Acquired angioedema (AAE) is a rare disorder that causes recurrent episodes of swelling (edema) of the face or body, lasting several days. People with AAE may have swelling of the face, lips, tongue, limbs, or genitals. People with AAE can have edema of the lining of the digestive tract, which can cause abdominal pain and nausea, as well as edema of the upper airway, which can be life-threatening.[1] Swelling episodes may have various triggers, such as mild trauma (such as dental work), viral illness, cold exposure, pregnancy, certain foods, or emotional stress.[2] The frequency of episodes is unpredictable and can vary widely.
There are two forms of AAE. Type 1 is associated with various other diseases including lymphoproliferative disorders, and autoimmune diseases that may not become apparent until years after the angioedema begins. Type 2 is associated with an autoimmune abnormality in which a person has autoantibodies against a protein in the blood called C1-INH.[1][3] In some cases, it is hard to distinguish between AAE types 1 and 2.[1]
Hereditary angioedema (HAE) is a disease characterized by recurrent episodes (also called attacks) of severe swelling of the skin and mucous membranes.[1] The age at which attacks begin varies, but most people have their first one in childhood or adolescence.[2] The frequency of attacks usually increases after puberty. Attacks most often affect 3 parts of the body:[2][3]
- Skin – the most common sites are the face (such as the lips and eyes), hands, arms, legs, genitals, and buttocks. Skin swelling can cause pain, dysfunction, and disfigurement, although it is generally not dangerous and is temporary.
- Gastrointestinal tract – the stomach, intestines, bladder, and/or urethra may be involved. This may cause symptoms such as nausea, vomiting, diarrhea, and abdominal pain.
- Upper airway (such as the larynx and tongue) – this can cause upper airway obstruction and may be life-threatening. The majority of attacks affecting the airway resolve before complete airway obstruction.
Causes
For most people who experience acute hives and angioedema, the exact cause can’t be identified. The conditions are sometimes caused by:
- Foods. Many foods can trigger reactions in people with sensitivities. Shellfish, fish, peanuts, tree nuts, soy, eggs and milk are frequent offenders.
- Medications. Many medications may cause hives or angioedema, including penicillins, aspirin, ibuprofen (Advil, Motrin IB, others), naproxen sodium (Aleve) and blood pressure medications.
- Airborne allergens. Pollen and other allergens that you breathe in can trigger hives, sometimes accompanied by upper and lower respiratory tract symptoms.
- Insect bites and infections. Other causes of acute hives and angioedema are insect bites and infections.
Mutations in the SERPING1 gene cause hereditary angioedema type I and type II. The SERPING1 gene provides instructions for making the C1 inhibitor protein, which is important for controlling inflammation. C1 inhibitor blocks the activity of certain proteins that promote inflammation. Mutations that cause hereditary angioedema type I lead to reduced levels of C1 inhibitor in the blood, while mutations that cause type II result in the production of a C1 inhibitor that functions abnormally. Without the proper levels of functional C1 inhibitor, excessive amounts of a protein fragment (peptide) called bradykinin are generated. Bradykinin promotes inflammation by increasing the leakage of fluid through the walls of blood vessels into body tissues. Excessive accumulation of fluids in body tissues causes the episodes of swelling seen in individuals with hereditary angioedema type I and type II.
Mutations in the F12 gene are associated with some cases of hereditary angioedema type III. This gene provides instructions for making a protein called coagulation factor XII. In addition to playing a critical role in blood clotting (coagulation), factor XII is also an important stimulator of inflammation and is involved in the production of bradykinin. Certain mutations in the F12 gene result in the production of factor XII with increased activity. As a result, more bradykinin is generated and blood vessel walls become more leaky, which leads to episodes of swelling in people with hereditary angioedema type III.
The cause of other cases of hereditary angioedema type III remains unknown. Mutatio
Risk factors
Hives and angioedema are common. You may be at increased risk of hives and angioedema if you:
- Have had hives or angioedema before
- Have had other allergic reactions
- Have a family history of hives, angioedema or hereditary angioedema
Symptoms
Hives
The welts associated with hives can be:
- Skin-colored, reddish on white skin, or purplish on black and brown skin
- Itchy, ranging from mild to intense
- Round, oval or worm-shaped
- As small as a pea or as large as a dinner plate
Most hives appear quickly and go away within 24 hours. This is known as acute hives. Chronic hives can last for months or years.
Angioedema
Angioedema is a reaction similar to hives that affects deeper layers of the skin. It can appear with hives or alone. Signs and symptoms include:
- Welts that form in minutes to hours
- Swelling, especially around the eyes, cheeks or lips
- Mild pain and warmth in the affected areas
When to see a doctor
You can usually treat mild cases of hives or angioedema at home. See your health care provider if your symptoms continue for more than a few days.
If you think your hives or angioedema was caused by a known allergy to food or a medication, your symptoms may be an early sign of an anaphylactic reaction. Seek emergency care if you feel your tongue, lips, mouth or throat swelling or if you’re having trouble breathing.
Diagnosis
Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.
Testing Resources
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment
The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.
Management Guidelines
- Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
FDA-Approved Treatments
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.
- C1 esterase inhibitor (human) (Brand name: Cinryze) – Manufactured by ViroPharma Biologics, Inc.
FDA-approved indication: Approved June 2018 for routine prophylaxis against angioedema attacks in adults, adolescents and pediatric patients (6 years old and above) with Hereditary Angioedema (HAE).
National Library of Medicine Drug Information Portal - Icatibant (Brand name: Firazyr) – Manufactured by Shire Orphan Therapies
FDA-approved indication: Treatment of acute attacks of hereditary angioedema in adults 18 years of age and older
National Library of Medicine Drug Information Portal
Medline Plus Health Information - C1-esterase-inhibitor, human, pasteurized (Brand name: Haegarda) – Manufactured by CSL Behring LLC
FDA-approved indication: For routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in adolescent and adult patients.
National Library of Medicine Drug Information Portal - Ecallantide (Brand name: Kalbitor) – Manufactured by Dyax Corp
FDA-approved indication: Treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older
National Library of Medicine Drug Information Portal - C1-esterase inhibitor (recombinant) (Brand name: Ruconest) – Manufactured by Pharming N.V.
FDA-approved indication: Treatment of acute attacks of hereditary angioedema (HAE) in adult and adolescent patients.
National Library of Medicine Drug Information Portal - Lanadelumab (Brand name: Takhzyro) – Manufactured by Dyax Corporation
FDA-approved indication: August 2018, lanadelumab(Takhzyro) was approved as a prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years and older.
References
