Angioedema

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

4. 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)

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

6. A cute allergic angioedema A lmost 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

7. N on-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

8. 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)

9. I diopathic 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

10. H ereditary 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

11. A cquired 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

12. 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

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

14. 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)

15. 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 R ole 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)

16. 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

17. Pedrosa et al, 2014

18. 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 P atients 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

19. 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.