Angioedema is a condition characterized by swelling and the formation of welts (raised marks) on the skin. It is similar to hives, except the welts are larger and form at a deeper layer in the skin. This causes swelling of the skin that usually affects the face near the eyes and mouth, as well as the hands and feet. However, swelling can also occur inside the throat, which can cause difficulty breathing.

There are two main types of angioedema: hereditary and allergic. Hereditary angioedema is caused by an abnormality of the immune system. It is an inherited disorder that results from the absence of or a defect in a protein called C1 inhibitor. This absence or defect affects the blood vessels, leading to symptoms such as rapid swelling of the hands, feet, limbs, face, intestinal tract or airway (larynx or trachea).

However, the term “angioedema” most often refers to the more common, allergic form of the disease. Like other allergic conditions, allergic angioedema symptoms are triggered by the release of histamine and other biochemicals in the body. Many different allergens can start this process, including foods, medications (particularly aspirin), cosmetics, soaps and detergents.

Angioedema may also be categorized as idiopathic. Idiopathic angioedema is caused by unknown factors or by exposure to certain medications. In over half the cases, the trigger for angioedema is unknown.

An episode of angioedema typically lasts from a few hours to a few days. For most people, angioedema is unpleasant, but does not cause long-term, serious harm or scarring.

Angioedema is a disorder that affects the deeper layers of the skin and triggers significant swelling, particularly in the hands, face and feet. Sometimes, angioedema appears in tandem with hives (urticaria). Hives are raised, red, itchy welts that form on the skin in response to an allergic reaction.

There are three types of angioedema:

• Allergic angioedema. Often simply called angioedema, this involves deep tissue swelling caused by an allergic reaction. Mast cells (cells involved in allergic reactions) release histamine and other chemicals into the bloodstream, which causes capillaries (tiny blood vessels) to dilate and leak fluids through their walls and into the dermis and subcutaneous tissues of the skin. This causes tissue swelling that usually appears in the soft tissues of the lips and other parts of the mouth, throat, eyelids, genitals, hands and feet. Hives and itching often accompany allergic angioedema.
  
  

  

• Hereditary angioedema. A genetic disorder associated with a deficiency of the blood protein C1 inhibitor. This protein belongs to a group collectively known as the complement system, which is involved in immune system function. A deficiency of C1 inhibitor hampers the normal flow of blood and lymphatic fluid, triggering swelling in local areas of skin and the tissue beneath it. Mucous membranes that line the body openings (such as the mouth) also are vulnerable. Hereditary angioedema often first develops during puberty.
  
  Sometimes, swelling of the upper airways occurs, which causes breathing problems that can become life-threatening. Hives and itching are not usually associated with hereditary angioedema. Androgens (male sex hormones such as testosterone) are among the medications used to prevent attacks. Treatments associated with allergic angioedema usually have little value in treating hereditary angioedema.
  
  
• Idiopathic angioedema. Swelling caused by unknown factors or by exposure to certain medications. Certain medications used to treat high blood pressure, called angiotensin-converting enzyme (ACE) inhibitors, increase the blood chemical bradykinin, which widens blood vessels. Increased bradykinin levels can cause angioedema in some patients. Hives typically accompany this form of angioedema.

An episode of angioedema typically lasts from a few hours to a few days. In some people, however, angioedema can be chronic (ongoing), recurring over weeks or months.

Angioedema symptoms are usually relatively mild and resolve by themselves. However, in rare cases, swelling in the mouth and throat can cause breathing problems and blood pressure can drop as a result of fluid moving out of the blood. This is potentially life-threatening and requires emergency medical treatment.

Hereditary angioedema is caused by an inherited absence of a protein called C1 inhibitor, which leads to deep tissue swelling. Similar symptoms are seen with allergic angioedema, which is caused by an allergic reaction. There are a number of other allergic and non-allergic skin conditions that are related to angioedema including:

• Eczema. Inflammatory skin disease with lesions that usually appear very dry, thickened or scaly. Contact dermatitis is one form of eczema associated with angioedema. It is a skin rash that is the result of direct contact between an allergen or irritant and the skin.
  
  

  

• Hives. Red, swollen patches of skin that occur in groups and may burn, sting or itch. Hives sometimes accompany angioedema. In general, hives are more common and less severe than angioedema. 
  
  
• Skin rashes. Any change in the color and/or texture of the skin (e.g., redness, itching, inflammation and raised bumps).
  

