OVERVIEW

What is acquired angioedema?

Acquired angioedema is a rare condition caused by certain diseases (such as lymphoma, autoimmune disorders, etc.) that lead to reduced levels of "C1 esterase inhibitor" in the blood. This results in recurrent swelling of the skin, respiratory tract, or gastrointestinal mucosa, manifesting as localized skin swelling, difficulty breathing, abdominal pain, diarrhea, etc., without accompanying hives.

Acquired angioedema mostly occurs in older adults with underlying medical conditions. The disease is neither hereditary nor contagious.

Is acquired angioedema common?

Acquired angioedema is rare.

SYMPTOMS

What are the common manifestations of acquired angioedema?

Symptoms vary from person to person, and each individual may experience different manifestations. Swelling can occur in one area or multiple areas simultaneously (e.g., skin, airways, gastrointestinal tract) and may last 2–5 days. It is not accompanied by hives or fever.

• If swelling occurs in the skin: Skin edema often appears on the face, limbs, or genitals. Symptoms may include tingling or a sense of tightness, or the appearance of non-itchy rashes, followed by swelling and tightness, possibly accompanied by pain and functional impairment. The swelling usually subsides gradually over several days or spreads to other parts of the body.
• If swelling occurs in the airways: Symptoms may include a feeling of obstruction or tightness in breathing, difficulty swallowing, and in severe cases, respiratory distress, chest tightness, or even suffocation and fainting.
• If swelling occurs in the gastrointestinal tract: Symptoms may include varying degrees of abdominal pain (colic), nausea, vomiting, bloating, and diarrhea.

Where does acquired angioedema commonly occur?

• Skin of the lips, face, limbs, and genitals;
• Respiratory tract, such as the throat and trachea;
• Tongue and gastrointestinal tract.

What serious complications can acquired angioedema cause?

• Swelling near or within the airways (e.g., face, neck, tongue, and throat) can lead to difficulty breathing or even fatal suffocation.
• Swelling in the digestive tract is often misdiagnosed as appendicitis, acute pancreatitis, or other conditions, potentially resulting in unnecessary exploratory laparotomy.

CAUSES

What causes acquired angioedema?

Depending on the etiology, acquired angioedema is divided into two types.

• Type I: Caused by lymphoma, leukocyte and lymphocyte proliferative disorders, or malignancies.
• Type II: Caused by autoimmune diseases or without underlying conditions.

What are the common triggers of acquired angioedema?

Patients with lymphoma, leukocyte and lymphocyte proliferative disorders, malignancies, or autoimmune diseases often develop angioedema under certain triggers. Common triggers include:

• Emotional disturbances: Such as excessive grief, anxiety, or high stress.
• Minor trauma: Such as tooth extraction or oral surgery.
• Infections: Illnesses like colds or flu, Helicobacter pylori infection, etc.
• Prolonged physical activity: Such as prolonged typing, writing, or other physical activities.
• Others: Medications like estrogen, ACE inhibitors, painkillers, as well as menstruation, pregnancy, etc.

Is acquired angioedema contagious?

No, it is not contagious.

Is acquired angioedema hereditary?

No, it is not hereditary. This is also one of the main differences between acquired angioedema and hereditary angioedema.

DIAGNOSIS

How is Acquired Angioedema Diagnosed?

Doctors need to comprehensively evaluate the patient's medical history, physical examination, and laboratory tests to determine whether it is hereditary angioedema.

• Medical History: Patients often have underlying conditions such as lymphoma, leukocyte and lymphocyte proliferative disorders, malignancies, or autoimmune diseases, but no family history of angioedema. Symptoms typically begin after the age of 30, with recurrent episodes of skin, airway, or gastrointestinal edema (specific symptoms are described earlier). Patients may have tried conventional antihistamine and corticosteroid treatments, which are usually ineffective.
• Physical Examination: Performed by a doctor, it may reveal localized subcutaneous (or submucosal) swelling, commonly affecting the eyelids, lips, face, throat, limbs, or external genitalia. The edema is asymmetric and non-pitting, and the skin may appear normal or slightly red.
• Laboratory Tests: Complement tests show low C4 levels, reduced C1 inhibitor antigen levels or function, positive anti-C1 inhibitor antibodies, and low C1q levels.

What Tests Are Needed for Acquired Angioedema?

