Angioedema

28 May

Angioedema is the swelling of parts of the body; usually sudden but can occur over a long period of time. This can be triggered by allergic reactions and often affects the face, mouth, hands, feet and genitals. The most severe form of swelling will affect the throat/upper airways. This can be severe so early interventions and treatment are important.

- The WHO notes that angioedema and itchiness in response to allergies affect up to 20% of the US population. [1]
- More than 40% of angioedema is idiopathic (caused by no obvious condition)
- The rarest type of angioedema is hereditary angioedema with is caused by a genetic defect. Impacting 1 in every 50,000 people globally according to the Rare Diseases Advisor. [2]
- Long-term idiopathic angioedema is more common in females than males
- The NHS Inform site states that angioedema affects about 10-20% of people during their life. [3]
- Allergens like dust, pollen
- Certain foods such as shellfish, nuts, peanuts, eggs etc
- Insect bites
- Certain drugs such as ACE inhibitors, aspirin, penicillins
- Genetics
- Stress
- Infections/ inflammation [3]
Medical Student
- Can be split into 4 categories of angioedema; allergic, non-allergic, idiopathic and hereditary.
  - Allergic angioedema
    Mast cell-mediated in more than 90% of cases with IgE-mediated reactions
    This reaction is usually associated with urticaria and wheals.
    Stimulants include allergens like dust, pollen, and certain foods [4,5]
  - Non-allergic angiodema
    Caused by the angiotensin drug, ACE inhibitor (angiotensin-converting enzyme inhibitor). The incidence of drug-induced angioedema is rare.
    ACE inhibitors increase the levels of bradykinin in the body as degradation is blocked. This causes drug-induced swelling as bradykinin increases vascular permeability and fluid extravasation. [6]
  - Idiopathic angioedema
    Occurs without itchiness and wheals. The condition is chronic and has no identifiable cause. [4]
  - Heriditary angioedema
    More than 150 genetic mutations in the C1 inhibitor gene on the 11th chromosome have been found to be associated with the condition.
    75% of the cases of hereditary angioedema follow an autosomal dominant pattern while 25% are caused by spontaneous genetic mutations [2]
Patients
- Can be split into 4 categories of angioedema; allergic, non-allergic, idiopathic (caused by no obvious condition) and hereditary (caused by a genetic defect).
  - Allergic angioedema
    Controlled by cells that are triggered in allergic reactions.
    This usually also causes itchiness, hives and redness.
    Stimulants include factors like dust, pollen, and certain foods [4,5]
  - Non-allergic angiodema
    Caused by a drug which is used to treat high blood pressure, heart diseases and heart failure called ACE inhibitors. This is rare.
    ACE inhibitors increase the level of a substance that promotes blood vessel widening and fluid invasion. This causes swelling. [6]
  - Idiopathic angioedema
    Occurs without itchiness and wheals. The condition is long-term and has no identifiable cause [4]
  - Heriditary angioedema
    Caused by genetic mutations on a non-sex determining chromosome (a structure in the DNA storing part of the cell).
    75% of the cases of hereditary angioedema follow an autosomal (non-sex determining) pattern while 25% are caused by spontaneous genetic mutations [2]
- Older age
- ACE inhibitor use
- Cardiopulmonary disease history
- Smoking history
- History of hives or angioedema
- History of allergic reactions [7,8]
- Asymmetric swelling
- Swelling of the upper airways/ throat can cause respiratory distress
- Stridor (high-pitched noise when breathing in) or wheeze (high-pitched noise when breathing out)
- Difficulty breathing
- Redness
- Itching
- Allergic angioedema can develop over minutes-hours
- Non-allergic angioedema can develop over hours- days (not associated with other symptoms of an allergic reaction)
- Gastrointestinal tract swelling can cause vomiting, abdominal pain and diarrhoea [4,9]
- Symptoms and medical history
- Skin prick test- stimulate a reaction to different allergic substances by adding a drop of liquid to the skin and then piercing the skin.
- If a raised bump is seen, it is labelled an allergen.
