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Anaphylaxis

Anaphylaxis. Jay Prochnau, MD Indiana University Health Arnett Allergy/Asthma Lafayette, IN. Disclosures. Conduct research in COPD and asthma for GSK and Genentech/Roche No conflicts of interest. Anaphylaxis. Definition Symptoms Mechanisms Causes Treatment Workup/prevention.

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Anaphylaxis

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  1. Anaphylaxis Jay Prochnau, MD Indiana University Health Arnett Allergy/Asthma Lafayette, IN

  2. Disclosures • Conduct research in COPD and asthma for GSK and Genentech/Roche • No conflicts of interest

  3. Anaphylaxis • Definition • Symptoms • Mechanisms • Causes • Treatment • Workup/prevention

  4. Definitions • “Ana” = against, “phylaxis” = protection • Coin termed in 1902 by Portier and Richet • Attempts to vaccinate dogs against the toxin of sea anemones led to death at much lower doses

  5. Definitions • “I know it when I see it” • Potter Stewart • World Allergy Organization: “A severe, life threatening, generalized or systemic hypersensitivity reaction” • NIAID/FAAN: “A serious allergic reaction that is rapid in onset and may cause death”

  6. Criteria • Criterion 1 – acute onset (minutes to hours) of an illness involving the skin, mucosal tissue or both (eg hives, pruritus, flushing, swollen tongue/lips/uvula) and at least one of the following: • Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia, reduced peak flow) • Reduced blood pressure or associated signs/symptoms (hypotonia, syncope) • Criterion 2 – 2 or more of the following that occur rapidly (minutes to hours) after exposure to a likely allergen: • Skin involvement • Respiratory compromise • Reduced BP • Persistent GI symptoms (abdominal cramping, vomiting) • Criterion 3 – reduced BP after known allergen (minutes to hours) • Systolic <90mmHg (<70 in children), or 30% decrease is SBP

  7. Working definition • An potentially fatal reaction that involves more than one organ system

  8. Definitions • Anaphylaxis can be immunologic or non-immunologic, IgE mediated or non-IgE mediated • Non-IgE mediated anaphylaxis used to be called “anaphylactoid”

  9. Signs and symptoms • Cutaneous >90% • Urticaria and angioedema 85-90% • Flushing 50% • Pruritus, no rash 2-5% • Respiratory 40-60% • Dyspnea, wheeze 45-50% • Upper airway swelling 50-60% • Rhinitis 15-20%

  10. Signs and symptoms • Circulatory • Dizziness, syncope, hypotension, tachycardia 30-35% • GI • Nausea, vomiting, diarrhea, cramping 25-30% • Miscellaneous • Headache 5-8% • Chest pain 4-6% • Seizures 1-2%

  11. Signs and symptoms

  12. Mechanisms of anaphylaxis • Main mediator of anaphylaxis is histamine • Histamine released from mast cells • Mast cell degranulation triggered by cross linking of IgE antibodies bound to IgE receptors

  13. Mechanisms of anaphylaxis

  14. Effects of histamine • Activation of itch receptors Pruritus, urticaria • Vasodilation Urticaria, edema • Smooth muscle contraction Wheezing • Increased vascular permeability edema, ↓ BP

  15. Other mast cell mediators • Neutral proteases • Tryptase, chymase, carboxypeptidase • Proteoglycans • Heparin, chondroitin sulfate • Leukotrienes • Prostoglandins • Platelet activating factor

  16. Causes of anaphylaxis • Medications • Most common cause of anaphylaxis (inpatient) • Drug reactions responsible for 230,000 hospital admissions in the US annually • Foods • Food allergy affects 6-8% of children, 3-4% of adults • Most common cause of anaphylaxis at home • Insect stings • 40 deaths/year estimated due to Hymenoptera stings • Blood products • Anti-IgA antibodies in an IgA deficient patient

  17. Causes of anaphylaxis • Exercise • May be food dependent • Vaccines • Gelatin, ovalbumin • Human seminal plasma anaphylaxis • Aeroallergens • uncommon cause of anaphylaxis (horse)

  18. Anaphylaxis to medications • Antibiotics • Most common medication classassociated with anaphylaxis • Penicillin, sulfonamides • Vancomycin – usually non IgE mediated/direct mast cell activation • NSAIDs • Second most common • Most probably not IgE mediated • Radiocontrast media • Usually not IgE mediated • Incidence appears to be diminishing

  19. Anaphylaxis to medications • Perioperative anaphylaxis • Most common neuromuscular blocking agents (62%) • Natural rubber latex (16%) • Intraoperative antibiotics • Protamine use to reverse heparin • Opioid analgesics • Non IgE mediated • Directly activate mast cells

