Hereditary Angioedema

Snapshot – Hereditary Angioedema

A 23-year-old woman with past medical history of multiple allergies leading to facial swelling presents with marked difficulty breathing, abdominal pain, and swelling of the face and neck. On physical exam, her extremities are also noted to be markedly swollen (picture). She is immediately sedated for intubation to maintain patency of airway. Chart review reveals newly-started ACE-inhibitor. She is given epinephrine, fluids, and fresh frozen plasma.

Introduction

Disorder of complement, causing angioedema
Genetics
- autosomal dominant
Pathogenesis
- C1 esterase inhibitor deficiency
  - C1 esterase inhibitor inhibits kallikrein-kinin pathway
    - remember kallikrein activates bradykinin
    - bradykinin
      - ↑ vasodilation
      - ↑ permeability
      - ↑ pain
- ACE-inhibitors are contraindicated
  - ACE inactivates bradykinin
  - ACE-inhibitors allows ongoing bradykinin, causing angioedema
Epidemiology
- attacks begin during childhood
Risk factors
- family history of angioedema
- family history of those contraindicated with ACE-inhibitors
autoimmune conditions

Presentation

Symptoms/physical exam
- recurrent episodes of angioedema without urticaria
  - as opposed to anaphylaxis, which typically has urticarial
  - angioedema of the face, oropharynx, extremities, or abdomen
  - angioedema of GI tract
    - severe abdominal pain
    - GI upset
  - worst at 24 hours
  - resolves over 48-72 hours
- often preceded by prodrome
  - fatigue
  - flu-like symptoms
not responsive to epinephrine (epi-pen) or antihistamines

Evaluation

Best initial test
- ↓ C4 and C2 levels
- if C4 are normal, C1 inhibitor deficiency is unlikely
To confirm diagnosis if ↓ C4
- ↓ C1 inhibitor antigenic levels
↓ C1 inhibitor functional levels

Differential Diagnosis

Anaphylaxis
Allergic angioedema
Facial cellulitis
SVC syndrome

Treatment

Anaphylaxis presents very similarly to angioedema and often cannot be differentiated immediately in an emergency room setting
- therefore, patients are often initially treated with medications for anaphylaxis given urgent, life-threatening nature of anaphylaxis
  - epinephrine
  - fluid replacement
  - anti-histamines
Assess airway, even after administering treatment
- intubate if necessary
As soon as possible, especially if epinephrine and anti-histamines are not effective, administer medications for hereditary angioedema
- plasma-derived C1 inhibitor
- recombinant human C1 inhibitor
fresh frozen plasma if above are not available

Prognosis, Prevention, and Complications

Prognosis
- mortaliy >30% in those with laryngeal angioedema
- angioedema is unpredictable
Complications
- small bowel obstruction
- compartment syndrom
- death by asphyxiation

Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe swelling in various parts of the body. This condition is caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), a protein that regulates the complement and contact systems in the blood. Understanding Hereditary Angioedema is crucial for medical professionals, especially those in immunology, allergy, and emergency medicine. This article provides a comprehensive overview of Hereditary Angioedema, including its types, function, related studies, treatment considerations, and clinical significance.

Types of Hereditary Angioedema:

There are three main types of Hereditary Angioedema:

Type I HAE: This type is characterized by a deficiency in the production of functional C1-INH protein.
Type II HAE: Type II involves the production of dysfunctional C1-INH protein that does not effectively regulate complement and contact system activation.
Type III HAE: This form is less common and primarily affects females. It is not associated with C1-INH deficiency but is often linked to mutations in the F12 gene, leading to increased production of bradykinin, a key mediator of angioedema.

Function of C1-INH:

C1-INH plays a crucial role in regulating two major blood pathways:

Complement System: C1-INH controls the complement system, preventing excessive activation and the release of proinflammatory mediators.
Contact System: C1-INH also regulates the contact system, which includes factors that, when activated, lead to the production of bradykinin—a potent vasodilator causing blood vessels to widen and become more permeable.

Clinical Manifestations:

Hereditary Angioedema is characterized by recurrent episodes of swelling that can affect various body parts, including:

Skin: Swelling often occurs in the face, lips, tongue, and extremities.
Gastrointestinal Tract: Swelling in the intestinal walls can cause severe abdominal pain, vomiting, and diarrhea.
Respiratory Tract: In some cases, swelling of the airways can lead to life-threatening respiratory distress.