Anaphylaxis Flashcards
What is tryptase? What sorts of reactions is this released in?
It is a mast cell serine protease. It is released in anaphylaxis AND anaphylactoid reaction
Only works 15 min – 3 hours after event
To support a diagnosis of anaphylaxis, need to have a level that normalises the next day
Negative does not exclude Can be high in someone with mast cell/mastocytosis
what is the risk of future anaphylaxis in someone that has had a large local reaction to bee sting?
less than 10%
what is the food allergy that is most likely to persist from childhood?
tree nut seems to be most likely, followed by peanut
what percentage of patients with peanut allergy also have tree nut reaction?
30- 70% about 5% react to legumes
how do we investigate penicillin allergy?
the sensitivity is low for penicillin allergy and so, intradermal testing is more appropriate
what can happen in circumstances where patients administer adrenaline, then get up and walk around?
this can lead to a condition terms “empty ventricle syndrome”. This is a condition where there is CVS compromise, then the patient stands, and there is no blood to the ventricle and then, sudden death
what is the greatest factors associated with anaphylaxis death?
90% of deaths occur in patients with asthma
90% are associated with nut allergies
90% of deaths, the epipen not available or not used prior to cardiac arrest
what is the most common cause of low complement in a blood test?
the most common cause is delayed transfer to the laboratory
is there any overlap between penicillium mould and penicillin?
no, they are now unrelated and cross reactivity does not occur
what occurs in immunotherapy?
describe the changes in the effector I-Ls and also the involved T cells
small amounts of antigen, apparently leads to a different response.
instead of the APC leading to Th2, it leads to Treg, which have a POSITIVE response on Th1, leading to IFNgamma and IgG
There is also production of IL10 and TGFbeta by the Treg
the downstream IgG4 and IgA are inhibitory immunoglobulins. They go to the mucosa and mop up antigen and stop it from being presented to Th2 cells
what is the most efficacious route for administering adrenalin (in the field)
intramuscular is much faster onset of action than sub/cut
therefore, IM is what we’re after here
which of the provocation testing is most appropriate in the following:
- reaction to drug ingestion
- reaction to bee/wasp sting
- tree nut anaphylaxis
- anaesthetic reaction
- intradermal has better predictive value
- intradermal
- skin prick testing
- intradermal
second generation H1 antagonists effectively relieve most of the symptoms of allergic rhinoconjunctivitis
which of the following is leads effectively relieved?
nasal congestion
nasal itch
ocular tearing
rhinorrhoea
sneezing
nasal congestion
dunno why
What causes hereditary angioedema (recurrent angioedema without uritcaria or other signs of infection)?
C1 esterase inhibitor
Serological tests for immunoglobulin G4 (IgG4) against food antigens are being used increasingly in the assessment of food allergies. When is this measurement most appropriate?
European Taskforce Statement (Endorsed by Australasian Society of Clinical Immunology & Allergy):
Food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints.
You must always assess three drugs a patient is using before ordering skin prick testing. Why is this?
Look for use of:
- Antihistamines, or agents with anthistaminergic properties.
Includes antidepressants such as doxepin and TCAs.
Rememeber OTC preparations (eg. cold & flu tablets).
- Topical steroids - can decrease reaction
- BETA-BLOCKERS are a CONTRAINDICATION to skin prick testing. ACEi relatively contraindicated.
They impair the normal compensatory mechanisms in anaphylaxis.
Beta-blockers interfere with the effect of adrenaline.
(In general though, the risk of anaphylaxis is low with SPT, so may choose to WH only if high risk features exist).
Tell me about positive and negative controls in skin prick testing for allergy.
Negative control: inject same solution that antigens are made up in, without the Ag (eg. saline / glycerol)
If >3mm wheal = severe dermatographism = uninterpretable test.
Different protocols if ≤3mm, eg. accept +ve wheal >6mm (caution, as dermatographism can be variable by site).
Positive control: inject histamine solution or codeine (degranulates cutaneous mast cells, indirectly causing wheal and flare). Result read at 10-15mins.
Should produce wheal of approx. 6mm.
≥4mm may still be acceptable (or 4mm >negative control).
<4mm means test is uninterpretable (eg. patient may have taken antihistamine).
Note: test wheal (allergen injection) is read at 15-20mins. If pos and neg control ideal, then a ≥3mm test wheal is considered positive for IgE response to that allergen, but interpretation is important.
The 3mm lower cutoff was determined because of reproducibility of measurement rather than clinical relevance.
Mechanisms of angioedema?
Due to kinins.
Importantly, angioedema is NOT pruritic (cf. urticaria, which are due to histaminergic effect).
