Hereditary angioedema (HAE) is a rare genetic disorder caused due to recurrent episodes of severe swelling.  

This condition affects various parts of the body including extremities, face, and airways. It is an autosomal dominant disease that causes low levels of the plasma protein C1 inhibitor. 

Types of HAE are: 

Type I: It is most common form, where C1-INH levels are reduced 

Type II: Normal levels of C1-INH are present, but the protein is dysfunctional 

Type III: It is rare and not linked to C1-INH deficiency 

Estrogen-dependent angioedema in women is caused due to HAE with normal C1 inhibitor levels and function. 

C1-INH dysfunction causes excessive complement and contact system activation to disrupt bradykinin production. Bradykinin promotes blood vessel dilation and swelling through increased permeability. 

Hereditary angioedema is rare disorder affects nearly 20% population.  

HAE affect individuals of all races with no ethnic bias. Both men and women are equally affected, but women may experience more severe attacks. 

C1-INH deficiency present from birth in HAE with perinatal angioedema rare their symptoms arise in first or second decade. 

Childhood swelling may go unnoticed and worsens in puberty for patients. HAE with normal C1 inhibitor levels rare before puberty. 

C1-INH, alpha-antitrypsin, antithrombin III, and angiotensinogen are serpin family protease inhibitors to inactivate target proteases. 

Regulation of production not fully understood, but patients respond to androgens and show increased levels. 

The C1 inhibitor binds to and inactivates proteins to cause low C1 inhibitor levels and removal from circulation. 

Causes of HAE are: 

Autosomal Dominant Inheritance 

Types of HAE 

Bradykinin Overproduction 

Trauma and Surgery 

Stress and Hormones 

Abdominal attacks can cause unnecessary surgery, diagnosis delays, and narcotic dependence. 

Worse prognosis for HAE patients with early attacks compared to late attacks. 

Mortality rate was 20% to 30% before effective therapy. Prognosis improved with prophylactic therapy for HAE. 

Patients with HAE do not require C1-INH for immune function or infection risk. 

Detailed information including initial episodes and family history of patient should be gathered. 

• Facial and Periorbital swelling assessment 
• Abdominal Examination 
• Airway Assessment 

Life-Threatening Acute symptoms are: 

Throat tightness, difficulty swallowing, and voice changes 

Severe symptoms are: 

Crampy abdominal pain, nausea, and vomiting 

Hypotensive patients with fluid sequestration may need extensive IV fluids for hemodynamic stability. 

For HAE types I and II, treat acute attacks with C1 inhibitor concentrates or kallikrein inhibitor. 

Ecallantide is a recombinant, selective, and reversible kallikrein inhibitor that increases the effectiveness of C1-INH concentrate. 

Use danazol doses to treat without normalizing C1-INH levels and long-term use may cause arterial hypertension. 

Antifibrinolytic agents like epsilon-aminocaproic acid or tranexamic acid can be used for prophylaxis but less effective. 

Treatment started with weakened androgens for prevention before adjusting for severity and side effects. 

Allergy and Immunology

Use of protective gear during activities that pose a risk of injury. 

Minor trauma should be managed like bumping into objects, which can trigger an episode of swelling. 

Create a calm environment at home and workplace to minimize stress. 

HAE is not triggered by allergens and avoid environmental irritants to reduce stress on the body. 

Proper awareness about HAE should be provided and its related causes with management strategies. 

Appointments with a physician and preventing recurrence of disorder is an ongoing life-long effort. 

Allergy and Immunology

Fresh frozen plasma: 

Administer 2 units of FFP to sustain control that prevents development of angioedema.  

Allergy and Immunology

Danazol: 

It reduces the frequency of attacks in most patients involving the airway. 

Allergy and Immunology

C1 inhibitor human: 

It increases plasma concentration and activity of C1 inhibitors.  

Allergy and Immunology

Ecallantide: 

It reduces conversion of kininogen to bradykinin. 

Lanadelumab: 

It inhibits proteolytic activity to control excess bradykinin generated with HAE.  

Allergy and Immunology

Icatibant: 

It is indicated for acute attacks of hereditary angioedema. 

Allergy and Immunology

Aminocaproic acid: 

It inhibits fibrinolysis through inhibition of plasminogen activator substances. 

Allergy and Immunology

The procedure should be performed to minimize trauma. Gentle atraumatic techniques should be indicated in dental work or surgeries. 

Allergy and Immunology

In initial treatment phase use of acute and preventive management therapies to resolve symptoms during an acute HAE attack. 

Pharmacologic therapy is effective in the treatment phase as it includes use of androgens, C1-inhibitor concentrates, and bradykinin receptor antagonists. 

In supportive care and management phase, patients should receive required attention such as lifestyle modification and intervention therapies. 

The regular follow-up visits with the physician are scheduled to check the improvement of patients along with treatment response.