OVERVIEW

What is hereditary angioedema?

Hereditary angioedema is a genetic disorder caused by reduced or dysfunctional C1 inhibitor in the serum, leading to recurrent swelling of the skin, respiratory tract, and other internal organs with corresponding symptoms, without accompanying urticaria or itching.

When edema occurs in the airways, delayed treatment can result in fatal asphyxiation. When it affects the gastrointestinal tract, it is often misdiagnosed as appendicitis or acute pancreatitis, leading to unnecessary surgeries. This disease can be life-threatening and impose significant financial and psychological burdens. However, it is extremely rare.

As a genetic disorder, the defect is present at birth but may not manifest immediately. Symptoms can appear at any age, though onset during childhood or adolescence is more common.

Is hereditary angioedema common?

Rare.

What are the types of hereditary angioedema?

Hereditary angioedema is a subtype of angioedema and can be further classified into four types based on etiology:

• Type I: Caused by C1 inhibitor deficiency.
• Type II: Caused by dysfunctional C1 inhibitor.
• Type III: Associated with mutations in the coagulation factor XII gene.
• Type IV: Etiology unknown.

SYMPTOMS

What are the common manifestations of hereditary angioedema?

Patients with hereditary angioedema are not always symptomatic. Acute attacks occur under certain triggers, leading to symptom presentation.

Symptoms during an acute attack vary from person to person, even within the same family.

Angioedema can occur in a single part of the body or multiple areas simultaneously. Without treatment, swelling may resolve on its own within days (though airway angioedema can be life-threatening and requires immediate medical attention). It is typically not accompanied by fever, itching, or hives.

• If swelling occurs in the skin: Skin edema often appears on the face, limbs, or genitals. Symptoms may include tingling, tightness, or non-itchy rashes, followed by swelling and discomfort, sometimes with pain and functional impairment. Swelling usually subsides gradually over days or spreads to other body parts.
• If swelling occurs in the airways: Symptoms may include a sensation of obstruction or tightness, difficulty swallowing, and worsening respiratory distress, chest tightness, or even suffocation and fainting.
• If swelling occurs in the gastrointestinal tract: Symptoms may include varying degrees of abdominal pain (cramping), nausea, vomiting, bloating, and diarrhea.

Where does hereditary angioedema commonly occur?

Lips, facial skin, limbs, genital skin, tongue, throat and other respiratory areas, and the gastrointestinal tract.

What serious complications can hereditary angioedema cause?

• Swelling near or inside the airways (e.g., face, neck, tongue, or throat) can lead to breathing difficulties or even fatal suffocation.
• Gastrointestinal swelling is often misdiagnosed as appendicitis, acute pancreatitis, or other conditions, sometimes resulting in unnecessary exploratory abdominal surgery.

CAUSES

What are the causes of hereditary angioedema?

Hereditary angioedema can be classified into four types based on etiology:

• Type I: Caused by C1 inhibitor deficiency.
• Type II: Caused by dysfunctional C1 inhibitor.
• Type III: Associated with mutations in the coagulation factor XII gene.
• Type IV: Unknown cause.

What are common triggers for hereditary angioedema?

Patients with hereditary angioedema typically experience attacks under certain triggers, including:

• Emotional disturbances: Such as excessive sadness, 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 sports.
• Others: Medications like estrogen, ACE inhibitors, painkillers, menstruation, pregnancy, etc.

Who is commonly affected by hereditary angioedema?

It commonly occurs in individuals with a family history of hereditary angioedema. It can develop at any age but is more frequently observed in children or adolescents.

Is hereditary angioedema contagious?

No, it is not contagious.

Is hereditary angioedema hereditary?

Yes, it is hereditary.

DIAGNOSIS

How is hereditary angioedema diagnosed?

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

• Medical history: Recurrent episodes of skin, airway, or gastrointestinal edema (specific symptoms are described earlier). Patients may have tried conventional antihistamines or corticosteroids, but these treatments are usually ineffective.
• Physical examination: Performed by a doctor, revealing localized subcutaneous (or submucosal) swelling, typically in the eyelids, lips, face, throat, limbs, or genitals. The edema is asymmetric and non-pitting, with skin appearing normal or slightly red.
• Laboratory tests: Complement tests show low C4 levels, low C1 inhibitor antigen levels, or reduced C1 inhibitor function.
• Family history: Patients often have a family history of angioedema. However, the absence of a family history does not rule out hereditary angioedema.

What laboratory tests are needed to diagnose hereditary angioedema?

• Complete blood count (CBC): Helps rule out infections.
• Complement tests: Include C4 levels, C1 inhibitor antigen levels, and C1 inhibitor function tests. Two complement tests should be performed, ideally at least one month apart.
• Factor XII gene testing: Used to diagnose type III hereditary angioedema.
• Abdominal ultrasound or CT: Helps determine if intestinal angioedema is present.

What diseases can hereditary angioedema be confused with, and how to differentiate them?

• Allergic angioedema: Much more common than hereditary angioedema. Typically occurs after exposure to allergens (e.g., food, insect bites, or medications) and may be accompanied by hives and itching. C4 and C1 inhibitor levels are normal.
• Drug-induced angioedema: Associated with medication use, particularly angiotensin-converting enzyme inhibitors (ACEIs) or NSAIDs. C4 and C1 inhibitor levels are normal.
• Contact dermatitis: Presents as swelling, redness, papules, or blisters at the contact site, with intense itching. Patch testing is positive, unlike hereditary angioedema.
• Autoimmune diseases: Such as systemic lupus erythematosus, polymyositis, dermatomyositis, or Sjögren's syndrome, which can cause persistent facial, eyelid, or hand swelling (unlike the sudden onset and resolution in hereditary angioedema). Autoimmune diseases often involve joint pain, fever, and other symptoms. Complement levels are normal.
• Hypothyroidism: Severe hypothyroidism can cause prolonged facial or lip swelling (not sudden onset/resolution). Thyroid function tests can differentiate.
• Superior vena cava syndrome or tumors: Cause persistent and progressively worsening swelling, unlike self-resolving angioedema. Complement levels are normal.

TREATMENT

Which department should I visit for hereditary angioedema?

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

Can hereditary angioedema resolve on its own?

Mild hereditary angioedema with only skin manifestations may subside on its own within a few days without treatment, leaving no traces, but it will recur in the future.

Severe hereditary angioedema requires medication to improve.

How is hereditary angioedema treated?

• Acute episode treatment: Currently, there are no effective drugs available domestically, only symptomatic relief medications 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 drugs include purified C1 inhibitor concentrate, ecallantide, and icatibant, with specific dosages determined by the condition.

Does hereditary angioedema require hospitalization?

Hospitalization is necessary for thorough examination and treatment.

Can hereditary angioedema be cured?

Hereditary angioedema is caused by genetic defects, and there is currently no cure. It often recurs.

DIET & LIFESTYLE

Does hereditary angioedema require follow-up examinations?

Follow-up examinations are necessary as advised by the doctor to adjust medication dosage and monitor complement C4 levels.

Does hereditary angioedema affect fertility?

Hereditary angioedema can be passed on to offspring. If planning for pregnancy, genetic counseling is recommended to assess the risk of the disease in future generations.

PREVENTION

Can Hereditary Angioedema Be Prevented? How to Prevent It?

If one or both partners have hereditary angioedema, it is advisable to seek genetic counseling before having children. If the risk of the offspring inheriting the condition is high, they may consider not having children or using assisted reproductive technologies.

If hereditary angioedema has already been diagnosed, avoiding known triggers can reduce the frequency of acute attacks. Specific measures include:

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