2. ANAPHYLAXIS  The first documented case of anaphylaxis was in 2641 B.C., when Pharaoh Menes of Egypt died from a Wasp sting. While the first fatal reaction to peanuts was described by a Canadian researcher Dr Evans in 1988.  Allergy to venom from wasp stings can cause anaphylaxis as can allergy to latex and drugs such as penicillin and aspirin. Bee sting allergy is less common in the UK.

3. ANAPHYLAXIS  The most common cause of anaphylaxis in the community is from eating a food to which you are allergic such as nuts, peanuts, eggs, mammalian milk, soya, wheat, fish and shellfish. These 8 foods account for 90% of cases of food induced anaphylaxis. Peanuts and tree nuts (such as Brazil nuts, Hazelnuts, Almonds and Walnuts) are the foods most likely to provoke a reaction.

4. ANAPHYLAXIS  Some people may develop anaphylaxis after eating certain foods such as celery, shrimps, wheat, apple, hazelnut, squid and chicken and then exercising shortly after ingesting the food – triggering Exercise Induced Anaphylaxis.

5. SYSTEMIC ANAPHYLAXIS * Most extreme over-reaction of immune system * Caused by allergens which reach bloodstream * Venomous insect stings * IV and IM drugs * PO drugs (rapid absorption and high bioavailability)

6. Anaphylaxis- IgE-mediated  Antibiotics and other medications Penicillins, β-lactams, tetracyclines, sulfas, vaccines, immunotherapy  Foreign proteins Latex, hymenoptera venoms, heterologous sera, protamine,  Foods Shellfish, peanuts, and tree nuts  Exercise induced

9. SYSTEMIC ANAPHYLAXIS * Mechanism is widespread activation of mast cells throughout body resulting in * Vascular permeability (circulatory collapse / anaphylactic shock) * Constriction of smooth muscles * Death by constriction of airways and swelling of epiglottis

12. ANAPHYLAXIS  Signs within 5 to 30 min (very rarely hours)  Recurrent (biphasic) anaphylaxis – occurs 8-10h after the initial attack  Persistent anaphylaxis – can last for up to 32h

13. SIGNS AND SYMPTOMS OF SYSTEMIC ANAPHYLAXIS Signs/Symptoms : * Skin and soft tissue * Flushing, pruritis, urticaria and angioedema * Cardiovascular : * Syncope, tachycardia or no pulse, hypotension, cardiac arrhythmias * Nervous * Apprehension, convulsions, headache, unconsciousness * Gastrointestinal * Vomiting, diarrhea, abdominal cramps, nausea, * Respiratory * Wheezing, dyspnoe, bronchospasm

14. Anaphylaxis Skin signs: - erythema, urticaria, pruritis,

15. Anaphylaxis Skin signs: - pruritis, angioedema

16. ANAPHYLAXIS  The most common symptoms were urticaria and angioedema, occurring in 88% of patients. The next most common manifestations were respiratory symptoms, such as upper airway edema, dyspnoe and wheezing. Cardiovascular symptoms of dizziness, syncope, and hypotension, were less common, but it is important to remember that cardiovascular collapse may occur abruptly, without the prior development of skin or respiratory manifestations.  Other symptoms of rhinitis, headache, substernal pain, and pruritus without rash were less commonly observed.

17. Most Common Clinical Manifestations of Anaphylaxis Symptom… How often?  Urticaria /Angioedema 88%  Upper airway oedema 56%  Dyspnoe / bronchospasm 50%  Flushing 51%  Cardiovascular collapse “Anaphylactic shock” 30%  GI 30%

18. ANAPHYLAXIS TREATMENT  Prevention- avoid the allergen  People with asthma and/or allergy have the risk of anaphylaxis, especially those with un- controlled asthma and/or severe allergy risk. These people should consult to an allergy specialist. When the anaphylaxis trigger has been identified by allergy testing, you must avoid the allergen very carefully.allergy testingallergen

19. TREATMENT OF SYSTEMIC ANAPHYLAXIS * Epinephrine is drug of choice * Sympathicomimetic drug acting on * Alpha receptors of vascular endothelium * Beta receptors of bronchial smooth muscles * Administered by I.M. injection into antero - lateral thigh * Do not inject into buttock * Do not inject I.V. * Cerebral hemorrhage * Epinephrine Auto-Injector (EpiPen) * Adult (0.3 mg) and pediatric (0.15)

