Hereditary angioedema (HAE, C1 Esterase inhibitor deficiency)
also see Complement deficiency

• autosomal dominant disorder
• 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 C1-INH.
  • Type II results from normal or abnormally elevated levels of a dysfunctional C1-INH.
• 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 and C4).

Clinical

• recurrent episodes of localized, painless subcutaneous or submucosal edema.
• 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

• 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 danazol 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 circumstances.

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 Dermatology specialty).

Reference: Sim T, Grant JA. Hereditary angioedema: its diagnostic and management perspectives. Am J Med. 1990;88:656-64.