Transcript Anaphylaxis_090615_final

Vinod Doreswamy, M.D.
Allergy, Asthma and Clinical Immunology
Northgate Office
11011 Meridian Ave. N
Suite 200
Seattle, WA 98133
Ph: 206-860-4454
Fax: 206-860-4756
Madison Office
904 7th Ave
5th Floor
Seattle, WA 98104
Ph: 206-860-4454
Fax: 206-860-4756
Ballard Office
1801 Market St
Suite 308
Seattle, WA 98107
Ph. 206-860-4454
Fax: 206-860-4756
ANAPHYLAXIS FOR THE PRIMARY CARE
PRACTITIONER
September 6th 2015
CME, Raleigh NC
Disclosures
None
Anaphylaxis - Summary
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What is Anaphylaxis?
Types, Epidemiology
Mechanisms
Causes
Risk Factors
Diagnosis
Treatment
Louis Pasteur, “In the fields
of observation, chance
favors the prepared mind.”
Anaphylaxis - Discovery
Anaphylaxis - Criteria
Anaphylaxis is highly likely when any 1 of the following 3
criteria is fulfilled:
1. Acute onset of an illness (minutes to several hours) with
involvement of the skin, mucosal tissue, or both (eg,
generalized hives, pruritus or flushing, and swollen lipstongue-uvula) AND at least 1 of the following:
A. Respiratory compromise (eg, dyspnea, wheezebronchospasm, stridor, reduced PEF, hypoxemia)
B. Reduced BP or associated symptoms of end-organ
dysfunction (eg, hypotonia [collapse], syncope, incontinence)
Anaphylaxis - Criteria
2. Two or more of the following that occur rapidly after
exposure to a likely allergen for that patient (minutes to several
hours):
A. Involvement of the skin–mucosal tissue (eg, generalized
hives, itch-flush, swollen lips-tongue-uvula)
B. Respiratory compromise (eg, dyspnea, wheezebronchospasm, stridor, reduced PEF, hypoxemia)
C. Reduced BP or associated symptoms (eg, hypotonia
[collapse], syncope, incontinence)
D. Persistent gastrointestinal symptoms (eg, cramping
abdominal pain, vomiting)
Anaphylaxis - Criteria
3. Reduced BP after exposure to a known allergen for that
patient (minutes to several hours):
A. Infants and children: low systolic BP (age-specific) or greater
than 30% decrease in systolic BP*
B. Adults: systolic BP of less than 90 mm Hg or greater than
30% decrease from that person’s baseline
Anaphylaxis - Burden
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0.05-2.0% lifetime prevalence
1% of ED visits for Acute Allergic reactions given Dx
40% of ED visits for food anaphylaxis given Dx
30,000 anaphylaxis, 150 deaths 2/2 Food/year
Anaphylaxis - Epidemiology
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Age
Sex
Atopy
Route of administration
Gaps in administration
Time since reaction
Asthma
Socioeconomic Status
Geography
Diurnal
Race
Anaphylaxis – Signs/Symptoms
Signs and symptoms
Cutaneous
Percentage of cases
>90
Urticaria/angioedema
85–90
Flush
45–55
Pruritus without rash
2–5
Respiratory
40–60
Dyspnea, wheeze
45–50
Upper airway angioedema
50–60
Rhinitis
15–20
Dizziness, syncope, hypotension
30–35
Nausea, vomiting, diarrhea, pain
25–30
Headache
5–8
Substernal pain
4–6
Seizure
1–2
Anaphylaxis – Cardiovascular changes
At onset of
reaction
Blood pressure
Pulse
Cardiac output
Peripheral
vascular
resistance
Intravascular
volume
Early stage (minutes)
with no treatment
Prolonged
shock
Anaphylaxis - Types
IgG -
II
Anaphylaxis - Causes
Immunologic mechanisms (IgE dependent)
Foods - peanut, tree nut, shellfish, fish, milk, egg, sesame, food additives
Food dependent Exercise induced
Medications - b-lactam antibiotics and NSAIDs, biological agents
Venoms - stinging insects (Hymenoptera)
Natural rubber latex
Occupational allergens
