hereditary angioedema

Hereditary Angioedema (HAE) is a rare genetic condition that affects approximately 1 in 50,000 people worldwide [3]. It is characterized by recurrent episodes of severe swelling, known as angioedema, which can occur in various parts of the body, including the face, hands, feet, and genitals [5].

The term "edema" refers to swelling caused by fluid accumulation outside the blood vessels. In HAE, this swelling can be life-threatening if it occurs in the airways or digestive tract [4]. The condition is often described as a "silent killer" due to its potential severity.

HAE is an autosomal dominant disease, meaning that only one copy of the mutated gene is needed for the condition to manifest. It is caused by low levels or dysfunction of the plasma protein C1 inhibitor (C1-INH), which plays a crucial role in regulating the immune system [6].

Symptoms of HAE can vary from person to person but often include:

• Severe swelling, typically in the face, hands, feet, or genitals
• Painful episodes of swelling
• Swelling that can occur in the airways or digestive tract, which can be life-threatening if not treated promptly

HAE is a rare and potentially life-threatening condition that requires prompt medical attention. If you suspect you or someone else may have HAE, it's essential to seek immediate medical help.

References:

[1] Not applicable (search results only)

[2] Not applicable (search results only)

[3] Mar 31, 2024 — Hereditary angioedema is a rare but serious problem with the immune system. The problem is passed down through families.

[4] Hereditary Angioedema, or HAE, is a very rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) ...

[5] The term “edema” means swelling. Hereditary angioedema causes painful episodes of swelling, typically in the face, hands, feet, or genitals. Dangerous swelling ...

[6] Jul 3, 2024 — Hereditary angioedema (HAE) is an autosomal dominant disease caused by low levels of the plasma protein C1 inhibitor (C1-INH). Deficiencies in ...

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurring episodes of severe swelling in various parts of the body. The symptoms of HAE can vary from person to person, but here are some common signs and symptoms:

• Severe abdominal pain: Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting [1].
• Swelling: Swelling is the main symptom of HAE, which can occur in different areas of the body, such as the face, lips, tongue, hands, feet, abdomen, intestines, and airway [2], [4], [5].
• Non-itchy rash: A painless, non-itchy rash may appear before or during an HAE attack [3], [6], [7]. This rash is often not raised and does not cause any discomfort.
• Tingling sensation: Some people experience a tingling sensation in the skin before an attack, which can be accompanied by other symptoms like fatigue, irritability, sudden mood changes, anxiety, or hoarseness [4], [6], [8].
• Abdominal cramping: Swelling of the gastrointestinal tract leads to cramping and severe abdominal pain [2].
• Breathing difficulty: Swelling in the airway can restrict breathing and lead to respiratory distress [1].
• Swollen eyes and mouth: The lining of the eyes (chemosis) and mouth may become swollen, which can be a sign of an HAE attack [9].

It's essential to note that not everyone with HAE will experience all of these symptoms. Some people may have early warning signs or prodromal symptoms before an attack, such as fatigue, nausea, or a tingling sensation in the skin.

References: [1] Mar 11, 2024 [2] Usually, this swelling is not accompanied by itching, as it might be with an allergic reaction. Swelling of the gastrointestinal tract leads to cramping. [3] Before an attack, some people with HAE experience early warning signs, also called prodromal symptoms, such as tingling, rash, fatigue, or nausea. Skin, or ... [4] The symptoms of hereditary angioedema (HAE) include recurring swelling in different areas of the body. Early signs of an attack may be tingling and a rash, ... [5] Sep 18, 2023 — Symptoms. The main symptom is swelling. You won't have the itching or hives that people often get with allergic reactions. A bout may last 2 to ... [6] The early warning signs of an HAE attack · painless, non-itchy rash · tingling skin · skin tightness · fatigue · irritability · sudden mood changes · anxiety ... [7] Some people experience a tingling sensation before an attack. They may also notice a nonraised, non-itchy rash before the swelling begins. [8] Many people have early warning signs of a HAE attack. For instance, extreme fatigue, a tingling of the skin, a hoarse voice or sudden mood changes may signal an ... [9] Symptoms · Abdominal cramping · Breathing difficulty · Swollen eyes and mouth · Swollen lining of the eyes (chemosis) ...

Hereditary Angioedema (HAE) can be diagnosed through various diagnostic tests, which help confirm the presence of this condition.

Blood Tests

• A serum C4 level test is considered the most reliable and cost-effective screening test for HAE. This test measures the concentration of C4 in the blood, which is almost always decreased during an HAE attack [3].
• To confirm a differential HAE diagnosis, perform an HAE blood test: measure your patient's serum levels of C4 and antigenic and functional C1-INH levels [2].
• Three blood tests are used to confirm HAE - a screening test called C4 and specific tests of the level and function of the C1-inhibitor protein [4].

