What are the other Names for this Condition? (Also known as/Synonyms)

• C1 Esterase Inhibitor Deficiency
• Hereditary Angioneurotic Edema
• Quincke’s Disease

What is Hereditary Angioedema? (Definition/Background Information)

• Hereditary Angioedema (HAE) is an uncommon, genetically inherited condition. Hereditary Angioedema is a severe disorder affecting the body's response to certain triggers
• The system which controls the regulation of tissue fluids, blood vessel dilation and constriction, and itching, results in hives (urticaria) and localized deep swelling (angioedema) when triggered. Multiple biochemical agents participate in triggering up and downregulating the clinical features of hives and angioedema
• In Hereditary Angioedema, there is a decreased amount of a particular protein known as C1 esterase inhibitor. The function of this protein is to maintain the fluid that enters and exits tissues at the normal level. A defect in this protein leads to an abnormal buildup of fluid. The excessive accumulation of fluid in the tissues creates an obstruction to normal blood flow
• Too much fluid causes swelling in various areas of the body such as the face, hands, leg, feet, and throat. Depending on the severity of the condition, some individuals may be affected by an obstruction of the airway passage. Airway obstruction is an acute emergency and requires urgent treatment. If Hereditary Angioedema is not diagnosed and treated early, the condition can be fatal
• The treatment options for Hereditary Angioedema are twofold. Acute attacks are treated with supportive care with the administration of oxygen and IV fluids. In attacks, ecallantide or icatibant can be administered, as well as C1 inhibitor medications. The same C1 inhibitor medications (landelumab and berotralstat) are available for self-administration to prevent attacks and are used as soon as a potential trigger is noted by the patient. These medications are not necessarily approved in all countries

Who gets Hereditary Angioedema? (Age and Sex Distribution)

• Hereditary Angioedema is a genetic disorder that is present at birth. In many individuals, the disorder remains silent until one reaches late childhood or early adulthood
• The condition can equally affect both males and females.
• Hereditary Angioedema is observed worldwide. Current research does not indicate that this disorder is more common among a particular racial or ethnic group

What are the Risk Factors for Hereditary Angioedema? (Predisposing Factors)

• The most important risk factor for Hereditary Angioedema is a positive family history
• Sometimes, dental procedures and surgeries can also provoke this disorder in susceptible individuals

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hereditary Angioedema? (Etiology)

• Presently, only an inherited genetic mutation can explain why individuals with a family history of the condition develop HAE
• HAE patients always have this abnormal protein issue. Attacks are triggered by a number of factors, which vary from one individual to another. These include:
  • Emotional stress
  • Minor trauma
  • Surgical or dental procedures
  • Infections
  • Hormonal influences during menstrual cycles or oral estrogen
  • Mechanical pressure during physical activities

What are the Signs and Symptoms of Hereditary Angioedema?

Individuals with Hereditary Angioedema may be present with:

• Swelling of the face, legs, arms, and genitalia
• Neck swelling leading to airway obstruction and deepening or hoarseness of the voice
• Protruding belly due to excessive fluid, which can cause signs and symptoms such as nausea, pain, diarrhea, or vomiting
• Stiff skin
• Headaches and blurred vision
• Muscle pain and cramping

How is Hereditary Angioedema Diagnosed?

Hereditary Angioedema (HAE) is a medical emergency and immediate treatment needs to be given. This factor needs to be kept under consideration while diagnosing HAE.

• A complete evaluation of medical and family history along with a thorough physical exam
• A positive family history is very important to diagnose this condition, as it is an inherited disorder
• Physical examination will show swelling in various parts of the body that can help make an accurate diagnosis

The following blood tests are usually performed:

• C1 inhibitor blood level
• C1 inhibitor functional blood level
• Complement component C2 and C4
• Abdominal ultrasound and CT scan to observe the degree of swelling or obstruction in the intestine

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hereditary Angioedema?

The most dangerous complication of Hereditary Angioedema is obstruction of the airways that can be fatal without immediate management of the condition. It is a grave emergency and requires urgent medical care.

How is Hereditary Angioedema Treated?

Presently, the treatment options for Hereditary Angioedema (HAE) are limited. It may involve:

• Pain-relief medications, oxygen, and intravenous fluids are given to manage the symptoms during an acute attack
• In acute attacks, the most effective treatments  include:
  • Administering C1 inhibitor concentrates, both from pooled human blood and recombinant products
  • Fresh frozen plasma if these are not available
  • Kallikrein inhibitor and bradykinin antagonists, ecallantide and icatibrant respectively
  • Monoclonal antibodies such as beroltralstat and lanadelumab
  • At or before a personal trigger factor, patients can self-administer lanadelumab

Epinephrine and corticosteroids are not effective in treating HAE.

How can Hereditary Angioedema be Prevented?

Currently, there are no specific methods or guidelines to prevent Hereditary Angioedema since it is a genetic condition.

• Trigger events can be avoided
• ACE inhibitor medications must be avoided, as they can make attacks from triggers more likely
• Lanadelumab can be injected to potentially block an acute event
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child

Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders.

What is the Prognosis of Hereditary Angioedema? (Outcomes/Resolutions)

• The prognosis for Hereditary Angioedema is based on its severity. It varies from individual to another and depends upon the symptoms that have developed
• In some cases, HAE can be life-threatening, given the limited treatment options currently available
• The mortality rate is as high as 15-33% mainly due to laryngeal edema, resulting in obstruction of the airway

Additional and Relevant Useful Information for Hereditary Angioedema:

Within North America the occurrence of Hereditary Angioedema is 1 in 10,000-50,000.