Anaphylaxis

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Anaphylaxis

• Jay Prochnau, MD
• Indiana University Health Arnett
• Allergy/Asthma
• Lafayette, IN

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Disclosures

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

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Anaphylaxis

• Definition
• Symptoms
• Mechanisms
• Causes
• Treatment
• Workup/prevention

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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

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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

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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 lt90mmHg (lt70 in children), or 30
  decrease is SBP

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Working definition

• An potentially fatal reaction that involves more
  than one organ system

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Definitions

• Anaphylaxis can be immunologic or
  non-immunologic, IgE mediated or non-IgE mediated
• Non-IgE mediated anaphylaxis used to be called
  anaphylactoid

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Signs and symptoms

• Cutaneous gt90
• 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

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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

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Signs and symptoms
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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

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Mechanisms of anaphylaxis
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Effects of histamine

• Activation of itch receptors Pruritus, urticaria
• Vasodilation Urticaria, edema
• Smooth muscle contraction Wheezing
• Increased vascular permeability edema, ? BP

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Other mast cell mediators

• Neutral proteases
• Tryptase, chymase, carboxypeptidase
• Proteoglycans
• Heparin, chondroitin sulfate
• Leukotrienes
• Prostoglandins
• Platelet activating factor

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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

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Causes of anaphylaxis

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

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Anaphylaxis to medications

• Antibiotics
• Most common medication class associated 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

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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

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Anaphylaxis to foods
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Anaphylaxis to foods

• Any food can cause anaphylaxis
• Most common peanut and tree nuts
• Big 6 foods
• Peanut/tree nuts
• Shellfish/fish
• Cows milk
• Egg
• Soy
• Wheat

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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

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Causes of anaphylaxis

• Up to 60 of cases of anaphylaxis referred to
  allergy specialty clinics have no apparent
  trigger idiopathic anaphylaxis

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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

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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

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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

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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

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Tryptase in anaphylaxis
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PAF in anaphylaxis

• N Engl J Med 2008 Jan 3358(1)28-35N

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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

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Treatment of anaphylaxis

• EASI
• Epinephrine 11000
• 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)

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Absorption by administration site
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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

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Prevention of anaphylaxis
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Prevention of anaphylaxis
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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

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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

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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)

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Questions