Genetic Testing

• Genetic testing is usually not essential since biologic tests are relatively accurate after the age of 1 year [7].
• The Invitae Hereditary Angioedema Panel analyzes genes that are associated with hereditary angioedema, such as F12, KNG1, and PLG genes. This test is designed to detect disease-causing variants in these genes and can be used for genetic confirmation of a clinical diagnosis [6].

Other Tests

• A complete physical examination along with a detailed family history is the best way to raise suspicion of HAE in the primary care clinic [1].
• To confirm an HAE diagnosis, laboratory testing is necessary. Patients should have serum levels of C4 measured, as well as antigenic and functional C1 esterase inhibitor levels [8].

In summary, diagnostic tests for hereditary angioedema include blood tests (serum C4 level test, C4 and specific tests of the level and function of the C1-inhibitor protein), genetic testing (Invitae Hereditary Angioedema Panel), and a complete physical examination along with a detailed family history.

References: [1] MP Henao · 2016 [2] [3] Jul 3, 2024 [4] [5] [6] [7] by A Abdulkarim · 2023 [8]

Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurring episodes of severe swelling, typically affecting the skin and mucosal tissues of the upper respiratory and gastrointestinal tracts.

Treatment Options:

Several medications are available to treat HAE, including:

• C1 esterase inhibitor concentrates: These are the treatment of choice for short-term prophylaxis and acute attacks. They work by replacing the deficient C1 esterase inhibitor protein in the body.
• Lanadelumab: A monoclonal antibody targeted against kallikrein, which is used to treat attacks of HAE.
• Icatibant: A bradykinin receptor antagonist that has been approved for the treatment of acute episodes in patients aged ≥ 18 years.
• Danazol: An attenuated androgen that can be used to prevent angioedema due to C1 esterase inhibitor deficiency.

Long-term Prophylaxis:

Medications available for long-term prophylaxis include:

• Lanadelumab: A kallikrein inhibitor that has been shown to reduce the frequency of HAE attacks.
• C1 esterase inhibitor concentrates: These can be used on a regular basis to prevent attacks.

On-demand Treatment:

Medications such as icatibant and C1 esterase inhibitor concentrates can be used on an as-needed basis to treat acute attacks of HAE.

It's worth noting that the management of HAE has undergone significant changes in recent years, with newer medicines becoming available. Optimal care requires a comprehensive management plan, including regular monitoring and adjustments to treatment as needed.

References:

• [5] Purified plasma-derived human C1 esterase inhibitor concentrate is the treatment of choice for short-term prophylaxis.
• [8] Berinert is indicated for treatment of acute abdominal, facial, or laryngeal attacks of HAE in adults and children.
• [9] C1-esterase inhibitor human injection (Cinryze, Haegarda) is used to prevent HAE attacks.
• [13] The 2013 United States Hereditary Angioedema Association Medical Advisory Board guidelines for the treatment and management of HAE have been updated.

Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurring episodes of severe swelling, particularly in the skin and mucous membranes. When diagnosing HAE, it's essential to consider other conditions that may present with similar symptoms. Here are some differential diagnoses for HAE:

• Acquired angioedema: This condition is caused by a deficiency or dysfunction of C1-inhibitor protein, similar to HAE. However, acquired angioedema is not inherited and can be triggered by various factors such as medications, autoimmune disorders, or infections.
• Acute allergic angioedema: This type of angioedema is typically caused by an allergic reaction to a specific substance, such as peanuts or shellfish. It often presents with rapid onset of swelling, usually within minutes to hours after exposure.
• ACE inhibitor-induced angioedema: Certain medications, particularly ACE inhibitors used to treat high blood pressure and heart failure, can cause angioedema in some individuals.
• Chronic urticaria: This condition is characterized by recurring episodes of hives or itchy skin that last for more than 6 weeks. While not directly related to HAE, chronic urticaria can present with similar symptoms.

According to a study published in 2021 [9], the differential diagnosis for swelling includes all types of Angioedema (AE) as well as urticaria, anaphylaxis, hydrostatic edema, oncotic edema, and less common syndromes. Another study from 2022 [10] highlights that several disorders have clinical features similar to those of hereditary angioedema (HAE), including cutaneous and/or upper airway involvement.

It's crucial for healthcare professionals to consider these differential diagnoses when evaluating patients with suspected HAE, as timely and accurate diagnosis can significantly impact treatment outcomes.