- Clinical science
Angioedema is a self-limited, localized swelling of the dermis, subcutaneous tissues, and/or submucosal tissues caused by fluid leakage into the interstitial tissue. It is mediated by vasoactive substances and can be classified as either mast cell-mediated (often secondary to allergic reactions and NSAIDs), bradykinin-mediated (due to ACE inhibitor use or enzyme deficiencies), and unknown (idiopathic). Patients usually present with swelling of the eyelids, lips, and tongue. However, life-threatening laryngeal edema may occur, which requires immediate airway protection. Treatment generally consists of supportive care and avoidance of triggers, if applicable. In acute cases, mast cell-mediated angioedema is treated with systemic glucocorticoids, antihistamines and if necessary, epinephrine for anaphylaxis. Bradykinin-mediated angioedema is treated with C1 inhibitor (C1-INH) concentrate, bradykinin-B2-receptor antagonists and kallikrein inhibitors.
Mast cell-mediated angioedema (histamine-mediated angioedema)
- Direct mast-cell activation
- Allergic reactions
- Hereditary angioedema ( )
Acquired angioedema: (acquired C1 inhibitor deficiency)
- Presents in older age (in or after the fourth decade of life)
- Often associated with lymphoproliferative diseases and B-cell malignancies
- ACE inhibitor-induced (rarely angiotensin-receptor blocker-induced): impaired bradykinin breakdown
Angioedema of unknown cause
Idiopathic angioedema :
- Recurrent episodes without known cause
- Possible triggers: cold, heat, stress, and exercise
- Drug-induced: calcium channel blockers, fibrinolytics, immunosuppressives (e.g., tacrolimus)
- Facial edema (mouth, eyelids, tongue)
- Laryngeal involvement: dyspnea and inspiratory stridor, potentially life-threatening
- Possibly swelling of extremities and urogenital area (e.g., hands, feet, scrotum)
Mast cell-mediated angioedema
- Often associated with urticaria and pruritus
- Other associated with clinical findings of allergic reactions (see )
- Presents within 30 minutes to 2 hours after exposure and resolves over hours to days
- Hereditary angioedema
- The diagnosis of angioedema is mainly based on history and clinical findings.
- In some cases:
- Allergy screening
- Evaluation of C1-INH deficiency
- Mast cell-mediated angioedema
- Hereditary angioedema
- ACE inhibitor-induced angioedema
If airway compromise is suspected (stridor, wheezing, diminished air movement) or the patient is in shock, treat immediately with IM epinephrine, start oxygen and IV fluids, and consider intubation to protect the airway. Once acute therapy has been initiated, the type and cause of angioedema should be determined.
- Treat anaphylaxis if present at any time.
- Administer supplemental oxygen and perform basic airway maneuvers.
- Urgent anesthesia and/or ENT consult if the airway is compromised
- Prepare for difficult airway and surgical airway as a backup.
- Administer case-based specific treatment:
- If histamine-mediated angioedema is suspected or the etiology is unknown: Administer standard therapy with antihistamines and steroids.
- If bradykinin-mediated angioedema is suspected: Administer targeted therapy with C1-INH protein replacement, ecallantide, or icatibant.
- If ACE-inhibitor-induced etiology is suspected: Administer FFP.
- Remove potential exposures or offending medications (e.g., ACE inhibitors).
- Continuous telemetry and pulse oximetry (with or without capnography)
- ICU consult