- Etiology
- Pathogenesis
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- Clinical Case Studies
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Medications
Antibiotics (especially penicillins); Cephalosporins
NSAIDs
Biological agents (chemotherapy and monoclonal antibodies).
Radiographic intravenous contrast agents or Iodinated drugs.
Bee and Wasp Stings
Hymenoptera (bee and wasp) stings are another cause of anaphylaxis. Anaphylaxis from stings results in an average of 50 deaths per year in the United States. Overall, the number of cases of arthropod anaphylaxis seen by physicians is small compared to the number of iatrogenic cases, but because exposures often occur miles from medical treatment, they can have serious outcomes.
Food Allergies
Food sources round out the major causes of serious allergic reactions. Food allergies are the most common cause of anaphylaxis in children. Peanuts and other tree nuts are the most common cause of serious allergic reactions. Other food allergens include milk, eggs, shellfish, fish, soybean, sesame, and mangos, but any food can be responsible.
| Dextran | |
| Insulin | |
| Lidocaine | |
| Penicillins | |
| Procaine |
https://www.auvi-q.com/pdf/Myth-vs-Fact.pdf
Anaphylaxis is a type 1 hypersensitivity reaction.
In type 1 hypersensitivity, B-cells are stimulated (by CD4+TH2 cells) to produce IgE antibodies specific to an antigen.
The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity, the antibody is IgE instead of IgA, IgG, or IgM. During sensitization, the IgE antibodies bind to FcεRI receptors on the surface of tissue mast cells and blood basophils.[2] Mast cells and basophils coated by IgE antibodies are "sensitized". Later exposure to the same allergen cross-links the bound IgE on sensitized cells, resulting in anaphylactic degranulation, which is the immediate and explosive release of pharmacologically active pre-formed mediators from storage granules and concurrent synthesis of inflammatory lipid mediators from arachidonic acid;[3] some of these mediators include histamine, leukotriene (LTC4 and LTD4 and LTB4), and prostaglandin, which act on proteins (e.g., G-protein coupled receptors) located on surrounding tissues.[3] The principal effects of these products are vasodilation and smooth-muscle contraction.
Type 1 hypersensitivity can be further classified into immediate and late-phase reactions. The immediate hypersensitivity reaction occurs minutes after exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the release of cytokines.[4]
1
This is an IgE immune-mediated activation of basophils and mast cells with subsequent release of prostaglandins, leukotrienes, and histamine.
When a patient is first exposed to a substance, binding antibodies trigger class switching and regulatory changes in gene expression, effectively priming the immune system for its next encounter with the offending agent.
In certain cases, this leads to immunoglobulin (IgE) binding to mast cells and basophils. In the classic anaphylactic reaction, the antigen again encounters the immune system, binds to the IgE on the mast cells and basophils, and releases a flood of cytokines that set the clinical response in motion. In an anaphylactoid reaction, the antigen causes direct release of cytokines by mast cells and basophils, without need for prior sensitization. In both cases, the end result is the same and is clinically indistinguishable.
The early stages of some anaphylactic reactions involve increased secretion by mucous membranes. In addition to watery eyes and rhinorrhea, increased bronchial secretions and increased smooth muscle tone cause wheezing and increase the work of breathing. Decreased vascular tone and increased capillary permeability lead to cardiovascular compromise and hypotension. Patients may lose over 30% of their blood volume to extravasation in the first 10 minutes of their allergic reaction. Other cytokines, specifically histamine, can cause urticaria and angioedema. There are numerous cytokines involved in the immunologic cascade following exposure, and no one major substance is felt to be primarily responsible. Leukotriene C4, prostaglandin D2, histamine, and tryptase are known key components in the reaction.
An anaphylactoid reaction also includes release of these compounds but through non–immune-mediated pathways. The only clinical significance of this difference is that anaphylactoid reactions can occur without prior sensitization. Regardless of the underlying mechanism, their effects are similar
Anaphylaxis is a severe allergic reaction that can happen within minutes of coming into contact with an allergen. During an anaphylactic reaction, your airway swells and obstructs your breathing.
After the initial signs and symptoms abate, patients are at a small risk for a recurrence of symptoms caused by a second phase of mediator release, peaking 8 to 11 hours after the initial exposure and manifesting symptoms and signs 3 to 4 hours after the initial clinical manifestations have cleared.
The late-phase allergic reaction is primarily mediated by the release of newly generated cysteinyl leukotrienes, the former slow-reacting substance of anaphylaxis. The incidence of this biphasic phenomenon has been reported to vary widely up to 20%, but prospective studies specifically searching for clinically important biphasic events report an incidence of 4% to 5%.
Epinephrine Intramuscular
IM administration in the anterolateral aspect of the middle third of the thigh (AHA [Vanden Hoek 2010]; WAO [Simons 2011]).
