First Aid, Chapter 7 Hypersensitivity Disorders, Anaphylaxis

Question 1

What is the lifetime prevalence of anaphylaxis?

Answer 1

0.05-2%

Question 2

What are the most common causes of anaphylaxis?

Answer 2

food and drugs

Question 3

What are risk factors for anaphylaxis?

Answer 3

Atopy - Increased risk for idiopathic anaphylaxis, exercise-induced anaphylaxis, radiocontrast material and latex-induced reactions Note: Atopy is not a risk factor for anaphylactic reactions to medications (PCN, insulin, or muscle relaxants)

Gender: male until age 15, female after that

Route of administration: more severe with IV or IM vs. oral

Intermittent administration: ex, DM of pregnancy with intermittent insulin use

Lenght of admin: ex prolonged antibiotic use (vs single doses)

Time since reaction: the longer the time between administrations, the lower the risk of reaction

Geography: Epipens prescribed more in the north than the south

SES: higher economic groups prescribed epi more frequently

Question 4

What are the 3 types of anaphylaxis?

Answer 4

Immunologic, nonimmunologic, idiopathic

Question 5

What is the pathogenesis of immunologic anaphylaxis?

Answer 5

• IgE-mediated: Most common; initiated by antigen interacting with allergen-specific IgE bound to high-affinity IgE receptors (FcεRI) on mast cells and/or basophils. Aggregation leads to cell activation, mediator release, and immediate hypersensitivity response. Examples include foods, venoms, latex, and drugs
• IgG-mediated: Animal models only
• Immune complex/complement-mediated reactions

Question 6

What is the pathogenesis of nonimmunologic anaphylaxis? What are some examples?

Answer 6

Initiated by certain drugs or events that induce a sudden release of mast cell or basophil mediators in the absence of IgE or other immunoglobulins. Examples include vancomycin, opiates, radiocontrast media, or cold urticaria.

Question 7

What gender is more frequently affected by idiopathic anaphylaxis?

Answer 7

Women

Question 8

Name all the mediators involved in anaphylaxis.

Answer 8

Histamine, leukotrienes, thromboxane, prostaglandins, and platelet activating factor

Neutral proteases: Tryptase, chymase, carboxypeptides, and cathepsin-G

Proteoglycans: Heparin and chondroitin sulfate

Chemoattractants: Chemokines, eosinophils chemotactic factors

Tumor necrosis factor (TNF)

Question 9

What is the pathophysiologic activity of Histamine, leukotrienes, thromboxane, prostaglandins, and platelet activating factor in anaphylaxis? What are the clinical signs?

Answer 9

Pathophysiologic activity:
Smooth muscle spasm, mucus secretion, increased vascular permeability, eosinophil chemotaxis, and activation.

Clinical signs:
Wheezing, urticaria, angioedema, flush, itch, diarrhea, abdominal pain, hypotension, rhinorrhea

Question 10

What is the pathophysiologic activity of Neutral proteases in anaphylaxis? What is the pathophysiologic activity? What are the clinical signs?

Answer 10

Pathophysiologic activity:
Cleaves complement components, chemoattractants for eosinophils and neutrophils, and converts angiotensin I to II

Clinical signs:
Recruits complement, increases blood pressure via conversion to angiotensin II

Question 11

What is the pathophysiologic activity of proteoglycans in anaphylaxis? What is the pathophysiologic activity? What are the clinical signs?

Answer 11

Pathophysiologic activity: Anticoagulation, inhibits complement, binds phospholipase A2, chemoattractant for eosinophils

Clinical signs: Can prevent intravascular coagulation, complement activation, recruits kinins

Question 12

What is the pathophysiologic activity of chemoattractants in anaphylaxis? What is the pathophysiologic activity? What are the clinical signs?

Answer 12

Pathophysiologic activity:
Attracts cells to the site

Clinical signs: Late-phase reaction symptoms, or protraction of symptoms

Question 13

What is the pathophysiologic activity of tumor necrosis factor (TNF) in anaphylaxis? What is the pathophysiologic activity? What are the clinical signs?

Answer 13

Pathophysiologic activity: Promotes platelet-activating factor production

Clinical signs: Vascular permeability and vasodilation, and late-phase reactions

Question 14

What is the percentage of time of each organ system involvement in anaphylaxis?

Answer 14

• Cutaneous (90%)
• Respiratory (70%)
• Gastrointestinal (30–45%)
• Cardiovascular (10–45%)
• Central nervous system (10–15%)

Question 15

What is the diagnostic criterion 1 for anaphylaxis? Why is criterion 1 the most useful?

