Angioedema

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.