IM: 0.2 to 0.5 mg or 0.01 mg/kg (maximum dose: 0.5 mg) using the 1 mg/mL solution; repeat every 5 to 15 minutes in the absence of clinical improvement (AAAAI [Lieberman 2015];
May administer epinephrine as a continuous IV infusion in patients not responding to IM injections (AAAAI [Lieberman 2015]; Campbell 2014).
IV: Note: In general, IV administration should only be done in patients who are unresponsive or profoundly hypotensive after failure to respond to IV fluid replacement and several epinephrine IM injections (WAO [Simons 2011]).
Slow IV bolus (off-label dose): 0.05 to 0.1 mg using the 0.1 mg/mL solution (further diluted in 10 mL of NS) administered over 5 to 10 minutes (AHA [Vanden Hoek 2010]; Barach 1984). If the patient is in cardiopulmonary arrest, use of higher IV/intraosseous bolus doses (ie, 1 mg every 3 to 5 minutes) should be employed (AAAAI [Lieberman 2015]; AHA [Neumar 2010]; Campbell 2014). Note: Rapid IV bolus administration is associated with cardiac arrhythmias, only use in this way if absolutely necessary (Campbell 2014).
Continuous infusion (off-label dose): May initiate with an infusion at 1 to 15 mcg/minute (with fluid resuscitation) (AAAAI [Lieberman 2015]; AHA [Vanden Hoek 2010]; Brown 2004; Campbell 2014).
Endotracheal (alternative route): 2 to 2.5 mg every 3 to 5 minutes until IV/intraosseous access established; dilute in 5 to 10 mL NS or sterile water (AAAAI [Lieberman 2015]; AHA [Neumar 2010]; Campbell 2014). Note: Absorption may be greater with sterile water (Naganobu 2000).
Self-administration following severe allergic reactions (eg, insect stings, food):Note: The World Health Organization (WHO) and Anaphylaxis Canada recommend the availability of one dose for every 10 to 20 minutes of travel time to a medical emergency facility. If anaphylactic symptoms persist after first dose, may repeat dose in 5 to 15 minutes (AHA [Vanden Hoek 2010]; WAO [Simons 2011]); more than 2 sequential doses should only be administered under direct medical supervision.
Adrenaclick: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Adrenaclick injector
Allerject [Canadian product]: IM: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Allerject injector
Auvi-Q: IM, SubQ: Weight ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated
EpiPen: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional EpiPen
Symjepi: IM, SubQ: Weight ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated
Twinject [Canadian product]: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5 to 15 minutes using the same device after partial disassembly
AUTOINJECTOR
Epinephrine
Dose:
Adults. IV bolus: 100 mcg of 1:100,000 over 5–10 min (mix 0.1 mL of 1:1,000 epi in 10 mL NS). ?????
IV inf: 1–4 mcg/min.
Peds.IV inf: 0.1–0.3 mcg/kg/min, max 1.5 mcg/kg/min
Diphenhydramine
Adults. IV/IM/PO 50 mg.
Peds. IV/IM/PO 1 mg/kg
Methylprednisolone
Dose: 1–2 mg/kg IV
Ranitidine (Zantac)
More potent histamine antagonist than cimetidine; less affinity for CYP450 enzymes
Adults. IV 50 mg over 5 min.
Peds. IV 0.5 mg/kg over 5 min
Adults. 2.5 mg nebulized.
Peds. 1.25 mg nebulized
Allergic Reaction with Systolic BP > 90 mm Hg
Supplemental drugs for anaphylaxis include:
Dose: Adults. IV/IM/PO 50 mg. Peds. IV/IM/PO 1 mg/kg
Dose: 1–2 mg/kg IV
Dose: Adults. IV 50 mg over 5 min. Peds. IV 0.5 mg/kg over 5 min
Dose: Adults. 2.5 mg nebulized. Peds. 1.25 mg nebulized
After the initial signs and symptoms abate, patients are at a small risk for a recurrence of symptoms caused by a second phase of mediator release, peaking 8 to 11 hours after the initial exposure and manifesting symptoms and signs 3 to 4 hours after the initial clinical manifestations have cleared. The late-phase allergic reaction is primarily mediated by the release of newly generated cysteinyl leukotrienes, the former slow-reacting substance of anaphylaxis. The incidence of this biphasic phenomenon has been reported to vary 4% up to 20%.
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Content 3
Content 11
An 18-year-old woman is brought to the ED with suspected anaphylaxis. Which of the following symptoms is most specific for anaphylaxis rather than a simple allergic reaction?
The correct answer is C.
C. Hypotension indicates a systemic reaction and cardiovascular compromise, thereby classifying this allergic reaction as anaphylaxis. The other options may all be part of an anaphylactic response but may also just be simple allergic reactions.