20. How to Give Epinephrine?

21. In the muscle…. Which Muscle? Lateral Thigh

22. How to Give Epinephrine?

23. EpiPen  /EpiPen  Jr: Directions for Use

24. EpiPen  /EpiPen  Jr: Directions for Use

25. EpiPen  /EpiPen  Jr: Directions for Use

26. Use of Epi Pen…. No contraindications in anaphylaxis !!! Failure or delay associated with fatalities I. M. may produce more rapid, higher peak levels vs S. C. Must be available at all times

27. ADMINISTRATION OF intramuscular ADRENALINE Intramuscular injection of epinephrine into the tigh – more effective than injection into the arm or subcutaneous administration

28. When to Repeat Epinephrine? Practice Parameter Update - US  – Repeat every 5 minutes as needed to control symptoms and blood pressure  – Some guidelines suggest liberalizing the frequency if deemed necessary – no absolute contraindication for epinephrine UK Consensus Panel on emergency Guidelines and International consensus guidelines for emergency cardiovascular care  – May judiciously be repeated as often as every 5 minutes

29. Who Should Get Epinephrine? Everyone with rapid progression of symptoms  Laryngeal edema  Bronchospasm  Severe GI symptoms  Hypotension  Highest fatality rates when epinephrine is delayed  Age is not a limiting factor

30. Anaphylaxis Treatment –First Line ESTABLISH AIRWAY and supplemental O2 I.V. fluids Pulmonary symptoms: Albuterol by nebulization or MDI Deterioration of pulmonary symptoms : Racemic epinephrine by nebulization; Consider intubation or tracheostomy

31. After The Epi –Second Line Therapy For Everyone Antihistamines: H1 + H2 blockers  Diphenhydramine 25-50 mg IV/IM/PO 1 mg/kg PO/ IM/ IV (kids)  Ranitidine 50 mg IV…….. 4 mg/kg PO up to 300 mg 1.5 mg/kg IM/IV up to 50 mg (kids)

32. What About Non-Sedating H-1 blockers?  Cetirazine (Zyrtec) 10 mg po q day  Loratidine (Claritin) 10 mg po q day  Desloratadine (Clarinex) 5 mg po q day  Fexofenadine (Allegra)180 mg po q day  Only available in oral form, long record of efficacy with urticaria

33. Other Second Line Considerations  Inhaled beta-agonists - if wheezing  Corticosteroids – 1-2 mg/kg prednisone PO – 1-2 mg/kg methylpredisolone IV (max 250 mg)  Not helpful acutely  ? Prevent recurrent anaphylaxis  Glucagon ( if beta blocked) 1-5 mg slow IV, 1-5 ug/min

34. Treatment of Anaphylaxis…  Observe for a minimum 8-12 hours  Rebound or persitant symptoms Repeat epinephrine, repeat antihistamine ± H 2 blocker

36. This is a simple instruction of injecting EpiPen:  Pull the seal cover.  Put the black tip on your upper thigh (no need to undress the patient, unless the fabrics is too thick).  Strongly press the EpiPen into your thigh until you feel the injection done.  Hold the EpiPen for 10 seconds.  Release the EpiPen while slowly massage the injected area.  Call for medical help/ambulance.  If the symptoms have not reduced after 30 minutes while you are waiting for medical help, give the second injection.

38. Anaphylaxis Fatalities  Estimated 500–1000 deaths annually  1% risk  Risk factors: Failure to administer epinephrine immediately Peanut, Soy & tree nut allergy (foods in general) Beta blocker, ACEI therapy Asthma Cardiac disease Rapid IV allergen Atopic dermatitis (eczema)  Miller RL. Epidemiology of anaphylaxis. Presented at: Anaphylaxis: Safely Managing Your Patients at Risk for Severe Allergic Reactions. Postgraduate Institute for Medicine; October 8, 1999; Washington, DC.Bocher BS. Anaphylaxis. N Engl J Med 1991:324:1785–1790

39. Food-induced Anaphylaxis: Incidence  35%–55% of anaphylaxis is caused by food allergy  6%–8% of children have food allergy  1%–2% of adults have food allergy  Incidence is increasing  Accidental food exposures are common and unpredictable Kemp SF, et al. Anaphylaxis. A review of 266 cases. Arch Intern Med 1995; 155:1749–54. Pumphrey RSH, et al. The clinical spectrum of anaphylaxis in northwest England. Clin Exp Allergy 1996; 26:1364–1370. Bock SA. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. Pediatrics 1987;79:683–688.

