A 28-year-old woman from Delhi presents with recurrent episodes of angioedema affecting her face, lips, and throat over the past 6 months. She denies urticaria. On examination, she is afebrile with normal vital signs. Serum C1 esterase inhibitor (C1-INH) level is 15% (normal 50–150%), and C1q level is normal. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis: Hereditary Angioedema Type I **Key Point:** This patient has hereditary angioedema (HAE) Type I — characterized by low C1-INH levels (< 50%) with normal C1q. The absence of urticaria and recurrent angioedema without anaphylaxis are hallmark features. ### Pathophysiology of Complement Defect C1-INH is the primary regulator of the contact (kallikrein-kinin) and complement cascades. Deficiency leads to: - Uncontrolled activation of Factor XII (Hageman factor) - Excessive bradykinin production - Increased vascular permeability → angioedema **High-Yield:** HAE does NOT involve mast cell degranulation, so antihistamines and corticosteroids are ineffective. ### Management Algorithm ```mermaid flowchart TD A[Recurrent angioedema without urticaria]:::outcome --> B{C1-INH level?}:::decision B -->|Low with normal C1q| C[HAE Type I or II]:::outcome B -->|Normal C1-INH| D[Type III HAE or acquired angioedema]:::outcome C --> E{Acute attack?}:::decision E -->|Yes| F[FFP or C1-INH concentrate]:::action E -->|No| G[Long-term prophylaxis]:::action G --> H[C1-INH concentrate or attenuated androgens]:::action ``` ### Immediate Management **For acute attacks:** - Fresh frozen plasma (FFP) 10–15 mL/kg — provides exogenous C1-INH - C1-INH concentrate (if available) — preferred over FFP - Avoid ACE inhibitors and NSAIDs (trigger attacks) **For long-term prophylaxis:** - C1-INH concentrate (IV, twice weekly) - Attenuated androgens (stanozolol 2 mg daily, or danazol 200 mg BD) — increase hepatic synthesis of C1-INH - Bradykinin receptor antagonist (icatibant) — newer option **Clinical Pearl:** Antihistamines, corticosteroids, and epinephrine are ineffective in HAE because the mechanism is bradykinin-mediated, not mast cell–mediated. ### Why C1q is Normal in Type I Type I HAE = quantitative C1-INH deficiency (gene mutation → reduced synthesis). Type II HAE = qualitative C1-INH deficiency (dysfunctional protein). Both have normal C1q (C1q is part of the C1 complex but is not the inhibitor). If C1q were low, suspect **Type III HAE** (normal C1-INH levels but dysfunctional) or **acquired angioedema** (low C1q due to consumption).