Diagnosis and Treatment

Steps in diagnosis

From Current Care and Support by Takahiko Horiuchi (Elsevier Japan)

Types of edema of sudden onset (acute edema) that have to be differentiated

  1. Allergic angioedema (allergic AE)*
  2. Hereditary angioedema (HAE)
    Type I: Deficiency of C1 inhibitor protein
    Type II: Dysfunctional forms of C1 inhibitor protein
    Type III: More prevalent in women, some affected individuals have a genetic defect in coagulation factor XII
  3. Acquired angioedema (AAE)
  4. Angioedema induced by angiotensin-converting enzyme (ACE) inhibitors (ACE inhibitor-related AE)
  5. Angioedema triggered by a physical stimulus (Physical AE)**
  6. Angioedema with eosinophilia (Gleich’s syndrome)**
  7. Idiopathic angioedema (Idiopathic AE)**

＊Associated with urticaria
＊＊Associated with urticaria in some instances

(Takahiko Horiuchi,　Japan Medical Journal, 2011)

Characteristics of edema of sudden onset

  Edema of sudden onset (angioedema) Many other forms of edema
Course ・Edema fully develops within several hours
・Disappears in about 3 days		 ・Chronic condition
Symptoms ・Localized
・Asymmetrical (excluding the face)
・No indentations (“pits”) left when
pressure is applied with the finger
・Develops in areas that are unrelated
to gravity
・Readily develops in the eyelids, lips,
pharynx, and gastrointestinal tract		 ・Extensive
・Symmetrical
・Indentations (“pits”) left when
pressure is applied with the finger

Complement tests to differentiate edema of sudden onset

  C4 C1-INH activity C1-INH assay C1q
Type I HAE ↓ ↓ ↓ Normal (or↓)*
Type II HAE ↓ ↓ Normal or↑ Normal
Type III HAE Normal Normal Normal Normal
Acquired angioedema ↓ ↓ ↓ ↓
Other forms of angioedema** Normal Normal Normal Normal

*May be ↓ depending on the individual.  In that event, type I HAE is difficult to differentiate from AAE
**Allergic angioedema, angioedema induced by angiotensin-converting enzyme (ACE) inhibitors, angioedema triggered by a physical stimulus, idiopathic angioedema

Treatment during an episode

Treatment during an episode Subcutaneous edema
(other than the face and neck)		 Subcutaneous edema
(face & neck)		 Abdominal pain Pharyngeal edema
Followed ＋ ＋ ＋ ＋
tranexamic acid* ＋ ＋ ＋ ＋
C1 inhibitor
Replacement therapy**		 ＋/－ ＋ ＋ ＋
Managed in the ICU － － － ＋

＊Tranexamic acid (Transamin 15 mg/kg every 4 hrs)
＊＊C1 inhibitor replacement therapy (under 50 kg: Berinert P 500 units IV, 50 kg or more:　1000-1500 units IV)
1 unit refers to C1 inactivator (＝C1 inhibitor) activity in 1 mL of normal human plasma