• Complete Blood Count (CBC): Helps assess the presence of infection.
• Complement Tests: Include C4 levels, C1 inhibitor antigen levels, C1 inhibitor function tests, anti-C1 inhibitor antibody detection, and C1q levels.
• Genetic Testing: Distinguishes between hereditary and acquired angioedema.
• Abdominal Ultrasound or CT Scan: Aids in diagnosing intestinal acquired angioedema.

Which Diseases Are Easily Confused with Acquired Angioedema? How to Differentiate?

• Hereditary Angioedema: Very similar to acquired angioedema and difficult to distinguish. However, hereditary angioedema usually has a family history, occurs at a younger age (first episode typically before age 20), and lacks underlying conditions like lymphoproliferative disorders, malignancies, or autoimmune diseases. C1q levels are normal.
• Allergic Angioedema: Much more common than acquired angioedema, it usually occurs after exposure to a known allergen (e.g., food, insect bites, or medication) and may be accompanied by hives and itching. Onset is more rapid, and complement C4 and C1 inhibitor levels are normal.
• Drug-Induced Angioedema: Associated with medication use, particularly angiotensin-converting enzyme inhibitors or NSAIDs. Edema most often affects the mouth and throat, and complement C4 and C1 inhibitor levels are normal.
• Contact Dermatitis: Presents with swelling, redness, papules, or blisters at the site of contact with an irritant, along with intense itching. Patch testing yields positive results, unlike acquired angioedema.
• Autoimmune Diseases: Conditions like systemic lupus erythematosus, polymyositis, dermatomyositis, and Sjögren's syndrome can cause facial and periorbital edema, sometimes with hand swelling. This edema is typically persistent rather than sudden and transient. Autoimmune diseases also often present with joint pain, fever, and other symptoms. Complement test results are normal, distinguishing them from acquired angioedema.
• Hypothyroidism: Severe hypothyroidism can cause persistent facial and lip edema that does not appear and disappear suddenly. Thyroid function tests can differentiate it.
• Superior Vena Cava Syndrome and Tumors: These cause persistent and progressively worsening localized swelling, whereas angioedema resolves spontaneously. Normal complement test results help distinguish them from hereditary angioedema.

TREATMENT

Which department should I visit for acquired angioedema?

Before diagnosis, depending on the location of the angioedema, patients may seek treatment in departments such as dermatology, emergency medicine, gastroenterology, ophthalmology, or otolaryngology. However, after diagnosis, they should generally visit the allergy department.

Can acquired angioedema resolve on its own?

Mild cases of acquired angioedema with only skin manifestations may resolve on their own within a few days without treatment, leaving no traces, but recurrence is common.

Severe cases of acquired angioedema require medication to improve.

How is acquired angioedema treated?

• Acute phase treatment: Currently, there are no effective medications available domestically, only symptomatic relief drugs can be given. If laryngeal edema causes difficulty breathing, emergency treatment should be sought immediately.
• Preventive treatment: During intervals between angioedema episodes, preventive treatment can be administered to reduce recurrence. Commonly used medications include purified C1 inhibitor concentrate, icatibant, and ecallantide, with dosages adjusted based on the condition.

Does acquired angioedema require hospitalization?

Hospitalization is necessary for comprehensive testing and treatment of acquired angioedema.

Can acquired angioedema be cured?

Acquired angioedema is often caused by lymphoma, leukocyte and lymphocyte proliferative disorders, malignancies, or autoimmune diseases, which are typically difficult to cure. Therefore, acquired angioedema is also challenging to eradicate completely.

DIET & LIFESTYLE

Does acquired angioedema require follow-up?

Follow-up is required as per the doctor's instructions, which may involve adjusting medication dosage and rechecking complement C4 levels.

Does acquired angioedema affect fertility?

No.

PREVENTION

Can Acquired Angioedema Be Prevented? How to Prevent It?

By avoiding relevant triggers, the frequency of acute angioedema episodes can be reduced. Specific measures include:

• Avoid emotional tension, anxiety, and stress.
• Maintain oral hygiene and care, and avoid tooth extraction or oral surgery whenever possible.
• Eat a balanced diet, exercise regularly, get vaccinated, and prevent infectious diseases like colds and flu.
• Avoid prolonged physical activity or other strenuous exercises to prevent overexertion.
• If possible, avoid medications such as estrogen and angiotensin-converting enzyme inhibitors.