Urticaria, Angioedema, and Anaphylaxis Flashcards
Urticaria
The medical term for hives. pruritic, erythematous papules or plaques, with an erythematous border and often a lighter center.
Angioedema
The medical term for swelling
It is estimated that __% of the population experiences urticaria at some point in their life.
It is estimated that 20% of the population experiences urticaria at some point in their life.
Urticaria
Three sources of edema
- Lymphedema (indicative of inflammatory process or failure of lymphatic system)
- Edema arising from heart failure
- Edema arising from liver failure
Reflection coefficient
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.
Pcap - Pint
The expression denoting the difference in hydrostatic pressure between the capillary space and the interstitial space
πcap - πint
The expression denoting the oncotic pressure difference between the capillary space and the interstitial space
Fick equation
J = σ { ( Pcap - Pint ) - ( πcap - πint ) }
Where J is the fluid flux rate between the capillary and the interstitial space
Anything that ___ will shift the balance towards the accumulation of fluid in the tissue and thus the development of (angio-)edema
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
As opposed to angioedema, “regular” edema is __
As opposed to angioedema, “regular” edema is gravity dependent
Angioedema classically affects the ___ and does not migrate based on ___.
Angioedema classically affects the lips, tongue, face, hands, feet, and genitals and does not migrate based on gravity.
Cutoff for acute vs chronic angioedema and urticaria
6 weeks
Differential diagnosis for angioedema with urticaria
- 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.
In dermal tissues, approximately __% of histamine receptors are of the H1 subtype
In dermal tissues, approximately 85% of histamine receptors are of the H1 subtype
Complement, Coagulation, and Contact Cascades in Angioedema
Chronic autoimmune urticaria
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.
What triggers bradykinin mediated angioedema?
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.
Bradykinin activates the endothelium via
Bradykinin type-2 receptors
Treatment and Prevention
- Antihistamines
- Montelukast (cysteinyl leukotriene antagonist)
- Corticosteroids (at least for short term)
- Omalizumab (IgG anti-IgE)
Treatment and Prevention for Bradykinin-mediated angioedema
- 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
Etymologically, anaphylaxis is the opposite of. . .
. . . 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). “
You should strongly suspect anaphylaxis when you see a patient with:
- Acute onset of illness (min to hr) involving skin or mucosa and either respiratory compromise or shock
- Rapid onset of symptoms following exposure to likely allergen involving two or more of: GI symptoms, skin/mucosa, respiratory, blood pressure
- Clear evidence of shock following exposure to a known allergen
Frequency of anaphylaxis manifestation in various organ systems
Grade I - Mild anaphylaxis
- Skin and subcutaneous only
- Generalized erythema, urticaria, periorbital edema, and angioedema
Grade II - Moderate Anaphylaxis
- Respiratory, cardiovascular, and gastrointestinal involvement
- Dyspnea, Stridor, Wheezing
- Nausea, Vomiting
- Dizziness, Diaphoresis (sweating), Chest or throat tightness, or abdominal pain
Grade III - Severe Anaphylaxis
- Hypoxemia, shock, neurologic involvement
- Cyanosis, Oxygen Saturation <92%
- Systolic blood pressure <90mmHg in adults
- confusion, syncope, incontinence
Careful observation indicates that virtually all patients who experience anaphylaxis have some __.
Careful observation indicates that virtually all patients who experience anaphylaxis have some skin involvement.
Diagnosing anaphylaxis
- Clinical and made based on history
Differential diagnosis for anaphylaxis (based on history from patient or observer)
- 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)
tryptase
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
Why are hives itchy?
Histamine and cysLT’s can trigger selected peripheral nerves to send signals to the sensory cortex, and those signals are interpreted as itching
The most common offenders for precipitating anaphylaxis
Drugs!!!
Penicillin is number 1, aspirin a close second
Detectable histamine lasts __ in peripheral blood.
Detectable histamine lasts ~30 minutes in peripheral blood.
Serum tryptase lifetime
~6-9 hours
A positive tryptase read may indicate. . .
. . . anaphylaxis OR systemic mastocytosis OR kidney damage
People with kidney damage have chronically high tryptase, and so it may yield false positives
Treatment for anaphylaxis, FAST
Intramuscular epinephrine
- Raises blood pressure (both HR and stroke volume)
- Reverses bronchoconstriction
- Vasoconstricts
- Reverses angioedema
Which complement component is the best test to assess for the possibility of hereditary or acquired angioedema?
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.
When kids anaphylax, the most dangerous symptom is ____.
When adults anaphylax, the most dangerous symptom is ____.
When kids anaphylax, the most dangerous symptom is ARDS.
When adults anaphylax, the most dangerous symptom is shock.
When an adult is in shock, they should . . .
. . . administer epinephrine intramuscularly, wait 10 seconds, then lie down and call 911
“Retractions”
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
