$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 (312) 982-7000 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 (203) 746-6518 NIH/National Heart, Lung and Blood Institute 9000 Rockville Pike Bethesda, MD 20892 (301) 496-4236 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 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.