CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0347/03470.txt

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$Unique_ID{BRK03470}
$Pretitle{}
$Title{Angioedema, Hereditary}
$Subject{Angioedema, Hereditary Hereditary Angioneurotic Edema
Complement-Mediated Urticaria Angioedema}
$Volume{}
$Log{}

Copyright (C) 1986, 1987, 1989, 1991, 1992 National Organization for Rare
Disorders, Inc.

98:
Angioedema, Hereditary

** IMPORTANT **
It is possible that the main title of the article (Hereditary Angioedema)
is not the name you expected.  Please check the SYNONYM listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Hereditary Angioneurotic Edema
     Complement-Mediated Urticaria Angioedema

General Discussion

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


In Hereditary Angioedema, parts of the skin, mucous membranes, and
sometimes the internal organs temporarily swell up due to localized
obstruction of lymphatic vessels or the veins.  The attacks recur and are
often difficult to treat.  The condition is rare.  It affects males and
females equally.  The most dangerous manifestation is edema of the upper
respiratory tract, which may obstruct the upper airways completely.

Symptoms

Edema occurs when excess fluid accumulates in the spaces between the cells in
a tissue.  Localized edema usually results when the lymphatic vessels or the
veins are obstructed, or become impermeable, so that fluid cannot enter the
vessels.

Edema usually occurs in circumscribed areas just beneath the skin surface
on the backs of the hands or feet, the eyelids, lips, and genitalia, and in
mucous membranes lining such areas as the respiratory and gastrointestinal
tracts.  Involvement of these internal organs occurs more often in Hereditary
Angioedema than in other forms.  Other differences are that, in the
hereditary disease, the swellings are painful rather than itchy, hard to the
touch, and seldom associated with urticaria (transient, reddish wheals on the
skin).

Attacks of Hereditary Angioedema are transient, but they recur and may
become worse.  Injury or severe pain, surgery, dental procedures, viral
illness, and emotional stress can precipitate or aggravate them.

Nausea, vomiting, acute abdominal pain, and sometimes even signs of
intestinal obstruction indicate that the gastrointestinal tract is involved.
Airway obstruction, which may be fatal if not treated quickly, occurs when
edema develops in the pharynx or the larynx (vocal cords) in the upper
airway.

Causes

Hereditary Angioedema passes from one generation to the next by an autosomal

dominant gene.  (Human traits including the classic genetic diseases, are the
product of the interaction of two genes for that condition, one received from
the father and one from the mother.  In dominant disorders, a single copy of
the disease gene (received from either the mother or father) will be
expressed "dominating" the normal gene and resulting in appearance of the
disease.  The risk of transmitting the disorder from affected parent to
offspring is 50% for each pregnancy regardless of the sex of the resulting
child.)

Two familial forms exist.  In about 85% of the cases, there is a
deficiency of a blood protein called complement component C1 Esterase
Inhibitor.  Members of the remaining group synthesize an abnormal form of
this protein.

Related Disorders

Acute, nonhereditary angioedema usually resolves within a day or two.  It is
basically an allergic reaction limited to the skin and mucous membranes.
Causes include drug allergy, insect stings and bites, and certain foods,
especially eggs, shellfish, nuts, fruits.  Chronic nonhereditary angioedema
may result from continuous exposure to some allergen, or from psychological
stress.  Similar symptoms may accompany certain illnesses, including systemic
lupus erythematosus, chronic sinus or dental infection.

Therapies:  Standard

Hereditary Angioedema does not respond to the usual treatments for acute or
chronic angioedema; a number of drugs can prevent attacks, however.

Drugs that can provide long-term prophylaxis include androgens such as
danazol, and oxymethalone.  Particularly in women, care must be taken that
androgens are used that have few masculinizing effects; dosages should be as
low as possible.  Another effective drug is the still experimental, epsilon-
aminocaproic acid.  Also being studied is tranexamic acid.

To prevent attacks associated with surgery, dental work, and similar
stresses, short-term preventive measures should be tried.  Epsilon-
aminocaproic acid, fresh frozen plasma, or preparations of the missing enzyme
partially purified from whole blood, are effective.

In acute attacks with a danger of airway obstruction, an airway must be
maintained or established.  A tracheotomy may be necessary, and oxygen may
have to be supplied.  Epinephrine and antihistamine may be given, even though
it is unclear whether these are effective in Hereditary Angioedema.

The orphan drug Tranexamic acid is used as a treatment for Hereditary
Angioneurotic Edema patients and those with other congenital coagulopathies
who are undergoing surgical procedures such as dental extractions.  This drug
has been approved for marketing for these procedures only.  The drug is
manufactured by Kabi Vitrum, Inc. of Alameda, CA.

Therapies:  Investigational

The FDA has approved the following orphan product for testing as prevention
and/or treatment of acute attacks of Hereditary Angioedema:

C1-Esterase-Inhibitor, Human, Pasteurized
     Sponsored by:

     Behringwerke Aktiegesellschaft
     Route 202-206
     P.O. Box 2500
     Somerville, NJ  08876-1258

The use of Mitronal (Cinnarizine) for treating Hereditary Angioedema is
being investigated by Searle Pharmaceuticals, Inc.  For more information,
please contact:

     Searle Pharmaceuticals, Inc.
     Box 5110
     Chicago, IL  60680
     [phone]

The orphan drug Cl-Inhibitor (Human) Vapor Heated Immuno) is being
developed by Immuno Clinical Research Corp., 155 E. 56th St., New York, NY,
10022, for the prevention of acute attacks of Angioedema, including short-
term protection for patients of Angioedema who require dental or other
surgical procedures.

For information on additional therapies that have been designated as
Orphan Drugs in the last few months, please return to the main menu of NORD
Services and access the Orphan Drug Database.

This disease entry is based upon medical information available through
November 1992.  Since NORD's resources are limited, it is not possible to
keep every entry in the Rare Disease Database completely current and
accurate.  Please check with the agencies listed in the Resources section for
the most current information about this disorder.

Resources

For more information on Hereditary Angioedema, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     NIH/National Heart, Lung and Blood Institute
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

For information on genetics and genetic counseling referrals, please
contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

THE MERCK MANUAL 15th ed.:  R. Berkow, et al:  eds; Merck, Sharp & Dohme
Research Laboratories, 1987.  P. 310.

CECIL TEXTBOOK OF MEDICINE, 18th ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Eds.:  W. B. Saunders Co., 1988.  Pp. 148, 1940.