Angioedema = swelling of skin or mucosal tissue, due oedema is in interstitium (.cf. urticaria where superficial dermis is affected)
Mechanisms:
- Mast cell-mediated:
- IgE mediatated - as in anaphylaxis / allergy
- Direct mast-cell degranulation - some medications
- Aspirin / NSAID effect
[Mast cell-mediated angioedema may be pruritic and have co-existing urticaria].
- Bradykinin-mediated:
- ACEi - inhibit bradykinin degradation
- C1 esterase inhibitor (C1-INH) deficiency:
C1-INH is asually constituitively active as a brake on complement activation , which leads to activation of the kallkrein-kinin system.
> Hereditary Angioedema:
- C1-INH deficiency (Type 1 = 85%)
- C1-INH dysfunction (Type 2 = 15%)
?Type 3
> Acquired Angioedema due to C1-INH deficiency:
- Consumption: malignant / lymphoproleiferative disease
- Antibody-mediated: AI disease (Abs to C1-INH)
Investigations for suspected hereditary (or acquired) angioedema?
C4 level - typically low during attack, may be low or normal between attacks; less reliable - used as a SCREEN as more quickly available.
C1-INH level - expected to be low in Type 1 HAE or in AAE. Likely to be normal in Type 2 HAE though.
C1-INH functional study - low in HAE (including Type 2) and AAE.
Treatment of Hereditary Angioedema?
** Attacks can be fatal even if previously mild, due to involvement of airway –> asphyxiation.
Even when airway not involved can cause significant morbidity (abdo pain, nausea, diarrhoea, poor oral intake, pain, functional impairment due to swelling).
- Trigger avoidance / planning:
often triggered by stress, including surgical or dental procedures. Pregnancy and hormonal triggers recognised.
- Acute attacks, or prophylaxis (eg. pre-op):
(a) C1-INH infusions: Require inpatient IV administration. Not currently govt. funded - cost +++
(b) Icatibant: competitive antagonist for bradykinin Rc (B2). Administered subcut. Now on PBS. - Prevention:
(a) Danazol = anabolic steroid. Stimulates production of C1-INH by liver.
Usually commenced between attacks, though commencing / increasing during acute attack may be of some benefit.
Limited by adverse effects: hepatoma / LFT derangement, endocrine (IR), hypertension, virilisation in women.
(b) Tranexamic acid is alternative
- alternative to danazol in women
- increased risk of VTE
What are the mechanisms for urticaria?
Is urticaria lasting <24 hours likely to be different to that lasting >24 hours?
Urticaria is mediated by cutaneous mast cells in the superficial dermis.
Mechanisms:
- IgE-mediated: medications, insect stings, latex, foods / additatives, transfusion, other allergenic proteins.
- Direct mast cell activation: eg. narcotics, muscle relaxants, rdiocontrast medium, vancomycin, stinging nettle.
- Infection: Viral and bacterial - mechanisms unlcear - ?immune complex-or complement mediated.
Parasitic - stimulate eosinophilia. - NSAIDs - can cause “pseudoallergic” urticaria via COX I pathway, or true immunologic allergy
- Physical urticarias: dermatographism, pressure, cold, vibratory, solar, cholinergic.
- Progesterone-associated urticaria
- Serum sickness (HSR type III)
- Systemic disorders: mastocytosis, CTD and AI diseases, vasculitides (eg. urticarial vasculitis and cutaneous small vessel vascultitis), malignancy (esp. paraproteinaemias).
<24hours duration: suggestive of IgE-mediated process - more likely to respond to antihistamines.
>24hours duration: more likely cell-mediated process. May still respond to antihistamines, but may require steroid therapy.
Note: urticaria is classed as ACUTE (<6-8 weeks) and CHRONIC (>8 weeks).
Alternative Dx to consider in Chronic Urticaria?
DDx Chronic Urticaria:
- Urticarial Vasculitis: differentiated on histology of punch Bx (leukoclastic vasculitis in UV).
Suspect if:
- Lesions are painful (not just pruritic), last >24 hours, leave residual pigmentation;
- Also has petechial / purpuric lesions;
- Raised CRP/ESR;
- Systemic features (arthralgia, fever);
- Unresponsive to appropriate doses of antihistamines.
2. SLE: urticaria and UV may be manifestation of SLE – looks for other SSx.
3. Cryogobulinaemia: cold-induced urticarial or vasculitic lesions (predominantly on buttocks and lower extremities) in HBV or HCV.
4. Schnitzler’s syndrome: associated with monoclonal gammopathy.
- Mastocytosis:
Rare.
Suspected if CU + episodic SSx of systemic mast cell mediator release (flushing, abdominal cramping, diarrhea, wheezing, presyncope / syncope).
May have Darier’s sign: wheals that appear with mild trauma, such as gentle stroking.
- Others: Hypereosinophilia; Polymorphic eruption of pregnancy (or PUPPP = prutitic urticarial papules and plasques and papules of pregnancy).
