myth: Epi is dangerous Reality: Risks of anaphylaxis far outweigh risks of Epi administration Minimal cardiovascular effects in children (Simons et al, 1998) Caution in: elderly, known cardiac disease and tachyarrythmias

41. Treating moderate anaphylaxis Angioedema or hypotension with BP>80mmHg Epinephrine 1:1000- 0.3 cc IM Benadryl 50mg IM or IV Pepcid IV Solumedrol 40-125mg IV Oxygen, IVF, cardiac monitor

42. Treating severe anaphylaxis Laryngeal edema, respiratory failure, shock Epinephrine 1:10,000- 1cc IV over 5 min, repeat every 3-5 min prn Benadryl 50-100mg IV over 3 min H2 blockers Solumedrol Nebulizers: racemic epi, albuterol

43. Laryngeal edema Chin lift, jaw thrust Naso-or oropharyngeal airway Racemic epi 0.5 cc neb Heliox (Boorstein et al, AEM, 1989) Tracheal intubation prn Surgical airway prn

44. Persistent bronchospasm Albuterol by continuous nebulization Aminophylline 5.6 mg/kg IV over 20-30 min Atrovent by nebulization Heliox Steroids Intubation

45. Persistent hypotension Trendelenberg 2 largebore IV’s infusing crystalloid Monitor urine output and CVP PASG Consider: Naloxone 0.4-0.8mg IV Vasopressors: dopamine, isoproterenol, levophed

46. What about Glucagon? When epi contraindicated, may be an option Positive inotropic and chronotropic cardiac effects Consider in patients: On beta blockers With known CAD Pregnant women No response to other drugs

47. Disposition Systemic features: observe for 6-8 hours Cannot predict biphasic reaction Admission mandatory for: Moderate to severe reaction, even if they respond rapidly to Rx Consider admission for: Elderly CAD Asthma On beta blocker

48. May be discharged home if Mild anaphylaxis No hypotension No signs of airway obstruction Rapid response to ED therapy Observed for 6 hours without recurrence Safe discharge to care of responsible adult

49. Outpatient management 4 day course of Benadryl Q6h 4 day course of Pepcid BID 4 day course of Prednisone 50mg/day (Ellis et al, CMAJ, 2003) Referral to an Allergist

50. Prevention Avoid the food Aerosol spray containing Epi-Primatene or Medihaler-Epi Epi-Pen Medic Alert bracelet

51. Board Type Questions A 27 year old man presents after a syncopal event following a long run. He c/o lightheadedness and itching, along with swelling of his hands and feet. His BP is 68/36 mmHg and pulse is 160. Lung examination shows he has diffuse wheezing. His blood glucose is 95 mg/dl. The most important initial IV therapy would be: Epinephrine Diphenhydramine Methylprednisolone Normal Saline Pepcid

52. Board Type Questions Type I Hypersensitivity: occurs 24 hours after the initial stimulus is produced by IgE antibodies is cell mediated is best treated with steroids is diagnosed by measuring serum histamine levels

53. Board Type Questions A 45 year old man with no PMH was playing golf when he complained of a sting on his hand, followed by shortness of breath and loss of consciousness. EMS at scene report a BP 70/40, HR 140 and bilateral wheezing. The most likely diagnosis is: Vasovagal syncope Asthma Psychogenic syncope related to bad golfing day Anaphylactic shock Myocardial Infarction

54. Board Type Questions A 19-year-old woman with a past history of seasonal allergic rhinitis is referred to the ED from her family doctor’s office. She had received her routine injection of allergen immunotherapy (ragweed). Twenty minutes later, she began to notice itching in the palms of her hands, followed by shortness of breath and a sensation of throat swelling. In the ED, patient is noted to be flushed, sweating and in moderate distress. Her BP is 110/60 and her HR is 120. She is speaking in full sentences. The most appropriate initial emergency treatment would be: Epinephrine 1:10,000- 1cc IV Racemic Epi 0.5 cc neb Epinephrine 1:1000- 0.3 cc IM Albuterol neb Benadryl 50mg po

55. Board Type Questions A 40 year old woman presents to the ED 30 minutes after eating chicken with cashews at a chinese restaurant. Patient complains of hives, itchy eyes, throat tightness as well as mild shortness of breath. The astute ED intern makes the diagnosis of urticaria and mild anaphylaxis. She administers IM Epi and Benadryl with immediate resolution of symptoms. Patient now feels well and wants to go home. You agree with patient and write discharge order You give her steroids first then discharge her You recommend observation in the ED for at least 6 hours You recommend discharge home under the care of an adult after 2 hours You recommend admission to the hospital

56. Any questions?