Angioedema: Symptoms, Causes, Diagnosis And Treatment

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In the most general terms, angioedema is swelling beneath your skin. However, it goes deeper than that, quite literally. Angioedema swelling occurs in some of the deepest layers of the skin, including the subcutaneous layers, which can lead to severe complications. Additionally, the condition often appears with hives, which is why some refer to it as “giant hives.” 

The causes of angioedema vary, from medication side effects to symptoms of an underlying condition. Mild angioedema doesn’t usually need treatment, although more severe cases may require medication or treatments to relieve intense swelling. 

Signs And Symptoms 

Angioedema typically involves swelling beneath the skin. This swelling typically localizes around your mouth, eyes, hands, feet, or genitals. However, it can spread to other areas of the body, including the intestines and airways. This swelling usually appears with hives or urticaria, which appear as a red, swollen, welt-like rash on the surface of your skin. 

Even though the swelling is deep below the surface of your skin, it can cause pain and redness and the area to feel warm and itchy. If angioedema localizes to your airways, your throat and tongue may feel thick and large, making it difficult to breathe or swallow. In addition, stomach pain, nausea, vomiting, cramping, or diarrhea may accompany angioedema in the digestive tract. 

Symptoms of Angioedema: 

  • Localized swelling 
  • Itchiness 
  • Redness
  • Raised hives/welts
  • Skin is painful or warm to the touch 
  • Stomach pain, nausea, or diarrhea 
  • Difficulty breathing or swallowing 

If angioedema causes you to have trouble breathing, call 911 or go to your nearest emergency room right away. 


Angioedema can be acute, chronic, or hereditary. 

Acute Angioedema

Acute angioedema is often the result of an allergic reaction. This type of angioedema is commonly referred to as allergic, histaminergic, or mast cell-mediated angioedema. Your mast cells are responsible for secreting histamine in response to allergens, which promotes inflammation and can cause itching and hives. So it makes sense that hives and swelling indicate allergic angioedema. Common triggers of allergic angioedema include: 

  • Shellfish or fish
  • Peanuts or tree nuts
  • Eggs
  • Soy
  • Milk
  • Animal dander
  • Poison oak or ivy 
  • Pollen
  • Latex 
  • Insect stings 

Medications can trigger drug-induced angioedema. Possible medication triggers include: 

  • Antibiotics
  • Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or naproxen sodium 
  • Aspirin 
  • Migraine and blood pressure medications

Many medications can indeed cause an allergic reaction, resulting in angioedema. However, non-allergic angioedema most commonly occurs without the presence of a rash or hives. It is believed to be connected to bradykinin. Your body makes bradykinin in some situations to signal to your body to widen blood vessels and make them more permeable. High levels of bradykinin are a side effect of some blood pressure medications. Angiotensin-converting enzyme (ACE) inhibitors often taken for high blood pressure are the leading cause of non-allergic angioedema. 

Also, NSAIDs can technically cause non-allergic angioedema. However, this specific condition, known as pseudo-allergic angioedema, is not mediated by bradykinin and resembles allergic angioedema like itching and hives. Pseudo-allergic angioedema triggers an immune response through a different mechanism than allergic angioedema.

Chronic Angioedema

If your swelling lasts more than 6 weeks, your doctor may diagnose you with chronic angioedema. In most cases, the cause of the chronic swelling is unknown. A diagnosis of chronic idiopathic angioedema means your doctor cannot determine the cause of the swelling, but possible triggers can include: 

  • Minor infections 
  • Hot or cold temperatures
  • Extreme exercise
  • Anxiety or stress

Although rare, regular ingestion of an unsuspected medication or chemical may be to blame (e.g., regularly consuming penicillin in milk or other food additives that may induce an allergic reaction). 

Acquired angioedema (AAE) is another type of bradykinin-mediated angioedema that may result from an infection, autoimmune disease, or serious medical condition, such as lymphoma. However, acute forms of angioedema can sometimes be classified as acquired angioedema. For example, ACE inhibitor-mediated angioedema is technically a type of acquired angioedema. AAE is chronic because it is typically recurrent and appears when your immune system is weak, or a certain trigger is present. 

Hereditary Angioedema

Although it tends to be rare, hereditary angioedema (HAE) is passed from parent to child and typically appears before 12 years of age. It is caused by a genetic defect that affects a blood protein called complement 1 (C1) inhibitor. In HAE, the C1 inhibitor is either absent or does not function properly, allowing blood to seep into other tissues in the body and cause swelling. 