Answer 15

Acute onset of symptoms (minutes to hours) with skin and/or mucosal involvement (Generalized hives, pruritus, Angioedema, flushing)

Plus at least 1 of the following:
Respiratory compromise (dyspnea, wheeze, hypoxemia) Decrease in BP or end-organ dysfunction (hypotonia, syncope) 

Skin findings most common presenting symptom of anaphylaxis (~90%). Therefore criterion 1 is the most useful for diagnosis

Question 16

What is the diagnostic criterion 2 for anaphylaxis? What percentage of patients are skin manifestations absent or unrecognized in?

Answer 16

Acute onset of symptoms (minutes to hours) after exposure to a likely allergen for that patient

Plus 2 or more of the following:
Skin/mucosal involvement Respiratory compromise Decreased BP Gastrointestinal symptoms (abdominal pain, vomiting)

Skin findings absent or unrecognized in ~20% of anaphylactic episodes. Therefore criterion 2 includes symptoms from other organ systems in patients with exposure to a likely allergen.

Question 17

What is the diagnostic criterion 3 for anaphylaxis? How many organ systems are involved?

Answer 17

Acute decrease in BP (minutes to hours) after exposure to a known allergen for that patient

Adults: Systolic 30% decrease from baseline Infants/children: Age-specific low systolic BP or >30% decrease from baseline

Criterion 3 is used to detect anaphylactic reactions in patients exposed to a known allergen when only one organ system is involved.

Question 18

How often do biphasic reactions occur in anaphylaxis? What is the time frame? How long should a patient be observed after a reaction? What is the most likely agent to cause biphasic anaphylaxis?

Answer 18

20%. Most occur within 10 hours after resolutation of the primary event, but can be observed up to 72 hours later. Some advocate 24 hour observation, but 8 hours is sufficient for most reactions. Foods are most likely to cause biphasic anaphylaxis.

Question 19

How long can protracted anaphylaxis last?

Answer 19

Anaphylactic reaction that lasts for hours, days, or even weeks in extreme cases

Question 20

What are the physiological attempts to correct hypotension in anaphylaxis?

Answer 20

The synthesis and release of epinephrine (adrenal gland) and endothelin (endothelium), activation of the renin-angiotensin axis, and the release of norepinephrine (ganglia).

Question 21

What drugs might interfere with the body’s physiologic compensatory mechanisms to anaphylaxis?

Answer 21

Beta blockers, ACE I, ARBs?, TCAs, MAOIs.

Question 22

How do beta blockers interfere with compensatory mechanisms in anaphylaxis? Are they allowed in IT?

Answer 22

Interfere with normal compensatory tachycardia and blunt the effect of epinephrine. Relative contraindication to immunotherapy

Question 23

How do ACE I interfere with compensatory mechanisms in anaphylaxis? Are they allowed in IT?

Answer 23

Angiotensin-converting enzyme inhibitors (ACEIs): Theoretical increased risk in venom immunotherapy, because it acts at two sites (no data supports its cessation in pollen immunotherapy):
o Blocks conversion of angiotensin I to angiotensin II
o Inhibits the same enzyme that destroys kinins, which are known to be active in anaphylactic episodes

Question 24

How do TCAs affect treatment of anaphylaxis?

Answer 24

Exaggerate the response to epinephrine by preventing the reuptake of catecholamines at ganglionic sites

Question 25

How do MAOIs affect treatment of anaphylaxis?

Answer 25

Prevent degradation of epinephrine systemically

Question 26

What is the ratio of total tryptase to mature in anapylaxis from mastocytosis vs. other forms?

Answer 26

Recall that the ratio of total tryptase (proβ+mature) to mature tryptase is helpful in distinguishing anaphylaxis in mastocytosis from other forms: Total/mature >20 = mastocytosis;

Question 27

What are the labs are elevated in anaphylaxis? When should they be checked? When does each finding peak and how long does it remain elevated?

Answer 27

serum histamine, urinary histamine, serum tryptase, PAF - Check serum histamine 15–60 minutes: Levels begin to rise by 5 minutes but remain elevated only 30–60 minutes. - Check urinary histamine: Metabolites may remain elevated as long as 24 hours. - Check serum tryptase 15–180 minutes: Peaks 60–90 minutes after the onset of symptoms and can remain elevated as long as 5 hours. - Platelet-activating factor (PAF): Recent studies suggest that PAF levels more accurately correlate with anaphylaxis severity scores than either histamine or tryptase levels

Question 28

What is the dose of epineprhine for anaphylaxis?

Answer 28

0.01 mg/kg IM (often as 0.3–0.5 mL of 1:1000)

Question 29

What is the immediate treatment for anaphylaxis?

Answer 29

- Epinephrine at dose of 0.01 mg/kg intramuscularly (often as 0.3–0.5 mL of 1:1000) - ABCs, supine positioning, and establishment of an airway - Skin inspection - Supplemental oxygen, insertion of one or more large-bore IVs for fluids - Even if on β blockers, administer epinephrine first but consider glucagon. (Also, recall IV fluids are particularly important for patients unresponsive to epinephrine)

Question 30

What is the treatment for radiocontrast, cold, and fluorescein-related anaphylaxis? What is the risk of reaction after you do this?

