Autoimmune Angioedema – Causes, Symptoms, Diagnosis, Treatment

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.

References