Acquired C1 inhibitor deficiency (ACID) angioedema tightly resembles HAE. However, as the name suggests, it is acquired and not hereditary. It is a type of chronic angioedema that can result from any of the factors mentioned above (see AAE), ultimately resulting in C1 inhibitor deficiency. This type of angioedema typically appears later in life. 

Typically, if angioedema results from a trigger or allergic reaction, the swelling is sudden and occurs within 60 minutes of exposure. In contrast, HAE and AAE do not come on as swiftly and occur over several hours or even days. These conditions are also a form of non-allergic angioedema, so the swelling is not accompanied by a rash or hives.  

Who Might Be At Risk for Angioedema? 

You may have an increased risk of angioedema if you: 

  • Have had angioedema, hives, or an allergic reaction in the past 
  • Take NSAIDs for the treatment of asthma 
  • Have thyroid disease, lupus, HIV, lymphoma, hepatitis, Epstein-Barr virus, or have had a blood transfusion
  • Have a family history of angioedema or hives
  • Take ACE inhibitors
  • Have had a stroke, and recombinant tissue plasminogen activator (rtPA ) therapy 

Several other factors have been linked to an increased risk of angioedema, including older age, race, sex, smoking, and other medications. However, because angioedema is such a complex condition, many of these risk factors are widely contingent on the type and specific cause of the angioedema.  

Diagnosis (Tests)

If you suspect you have angioedema, your doctor will want to evaluate you. They will palpate your areas of swelling and listen to your breathing. Swelling without the presence of a rash or hives is typically linked to non-allergic angioedema, which is commonly caused by the use of ACE inhibitors for blood pressure. Your doctor will want to discuss your family and medical history, including any medications you may be taking. 

If the cause of your angioedema isn’t apparent, blood tests may be required. These tests usually aren’t beneficial for allergic or acute angioedema because the effects are often self-limited and do not happen more than once. However, elevated tryptase levels can indicate allergic angioedema or other mast cell disorders associated with angioedema. Nonetheless, chronic angioedema warrants a medical and dietary review and blood tests to check for a C1 inhibitor deficiency and assess your C4 levels, which can indicate HAE or an underlying health condition (AAE). 

Treatments (Procedures)

Mild angioedema typically doesn’t require treatment. This is especially true if it results from an allergic reaction and you have since ceased contact with the allergen or trigger. Mild swelling generally resolves on its own within a few days. 

Treatment for severe swelling may be necessary if you have high levels of pain or discomfort or have difficulty breathing. Medications are commonly prescribed for acute angioedema and can include: 

  • Antihistamines, oral corticosteroids, or epinephrine
  • Non-steroidal anti-inflammatories like leukotriene antagonists 
  • Drugs to slow down or suppress your immune system 

If you are having difficulty breathing, airway management will most likely be necessary. 

Bradykinin-mediated angioedema, like AAE, HAE, and ACE inhibitor-mediated angioedema, 

may require different treatments. Usually in the form of blood protein controllers. These can include: 

  • Purified human C1 inhibitor
  • Fresh frozen plasma treatment 
  • Icatibant to block bradykinin
  • Ecallantide to stop the activation of bradykinin

If you are undergoing treatment for angioedema or looking for home remedies to treat mild swelling, the following may help: 

  • Apply a cool, wet compress to the area
  • Wear loose clothing to decrease discomfort 
  • Take an oatmeal bath to alleviate any itching 

Next Steps 

Suppose your angioedema is caused by a known allergen, such as a specific food or medication. In that case, you’ll want to limit contact with your trigger. Talk to your doctor about switching to a new drug to reduce your chances of future angioedema attacks. If the cause of your swelling is unknown, your doctor may ask you to keep a log of your food and activities and track your symptoms. 

Your doctor may prescribe daily antihistamines, especially if you experience hives with your angioedema. In severe cases, your doctor may suggest you carry an auto-injector of epinephrine or an EpiPen. 

For those dealing with hereditary angioedema, joining support groups and forums can be beneficial. You can connect with others in similar situations and learn about coping mechanisms and resources that may help with your symptoms. The US Hereditary Angioedema Association provides a wealth of knowledge on the latest treatments for those with HAE. 

Although angioedema often isn’t severe, it can be a bothersome recurring problem for some individuals. Talking with your doctor about your symptoms and possible treatment options should always be the first step.  

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