  

Hereditary angioedema has no known cause other than a family history of this genetic condition.

Allergic angioedema occurs when an allergic reaction is triggered by one of many common allergens (harmless substances that trigger an exaggerated immune system reaction). It is not always easy to trace the source of an outbreak. Still, patients should try to be aware of the circumstances surrounding a bout of angioedema to determine which allergens might be responsible. Common angioedema triggers include the following:

• Allergy shots (immunotherapy). Allergy shots are a form of allergy treatment in which low doses of an allergen are injected into a patient over a period of time in an attempt to build up a tolerance to the allergen. Occasionally, allergy shots can actually trigger angioedema.
  
  
• Certain foods. Common food allergies can cause allergic angioedema, including allergies to cow’s milk, eggs, peanuts, wheat, soybeans, fish, shellfish, berries and tree nuts. Foods containing sulfides (e.g., maraschino cherries, frozen or dried potatoes) can also trigger the condition.  
  
  
• Environmental factors. Cold, heat, sunlight or water can cause angioedema in some people.
  
  
• Infections, injury and illness. These may include autoimmune disorders (such as lupus or cancer), leukemia, thyroid disorders, colds, and infections such as hepatitis B or C.
  
  
• Insect stings or bites. Allergies to venom released in the stings and bites of bees, yellow jackets, hornets, wasps and fire ants can trigger allergic angioedema.
  
  
• Latex. Natural rubber used in many products. Latex allergies may cause angioedema.
  
  
• Physical factors. Pressure on the skin or scratches to the skin can result in raised lines that result from histamine-based angioedema that causes swelling beneath the skin. This condition is known as dermatographism, which means “write on the skin.” Physical strain (e.g., intense exercise, prolonged writing, mowing the lawn) can also trigger the condition. In women, angioedema may be caused by pregnancy and menstruation.
  
  
• Pollen. A common cause of allergic rhinitis (hay fever), allergies to pollens can also cause allergic angioedema.
  
  
• Some medications. Many medications can trigger angioedema, including penicillin and other antibiotics, painkillers (particularly aspirin and ibuprofen), angiotensin-converting enzyme (ACE) inhibitors and others. Over-the-counter medications, such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and cold medicine with acetylsalicylic acid, can also cause the condition. Symptoms may not occur for days to months after a patient first starts taking the drug.
  
  
• Stress. Emotional stress can trigger symptoms related to angioedema.
  
  
• Surgery and other medical procedures.   

Risk factors for developing angioedema include a family history of this condition or other allergies. In addition, a person who has had angioedema or other allergic reactions in the past has a higher likelihood of developing angioedema in the future.

In a significant percentage of cases, the trigger for allergic angioedema remains a mystery. In some cases, angioedema is an indicator of an underlying condition such as leukemia or a connective tissue disorder.

Symptoms of allergic angioedema usually occur suddenly. In some cases, exposure to a tiny amount of an allergen (harmless substances that trigger an exaggerated immune system reaction) can trigger a significant outbreak. In other situations, a person must be exposed to a large amount of an allergen before symptoms become apparent.

Allergic angioedema swelling usually covers a large area and extends deep under the skin. Many cases of angioedema are relatively mild and do not require treatment, although they may cause discomfort. Other symptoms – particularly those that trigger breathing difficulties – should be checked by a physician. Allergic angioedema symptoms include:

• Marked skin swelling, usually around the eyes and mouth, but also on the hands, feet, genitalia and inside the throat
  
  
• Abdominal pain or cramping due to swelling in the intestines and swelling of the stomach
  
  
• Eyes may appear swollen shut
  
  
• Hives (groups of red, swollen patches of skin that may burn, sting or itch)
  
  
• Hoarseness, wheezing and shortness of breath due to voice box (larynx) swelling
  
  
• Skin swelling which usually does not itch, but may be painful or burn
  
  
• Swelling which may be worse on one side of body than on the other (asymmetrical)

Symptoms of hereditary angioedema are often very similar to those of allergic angioedema, although itching and hives are usually not present. Symptoms include:

• Abdominal cramping, nausea and vomiting due to swelling of the intestinal tract
  
  
• Airway obstruction from swelling in the throat
  
  
• Hoarseness
  
  
• Intestinal swelling, which can trigger vomiting, dehydration, pain and shock
  
  
• Rash which occurs before the swelling
  
  
• Swelling of the hands, feet, limbs and face

A physician will perform a physical examination on a patient suspected of having angioedema. A complete medical history, including a list of symptoms and a complete list of current medications, also will be compiled.  Particular attention will be focused on the appearance of the skin and the physician will check for presence of stridor, a crowing sound during inhalation that may indicate angioedema in the throat. Stridor requires immediate medical treatment.

