Angioedema

This Cook's tour of the topic is included largely for personal/clinical interest; angioedema as a disease entity is absent from both core and intermediate FRCA curricula.

Resources

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations (BJA, 2019)
Evaluation and Management of Angioedema in the Emergency Department (Western Journal of Emergency Medicine, 2019)
Angio-oedema: an overview of differential diagnosis and clinical management (BJA Education, 2012)

Angioedema is a "painless swelling of subcutaneous or submucosal tissues in any part of the body due to increased vascular permeability"
It causes issues owing to:

Direct pressure effects
Airway obstruction
± Haemodynamic compromise

Said increased vascular permeability arises due to a number of pathophysiological mechanisms, including excess histamine, excess bradykinin or via other mechanisms

Histamine-mediated	Bradykinin-mediated	Assorted drugs	Other
Anaphylaxis	C1-esterase inhibitor deficiency (hereditary or acquired)	NSAID-induced	Idiopathic (up to 40%)
Anaphylactoid reactions	ACE-inhibitor-induced	DPP4 inhibitors - the 'gliptins'	Following airway manipulation or trauma
		Fibrinolytics e.g. tPA stroke thrombolysis	Lupus
		'Limus' calcinuerin inhibitors e.g. tacrolimus	Lymphoma, leukaemia

The incidence of angioedema depends somewhat on the underlying process:

Cause	Incidence
Anaphylaxis	Angioedema is a symptom in ∽12% of cases
Congenital C1-esterase-inhibitor deficiency	1:50,000
Acquired C1-esterase-inhibitor deficiency	1:100,000 - 500,000
ACE-inhibitors	0.2 - 0.5%
NSAIDs	0.1 - 0.3%
Fibrinolytics i.e. t-PA	1 - 5%

FBC - there may be a leukocytosis even in the absence of an infectious process
Serum tryptases as per anaphylaxis management
C3 and C4 complement levels - C4 is low in C1-esterase-inhibitor deficiency
C1-esterase-inhibitor antigenic and functional levels - helps differentiate hereditary and acquired C1-esterase-inhibitor deficiency
C1q levels - helps differentiate hereditary (normal levels) and acquired (low levels) C1-esterase-inhibitor deficiency

Stratification

The Ishoo classification system is a way of stratifying the severity of facial angioedema
It divides patients into four categories based on sites of involvement:

Face and lip(s)
Soft palate
Tongue
Larynx

This largely intuitive system doesn't necessarily help guide management, and unsurprisingly those with Grade III or IV disease are more likely to require both active intervention and critical care involvement

Obligatory ABCDE approach, call for senior (anaesthetic/ICU) help and application of oxygen should start the ball rolling
Patients with severe, refractory and/or progressive symptoms may require securing of their airway

This is likely to prove challenging and awake tracheal intubation or FONA could be necessary

Cessation of the offending agent
Patients with suspected anaphylaxis should be managed as such i.e. with IM (or IV) adrenaline as per Resus Council guidelines
Nebulised adrenaline can be effective at reducing oro-lingual swelling across most of the aetiologies
There is no robust evidence of efficacy, nor a great deal of harm, in giving:

Steroids (e.g. hydrocortisone, dexamethasone)
H₁ histamine receptor antagonists (promethazine, chlorphenamine)

Red allergy band and documentation of offending agent
Appropriate allergy/immunology/medical follow-up

Specific management steps in C1-esterase-inhibitor deficiency

Things you may have to hand in your hospital:

FFP
TXA
The patient taking an increased dose of their prophylactic anabolic attenuated androgen (e.g. danazol or stanozolol)

Things you may have some difficulty getting hold of:

Icatibant - a selective, competitive bradykinin B₂ receptor antagonist
Ecallantide - a kallikrein inhibitor (especially as is it is only licensed in the USA)

Acquired C1-esterase-inhibitor deficiency is sometimes associated with B-cell lymphoproliferative diseases or connective tissue diseases, so screening for these may be pertinent