1. Background

• the C1 inhibitor gene has been cloned and contains 7 exons with intervening introns containing many Alu repeats
• the C1 inhibitor protein is composed of 478 amino acids which is cleaved between positions 444-445 and it is the amino terminal (444 amino acids) which is the active protein involved in the classsical pathway

2. Genetic Defects

• genetic defects -> deficiency of C1 inhibitor protein -> uncon-trolled C1 activity -> increased breakdown of C4 & C2 (classical pathway) -> release of kinin (vasoactive peptide) from C2 -> vasodilation of postcapillary venules -> areas of swelling:
  • localized areas
  • intestinal wall - abdominal cramps, diarrhea, vomiting
  • laryngeal wall - upper airway obstruction
• it appears that C1 activity is stimulated under certain stressful situations which can precipitate an attack:
  • emotional stress
  • menses
  • trauma
  • vigorous exercise
  • temperature extremes
• a C1 inhibitor deficiency may also be acquired with certain conditions:
  • autoimmune (autoantibodies to C1 inhibitor)
  • lymphoid cancer
  • oral birth control pill
  • pregnancy
  • SLE

3. Types

1. Attack Manifestations

• triggered by stress (see above)
• last 2-3 days then abate
• may begin in the first 2 years of life but do not become severe until late childhood or adolescence
• unable to distinguish between Types 1 and 2 clinically
• characteristics
  • rapid swelling in circumscribed areas
    • may affect any part of the body
    • tense but nonpitting edema
    • not associated with pain, urticaria, itching, redness, or discolouration
  • Gastrointestinal manifestations
    • abdominal cramps with distension
    • severe watery diarrhea
    • nausea and vomiting (may be bilious)
  • Respiratory manifestations
    • edema may begin in the mouth and spread distally to produce an upper airway obstruction with stridor, respiratory distress, and pulmonary edema
    • death from obstruction in 10-30% of patients

1. Serum

• deficiency of C1 inhibitor protein by immunochemistry
  • will miss the Type 2 form
• reduced C4 between attacks and particularly during an attack
• reduced C2 during an attack but normal between attacks
• normal C3

2. Imaging Studies

MANAGEMENT:

1. Supportive

• avoid precipitating factors
• treat airway obstruction (no role for epinephrine or antihistamines)
• treat abdominal pain with demerol
• treatment with FFP is contraindicated as it may exacerbate an attack

2. Danazol

• a synthetic androgen given orally
• recommended for use in adults but not in children because of the side effects (accelerates bone growth)
• acts to increase the level of C1 inhibitor 3-4 times and prevents attacks in both forms of the disease
• can be used for short-term prophylaxis by giving for one week prior to a precipitating event, i.e., surgery (even in children)

3. Infusion of Purified C1 Inhibitor

• experimental