- Blood tests to check for the level of C1 inhibitor in the body. Low levels can indicate angioedema.
- Genetic tests can search for mutations that reduce the level of C1 inhibitors
- If these tests are inconclusive, idiopathic angioedema may be labelled as the cause of the symptoms.
- If itchiness is not present and reoccurs without a clear cause or is present in family members, may consider hereditary angioedema. [10]
- Allergic contact dermatitis
- Connective tissue disease
- Endocrine disorders
- Parasitic disease (eg. insect bites)
- Tumor masses
- Drug hypersensitivity syndrome
- Anaphylaxis [11,12]
Medical Student
- Airway protection is critical in cases with airway swelling
- Epinephrine/adrenaline can be given intramuscularly (IM) or subcutaneously (SC) for allergic angioedema
- Patients with severe mast cell-mediated reactions should carry:
  - Pre-filled epinephrine auto-injector
  - Oral antihistamines
Allergic (Mast Cell-Mediated) Angioedema
- Remove or avoid the triggering allergen
- H1 blockers (antihistamines) for symptom relief
- Prednisolone for more severe cases
- IV corticosteroids combined with antihistamines for systemic involvement
Non-Allergic (Bradykinin-Mediated) Angioedema
- Discontinue ACE inhibitors; symptoms usually resolve within 24–48 hours
- Endotracheal intubation often required in severe cases
- Response to treatment typically takes more than 30 minutes
Hereditary Angioedema
- Fresh frozen plasma
- C1 inhibitor concentrate
- Ecallantide (plasma kallikrein inhibitor)
- Icatibant (bradykinin receptor antagonist)
Idiopathic Angioedema
- Trial of high-dose, non-sedating oral antihistamines
Patients
- In serious cases with swollen airways, a secure airway is needed to help breathing
- Epinephrine (adrenaline) can be injected into the muscle or under the skin to quickly reduce swelling in allergic angioedema
- People with severe allergic reactions should always carry:
  - An epinephrine auto-injector (e.g. EpiPen)
  - Antihistamines
Allergic Angioedema
- Avoid the substance causing the allergy
- Antihistamines help relieve swelling and itching
- Prednisolone (a steroid) may be needed for more serious symptoms
- In some cases, medication is given through a vein in the hospital
Non-Allergic Angioedema
- Caused by some medications like ACE inhibitors — stopping the drug usually improves symptoms in 1–2 days
- A breathing tube may be needed in serious cases to keep the airway open
Hereditary Angioedema
- Treated with:
  - Plasma from donors (fresh frozen plasma)
  - Special proteins (C1 inhibitor)
  - Medicines that block substances in the body that cause swelling (ecallantide, icatibant)
Unknown Cause (Idiopathic)
- High-dose antihistamines may be used to control symptoms [4]
- Tongue or throat swelling that can cause difficulty breathing
- Airway swelling, causing that can cause difficulty breathing [12]
- Angiodema is never dangerous
- Itching is always associated with angioedema
- How do I manage an episode of swelling?
- How did I know how severe my swelling episode is?
- What foods should I avoid with allergic angioedema?
- When should I call emergency services during an episode?
- Will I have to use alternative drugs if they trigger my swelling?
- Hereditary Angioedema Association
- NHS inform
- nidirect.gov.uk
[1] https://emedicine.medscape.com/article/135208-overview#a5
[2] https://www.rarediseaseadvisor.com/disease-info-pages/hereditary-angioedema-epidemiology/#:~:text=Prevalence,%3A10%2C000
[3] https://www.nhsinform.scot/illnesses-and-conditions/skin-hair-and-nails/angioedema#:~:text=Hereditary
[4] https://www.msdmanuals.com/en-gb/professional/immunology-allergic-disorders/allergic,-autoimmune,-and-other-hypersensitivity-disorders/angioedema?query=angioedema
[5] https://www.nhs.uk/conditions/angioedema/
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031276/#:~:text=extravasation
[7] https://pubmed.ncbi.nlm.nih.gov/24938823/
[8] https://www.mayoclinic.org/diseases-conditions/hives-and-angioedema/symptoms-causes/syc-20354908#:~:text=You
[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188378/
[10] https://angioedemanews.com/angioedema-diagnosis/?cn-reloaded=1
[11] https://pubmed.ncbi.nlm.nih.gov/12476544/
[12] https://dermnetnz.org/topics/angioedema