Angioneurotic edema (AE) occurs as a result of a C1-inhibitor deficiency, which may be either quantitative or qualitative. The deficiency results in a lack of inhibition to a series of serum proteases, which then act unchecked. The disorder may be either hereditary or acquired.
Targets of C1-inhibitor are proteases that include:
(1) complement system: C1r and C1s
(2) contact system: Factor 12a and kallikrein
(3) coagulation cascade: Factors 11a, 12a and 12f
(4) fibrinolysis: plasmin
Clinical features of deficiency state:
(1) sudden onset of recurrent, subepithelial swellings which are circumscribed and non-pitting and which may involve the extremities, face, mouth, larynx and bowel wall.
(2) family history in the hereditary form
(3) absence of pruritus and accompanying urticaria
(4) recurrent gastrointestinal colics, with pain, nausea, vomiting and/or watery diarrhea
(5) CNS symptoms including headaches, hemiparesis or seizures
Factors precipitating attacks:
(1) stress
(2) minor trauma, dental procedures or surgery
(3) insect stings
(4) food or alcohol
(5) drugs, especially angiotensin-converting enzyme (ACE) inhibitors, oral contraceptives or estrogen replacement therapy
(6) menstruation or pregnancy (associated with increased estrogen levels)
(7) nothing specific
Pathogenesis:
(1) hereditary (HAE)
(1a) autosomal dominant disorder with a frequency of 1 in 50,000 persons
(1b) de novo mutations
(2) acquired (AAE)
(2a) paraprotein associated (resulting in a Type I pattern)
(2b) antibodies to C1-INH, typically as autoantibodies associated with CLL or other lymphoproliferative disorder (resulting in a Type II pattern)
Type |
C1-INH antigen |
C1-INH functional activity |
C4 Level |
C1q Level |
Hereditary Type I |
decreased |
decreased |
decreased |
normal |
Hereditary Type II |
normal or increased |
decreased |
decreased |
normal |
Acquired Type I |
decreased |
decreased |
decreased |
decreased |
Acquired Type II |
normal or increased |
decreased |
decreased |
decreased |
after Table 1, page 26, Ebo and Stevens (2000)
Specialty: Immunology/Rheumatology
ICD-10: ,