Seminal fluid (prostate-specific antigen)
Inhalants - horse, hamster, other animal dander, grass pollen (rare)
Radiocontrast media
Allergy shots
Anaphylaxis - Causes
Immunologic mechanisms (IgE independent,
formerly classified as anaphylactoid reactions)
Dextran, such as high-molecular-weight iron dextran
Cytotoxic
IgG Anti-IgA
AA Metabolism disturbance – NSAIDs
Kallekrein-Kinin Contact system activation – Dialysis membranes, RCM
Multimediator recruitment – Complement, Clotting, lysis, Kallekreincontact
Anaphylaxis - Causes
Non-immunologic mechanisms
Physical factors, such as exercise, cold, heat, and sunlight/UV radiation
Ethanol
Medications - Opioids
Idiopathic anaphylaxis
Hidden or previously unrecognized allergens
Mastocytosis/clonal mast cell disorder
FcεRI
Figure 19-2 Polypeptide chain structure of the high-affinity IgE Fc receptor (FcεRI). IgE binds to the Ig-like domains of the α chain. The β chain and the
γ chains mediate signal transduction. The boxes in the cytoplasmic region of the β and γ chains are ITAMs, similar to those found in the T cell
receptor complex (see Fig. 6-5). A model structure of FcεRI is shown in Chapter 14, Box 14-1.
© 2005 Elsevier
Mast Cell Activation
Mast cell activation
Figure 19-3 Mast cell activation. Antigen binding to IgE cross-links FcεRI molecules on mast cells, which induces the release of mediators that cause the
hypersensitivity reaction (A, B). Other stimuli, including the complement fragment C5a, can also activate mast cells. A light photomicrograph of a resting mast cell with
abundant purple-staining cytoplasmic granules is shown in C. These granules are also seen in the electron micrograph of a resting mast cell shown in E. In contrast, the
depleted granules of an activated mast cell are shown in the light photomicrograph (D) and electron micrograph (F). (Courtesy of Dr. Daniel Friend, Department of
Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.)
Downloaded from: StudentConsult (on 11 May 2010 09:13 PM)
© 2005 Elsevier
ANAPHYLAXIS - MEDIATORS
Table 19-3. Mediators Produced by Mast Cells, Basophils, and Eosinophils
Mediator
Mediator category
Mast cells and basophils
Histamine
Stored preformed in
cytoplasmic granules
Enzymes: neutral proteases
(tryptase and/or chymase), acid
hydrolases, cathepsin G,
carboxypeptidase
Prostaglandin D2
Major lipid mediators
produced on activation
Leukotrienes C4, D4, E4
Platelet-activating factor
Cytokines produced on IL-3
activation
TNF, MIP-1α
IL-4, IL-13
IL-5
Function/pathologic effects
Increases vascular permeability; stimulates
smooth muscle cell contraction
Degrade microbial structures; tissue
damage/remodeling
Vasodilation, bronchoconstriction, neutrophil
chemotaxis
Prolonged bronchoconstriction, mucus
secretion, increased vascular permeability
Chemotaxis and activation of leukocytes,
bronchoconstriction, increased vascular
permeability
Mast cell proliferation
Inflammation/late phase reaction
IgE production, mucus secretion
Eosinophil production and activation
Effects of Mediators
© 2005 Elsevier
GENETIC SUSCEPTIBILITY
Table 19-4. Examples of Chromosomal Locations and Genes Associated with Atopy and Asthma
Chromosomal
location
Candidate genes
Putative role of gene products in disease
5q
Cytokine gene
IL-4 and IL-13 promote IgE switching, IL-5 promotes
cluster (IL-4, IL-5, IL- eosinophil growth and activation; CD14 is a component of
13), CD14, β2the LPS receptor which, via interaction with TLR4, may
adrenergic receptor influence the balance between TH1 vs. TH2 responses to
