Angioedema

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
  • Non-IgE-mediated
  • Possible triggers: NSAIDs (most commonly aspirin) , opiates, radiocontrast media
• Allergic reactions
  • IgE-mediated
  • Possible triggers: food, insect bites/stings, antibiotics, latex, NSAIDs (less commonly), other allergens

Bradykinin-mediated angioedema

• Hereditary angioedema (C1 inhibitor deficiency ):
  • Autosomal dominant inheritance
  • Possible triggers: trauma, surgery, dental procedure, menstruation, infections (e.g., Helicobacter pylori), or pharmacotherapeutic agents (e.g., ACE inhibitors, estrogens)
• 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
• Infections
  • More common in children
  • Possible triggers: common cold, streptococcal pharyngitis, urinary tract infections
• Drug-induced: calcium channel blockers, fibrinolytics, immunosuppressives (e.g., tacrolimus)

References:^{[1][2][3][4][5]}

Common symptoms

• 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 type 1 hypersensitivity reaction)
• Presents within 30 minutes to 2 hours after exposure and resolves over hours to days

Bradykinin-mediated angioedema

• Hereditary angioedema
  • Family history often present
  • Clinical manifestations in childhood or adolescence
  • Abdominal symptoms : colicky abdominal pain, nausea/vomiting, diarrhea
  • Angioedema of the extremities or trunk
  • Not associated with urticaria or pruritus

References:^[5]

• Mast cell-mediated angioedema
  • Anaphylaxis: IM epinephrine, oxygen, IV fluids, intubation if necessary
  • Acute: IV corticosteroids, IV antihistamines
  • Prophylaxis: avoid allergens and medications
• Hereditary angioedema
  • Acute: purified C1-INH concentrate; , bradykinin-B₂-receptor antagonist (icatibant), kallikrein inhibitor (ecallantide); FFP if other therapies are unavailable
  • Prophylaxis: long-term prophylaxis with attenuated androgens (e.g., danazol) or plasma-derived C1-INH concentrate
• ACE inhibitor-induced angioedema
  • Discontinue ACE inhibitors
  • Monitor airway until swelling is resolved

Epinephrine, glucocorticoids and antihistamines are ineffective in acute hereditary angioedema attacks!

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.
References:^[6][7][8]