You are working in the emergency department when a 3-year-old boy arrives by ambulance. He was eating tonight when he suddenly starting wheezing, coughing, and then became progressively less responsive. His parents are certain he did not aspirate. On arrival, his blood pressure is low, and he is working hard to breath. You auscultate a tight wheeze bilaterally. You accurately diagnose him with anaphylaxis and initiate appropriate therapy. Which of the following is true regarding anaphylaxis?
The answer is D. There is no convincing evidence that age, sex, race, or geographic location predisposes a human to anaphylaxis except through exposure to specific immunogens. According to most studies, atopy does not predispose individuals to anaphylaxis from penicillin therapy or venom of a stinging insect but is a risk factor for allergens in food or latex. Risk factors for a poor outcome, however, include older age, use of β-blockers, and the presence of preexisting asthma. Individuals differ in the time of appearance of symptoms and signs, but the hallmark of the anaphylactic reaction is the onset of some manifestation within seconds to minutes after introduction of the antigen. Early recognition of an anaphylactic reaction is mandatory, because death can occur within minutes to hours after the first symptoms.
Mild symptoms such as pruritus and urticaria can be controlled by administration of 0.3–0.5 mL of 1:1000 (1 mg/mL) epinephrine subcutaneously (SC) or intramuscularly (IM), with repeated doses as required at 5- to 20-minute intervals for a severe reaction. The failure to use epinephrine within the first 20 minutes of symptoms is a risk factor for poor outcome in studies of anaphylaxis to food. An intravenous (IV) infusion should be initiated to provide a route for administration of 2.5 mL epinephrine, diluted 1:10,000, at 5- to 10-minutes intervals, volume expanders such as normal saline, and vasopressor agents such as dopamine if intractable hypotension occurs. Replacement of intravascular volume due to postcapillary venular leakage may require several liters of saline. Epinephrine provides both α- and β-adrenergic effects, resulting in vasoconstriction, bronchial smooth muscle relaxation, and attenuation of enhanced venular permeability. Ancillary agents such as the antihistamine diphenhydramine, 50–100 mg IM or IV, and aminophylline, 0.25–0.5 g IV, are appropriate for urticaria-angioedema and bronchospasm, respectively. IV glucocorticoids (0.5–1 mg/kg of methylprednisolone) are not effective for the acute event but may alleviate later recurrence of bronchospasm, hypotension, or urticaria.
Content 3
You are working in the emergency department when a 3-year-old boy arrives by ambulance. He was eating tonight when he suddenly starting wheezing, coughing, and then became progressively less responsive. His parents are certain he did not aspirate. On arrival, his blood pressure is low, and he is working hard to breath. You auscultate a tight wheeze bilaterally. You accurately diagnose him with anaphylaxis and initiate appropriate therapy. Which of the following is true regarding anaphylaxis?
The answer is D. There is no convincing evidence that age, sex, race, or geographic location predisposes a human to anaphylaxis except through exposure to specific immunogens. According to most studies, atopy does not predispose individuals to anaphylaxis from penicillin therapy or venom of a stinging insect but is a risk factor for allergens in food or latex. Risk factors for a poor outcome, however, include older age, use of β-blockers, and the presence of preexisting asthma. Individuals differ in the time of appearance of symptoms and signs, but the hallmark of the anaphylactic reaction is the onset of some manifestation within seconds to minutes after introduction of the antigen. Early recognition of an anaphylactic reaction is mandatory, because death can occur within minutes to hours after the first symptoms.
Mild symptoms such as pruritus and urticaria can be controlled by administration of 0.3–0.5 mL of 1:1000 (1 mg/mL) epinephrine subcutaneously (SC) or intramuscularly (IM), with repeated doses as required at 5- to 20-minute intervals for a severe reaction. The failure to use epinephrine within the first 20 minutes of symptoms is a risk factor for poor outcome in studies of anaphylaxis to food. An intravenous (IV) infusion should be initiated to provide a route for administration of 2.5 mL epinephrine, diluted 1:10,000, at 5- to 10-minutes intervals, volume expanders such as normal saline, and vasopressor agents such as dopamine if intractable hypotension occurs. Replacement of intravascular volume due to postcapillary venular leakage may require several liters of saline. Epinephrine provides both α- and β-adrenergic effects, resulting in vasoconstriction, bronchial smooth muscle relaxation, and attenuation of enhanced venular permeability. Ancillary agents such as the antihistamine diphenhydramine, 50–100 mg IM or IV, and aminophylline, 0.25–0.5 g IV, are appropriate for urticaria-angioedema and bronchospasm, respectively. IV glucocorticoids (0.5–1 mg/kg of methylprednisolone) are not effective for the acute event but may alleviate later recurrence of bronchospasm, hypotension, or urticaria.
Reference
https://www.cps.ca/en/documents/position/emergency-treatment-anaphylaxis