40. Food-induced Anaphylaxis: Common Symptoms  Oropharynx: Oral pruritus, swelling of lips and tongue, throat tightening  GI: Crampy abdominal pain, nausea, vomiting, diarrhea  Cutaneous: Urticaria, angioedema  Respiratory: Shortness of breath, stridor, cough, wheezing

41. Food-induced Anaphylaxis: Fatal Reactions  Fatal reactions are on the rise ~150 deaths per year ( in US ) Usually caused by a known allergy  Patients at risk: Peanut and tree nut allergy Asthma Prior anaphylaxis Failure to treat promptly epinephrine  Many cases exhibit biphasic reaction Anaphylaxis Committee, AAAAI. Anaphylaxis. Teaching Slides. 2000.

42. Venom-induced Anaphylaxis: Incidence  0.5%–5% (13 million) Americans are sensitive to one or more insect venoms  Incidence is underestimated  Incidence increasing due  Incidence rising due to more outdoor activities  At least 40–100 deaths per year

43. Venom-induced Anaphylaxis: Common Culprits  Hymenoptera Bees Wasps Hornets

44. Hymenoptera

45. Venom-induced Reactions: Common Symptoms  Normal: Local pain, erythema, mild swelling  Large local: Extended swelling, erythema  Anaphylaxis: Usual onset within 15–20 minutes Cutaneous: urticaria, flushing, angioedema Respiratory: dyspnoe, stridor Cardiovascular: hypotension, dizziness, loss of consciousness  30%–60% of patients will experience a systemic reaction with subsequent stings

46. Venom-induced Anaphylaxis: Prevention Risk Management Keep EpiPen  or EpiPen  Jr on hand at all times Educate and train on EpiPen  use Develop emergency action plan Wear a MedicAlert  bracelet Consult an allergist to determine need for venom immunotherapy

47. Venom-induced Anaphylaxis: Immunotherapy  Medical criteria Venom immunotherapy is medically indicated in any adult with a history of a systemic reaction to an insect sting, and in children who have had life- threatening sting reactions. Positive venom skin test & sIgE  97% effective  Can be discontinued in most after 3–5 years;

48. Exercise-Induced Anaphylaxis  First reported in 1979  Mechanism of action is unclear  Predisposing factors: ASA, Food, including: shell fish, cheese, dense fruits, snails.  Triggered by almost any physical exertion  Most common in very athletic children

49. Exercise-Induced Anaphylaxis  Four Phases Prodromal phase is characterized by fatigue, warmth, pruritus, and cutaneous erythema The early phase: urticarial eruption that progresses from giant hives may include angioedema of the face, palms, and soles. Fully established phase: hypotension, syncope, loss of consciousness, choking, stridor, nausea, and vomiting ( 30 minutes to 4 hours.) Late or postexertional phase, Prolonged urticaria and headache persisting for 24-74 hours.

50. NON-IgE ANAPHYLAXIS Drugs  Opiates  NSAIDs  ACE inhibitors Foods  Strawberries  Fish e.g. Tuna (Scrombotoxin)

51. Diagnosing Anaphylaxis  Based on clinical presentation, exposure  Cutaneous, respiratory symptoms most common  Some cases may be difficult to diagnose Vasovagal syncope Systemic mastocytosis

52. Diagnosing Anaphylaxis  Careful history to identify possible causes  Can be confirmed by serum tryptase Specific for mast cell degranulation Remains elevated for up to 6-12 hours  Serum histamine - rises w/in 5 minutes, returns to baseline after 30-60 minutes  Other labs to rule out other diagnoses  Refer to allergist for specific testing

53. Diagnosing Anaphylaxis  Skin tests/RAST Foods Insect venoms Drugs  Challenge tests Foods NSAIDs Exercise Allergists can identify specific causes by:

54. Anaphylaxis summary…  Signs and Symptoms of Anaphylaxis: Urticaria, itching, hives Rash Rhinitis Bronchospasm Laryngeal Edema Syncope Cardiac Arrest  Treatment: Basic Life Support: ○ Airway ○ Breathing ○ Circulation Epinephrine  0.3-0.5 ml of 1:1000 IM  Repeat of no response Oxygen Diphenhydramine (antihistamine)  50ml IM Corticosteroids Intubation or cricothyrotomy

55. Can I Predict Severe Anaphylaxis? Risk Factors  Male  Consistent antigen administration  Shorter time elapsed since last reaction < 1 year  Asthma

56. Meet M. J.  A 13 y/o girl with a bee sting to hand one hour ago  Symptoms: swelling, erythema and pain  Treatment and advice?

57. Treatment and Advice  Clean area, ice for comfort  Remove stinger  Anti-histamines  ? Topical intermediate potency corticosteroid cream (triamciniline 0.1%)  ? Systemic steroids  Education/Plan  Referral to allergist  EpiPen