Hereditary angioedema

Overview Of Hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe swelling (angioedema) in various parts of the body, including the skin, gastrointestinal tract, and upper airways. Unlike allergic angioedema, HAE is not caused by histamine release and does not respond to antihistamines or corticosteroids. Instead, it is caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), a protein that regulates the complement and contact systems involved in inflammation and blood clotting. HAE can lead to life-threatening swelling of the airways, making early diagnosis and treatment critical. The condition is inherited in an autosomal dominant pattern and affects approximately 1 in 50,000 individuals worldwide.

Causes of Hereditary angioedema

• Hereditary angioedema is caused by mutations in the SERPING1 gene, which encodes the C1 esterase inhibitor (C1-INH) protein. There are three types of HAE:
• Type I: Characterized by low levels of C1-INH, accounting for about 85% of cases.
• Type II: Characterized by normal or elevated levels of dysfunctional C1-INH, accounting for about 15% of cases.
• Type III: A rare form with normal C1-INH levels and function, often associated with mutations in the F12 gene. These genetic mutations lead to uncontrolled activation of the bradykinin pathway, causing fluid leakage from blood vessels and resulting in swelling.

Risk Factors of Hereditary angioedema

• Several factors increase the risk of hereditary angioedema attacks:
• Family History: HAE is inherited in an autosomal dominant pattern, so a family history of the condition is a significant risk factor.
• Stress: Physical or emotional stress can trigger episodes.
• Trauma: Minor injuries, surgeries, or dental procedures may provoke swelling.
• Infections: Viral or bacterial infections can precipitate attacks.
• Hormonal Changes: Puberty, pregnancy, or the use of estrogen-containing medications can increase attack frequency.
• Medications: ACE inhibitors or other drugs that affect the bradykinin pathway may worsen symptoms.

Prevention of Hereditary angioedema

• Preventing hereditary angioedema attacks involves a combination of lifestyle modifications and medical interventions:
• Prophylactic Therapy: Regular use of C1-INH concentrates or oral medications to reduce attack frequency.
• Trigger Management: Avoiding stress, trauma, infections, and medications that exacerbate symptoms.
• Patient Education: Understanding the condition and recognizing early signs of an attack.
• Emergency Plan: Having access to acute treatments like C1-INH or icatibant for immediate use during attacks.
• Regular Monitoring: Routine check-ups to assess treatment efficacy and adjust as needed.

Prognosis of Hereditary angioedema

• The prognosis for hereditary angioedema has improved significantly with advances in treatment. Prophylactic therapies and acute attack management have reduced the frequency and severity of episodes, improving quality of life. However, HAE remains a chronic condition, and patients require lifelong monitoring and treatment. Early diagnosis and access to specialized care are essential for preventing life-threatening complications, such as airway obstruction. Regular follow-up with a healthcare provider ensures optimal management and adjustment of treatment plans as needed.

Complications of Hereditary angioedema

• Hereditary angioedema can lead to several complications, including:
• Airway Obstruction: Swelling of the throat or larynx can cause asphyxiation if untreated.
• Abdominal Complications: Severe gastrointestinal swelling can mimic surgical emergencies, leading to unnecessary surgeries.
• Psychological Impact: Chronic pain, anxiety, or depression due to recurrent attacks.
• Medication Side Effects: Long-term use of treatments may have adverse effects.
• Misdiagnosis: Delayed or incorrect diagnosis can lead to inappropriate treatment.

Related Diseases of Hereditary angioedema

• Hereditary angioedema is often associated with several related conditions, including:
• Acquired Angioedema: A similar condition caused by autoantibodies against C1-INH, often associated with lymphoproliferative disorders.
• Allergic Angioedema: Swelling caused by histamine release, typically responsive to antihistamines.
• ACE Inhibitor-Induced Angioedema: Swelling triggered by medications that affect the bradykinin pathway.
• Autoimmune Disorders: Conditions like lupus or rheumatoid arthritis may coexist with HAE.
• Complement Deficiencies: Other disorders of the complement system that affect immune function.
• Recurrent Idiopathic Angioedema: Swelling episodes with no identifiable cause. Understanding these related conditions helps ensure comprehensive evaluation and management.

Treatment of Hereditary angioedema

Treatment for hereditary angioedema focuses on preventing attacks, managing acute episodes, and addressing underlying genetic factors. Options include: 1. **Acute Attack Management**: - **C1-INH Concentrates**: Berinert or Cinryze for rapid symptom relief. - **Bradykinin Receptor Antagonists**: Icatibant to block bradykinin effects. - **Kallikrein Inhibitors**: Ecallantide to prevent bradykinin production. 2. **Prophylactic Treatment**: - **Long-term C1-INH Therapy**: Cinryze or Haegarda to prevent attacks. - **Oral Medications**: Lanadelumab or berotralstat to reduce attack frequency. 3. **Avoiding Triggers**: Managing stress, infections, and avoiding medications that exacerbate symptoms. 4. **Surgical Precautions**: Administering prophylactic C1-INH before surgeries or dental procedures.