Urticaria, Angioedema, and Anaphylaxis

Question 1

Urticaria

Answer 1

The medical term for hives. pruritic, erythematous papules or plaques, with an erythematous border and often a lighter center.

Question 2

Angioedema

Answer 2

The medical term for swelling

Question 3

It is estimated that __% of the population experiences urticaria at some point in their life.

Answer 3

It is estimated that 20% of the population experiences urticaria at some point in their life.

Question 4

Answer 4

Urticaria

Question 5

Three sources of edema

Answer 5

1. Lymphedema (indicative of inflammatory process or failure of lymphatic system)
2. Edema arising from heart failure
3. Edema arising from liver failure

Question 6

Reflection coefficient

Answer 6

Denoted σ, ranges from 0 to 1. A measure of how open the capillaries are to fluid exchange, 1 being maximally open and 0 being impenetrable to fluid.

Question 7

P_cap - P_int

Answer 7

The expression denoting the difference in hydrostatic pressure between the capillary space and the interstitial space

Question 8

π_cap - π_int

Answer 8

The expression denoting the oncotic pressure difference between the capillary space and the interstitial space

Question 9

Fick equation

Answer 9

J = σ { ( P_cap - P_int ) - ( π_cap - π_int ) }

Where J is the fluid flux rate between the capillary and the interstitial space

Question 10

Anything that ___ will shift the balance towards the accumulation of fluid in the tissue and thus the development of (angio-)edema

Answer 10

Anything that increases the net hydrostatic pressure, decreases the net oncotic pressure, increases the reflection coefficient, or impairs lymphatic drainage will shift the balance towards the accumulation of fluid in the tissue and thus the development of (angio-)edema

Question 11

As opposed to angioedema, “regular” edema is __

Answer 11

As opposed to angioedema, “regular” edema is gravity dependent

Question 12

Angioedema classically affects the ___ and does not migrate based on ___.

Answer 12

Angioedema classically affects the lips, tongue, face, hands, feet, and genitals and does not migrate based on gravity.

Question 13

Cutoff for acute vs chronic angioedema and urticaria

Answer 13

6 weeks

Question 14

Differential diagnosis for angioedema with urticaria

Answer 14

• Urticarial vasculitis: occurs when IgG or IgM containing immune complexes, such as form in a serum sickness reaction or some autoimmune diseases, trigger mast cell activation. Often results in complement cascade and complement mediated inflammation as well.
• Hereditary and Acquired Angioedema: It occurs without hives or itching, and is the result of the action of a chemical called bradykinin on vascular endothelial cells. It does not involve histamine or other mast cell mediators much if at all.
• Angiotensin converting enzyme inhibitor (ACE-I) associated angioedema: Also a bradykinin mediated swelling. The ACE enzyme, which catabolizes bradykinin, is antagonized by the ACE-I antihypertensive drug and can lead to the accumulation of bradykinin and thus itchless and hiveless angioedema.

Question 15

In dermal tissues, approximately __% of histamine receptors are of the H1 subtype

Answer 15

In dermal tissues, approximately 85% of histamine receptors are of the H1 subtype

Question 16

Complement, Coagulation, and Contact Cascades in Angioedema

Answer 16

Question 17

Chronic autoimmune urticaria

Answer 17

Represents an important subset of patients who have no clear external triggers for hives and swelling, and previously were told they had idiopathic urticaria/angioedema. Many patients with autoimmune urticaria and angioedema have an IgG autoantibody that binds to FcεRI, leading to cross-linking and mast cell activation and degranulation.

Question 18

What triggers bradykinin mediated angioedema?

Answer 18

In disease such as hereditary angioedema (HAE), there is a congenital defect in one or both of the genes encoding the enzyme C1 esterase inhibitor (C1INH). Lack of C1INH activity allows for the abnormally high conversion of prekallikrein to kallikrein, which in turn generates excess bradykinin.

Angiotensin converting enzymes inhibitors (ACE-Is), a class of anti-hypertensive medications, block the activity of the ACE enzyme that helps degrade bradykinin.

Question 19

Bradykinin activates the endothelium via

Answer 19

Bradykinin type-2 receptors

Question 20

Treatment and Prevention

Answer 20

• Antihistamines
• Montelukast (cysteinyl leukotriene antagonist)
• Corticosteroids (at least for short term)
• Omalizumab (IgG anti-IgE)

Question 21

Treatment and Prevention for Bradykinin-mediated angioedema

Answer 21

• Very different from the rest, so deserves its own category
• Will not respond to antihistamines or mast cell degranulation inhibitors
• Infusion of C1INH may arrest attack
• Bradykinin type-2 receptor blockers
• Kallikrein inhibitors

Question 22

Etymologically, anaphylaxis is the opposite of. . .

