Angioedema

Angioedema - Swelling Showdown

• Localized, transient, non-pitting subcutaneous or submucosal swelling.
• Key features: Asymmetric, well-demarcated.
• Classification:
  • Histaminergic (Allergic):
    • Most common.
    • Pruritus, urticaria often present.
    • Responds to antihistamines, steroids, epinephrine.
  • Non-histaminergic (Bradykinin-mediated):
    • No pruritus/urticaria.
    • Poor response to antihistamines/steroids.
    • Types:
      • Hereditary Angioedema (HAE): C1-INH deficiency/dysfunction.
      • Acquired Angioedema (AAE): C1-INH deficiency.
      • ACE inhibitor-induced: Commonest bradykinin type.

⭐ ACE inhibitor-induced angioedema can occur at any time, even years after initiating therapy.

Angioedema - Cascade Chaos

• Two main cascades: Mast cell (histaminergic) vs. Bradykinin-mediated.
• Mast Cell Pathway:
  • Mediators: Histamine, Prostaglandins (PGs), Leukotrienes (LTs).
  • Clinical: Urticaria & pruritus common. Responds to antihistamines, steroids, epinephrine.
• Bradykinin Pathway:
  • Mediator: Bradykinin (via contact system activation or ↓degradation).
  • Clinical: No urticaria/pruritus. Poor response to standard allergy Rx.
  • Key Causes: ACE inhibitors, Hereditary Angioedema (HAE: C1-INH deficiency/dysfunction), Acquired Angioedema (AAE).

⭐ In HAE (Types I & II), C4 levels are characteristically low during acute attacks and for screening.

Angioedema - The Usual Suspects

Angioedema - Spotting Swells

• Localized, transient, non-pitting edema of deep dermis, subcutaneous/submucosal tissues.
• Sites: Face (lips, eyelids, tongue), larynx, extremities, GIT. Resolves 24-72 hrs.
• Triggers: Allergens, drugs (ACEi, NSAIDs), C1-INH deficiency (HAE).
• Key Distinction:
  • With Urticaria: Mast cell-mediated (histamine). Often allergic/idiopathic.
  • Without Urticaria: Bradykinin-mediated (e.g., HAE, ACEi-induced).
    • Abdominal pain, N/V/D common in HAE (bowel wall edema).
    • Laryngeal edema: Stridor, dysphonia. Airway emergency!

⭐ Bradykinin, not histamine, mediates HAE & ACEi-AE; antihistamines/steroids ineffective.

• Diagnosis: Clinical. History (triggers, family Hx, drug Hx), exam.
  • HAE workup (if recurrent, no urticaria, +ve family Hx): ↓C4 (screening), then C1-INH level & function.

Angioedema - Swelling Solutions

• Types & Key Rx:
  • Allergic (histaminergic): Antihistamines, Steroids, Epinephrine (0.3-0.5 mg IM).
  • Bradykinin-mediated (HAE, ACEi):
    • HAE Acute: C1-INH concentrate (20 IU/kg IV), Icatibant (30 mg SC), Ecallantide (30 mg SC), FFP.
    • ACEi: Stop ACEi.
• Acute Attack Management:

• HAE Long-Term Prophylaxis:

  Therapy	Examples	Key Point
  Attenuated Androgens	Danazol	↑ C1-INH synthesis
  Antifibrinolytics	Tranexamic Acid	Inhibit plasmin
  C1-INH Concentrate	Berinert, Cinryze	Replacement therapy (IV/SC)
  Kallikrein Inhibitor	Lanadelumab	MAb, SC inj.

⭐ Hereditary Angioedema (HAE) is bradykinin-mediated, thus unresponsive to antihistamines, corticosteroids, and epinephrine.

High‑Yield Points - ⚡ Biggest Takeaways

• Angioedema: Acute, localized swelling of dermis, subcutaneous tissue, or submucosa.
• Bradykinin-mediated (e.g., HAE, ACE-inhibitor induced): Non-pruritic, no urticaria; unresponsive to antihistamines/steroids.
• Mast cell-mediated (allergic): Often with urticaria, pruritus; responds to antihistamines, steroids, epinephrine.
• Hereditary Angioedema (HAE): C1-inhibitor deficiency/dysfunction causes ↑ bradykinin.
• Airway compromise: A life-threatening emergency requiring prompt intervention.
• Acute HAE Tx: C1-INH concentrate, icatibant, ecallantide; FFP if others unavailable.