Angioedema is rapid swelling of subcutaneous tissues caused by increased vascular permeability. There are four main types: allergic angioedema caused by allergens, drug-induced non-allergic reactions, idiopathic angioedema of unknown cause, and hereditary angioedema (HAE) caused by C1 inhibitor deficiency. HAE is treated with C1 inhibitor concentrate, icatibant, or ecallantide while other types may be treated with antihistamines, steroids, and epinephrine if anaphylaxis is possible. Early airway management is important as angioedema can affect the tongue, larynx, and uvula and potentially cause

1. Angioedema
Rosie Stroud

2. What is angioedema?
• Heinrich Irenaeus Quincke (1842 –1922) was
a German doctor. He introduced the
lumbar puncture and in 1882 was the
first to recognise angioedema.
William Osler remarked in 1888
that some cases may have a
hereditary basis

3. What is angioedema?
• It is the rapid swelling of the dermis,
subcutaneous tissue, mucosa and submucosal
tissues
• It is very similar to urticaria
• You can try to differentiate through history
and examination
• Etiologies of angioedema are divided into
mast cell mediated and non-mast cell
mediated

5. What is angioedema?
• Non pitting, rapid onset, self limiting swelling
• Results from increased vascular permability
• Generally resolves in 24-48 hours
• But has the potential to ruin your day (and the
patient’s)

6. What are the types of angioedema?
The causes of angioedema depend on the type
of angioedema a patient has:
1) acute allergic angioedema
2) non-allergic drug reactions
3) idiopathic angioedema
4) hereditary angioedema (HAE) / acquired C1
inhibitor deficiency

7. Acute allergic angioedema
• Almost always occurs with urticaria within 1-2
hours of exposure to the allergen
• Nuts, shellfish, milk, eggs
• Drugs, e.g. penicillin, NSAIDS, vaccines
• Radiocontrast media
• Natural rubber latex e.g. gloves, catheters
• Reactions will recur with repetitive exposures
or exposure to cross-reactive substances

8. Non-allergic drug reactions
• Onset may be days to months after taking the
medication
• Commonly ACE inhibitors
• Cascade of effects via kinin production and
nitric oxide generation
• Occurs without urticaria

9. ACE inhibitors increase bradykinin activity >>> Transient
vasodilation >>> fluid in extracellular space
The incidence of angioedema from ACE inhibitors ranges in
the literature from 0.1 to 2.2%
(Allergy Asthma Proc 30:11–16, 2009; doi: 10.2500/aap.2009.30.3188)

10. Idiopathic angioedema
• Similar to acute allergic but angioedema keeps
on recurring and often no known cause is
found
• Usually occurs with urticaria
• 30-50% of this type of angioedema may be
associated with some types of autoimmune
disorders including SLE
http://www.dermnetnz.org/reactions/angioedema.html

11. Hereditary angioedema (HAE)
• 3 types:
Type 1 and II mutation of C1NH gene on chromosome 11,
(encoding C1 inhibitor protein)
Type III mutation in F12 gene on chromosome 12,
(encoding coagulation factor XII)
• Type 1 results in low levels and function of circulating C1
inhibitor;
• Type II has normal levels of C1 inhibitor protein but
reduction in function
• Occurs in 1 in 50,000 males and females (rare)
• Decreased C1 inhibitor activity leads to excessive kallikrein,
which in turn produces bradykinin, which we know is a
potent vasodilator

12. Acquired C1 inhibitor deficiency
• Acquired during life rather than inherited
• May be due to B-cell lymphoma or antibodies
against C1 inhibitor
• Treatment is the same as HAE

13. Acquired and Hereditary:
• Patients often experience no symptoms until they reach
puberty
• Swellings can occur without any provocation
• Sometimes local trauma, vigorous exercise, emotional
stress, alcohol, and hormonal factors
• Some may get a transitory prodromal non-itchy rash,
headache, visual disturbance or anxiety
• Face, hands, arms, legs, genitals, digestive tract and airway
may be affected; swellings spread slowly
• Abdominal cramps, nausea, vomiting, difficulty breathing
• Urticaria does not usually occur

14. Treatment
There isn’t much treatment out there…but
AIRWAY!
AIRWAY!
AIRWAY!
HAVE A LOW THRESHOLD FOR INTUBATION
USE CLINICAL EXAMINATION

15. Investigations
There are no point-of-care tests! Treat what you see and from the patient’s history.
Bedside
Fiberoptic laryngoscopy
Laboratory - Identify underlying cause (help with long term management):
C1 esterase inhibitor (C1-INH) assays (low/ abnormal in HAE)
C4 levels (low in HAE attacks, usually normal between attacks)
serial tryptase levels (may be elevated in anaphylaxis/ mast cell-mediated angioedema)
Imaging
CT abdomen may show evidence of angioedema in patients presenting with abdominal pain:
CT neck primarily has a role in excluding conditions that may mimic angioedema (e.g. soft tissue
infection)

16. Specific treatments
FFP – approx 40 case reports only. Limited evidence.
possible therapy for ACEI-related angioedema
FFP contains ACE, which degrades bradykinin
Therapies for HAE
– icatibant — a bradykinin 2 receptor inhibitor
– ecallantide — a kallikrein inhibitor (kallikrein is the enzyme that produces bradykinin)
– C1-INH concentrate
Role of adrenaline, steroids and antihistamines….
• unlikely to be be effective for ACEI-related angioedema
– this a bradykinin-mediated condition, not related to mast cell degranulation
– many ACEI-related angioedema cases can be managed by observation alone, without
pharmacotherapy or intubation
…..Should be adminstered if the underlying cause of angioedema is uncertain (i.e.
anaphylaxis is possible)

17. Treatment
• H1 antihistamine e.g IV
chlorpheniramine 10 mg or diphenhydramine
25–50 mg
• Limited evidence for adding in H2 blocker e.g
ranitidine IV 50mg
• Intravenous corticosteroids e.g. hydro-
cortisone 200 mg or methylprednisolone 50–
100 mg
• Adrenaline IM 1:1000

18. Pedrosa et al, 2014

19. Disposition
Consider admission to hospital in the following situations
(Winters et al, 2013):
• previous history of angioedema
• tongue edema
• pharyngeal edema (palate, uvula)
• laryngeal edema / upper airway oedema
• lack of improvement during stay in ED
Patients with isolated angioedema of the face or lips and
be usually be observed in ED for 4 to 8 hours for
progression of symptoms, then discharged

20. Conclusion
• 4 main types of angioedema
• Pharmacological treatment is limited
• Early airway management is key
Guidelines:
http://www.aaem.org/em-resources/position-statements/2006/clinical-practice-guidelines
http://lifeinthefastlane.com/ccc/angioedema/
Pedrosa M, Prieto-García A, Sala-Cunill A; Spanish Group for the Study of Bradykinin-Mediated
Angioedema (SGBA) and the Spanish Committee of Cutaneous Allergy (CCA). Management of
angioedema without urticaria in the emergency department. Ann Med. 2014 Dec;46(8):607-18.
doi: 10.3109/07853890.2014.949300. PubMed PMID: 25580506.