Anaphylaxis and Angioedema
Physiology Explainer and a look at the current Advanced Life Support Protocols
Anaphylaxis
- Severe life threatening hypersensitivity reaction
- Characterized by rapid development
o Airway (pharyngeal or laryngeal oedema)
o Breathing (Bronchospasm and or tachypnoea)
o Circulation (Hypotension and or tachycardia)
o Often with associated skin or mucosal changes
Angioedema
- Swelling of the deeper layers of the skin/mucus membranes
Why is the distinction important?
- Causes and treatment varies
- We don’t want to be treating angioedema as anaphylaxis and likewise we don’t want to miss anaphylaxis (by definition its life threatening)
So anaphylaxis then:
Can be allergic mediated, non allergic mediated or idiopathic
Approx 20 deaths a year in the UK, half are iatrogenic. (suspected to be an underestimate)
- Lets start with the treatment, What is it?
o Remove the cause – stop the infusion, remove the bee sting
o Adrenaline
Adrenaline
Adrenaline
Dosing? 0.5ml 1:1000 IM in an adult
Child? Based on age
>12 500mcg (0.5ml)
6-12 300mcg (0.3ml)
6 months to 6yrs 150mcg (0.15ml)
<6months 100-150mcg (0.1-0.15ml)
Rpt after 5 mins if insufficient response
There is no other treatment for anaphylaxis
Every other treatment is for allergic reaction
If its anaphylaxis all we do is Adrenaline
It makes no difference what the cause is
What if IM adrenaline doesn’t work? Adrenaline infusion
- What are the investigations?
o Mast Cell Trypase levels
§ Take at initial presentation
§ Then at 1-2 hrs from symptom onset (definitely before 4hrs)
§ They will need a baseline level >24hrs post event
- How long do we observe them for?
o 6-12hrs
o Why? – biphasic reactions are a risk
- Do we admit them?
o All children get admitted
o Adults can go home after their period of observation – it maybe that in the time they have waited to be seen/time take to attend that they may have reached that point
- Follow up and discharge plan
o Allergy clinic referrals for all
o Epipens for all
- Saftey netting advice?
o Info on anaphylaxis
o Biphasic reaction
o Self-administration of epipens
o Triggers
So that’s the real world clinical summary, More detail? Yes please
So allergic, non allergic – but the treatment is the same
Allergic is an example of a Type 1 Hypersensitivity reaction (see below)
The response is caused by antigen binding to specific antibody leading to mast cell activation
- Histamine, Leukotrienes, tumour necrosis factor and a range of cytokines are released from the mast cells and basophils
o Increased bronchial smooth muscle tone -> wheeze, SOB
o Decreased vascular tone and increased capillary permeability -> rash and hypotension (reduction in PVR)
- Biphasic reaction in 20% ish
Common Causes?
- Antibiotics (penicillin, teicoplanin), Asprin and NSAIDs
- ACEi
- Food ie nuts, egg and seafood
- Insect bites and stings
- Herediary C1 esterase inhibitor deficiency (autosomal dominant but also occurs in lymphoma and connective tissues disorders)
- Idiopathic
Uncommon Causes?
- Exercise, cold
- Transfusions, Semen
- Latex
Weve spoken about management
But what about antihistamines and steroids?
- Antihistamines have no role in the immediate management, once stablised they can be used to treat cutaneous symptoms
- Steroids are not advised to treat anaphylaxis
o Ongoing bronchospasm or shock after intial management they maybe used – little evidence they do anything to prevent biphasic reactions or shorten symptoms
And in C1 esterase inhibitor deficiency?
Often resistant to adrenaline, antihistamines and steroids
Treat with C1 esterase inhibitor concentrate or FFP
What if its looking spicey?
So adrenaline remains the main treatment – rpt IM administration is acceptable. About 1/3 of anaphylaxis deaths receive no adrenaline
Whatabout IV?
50mcg boluses of 1:10000 is they way to approach it
You can given fluid boluses – think big volume if periarrest/arrested (4-8ls) but be wary of congestion and overload
Now on to angioedema:
Vital to distinguish between angioedema and anaphylaxis
One more time: what is the difference??
- Life threatening system compromise vs subdermal swelling (typically around lips and eyes)
Urticaria and angioedema are common presentations often of allergic (but not always) aetiology
- Urticaria is histamine mediated localized oedema of the dermis
o One end of the allergic spectrum with anaphylaxis at the other end
o Allergic protein exposure produces IgE mediated mast cell degranulation and histamine release
90% of angioedema is allergic mediated. Non Allergic can be further divided
1. Drug induced Ie ACEi, Bupropion, Vaccines, SSRIs, COX2 inhibitors, Angiotensin 2 antagonists, NSAIDs, Statins, PPIs
2. Hereditary C1 esterase inhibitor deficiency, autosomal dominant or functional deficiency, confirmed by clinically lowe C4 and C1 esterase inhibitor function
3. Acquired
4. Idiopathic
5. Pseudoallergenic
Non allergic is bradykinin mediated
Type 1 hypersensitivity reactions will produce angioedema within minutes, where as bradykinin mediated may take months
Management of Angioedema/uritcaria
Antihistamines – think H1 (chlorphenamine) and H2 inhibitors (ranitidine)
Steroids
Adrenaline
In HAE TXA can be used in conjunction with FFP/C1 esterase inhibitors as it reduces bradykinin production (inhibits plasminogen to plasmin conversion)
There are new drugs coming online for treatment of angioedema. An example of which is conestat alfa. This is recombinant C1 esterase inhibitor and has been approved to treat HAE. The interesting part about Conestat Alfa, is that its made by genetically modifed rabbits in a lab in the Netherlands. They have been genetically modified to produce the C1esterase inhibitor in their milk, and so through milking these rabbits and then refining the milk, the drug can be produced.
There is also Icatibant, which works by preventing bradykinin binding onto the B2 receptor, inhibiting the vasodilatory and increased permeability from bradykinin release. It can be used for any bradykinin mediated angioedema including HAE. The current indication if for angioedema compromising the airways in non anaphylaxis angiodema that hasnt responded to the standard treatment regimens