antigens; β2-adrenergic receptor regulates bronchial
smooth muscle contraction
6p
Class II MHC
Some alleles may regulate T cell responses to allergens
11q
FcεRI β chain
Mediates mast cell activation
12q
Stem cell factor,
Stem cell factor regulates mast cell growth and
interferon-γ, STAT6 differentiation; interferon-γ opposes actions of IL-4;
STAT6 mediates IL-4 signal transduction
16
IL-4 receptor α chain Subunit of both IL-4 and IL-13 receptors
20p
Metalloproteinase involved in airway remodeling
ADAM33
2q
Peptidase that may regulate chemokine and cytokine
DPP10
activity
13q
Transcriptional regulator involved in B cell clonal
PHF11
expansion and Ig expression
Risk factors for severe anaphylaxis and fatality
Age
•Infants
•Adolescents/young adults
•Pregnancy
•Elderly
Comorbidities
•Asthma/respiratory diseases
•CVDs
•Mastocytosis/clonal mast cell
disorders
•Allergic rhinitis/eczema
•Depression/psychiatric diseases
•Thyroid disease
Medication/chemical use
•Sedatives/hypnotics/antidepressants/
ethanol/recreational drugs
•B-Blockers and ACE inhibitors
Anaphylaxis – Differential Diagnosis
Flush Syndromes
Carcinoid
Medullary Ca Thyroid
Perimenopause
Autonomic Epilepsy
Excess endogenous
Histamine
Mastocytosis
Basophilic Leukemia
Acute PML
Restaurant Syndromes
Scrombroidosis
MSG
Sulfite
Miscellaneous
Hereditary Angioedema
Progesterone Anaphylaxis
Panic attacks
VCD
Redman Syndrome
Urticarial Vasculitis
Munchausen Syndrome
Shock
Anaphylaxis - Diagnosis
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History
Histamine, Tryptase, Other mediators
IgE tests – Skin, Blood
Allergen challenge – food, drug
Work up for DDx
Schwartz DA, Immunol Allergy Clin N Am 26 (2006) 451–463
Management of Anaphylaxis
1. Immediate intervention:
a. Assessment of airway, breathing, circulation, and adequacy
of mentation
b. Administer IM epinephrine every 5 to 15 minutes, as
necessary, to control anaphylaxis signs and symptoms and
prevent progression to more severe symptoms (eg,
respiratory distress, hypotension, and unconsciousness)
c. Place patient in recumbent position and elevate lower
extremities, as tolerated
The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010;126:480,
e32.
Management of Anaphylaxis
2. Subsequent measures depending on response to IM
epinephrine:
a. Consider call for assistance and transportation to an
emergency department or an intensive care facility
b. Establish and maintain airway
c. Administer oxygen
d. Establish venous access
e. Use IV (IO) crystalloid (eg, 0.9% saline or Ringer’s
lactate) for fluid replacement
Management of Anaphylaxis
3. Specific measures to consider after epinephrine
injections, where appropriate:
a. Consider dilute epinephrine infusion
b. Consider H1 and H2 antihistamines
c. Consider nebulized beta2-agonist (eg, albuterol) for
bronchospasm resistant to epinephrine
d. Consider systemic glucocorticoids
e. Consider vasopressor (eg, dopamine)
f. Consider glucagon for patient taking b-blocker
Management of Anaphylaxis
4. Observation and subsequent outpatient follow-up:
a. Observation periods after apparent resolution must be
individualized
b. After recovery from the acute episode, every patient
should receive epinephrine autoinjectors and be instructed
in proper technique
c. Every patient after anaphylaxis requires a careful
diagnostic evaluation in consultation with an allergistimmunologist
Anaphylaxis in the Community
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