  20. Anaphylaxis to foods

  21. Anaphylaxis to foods • Any food can cause anaphylaxis • Most common peanut and tree nuts • “Big 6” foods • Peanut/tree nuts • Shellfish/fish • Cow’s milk • Egg • Soy • Wheat

  22. Anaphylaxis to insect stings • Hymenoptera venoms most common • Hymenoptera = “membrane winged” insects • Yellow jacket, yellow hornet, white faced hornet, paper wasp, honeybee, imported fire ant (in the south) • Anaphylaxis reported to multicolored asian lady beetles

  23. Causes of anaphylaxis • Up to 60% of cases of anaphylaxis referred to allergy specialty clinics have no apparent trigger = “idiopathic anaphylaxis”

  24. Differential diagnosis of anaphylaxis • ACE inhibitor mediated angioedema • Mediated by bradykinin, not histamine • May affect up to 2.2% of patients on ACE inhibitors • Restaurant syndromes • Scombroid fish poisoning • Anisakiasis • MSG • Sulfites • Mastocytosis • Systemic mastocytosis, mast cell activation syndrome

  25. Differential diagnosis of anaphylaxis • Nonorganic disease • Vocal cord dysfunction, globus hystericus, panic attack • Vasovagal syncope • Pallor as opposed to flushing • Bradycardia as opposed to tachycardia • Myocardial infarction or stroke • Flushing disorders • Menopause • Medications that cause flushing (niacin) • Alcohol

  26. Differential diagnosis of anaphylaxis • Tumors • Carcinoid • Pheochromocytoma • GI tumors: VIPoma • Medullary carinoma of the thyroid • Idiopathic capillary leak syndrome • Rare, can be fatal • Undifferentiated somatoform anaphylaxis

  27. Diagnosis of anaphylaxis • Diagnosis of anaphylaxis is primarily clinical • Laboratory workup may be helpful • Histamine • Stays elevated for 30-60 minutes • Urinary metabolites may stay elevated for 24 hours • Tryptase • Stays elevated for 4-6 hours • May not be elevated in anaphylaxis due to food allergy • Platelet activating factor (PAF) • “BNP” of anaphylaxis • Increasing levels of PAF may indicate greater severity

  28. Tryptase in anaphylaxis

  29. PAF in anaphylaxis • N Engl J Med 2008 Jan 3;358(1):28-35N

  30. Treatment of anaphylaxis • ABCs • Protection of airway crucial, early intubation if necessary • Laryngeal edema most common cause of death from anaphylaxis • Supplemental oxygen • Pressure support • Place patient in recumbent position, elevate lower extremities • IV fluids, pressors if necessary

  31. Treatment of anaphylaxis • “EASI” • Epinephrine 1:1000 • First line therapy for anaphylaxis • Should be given IM (as opposed to SC or IV), lateral thigh (vastus lateralis muscle) for optimal absorption • Dose 0.3 to 0.5ml for adults, 0.01ml/kg for children • Can be repeated every 5-15 minutes as needed • Antihistamines • Diphenhydramine or hydroxyzine 50mg every 6 hours • Steroids • Methylprednisolone or prednisone to prevent biphasic reaction • Inhaled beta-agonists (e.g., albuterol)

  32. Absorption by administration site

  33. Prevention of anaphylaxis • Allergy referral • Careful history and directed testing to identify trigger of anaphylaxis • Skin testing vs RAST testing • Skin testing to medications is of limited utility with the exception of penicillin • Patients should have access to an epinephrine autoinjector

  34. Prevention of anaphylaxis

  35. Prevention of anaphylaxis

  36. Prevention of anaphylaxis • Medication allergy • Avoidance • Desensitization if necessary • Food allergy • Avoidance • Trials with oral immunotherapy look promising • Hymenoptera allergy • Venom immunotherapy 98% curative, 100% effective

  37. Prevention of anaphylaxis • Radiocontrast media allergy • Use of lower osmolar or nonionic contrast media • Pretreatment with steroids and antihistamines • Prednisone 50mg 12h, 6h and 1h and diphenhydramine 50mg 1h prior to RCM administration • Hydrocortisone 200mg and diphenhydramine 50mg pre-procedure • Risk of reaction 60% if high osmolar contrast is used again, 6% with either low osmolar contrast media or with pretreatment, 0.6% with low osmolar contrast media and pretreatment

  38. Mast cell activation disorders • Primary mast cell disorders • Mastocytosis • Monoconal mast cell activation disorder (MMAD) • Secondary mast cell disorders • Allergic disorders (IgE mediated urticaria/anaphylaxis) • Chronic autoimmune urticaria/angioedema • Idiopathic mast cell disorders • Idiopathic anaphylaxis • Idiopathic urticaria/angioedema • Idiopathic mast cell activation syndrome (MCAS)

  39. Questions

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