Disorder of complement regulation in which C1 esterase
inhibitor (C1INH), an inhibitor of spontaneous activation of C1, is lacking.
This produces circumscribed, nonpitting subepithelial edema involving the
lips, eyelids, tongue, larynx, pharynx, respiratory tract, gastrointestinal
tract, renal system, and occasionally the central nervous system.
Angioedema; Hereditary Angioneurotic Edema; HANE
Syndrome; C1 Esterase Inhibitor Deficiency.
Estimated incidence of the hereditary form is
1:50,000-150,000 live births in the United States.
In the hereditary form, transmission is via an
autosomal dominant pattern, with males affected twice as often as females.
Human C1 inhibitor gene is localized to chromosome 11q11-q13.1. In more than
20% of patients with hereditary angioedema, the mutations are de novo;
thus there is no family history of the disease.
Hereditary angioneurotic edema (HANE) is caused by
either the absence of C1INH (type I) or the presence of inactive C1INH (type
II). Acquired forms result from either consumption of C1INH in association
with benign or malignant B-cell lymphoproliferative disorders, connective
tissue diseases, and monoclonal gammopathies (type I), or the presence of
antibodies to C1INH (type II).
Positive family history and characteristic clinical
presentation. Serum C1 esterase inhibitor deficiency in the hereditary form
(5-30% of normal) and low C4.
Age at onset of HANE syndrome (Milton disease) is before 7 years in 50%
of cases. Both inherited or acquired forms are characterized by recurrent
attacks of nonpruritic and nonerythematous, often asymmetrical, edema
affecting the extremities, abdomen, and face. Edema of the larynx and other
portions of the airways is the most fearsome feature of this disorder and is
the major cause of mortality, an outcome that could occur in up to 50% of
these patients. Precipitating factors are minor trauma or emotional upset.
Visceral involvement with crampy abdominal pain without peritoneal signs can
lead to unnecessary laparotomy. Severe attacks of watery diarrhea are another
manifestation of HANE. Edema of the airway is slowly progressive over hours,
but local trauma, as in attempted tracheal intubation, can precipitate or
aggravate the edema. During an attack, levels of C1 inhibitor and C4 and C2
are depressed. There are increased levels of thyroglobulin antibodies
and thyroid microsomal antibodies in patients with hereditary angioedema.
Androgen derivatives are useful for long-term prophylaxis because they
increase hepatic synthesis of C1INH. Concentrates of C1 inhibitor are
effective and without side effects in the treatment of severe acute attack.
Skin testing for anesthetic drugs is
useless. Suitable premedication to allay anxiety. Investigations include
coagulation status, C1NH and C4 levels in HANE, and electrolytes when there
is diarrhea associated with gastrointestinal attacks. Because androgen
derivatives used for prophylaxis may affect hepatic function, liver function
tests should be performed. In HANE, attempts should be made to increase C1NH
levels preoperatively by using androgens, antifibrinolytics, fresh-frozen
plasma (FFP), or purified C1NH concentrate. If the patient is not receiving
long-term therapy with androgens (e.g., danazol 200 ...