Hereditary angioedema (HAE, C1 Esterase inhibitor deficiency)
- autosomal dominant
- deficiency of C1 esterase inhibitor protein (C1-INH).
- There are 2 varieties of the disorder.
- Type I is most common and results from an abnormally low level of normal
- Type II results from normal or abnormally elevated levels of a
- In both types of the disease, initial proteolytic components of the
complement cascade (eg, C1r, C1s) go relatively unopposed and lead to the
characteristic presentation and laboratory abnormalities (eg,
low levels of C2
- recurrent episodes of localized, painless subcutaneous or
- Rapid onset of swelling without redness, discoloration, itching after
trauma, stress, anxiety, exercise.
- The episodes may have no clear precipitating event, or they may be
initiated by minor trauma, anxiety, or instrumentation of the oropharynx.
- Angioedema lasting 24-72 hours
- Attacks begin in first 2 years of life but usually not severe until late
childhood or adolescence
- Symptoms may be mild or, in severe cases, include incapacitating cutaneous
swelling, gastrointestinal colic/cramping, and life-threatening upper airway
obstruction requiring tracheostomy.
- High estrogen states, such as those observed during menstruation,
pregnancy, or estrogen-containing contraception have been linked to increased
severity of episodes.
- Treatment of acute episodes with standard agents used in anaphylactic or
allergic reactions, such as epinephrine, antihistamines, and corticosteroids,
is of limited effectiveness.
- Fluid hydration and replacement of the consumed or deficient factors of
the complement cascade with commercially available C1-INH concentrate or fresh
frozen plasma is the treatment of choice.
- Patients with evidence of progressive symptoms or those with systemic
manifestations or evidence of upper airway involvement should be observed and
treated in an intensive care environment.
- Prophylactic treatment is with androgen-containing agents, such as
and stanozolol. These agents help by increasing levels of C1-INH and later
components of the complement cascade such as C4.
Unfortunately, these androgen
derivatives are class X drugs, or those highly unsafe for use in pregnancy
because of a significantly increased risk of genital anomalies in newborns.
- Amicar (aminocaproic acid), which inhibits fibrinolysis, is another
therapeutic agent, but it is a class D drug, or one unsafe for use in
pregnancy with evidence of risk that may be justifiable in certain clinical
In this case, an otolaryngologist was consulted, and on direct
rhinolaryngoscopy, the patient's airway was widely patent. As a precaution, she
was admitted to the medical intensive care unit for observation, and an allergy
specialist was consulted. The patient was ultimately given fresh frozen plasma,
did not develop airway compromise, and had a good recovery from the episode.
For more information on HAE, see the eMedicine articles
C1 Esterase Deficiency (within the
Internal Medicine specialty) and
Angioedema, Hereditary (within the
Reference: Sim T, Grant JA. Hereditary angioedema: its diagnostic and
management perspectives. Am J Med. 1990;88:656-64.