Download Allergy to Stinging Insects

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
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Definition
Symptoms
Mechanisms
Causes
Treatment
Workup/prevention
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
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”
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:
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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
Working definition
• An potentially fatal reaction that involves more than one
organ system
Definitions
• Anaphylaxis can be immunologic or non-immunologic,
IgE mediated or non-IgE mediated
• Non-IgE mediated anaphylaxis used to be called
“anaphylactoid”
Signs and symptoms
• Cutaneous
– Urticaria and angioedema
– Flushing
– Pruritus, no rash
• Respiratory
– Dyspnea, wheeze
– Upper airway swelling
– Rhinitis
>90%
85-90%
50%
2-5%
40-60%
45-50%
50-60%
15-20%
Signs and symptoms
• Circulatory
– Dizziness, syncope, hypotension, tachycardia
30-35%
• GI
– Nausea, vomiting, diarrhea, cramping
25-30%
• Miscellaneous
– Headache
– Chest pain
– Seizures
5-8%
4-6%
1-2%
Signs and symptoms
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
Mechanisms of anaphylaxis
Effects of histamine
• Activation of itch receptors
Pruritus, urticaria
• Vasodilation
Urticaria, edema
• Smooth muscle contraction
Wheezing
• Increased vascular permeability
edema, ↓ BP
Other mast cell mediators
• Neutral proteases
– Tryptase, chymase, carboxypeptidase
• Proteoglycans
– Heparin, chondroitin sulfate
• Leukotrienes
• Prostoglandins
• Platelet activating factor
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
Causes of anaphylaxis
• Exercise
– May be food dependent
• Vaccines
– Gelatin, ovalbumin
• Human seminal plasma anaphylaxis
• Aeroallergens
– uncommon cause of anaphylaxis (horse)
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
Anaphylaxis to medications
• Perioperative anaphylaxis
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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
Anaphylaxis to foods
Anaphylaxis to foods
• Any food can cause anaphylaxis
• Most common peanut and tree nuts
• “Big 6” foods
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Peanut/tree nuts
Shellfish/fish
Cow’s milk
Egg
Soy
Wheat
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
Causes of anaphylaxis
• Up to 60% of cases of anaphylaxis referred to allergy
specialty clinics have no apparent trigger = “idiopathic
anaphylaxis”
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
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Scombroid fish poisoning
Anisakiasis
MSG
Sulfites
• Mastocytosis
– Systemic mastocytosis, mast cell activation syndrome
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
Differential diagnosis of anaphylaxis
• Tumors
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Carcinoid
Pheochromocytoma
GI tumors: VIPoma
Medullary carinoma of the thyroid
• Idiopathic capillary leak syndrome
– Rare, can be fatal
• Undifferentiated somatoform anaphylaxis
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
Tryptase in anaphylaxis
PAF in anaphylaxis
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N
N Engl J Med 2008 Jan 3;358(1):28-35
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
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)
Absorption by administration site
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
Prevention of anaphylaxis
Prevention of anaphylaxis
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
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
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)
Questions