An allergy skin test may be recommended to pinpoint allergens that may be triggering angioedema. During this procedure, a tiny dose of an allergen is introduced to the skin. If the skin reacts with a wheal (raised, red bump), it indicates an allergic response to the allergen.

In some cases, an allergy blood test – such as a RAST (radioallergosorbent test) – may be used to diagnose an allergy. This type of blood test allows a laboratory to directly test a blood sample for antibodies that correspond to specific allergens. Though less sensitive than a skin test, it can be used on individuals who are taking antihistamines (drugs that can suppress or interfere with skin test results), or have reactions too severe for a skin test.

Blood tests can measure C1 inhibitor levels and activity to establish whether or not the patient has hereditary angioedema. A patient’s family medical history is useful in this diagnosis, as well, because of the inherited nature of the disorder. In some cases, genetic testing and counseling may be advised for prospective parents who have a family history of hereditary angioedema.

Angioedema that does not affect breathing will usually go away on its own and does not require medical treatment. However, there are several self-care steps people can take at home to soothe associated symptoms. They include:

• Avoid activity that might cause perspiration.
  
  
• Avoid foods or nonessential medicines that have been identified as triggers. It is extremely important to speak with a physician before stopping any prescribed medications.  
  
  
• Avoid hot baths or showers, which can worsen swelling.
  
  
• Cool compresses and baths can help reduce discomfort.
  
  
• Over-the-counter antihistamines may help relieve minor symptoms, such as itching and swelling. However, never take any medicine without first consulting a physician.
  
  

  

• Relax and reduce stress as much as possible.
  
  
• Wear light clothes that are not too snug. Tight clothing can trigger a new outbreak.

In some cases, patients may require prescription drugs to treat angioedema symptoms. Long-acting antihistamines are the primary drug prescribed to treat mild cases of angioedema. Corticosteroids may be prescribed to treat moderate to severe cases of angioedema.

Combination H1- and H2-blocking drugs have also been prescribed to treat stubborn cases of hives and angioedema. These drugs are intended to be used as antidepressants, but they have strong histamine-blocking properties. However, the Food and Drug Administration (FDA) has not specifically approved these drugs for treating hives or angioedema.

In very rare cases, angioedema can trigger anaphylactic shock, a life-threatening allergic reaction. An immediate dose of the drug epinephrine (adrenaline) is necessary to reverse these symptoms. Patients with a history of anaphylactic reactions may require a prescription for an epinephrine auto-injector kit. This contains a dose of epinephrine that can be self-administered in emergency situations.

The best way to prevent angioedema symptoms is to avoid allergens that trigger them. This is not always easy, but identifying triggers that cause a reaction is a first step to making lifestyle adjustments that reduce exposure to the allergen.

Hereditary angioedema may be treated with other medications. Androgens (male sex hormones) can stimulate the body to produce more C1 inhibitor proteins and may be prescribed on a preventative basis. To reduce swelling during an episode, the drug aminocaproic acid may be prescribed.

In some cases, a patient with hereditary angioedema is given a transfusion of fresh plasma (the pale yellow fluid portion of whole blood) to increase the levels of C1 inhibitor in their blood. This method may be used to prevent attacks before a dental or surgical procedure. 

Patients who suffer from angioedema are encouraged to wear a medical alert bracelet containing information about their condition. This can alert healthcare providers to the condition in case the patient is unable to communicate during treatment.  

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions regarding angioedema:

1. Do my symptoms suggest angioedema?
   
   
2. What tests will you use to determine if I have angioedema?
   
   
3. What type of angioedema do I have?
   
   
4. What may have caused me to develop angioedema?
   
   
5. Does angioedema pose a danger to my overall health?
   
   
6. Will I require medication to treat my angioedema?
   
   
7. When will my symptoms subside?
   
   
8. What steps can I take to relieve symptoms?
   
   
9. Am I likely to develop angioedema again in the future?
   
   
10. Are there steps I can take to prevent future episodes of angioedema?
    
    
11. Under what circumstances should I seek emergency medical attention for angioedema?
    
    
12. Are my children likely to develop angioedema because I have the condition?