What Causes Angioedema?

Angioedema is the swelling of tissue under the skin. Allergies are a common cause.

Angioedema is the swelling of tissue under the skin (the deep dermis). Angioedema can affect any part of the body through acute episodes typically affect the lips and mouth, eyelids, face, and tongue. Angioedema can also occur in other parts of the body, including the respiratory and gastrointestinal (GI) mucosa. Laryngeal swelling in the throat or tongue swelling can be life-threatening.

Angioedema may affect many organ systems and visible swelling is usually the main symptom. Swelling may be accompanied by:

• Local Burning Sensation 
• Pain 
• Itchiness 
• Local Redness
• Bleeding
• Hives 

The parts of the body most commonly affected by angioedema include:

• Peripheral swelling
  • Affects the skin and urogenital area (e.g., eyelids, lips, tongue, hands, feet, scrotum, etc.)
• Abdomen
  • Abdominal pain
  • Nausea and vomiting
  • Severely decreased appetite 
• Larynx – can be life-threatening
  • Throat tightness
  • Voice changes
  • Difficulty breathing
• Tongue and lip swelling
  • Sometimes so severe that tongue protrudes from the mouth 

Allergies are a common cause of angioedema. Common allergens include:

• Foods - commonly nuts, shellfish, or eggs
• Insect bites
• Something that comes in contact with the skin such as latex, animal saliva or dander, or plants
• Exercise
• Medications
  • Antibiotics 
  • Medicines used to treat high blood pressure (hypertension) or heart disease called angiotensin-converting enzyme (ACE) inhibitors 
  • Over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) for pain and fever, such as aspirin, ibuprofen (Motrin, Advil), and naproxen (Aleve)

Angioedema can also be caused by rare genetic diseases such as hereditary angioedema. 

A doctor can usually diagnose angioedema with a medical history and physical exam. Most mild cases of angioedema do not require testing. 

Tests can be done to determine allergies that may cause angioedema, and for the rare genetic diseases that cause angioedema. 

In chronic or recurrent cases angioedema without a known trigger, doctors may order tests to help determine the cause, such as:

• CBC with differential
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP) level
• D-dimer level
• Urinalysis
• Comprehensive metabolic profile
• Antinuclear antibody (ANA) testing
• CH50 level
• Thyroid studies, including levels of thyroid stimulating hormone, free T4, and thyroid autoantibodies 
• Stool analysis for ova and parasites
• Helicobacter pylori workup
• Hepatitis B and C virus workup
• Rheumatoid factor
• Cryoglobulin levels

Imaging studies may be indicated if internal organ involvement is suspected during acute attacks:

• Plain abdominal X-rays – may show a “stacked coin” or “thumbprint” appearance of the intestines 
• Abdominal ultrasound – may reveal ascites
• Abdominal computed tomography (CT) scan – may show edema of the bowel wall 
• Chest X-ray – may show fluid around the lungs (pleural effusion)
• Soft-tissue neck X-ray – may show soft-tissue swelling

The goal of treatment for angioedema is to reduce and prevent swelling, discomfort, and complications. If swelling is in the face, mouth, or throat, special attention and treatment are needed so the patient’s airway is not closed off.

Medications used to treat hives and severe allergic reactions (anaphylaxis) may also be to treat many types of angioedema such as: 

• Alpha- and beta-adrenergic agonist agents such as epinephrine (EpiPen, EpiPen Jr, Auvi-Q, Symjepi, Adrenalin)
• First-generation antihistamines such as diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), cyproheptadine (Periactin), hydroxyzine hydrochloride (Atarax, Vistaril)
• Second-generation antihistamines such as cetirizine (Zyrtec), desloratadine (Clarinex), fexofenadine (Alleegra), levocetirizine (Xyzal), loratadine (Claritin)
• Histamine H2 antagonists such as ranitidine (Zantac), cimetidine (Tagamet)
• Leukotriene receptor antagonists such as montelukast (Singulair), zafirlukast (Accolate)
• Tricyclic antidepressants such as doxepin (Silenor)
• Corticosteroids such as prednisone (Deltasone, Rayos, Prednisone Intensol, Sterapred, Sterapred DS), methylprednisolone (Medrol, Medrol Dosepak, DepoMedrol, SoluMedrol, A-Methapred), prednisolone (Pediapred, FloPred, Orapred, Millipred, Prelone Syrup, Veripred 20)
• Androgen derivatives such as danazol (Danocrine), oxandrolone (Oxandrin), progesterone-based birth control pills
• Antifibrinolytic agents such as aminocaproic acid (Amicar), tranexamic acid (Cyklokapron, Lysteda)
• Immunomodulators such as cyclosporine (Sandimmune), mycophenolate (CellCept), methotrexate (Rasuvo, Otrexup)
• Agents for treatment or prophylaxis: C1 INH concentrates (Berinert, Cinryze, Haegarda), ecallantide (Kalbitor), lanadelumab (Takhzyro), and icatibant (Firazyr)
• Fresh frozen plasma (FFP)

In severe cases of facial swelling, intubation (placing a tube down the throat to keep the airway and lungs open) may be an emergency necessary. If intubation is unsuccessful, surgery may be required in severe cases of laryngeal edema (throat swelling) to create an airway via cricothyrotomy or tracheotomy.

If angioedema affects the larynx and upper airways, it can cause trouble breathing, suffocation, and even death. Symptoms of laryngeal angioedema include throat pain or discomfort, trouble speaking, and difficulty swallowing. 

Angioedema may also cause severe pain and disfiguration that can interfere with daily tasks and affect a patient’s quality of life.

Most patients who have angioedema will have no complications and the symptom is temporary and goes away on its own or with treatment, and life expectancy is not affected.

Ten to 25 percent of cases of angioedema of the larynx and upper airways that enter an emergency department have life-threatening cases, and between 3-40% of patients who have suffocation (asphyxiation) due to laryngeal edema will die. 

Patients with known allergies can avoid symptoms of angioedema by avoiding allergic triggers. Blood pressure medications such as ACE inhibitors may need to be changed permanently by your doctor. (Do not stop taking any medication without first talking to your doctor.)