Answer 22

. . . prophylaxis

” During attempts by Portier and Richet (1902) to immunize dogs, animals accidentally sensitized to previously sub-lethal doses of sea anemone venom died in a rapid, dramatic reaction the researchers termed ana (the opposite of pro = for)-phylactic (protection). “

Question 23

You should strongly suspect anaphylaxis when you see a patient with:

Answer 23

1. Acute onset of illness (min to hr) involving skin or mucosa and either respiratory compromise or shock
2. Rapid onset of symptoms following exposure to likely allergen involving two or more of: GI symptoms, skin/mucosa, respiratory, blood pressure
3. Clear evidence of shock following exposure to a known allergen

Question 24

Frequency of anaphylaxis manifestation in various organ systems

Answer 24

Question 25

Grade I - Mild anaphylaxis

Answer 25

• Skin and subcutaneous only
• Generalized erythema, urticaria, periorbital edema, and angioedema

Question 26

Grade II - Moderate Anaphylaxis

Answer 26

• Respiratory, cardiovascular, and gastrointestinal involvement
• Dyspnea, Stridor, Wheezing
• Nausea, Vomiting
• Dizziness, Diaphoresis (sweating), Chest or throat tightness, or abdominal pain

Question 27

Grade III - Severe Anaphylaxis

Answer 27

• Hypoxemia, shock, neurologic involvement
• Cyanosis, Oxygen Saturation <92%
• Systolic blood pressure <90mmHg in adults
• confusion, syncope, incontinence

Question 28

Careful observation indicates that virtually all patients who experience anaphylaxis have some __.

Answer 28

Careful observation indicates that virtually all patients who experience anaphylaxis have some skin involvement.

Question 29

Diagnosing anaphylaxis

Answer 29

• Clinical and made based on history

Question 30

Differential diagnosis for anaphylaxis (based on history from patient or observer)

Answer 30

• Flushing syndromes
• Postprandial or so called “restaurant” syndromes (e.g. scrombroid fish poisoning)
• Systemic Mastocytosis: Genetic, caused by excessive c-Kit activity
• Pheochromocytoma (adrenal hormone-secreting tumor)
• Vasovagal reactions
• Panic attack or related psychiatric condition with acute episodes
• Hypoglycemia
• Shock of different etiology
• Menopausal hot flash
• Sudden Infant Death Syndrome (SIDS)

Question 31

tryptase

Answer 31

A mast cell protease that can be measured in the peripheral blood as evidence of mast cell activation and degranulation, used to help diagnose anaphylaxis and mastocytosis; basophils make much less tryptase than mast cells

Question 32

Why are hives itchy?

Answer 32

Histamine and cysLT’s can trigger selected peripheral nerves to send signals to the sensory cortex, and those signals are interpreted as itching

Question 33

The most common offenders for precipitating anaphylaxis

Answer 33

Drugs!!!

Penicillin is number 1, aspirin a close second

Question 34

Detectable histamine lasts __ in peripheral blood.

Answer 34

Detectable histamine lasts ~30 minutes in peripheral blood.

Question 35

Serum tryptase lifetime

Answer 35

~6-9 hours

Question 36

A positive tryptase read may indicate. . .

Answer 36

. . . anaphylaxis OR systemic mastocytosis OR kidney damage

People with kidney damage have chronically high tryptase, and so it may yield false positives

Question 37

Treatment for anaphylaxis, FAST

Answer 37

Intramuscular epinephrine

1. Raises blood pressure (both HR and stroke volume)
2. Reverses bronchoconstriction
3. Vasoconstricts
4. Reverses angioedema

Question 38

Which complement component is the best test to assess for the possibility of hereditary or acquired angioedema?

Answer 38

C4

The lack of enzymatic activity of C1 esterase inhibitor not only leads to the accumulation of bradykinin, the key mediator in this type of angioedema, but to the depletion of early complement components as well. As it happens, C4 is most sensitive.

Question 39

When kids anaphylax, the most dangerous symptom is ____.

When adults anaphylax, the most dangerous symptom is ____.

Answer 39

When kids anaphylax, the most dangerous symptom is ARDS.

When adults anaphylax, the most dangerous symptom is shock.

Question 40

When an adult is in shock, they should . . .

Answer 40

. . . administer epinephrine intramuscularly, wait 10 seconds, then lie down and call 911

Question 41

“Retractions”

Answer 41

In neck. Basically means you can see the sternocleidomastoid really working as an accessory breathing muscle. Means that the patient is having trouble breathing and needs to use accessory muscles regularly