Hereditary Angioedema

Hereditary angioedema is a genetic blood disorder characterized by episodes of swelling affecting various parts of the body, such as the face, limbs, and airways. These swelling attacks can be severe and require medical attention. The condition is primarily managed with medication. Treatments include the use of C1 inhibitors, plasma kallikrein inhibitors, and bradykinin receptor antagonists, which help alleviate symptoms and prevent the frequency of these attacks.

Causes

Hereditary angioedema stems from genetic mutations that impair the body’s ability to produce a protein called C1 inhibitor. Typically, mutations in the SERPING1 gene, responsible for instructing the production of this protein, are the primary culprits. There are two main types:

• Type I: Reduced production of functional C1 inhibitor leads to episodes of swelling due to fluid imbalance.

• Type II: Normal production occurs, but the C1 inhibitor does not function properly, causing similar symptoms.

Another form, known as hereditary angioedema with normal C1 inhibitor, involves different genetic factors but also causes swelling. The condition follows an autosomal dominant inheritance pattern, meaning one mutated gene from either parent can cause the disorder. Spontaneous mutations may also lead to hereditary angioedema, even without a family history.

Symptoms

Hereditary angioedema is marked by sudden, unpredictable swelling in various body parts. Key symptoms include:

• Swelling in the hands, feet, face, and genitals, without accompanying itching or hives.

• Gastrointestinal issues like severe abdominal pain, nausea, vomiting, and diarrhea.

• The most serious symptom is throat swelling, which can obstruct airways and become life-threatening.

• Early signs before swelling starts may include fatigue, muscle aches, or tingling.

• Swelling episodes typically last two to five days, varying in frequency and intensity.

• Identifying triggers such as stress or physical injury can assist in managing and potentially preventing these episodes.

Diagnosis

Diagnosing hereditary angioedema involves a detailed medical history, physical examination, and specialized blood tests. Healthcare providers measure and assess the C1 inhibitor protein’s levels and function, crucial in regulating immune responses. In Type I hereditary angioedema, there are typically low levels of the C1 inhibitor protein. Type II shows normal levels, but with improper functionality. Low C4 protein levels in the blood often occur during episodes and serve as indicators. Genetic testing may be used for recurrent symptoms without a known cause to detect gene mutations. Distinguishing hereditary angioedema from other forms of swelling, especially those related to allergies, helps in accurate diagnosis since it lacks itching.

Treatments

Managing Hereditary Angioedema (HAE) involves therapies targeting the unpredictable swelling episodes that pose serious health risks. Treatment strategies are divided into:

• On-Demand Treatments: Medications like Berinert and Kalbitor are used during acute attacks, providing rapid relief and minimizing swelling to avert complications.

• Prophylactic Treatments: Drugs such as Cinryze, Haegarda, and Takhzyro are administered regularly to decrease attack frequency and intensity. Home administration is often an option, enhancing quality of life by reducing emergency medical care reliance. Accessibility to these medications is critical, especially for potential airway obstructions.

Medications

Medications are vital in managing hereditary angioedema and preventing unexpected attacks. Here's a rundown:

• On-Demand Treatments: Medications like Berinert and Firazyr are used at the onset of an attack, providing quick relief from symptoms.

• Prophylactic Medications: Drugs like Cinryze and Takhzyro are taken regularly to lower attack frequency, reducing hospital visits and enhancing life quality.

Self-administration is encouraged, allowing for quicker intervention and better condition control. Patients must maintain access to their treatments and keep detailed usage records to ensure effective management and meet insurance requirements.

Prevention

For individuals managing hereditary angioedema, preventive strategies focus on trigger control and preventive medications. Key considerations include:

• While complete prevention isn't possible, identifying and avoiding triggers such as physical trauma, stress, and specific medical procedures is critical.

• Keeping an accurate record of triggers helps recognize and avoid them in the future.

• Preventive medications, like berotralstat, reduce attack frequency by inhibiting plasma kallikrein and lowering bradykinin levels, which cause swelling.

• Working with healthcare providers to explore preventive medication can aid in crafting a personalized management plan.