Review
Forms of angioedema
Pathophysiology of angioedema
Histamine-mediated angioedema
Bradykinin-mediated angioedema
Hereditary angioedema
ACE inhibitor-induced angioedema
Acquired angioedema
Clinical manifestation of angioedema
Histamine-mediated angioedema
Angioedema type | Clinical and diagnostic features |
---|---|
Histamine-mediated
| |
Allergic angioedema | Angioedema usually accompanied by urticaria and sometimes anaphylaxis; may be pruritic; associated with exposure to allergens; attacks last for 24–48 h; responsive to antihistamines or corticosteroids |
Angioedema with urticarial vasculitis | Angioedema accompanied by urticaria; there may be petechiae or purpura after swelling resolves; symptoms of underlying vasculitis |
Bradykinin-mediated
| |
Hereditary angioedema types I and II | Recurrent attacks without urticaria; erythema marginatum is a cardinal finding; onset in childhood or young adulthood, worsening at puberty; family history in 75% of patients; attacks unresponsive to antihistamines or corticosteroids |
Hereditary angioedema type III | Associated with mutations in factor XII; more common in women; may be estrogen dependent; typical onset after childhood; face, tongue, extremity involvement is more frequent than abdominal; recurrent tongue swelling is cardinal symptom; more disease-free intervals than in HAE types I and II; family history of angioedema; attacks unresponsive to antihistamines or corticosteroids |
Acquired angioedema | Attacks similar to HAE; onset in middle age or later; no family history; attacks unresponsive to antihistamines or corticosteroids |
ACE inhibitor-induced angioedema | History of ACE inhibitor use; no urticaria; face and tongue most frequent sites; more common in blacks and smokers; patients usually can tolerate ARBs |
Not mediated by histamine or bradykinin
| |
Idiopathic angioedema | Angioedema sometimes accompanied by urticaria; swelling may persist for up to 48 h; attacks may occur daily; responsive to antihistamines or corticosteroids |
Pseudoallergic angioedema | Urticaria typically present; usually class-specific reaction; thought to be mediated by cysteinyl-leukotrienes; includes NSAID-induced angioedema, which occurs because of cyclooxygenase inhibition and subsequent release of cysteinyl-leukotrienes |
HAE type III
Bradykinin-mediated angioedema, HAE types I and II
ACE inhibitor-induced angioedema
Acquired angioedema
Differential diagnosis of angioedema
Laboratory evaluation of angioedema
Histamine-mediated angioedema
Angioedema type | Urine histamine | Serum tryptase | C4 level | C1-INH Level (antigenic) | C1-INHLevel (functional) | C1q level | C3 level |
---|---|---|---|---|---|---|---|
Histamine-mediated angioedema
| ↑ | ↑ |
NL
|
NL
|
NL
|
NL
|
NL
|
Hereditary angioedema types I and II
|
NL
|
NL
|
↓
|
↓ (type I)
|
↓
|
NL
|
NL
|
NL (type II)
| |||||||
Hereditary angioedema type III
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
Acquired angioedema
|
NL
|
NL
|
↓
|
↓ or NL
|
↓
|
↓
|
↓ or NL
|
ACE inhibitor-induced angioedema
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
Idiopathic angioedema
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
Pseudoallergic angioedema
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
NL
|
HAE type III
Bradykinin-mediated angioedema: HAE types I and II
ACE inhibitor-induced, idiopathic, and acquired angioedema
Management of acute attacks of angioedema
Severe histamine-mediated angioedema, or anaphylaxis
ACE inhibitor-induced angioedema
Hereditary angioedema
Therapy and indication | Dosage | Monitoring tests |
---|---|---|
C1 esterase inhibitor [human] (Berinert; CSL Behring) | 20 U/kg body weight IV at a rate of 4 ml/ minute | · Monitor patients with known risk factors for thrombotic events |
Indicated for the treatment of acute abdominal or facial attacks of HAE in adult and adolescent patients
| ||
· Epinephrine should be immediately available to treat any acute severe hypersensitivity reactions following discontinuation of administration | ||
Plasma kallikrein inhibitor (Kalbitor [ecallantide]; Dyax Corp) | 30 mg (3 ml) SC in three 10-mg (1 ml) injections. If attack persists, additional dose of 30 mg (3 ml) may be administered within a 24-h period | · Given the similarity in hypersensitivity symptoms and acute HAE symptoms, monitor patients closely for hypersensitivity reactions |
Indicated for attacks at all anatomic sites
| ||
· Administer in a setting equipped to manage anaphylaxis and HAE | ||
Fresh-frozen plasma
| 2 U at 1 to 12 h before the event (only for use when C1-INH concentrate is not available) | · Baseline: liver function tests, hepatitis virology |
Bradykinin β2 receptor antagonist
| 30 mg (3 ml) injected SC in the abdominal area. If attack persists, additional injections of 30 mg (3 ml) may be administered at intervals of ≥6 h. No more than 3 injections in 24 hours | For patients who never received Firazyr previously, the first treatment should be given in a medical institution or under the guidance of a physician |
(Firazyr [icatibant]; Shire Orphan Therapies) | ||
Indicated for attacks at all anatomic sites
|