Summary about Disease
Hereditary Angioedema (HAE) is a rare genetic disorder that causes episodes of severe swelling (angioedema), particularly in the skin, gastrointestinal tract, larynx (airway), and genitals. It is caused by a deficiency or dysfunction of C1-inhibitor (C1-INH), a protein that helps regulate the body's inflammatory response. HAE is characterized by recurrent attacks that can be debilitating and potentially life-threatening if the airway is involved.
Symptoms
Swelling: Affects the skin (face, limbs, genitals), gastrointestinal tract (causing abdominal pain, nausea, vomiting, diarrhea), and/or larynx (causing difficulty breathing, hoarseness).
Abdominal Pain: Severe cramping, often described as colicky.
Nausea and Vomiting.
Difficulty Breathing: Due to swelling in the airway.
Hoarseness: If the larynx is affected.
Skin Rashes: Non-itchy, reddish rash called erythema marginatum can precede attacks in some individuals.
Fatigue
Causes
HAE is caused by a genetic defect in the SERPING1 gene, which provides instructions for making the C1-inhibitor protein. The genetic defect can lead to:
Type I HAE: Reduced levels of C1-INH protein. (Most common)
Type II HAE: Normal levels of a dysfunctional C1-INH protein.
Type III HAE: (Less common) Occurs almost exclusively in women and is linked to increased estrogen levels, sometimes associated with mutations in the Factor XII gene. In some cases, the genetic cause is unknown. HAE is typically inherited in an autosomal dominant pattern, meaning that only one copy of the defective gene is needed to cause the disorder. However, spontaneous mutations can also occur, meaning a person can develop HAE even if neither parent has the condition.
Medicine Used
Treatment for HAE focuses on both acute (on-demand) treatment of attacks and long-term prophylaxis (prevention) to reduce the frequency and severity of attacks. Medications include:
C1-INH Concentrate: (e.g., Berinert, Cinryze, Ruconest) Replaces the missing or dysfunctional C1-INH protein.
Ecallantide: (Kalbitor) A plasma kallikrein inhibitor that blocks the activity of kallikrein, a protein involved in the angioedema pathway.
Icatibant: (Firazyr) A bradykinin receptor antagonist that blocks the effects of bradykinin, a key mediator of angioedema.
Lanadelumab: (Takhzyro) A monoclonal antibody that inhibits plasma kallikrein and is used for prophylaxis.
Oral attenuated androgens: (e.g., danazol, stanozolol) Increase C1-INH levels (used less frequently due to side effects).
Tranexamic acid: (Lysteda, Cyklokapron) A synthetic lysine analog which inhibits fibrinolysis.
Plasma Derived C1-INH: (Cinryze) Used for prophylaxis.
Is Communicable
No. Hereditary Angioedema is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Medical Alert: Wear a medical alert bracelet or carry a card identifying that you have HAE and listing emergency contacts and medications.
Avoid Triggers: Identify and avoid potential triggers of attacks, such as stress, trauma (including dental procedures), certain medications (e.g., ACE inhibitors, estrogens), and infections.
Emergency Plan: Develop a detailed emergency plan with your doctor, including when and how to administer on-demand medications and when to seek emergency medical care.
Family Screening: Family members should be screened for HAE, as it is a hereditary condition.
Dental Procedures: Inform your dentist about your HAE diagnosis before any dental work. Pre-treatment with C1-INH concentrate might be necessary.
Surgery: Similar to dental procedures, inform your surgeon and anesthesiologist about your HAE diagnosis before any surgical procedure. Pre-treatment might be needed.
Avoid ACE Inhibitors: These blood pressure medications can trigger or worsen HAE attacks.
How long does an outbreak last?
Without treatment, HAE attacks typically last for 24 to 72 hours, but can last longer in some cases (up to 5 days). The duration can vary depending on the location and severity of the swelling. With appropriate on-demand treatment, the duration of attacks can be significantly reduced.
How is it diagnosed?
HAE is diagnosed through blood tests that measure:
C4 levels: Often low during and between attacks.
C1-INH protein level: Reduced in Type I HAE.
C1-INH function: Reduced in Type I and Type II HAE.
Genetic testing: To confirm the diagnosis and identify the specific gene mutation. A doctor will also consider the patient's medical history, family history, and symptoms.
Timeline of Symptoms
The timeline of symptoms in HAE can vary, but a typical attack might follow this sequence:
Prodrome (Optional): Some individuals experience a prodrome (early symptoms) hours or days before the swelling begins. This might include fatigue, a tingling sensation in the skin, or a non-itchy rash (erythema marginatum).
Onset: Swelling begins gradually, usually without itching or hives.
Progression: Swelling worsens over 12-24 hours. Abdominal pain may develop during this phase.
Peak: Swelling reaches its maximum extent. If the larynx is involved, breathing difficulties may become severe.
Resolution: Swelling gradually subsides over 24-72 hours (or longer without treatment).
Important Considerations
Life-Threatening Attacks: Laryngeal attacks can be life-threatening due to airway obstruction. Prompt recognition and treatment are crucial.
Variability: The severity and frequency of attacks can vary significantly between individuals and even within the same individual over time.
Individualized Treatment: Treatment plans should be tailored to the individual's specific needs and the severity of their disease.
Psychological Impact: HAE can have a significant psychological impact due to the unpredictability and potential severity of attacks. Mental health support is often beneficial.
Pregnancy: Pregnancy can affect HAE symptoms, and management during pregnancy requires careful consideration and collaboration between the patient, obstetrician, and HAE specialist.
Children: HAE can present differently in children and diagnosis can be delayed. Early diagnosis and management are important.