Answer 30

A common protocol consists of 50 mg prednisone 13, 7, and, 1 hour before the procedure, with 50 mg of diphenhydramineone 1 hour before the procedure, along with the use of low osmolar contrast material. This intervention has been shown to lower the risk for reaction to less than 1%.

Question 31

What does each type of histamine receptor cause in anaphylaxis?

Answer 31

H1: Coronary artery constriction, bronchoconstriction, systemic vasodilation, increased capillary permeability, tachycardia, pruritus, rhinorrhea H2: Coronary artery vasodilation, increase force and rate of atrial and ventricular contractions, increased capillary permeability, increase secretion of mucus H3: Autonomic receptor downregulator (prevents release of additional epinephrine from autonomic ganglion, leads to heightened hypotension) H4: The histamine H4 receptor is the most recently identified in the histamine receptor family and in murine models may be involved in pruritus, chemotaxis, and mast cell cytokine release.

Question 32

Name the common causes of perioperative anaphylaxis.

Answer 32

- Neuromuscular blocking agents (NMBAs) - Hypotonic induction agents (barbiturates) - Antibiotics - Opioids - Latex - Colloids

Question 33

What are risk factors for perioperative anaphylaxis?

Answer 33

Asthma female sex atopy multiple past surgeries mast cell disorders

Question 34

What form of anaphylaxis carries to highest mortality rate? Why?

Answer 34

Perioperative anaphylaxis due to impaired early recognition (surgical drapes obscuring view, inability of patient to report symptoms), additional stress of surgery/illness, and IV administration of medications.

Question 35

What lab markers suggest anaphylaxis?

Answer 35

Elevated serum total tryptase, plasma histamine, or histamine metabolites in the urine.

Question 36

How long anaphylaxis should you wait to skin test to agents?

Answer 36

4-6 weeks.

Question 37

What is natural rubber latex (NRL) made from?

Answer 37

Cytoplasmic exudate of the Hevea brasiliensis tree.

Question 38

Who is at risk of developing a latex allergy?

Answer 38

Health care workers and patients who use latex-containing medical devices. Risk is directly related to duration of exposure and cumulative use of latex-containing products.

Question 39

How can people who don't wear latex gloves be sensitized otherwise?

Answer 39

Cornstarch powder in latex gloves absorbs allergens and acts as an airborne vehicle to sensitize nearby people by inhalation.

Question 40

Why do dipped rubber products cause more reactions? What are some examples?

Answer 40

Dipped rubber products (gloves, condoms, balloons) cause most reactions because these are heat-vulcanized at lower temperatures and have more proteins intact.

Question 41

What are the major latex protein allergens in spina bifida? Who is less likely to be sensitized to them? What is a characteristic of the protein?

Answer 41

Hev b 1 and 3 are less water-soluble and are more commonly identified as allergens in sensitized patients with spina bifida, but are minor in vivo allergens in health care workers.

Question 42

What latex proteins do healthccare workers most frequently react to?

Answer 42

Health care workers react most frequently to Hev b 5, 6, and 7.

Question 43

Which latex protein sensitizations correlate with which food sensitizations?

Answer 43

-Hev b 2 β-1 and 3-glucosidase Defense-related protein Bell pepper, olive -Hev b 5 Acidic protein Kiwi, potato, and sugar beet -Hev b 6 Hevein and prohevein proteins Defense-related protein (latex coagulation) Avocado, banana, chestnut, sweet pepper -Hev b 7 Patatin-like proteins Defense-related protein or inhibitor of biosynthesis Potato and tomato -Hev b 13 Latex esterase Potato

Question 44

How is latex allergy diagnosed? What is the sensitivity and specificity?

Answer 44

Identification of NRL-specific IgE associated with symptoms that are consistent with IgE-mediated reactions to latex protein allergens. There are no standardized skin test extracts. The in vitro assays have wide ranges of sensitivity (73–92%) and specificity (73–97%).

Question 45

In Food-dependent exercise-induced anaphylaxis, what are associated foods? What are the most common foods that trigger it?

Answer 45

- Crustaceans - Cephalopods - *Celery* - Grapes - Chicken - *Wheat* - Buckwheat - Tomato - Dairy product - Mushrooms

Question 46

Is food dependent exercise-induced anaphylaxis more common with any food or specific foods?

Answer 46

More common with specific foods.

Question 47

What is the management of food dependent exercise induced anaphylaxis?

Answer 47

Management of food-dependent EIA includes avoiding exercising in proximity (4–6 hr) to food consumption, carrying self-injectable epinephrine, exercising with a partner, and wearing a medical alert bracelet.