Merck Manual

Please confirm that you are not located inside the Russian Federation

honeypot link

Hereditary and Acquired Angioedema

(Acquired C1 Inhibitor Deficiency)

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Medically Reviewed Oct 2022
VIEW PROFESSIONAL VERSION
GET THE QUICK FACTS
Topic Resources

Hereditary angioedema (a genetic disorder) and acquired angioedema (acquired C1 inhibitor deficiency) are caused by a deficiency or malfunction of C1 inhibitor, which is part of the immune system. Both disorders result in repeated episodes of swelling under the skin.

Hereditary angioedema is a genetic disorder that causes a deficiency or malfunction of C1 inhibitor. C1 inhibitor is one of the proteins in the complement system Complement System One of the body's lines of defense (immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more , which is part of the immune system. Symptoms usually start during childhood or adolescence.

In both hereditary and acquired angioedema, swelling (angioedema) may be triggered by

  • A minor injury, as may occur during a dental procedure

  • A viral infection

  • Certain foods

  • Pregnancy

  • Drugs that contain or are related to estrogen (such as tamoxifen)

  • Certain medications for high blood pressure such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)

  • Exposure to cold

Although certain foods and drugs may trigger the angioedema, it is not an allergic reaction to those substances.

Stress, such as that felt before having a dental or surgical procedure, can make angioedema worse.

Symptoms

The face, lips, tongue, the back of the hands or feet, genitals, and/or other areas of the body may swell. Typically, the swollen areas are slightly painful and not itchy. Hives do not appear. Swelling usually resolves in 1 to 3 days.

The membranes lining the mouth, throat, and airways may also swell. People may make a gasping sound when they breathe in. Such swelling can interfere with breathing and be life threatening. If these symptoms develop, people should see a doctor right away.

The membranes lining the digestive tract may also swell. Nausea, vomiting, and cramps are common.

Images of Angioedema

Diagnosis

  • Blood tests

Doctors suspect hereditary or acquired angioedema if both of the following are present:

  • People have swelling in the face, lips, tongue, hands, feet, genitals, and/or other areas of the body but do not have hives.

  • The swelling recurs, and no cause is apparent.

Doctors also suspect one of these disorders if angioedema is triggered by a minor injury.

If family members also have these symptoms, doctors suspect hereditary angioedema.

Doctors diagnose hereditary or acquired angioedema by measuring C1 inhibitor levels or activity in a sample of blood.

Treatment

  • Drugs such as ecallantide, icatibant, or C1 inhibitor

  • Fresh frozen plasma

  • Drugs to prevent future attacks

Drugs that can sometimes relieve the swelling include ecallantide, icatibant, purified C1 inhibitor (which is derived from human blood), and recombinant C1 inhibitor (which is obtained from the milk of genetically modified rabbits). Giving C1 inhibitor replenishes the missing or malfunctioning C1 inhibitor. These drugs are given by vein or injection under the skin.

Because hereditary angioedema is rare, the person's doctor usually checks whether the local health care facility has one of these necessary drugs. If the person has had a severe reaction, the doctor may give the person one of these drugs to keep at home and use when an attack starts. The person or family members are taught how to inject the drugs themselves. The earlier treatment begins, the better.

Pain relievers, drugs to relieve nausea (antiemetic drugs), and fluids may help relieve symptoms.

Emergency treatment

Sometimes if the airway suddenly swells and people have difficulty breathing, doctors must open the airway. To do so, they may inject epinephrine under the skin or into the muscle to reduce the swelling. However, epinephrine may not reduce the swelling quickly or long enough. Then doctors insert a breathing tube in the windpipe through the person’s mouth or nose (intubation).

Sometimes doctors have to make a small incision in the skin over the windpipe (trachea) to insert the breathing tube.

Drugs to prevent attacks of angioedema

Several treatments can be used to help prevent episodes of angioedema in people with hereditary angioedema. They include

  • C1 inhibitor derived from human blood

  • Lanadelumab

  • Berotralstat

  • Synthetic male hormones

  • Antifibrinolytics (eg, tranexamic acid)

C1 inhibitor derived from human blood can be used to prevent attacks. However, recombinant C1 inhibitor cannot.

Lanadelumab is a monoclonal antibody Monoclonal Antibodies Immunotherapy is the use of drugs that mimic or modify components of the immune system (such as tumor antigens and immune checkpoints—see also Overview of the Immune System) to fight disease... read more (a manufactured antibody) that targets and suppresses one of the substances involved in causing angioedema. Lanadelumab is given by injection under the skin every 2 weeks. It can be used to prevent attacks in people 12 years of age and older.

Berotralstat suppresses the same substance as lanadelumab and is taken by mouth 3 times a day.

Stanozolol and danazol (which are synthetic male hormones) may help prevent subsequent attacks. These drugs, taken by mouth, can stimulate the body to produce more C1 inhibitor, but they may be less effective for acquired angioedema. Because these drugs can have masculinizing side effects, the dose is reduced as soon and as much as possible when these drugs are given to women for a long time.

Stanozolol or danazol may be given 5 days before until 2 days after a dental or surgical procedure. Or C1 inhibitor, if available, may be given 1 hour before dental or surgical procedures instead of stanozolol or danazol.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Nolvadex, Soltamox
GIAPREZA
Kalbitor
FIRAZYR, SAJAZIR
Cyklokapron, Lysteda
Adrenaclick, Adrenalin, Auvi-Q, Epifrin, EpiPen, Epipen Jr , Primatene Mist, SYMJEPI, Twinject
TAKHZYRO
Orladeyo
Danocrine
NOTE: This is the Consumer Version. DOCTORS: VIEW PROFESSIONAL VERSION
VIEW PROFESSIONAL VERSION
quiz link

Test your knowledge

Take a Quiz!
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP