Allergy Flashcards
What is anaphylaxis (definition)?
any acute onset illness with typical skin features (urticarial rash, errythema / flushing, and/or angioedema) with resp and or cardio involvement. Can also get severe GI involvement
How does anesthetic related anaphylaxis present compared to regular anaphylaxis?
often presents only with spontaneous refractory hypertension during anesthetic (if no other cause found)
- Often don’t get a rash or other features (pt is asleep)
Is elevated tryptase involved in Dx anaphylaxis?
No
- It can be elevated in ana but not always
- Most often elevated in venous or drug anaphylaxis (not often food anaphylaxis)
What time does Mast cell tryptase peak following anaphylaxis? How long does it take to return to normal?
1-1.5hrs post
returns to normal 24 hrs post usually
Why is baseline tryptase recomended following complete resolution of anaphylaxis?
Because anaphylaxis can be an initial presentation of systemic mast cell disorder such as systemic mastocytosis
- If baseline tryptase elevated then this is concerning
Presentation of systemic mastocytosis?
Symptoms of mast cell mediator release
- flushing and pruritis
Skin findings:
- Urticaria pigmentosa
Symptoms arising from organ infiltration
Recurrent anaphylaxis which may be severe
What are teh two types of angioedema? How can these be clinically distinguished?
Histaminergic angioedema (ie as part of ani IgE mediated allergy or anaphylaxis)
- often occures in conjunction with other symptoms of allergy or anaphylaxis
- Shorter duration 2-24 hrs
Bradykinin mediated angioedema
- often occurs in isolation (ie well person with swelling)
- Last longer (24-72hrs)
What are the two types of histaminergic angioedema?
IgE mediated
Non IgE mediated (mast cell degran that is not cuased by IgE crosslinking)
Explain the pathophysiology of hereditary angioedema?
Most commonly caused by a def in C1 inhibitor (aka C1 esterase)
- C1 inhibitor inhibits multiple points in the kallikrein-bradykinin pathway. Hence a deficiency in C1 inhibitor leads to excess bradykinin leading to vascular permeability and angioedema
Note C1 is also invo9lved in complement obviously, but this has nothing to doe with how it causes HAE. Can be used for Dx tho due to low C4 levels
Why do pts with Hereditary angioedema often have low C4?
The have deficiency in C1 inhibitor
C1 inhibitor binds to an inactivates C1r and C1s which stops the cleavage of C4 and activation of classical complement pathway
therefore if dont have this inhibitor, C4 is always being cleaved resulting in low levels of C4
What distribution of angioedema would be more concerning for HAE rather than ACEI mediated angioedema?
Genitral or GIT angioedema = HAE
What are the 4 types of HAE?
Type 1 (most common)
- Quantatative C1 inh def
Type 2
- Qualatative C1 inh def
Type 3
- Abnormalities in other proitiens involved in pathway (often get normal C4 level in T3)
type 4
- aquired def due to antibodies against C1 inh (usually old pts with haem malig or autoimmunity)
what is the utility in testing for C1q in HAE?
It is low in acquired HAE (ie Type 4), normal in all others
Management of HAE? (acute attacks, short term prophylaxis, long term prophylaxis)
Acute attack:
- Icatibant (bradykinin receptor antagonist)
- Berinert IV (recombinant C1 inh)
Short term prophylaxis:
- Berinert IV stat prior to procedure (ie dental procedures or intubation
Long term prophylaxis:
- Berinert IV or SC
- Lanadelumab ( kallikreinin inhibitor mab)
What time frame can ACEI related angioedema develop?
Can occurs many years after starting drug
What is the treatment for ACEI associated angioedema?
Cease ACEI
- note can still get ACEI related AE for several months post stopping drug
What is chronic spontaneous urticaria? Explain the pathophys, and treatment?
Chronic spontaneous urticaria is defined by the presence of hives daily or almost daily for at least six weeks (NOT ALLERGIC)
- pathophys not understood. Thought to relate to autoiummunity
Treatment:
- First line: non sedating antihistamines
- Second line: montelukast
- Refractory: omalizumab ( MAB to IgE)
What is the difference between sensitization and allergy?
Sensitisation:
- precence of IgE to allergen
- Not everyone who is sensation is allergic to the antigen
Allergy:
- clinical manifestations of IgE medicated MAST cell de granulation
What is skin prick testing? What is intradermal testing?
How do they differ?
Skin prick testing:
- scratch skin then topically apply allergen to skin
Intradermal testing
- inject drug intermediately
Differences:
- Intradermal testing only used for drugs (because food isnt sterile)
- Intradermal testing is slightly more sensitive
- Intradermal testing has slightly higher risk of systemic reaction
What drugs need to be WH prior to skin prick / intradermal testing?
- Anti histamines 72hrs prior
- Antidepressants esp Doxepin and TCAs as these have antihistamine activity
How is wheel size interpreted in skin prick testing?
Wheel > 3mm is positive
Wheel size informs the likelihood of reaction but not the severity of the reaction
Can skin prick testing be used for delayed hypersensitivity reactions?
No, only used for IgE mediated reactions
What is the allergen in Mamalian meat allergy? Expalain the pathophys
Alpha Gal
Exposed to allergen via tick bite
then when eat mamalian meat (which has this allergen in it), they have anaphylaxis
How does anaphlaxis from mamalian meat allergy differ from otehr food anaphylaxis clinically?
Time course - MMA ana usually dfelayed by several hours
How do we test for MMA?
Specific IgE for alpha-gal (blood test)
What is Wheat dependant, exercise induced anaphylaxis?
Rare food allergy characterised by anaphylaxis occurring 1-4 hrs following ingestion of wheat followed by exersise
What is the blood test for wheat dependant, exercise induced anaphylaxis?
Specific IgE to Omega 5 gliadin
What are the 4 types of drug allergy?
Type 1 - Allergic (IgE mediated)
- only one to have reliable diagnostic test (skin prick testing, drug challenge, specific IgE)
Type 2 - Cytotoxic (antibody dependent)
Type 3 - Immune complex
Type 4 - Delayed (T cell mediated)
the difference between type II and III is that the antigen in type II is bound (ie to a cell surface), whereas the antigen in T3 is free floating (hence forms immune complexes with antibodies
Which vaccines are contraindicated in egg allergy pts?
Yellow fever
Q fever
What is the HLA associated with Type 4 allopurinol hypersensitivity?
HLAB5801 (esp Han chinese)
What is the HLA associated with Type 4 vancomycin hypersensitivity?
HLA A 3201 (DRESS to vancomycin)
What is the HLA associated with Type 4 anticonvulsant hypersensitivity?
HLA B 1502
When is desensitization to penecillin most often used?
For pts with tertiary syphilis (really require penecillins)
