Angioedema Types

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TYPE	DESCRIPTION	COMMON SYMPTOMS(1)	COMPLEMENT SYSTEM	POSSIBLE TREATMENT*
Hereditary Type I (HAE-I)	Represents approximately 80 to 85% of HAE cases. C1 inhibitor is considerably below normal due to a defective gene on chromosome 11. There is usually a family history of angioedema, but a number of cases are due to a spontaneous mutation of the gene.	Swelling can occur in the extremities, abdomen, throat and other organs. Swelling of the airway can be fatal. Abdominal swelling usually involves pain, vomiting and diarrhea. Symptoms usually appear early in life, most often by age 13 and may increase in severity after puberty. Episodes may be spontaneous or triggered by physical trauma or emotional stress.	Low levels of C1 inhibitor. C4 is almost always low. C1, C3 and C1q are normal. Abnormal complement (above) is the same whether the condition is hereditary or spontaneous.	C1 inhibitor concentrate (2) is the gold standard acute attack therapy, but is not yet licensed in the US for acute attacks. However, on Oct 10, 2008, ViroPharma announced that the FDA has approved the use of its C1-Inh product, Cinryze, for prophylaxis use in adolescent and adult patients with Hereditary Angioedema. Cinryze is now commercially available in the US. ViroPharma has put together an infrastructure, Cinryze Solutions, to make Cinryze available to every HAE patient that could benefit from the medicine. Please contact the HAEA's Patient Services group for more information-- Donna Davis donna-davis@haea.org or Michelle Williamson michellewilliamson@haea.org While some clinicians use 2 units of FFP to treat acute attacks, there are reports that the therapy could exacerbate an ongoing attack. Androgens such as winstrol (stanozolol), danazol, and oxandrolone are preventive therapies that are not effective acute attack treatments. Fluid replacement, pain management, and maintaining an open airway are the key elements of acute attack therapy.
Hereditary Type II (HAE-II)	Represents approximately 15 to 20% of HAE cases. Similar description to Type I, but C1 inhibitor does not function properly.	Same as HAE-I.	C1 inhibitor level may be normal or elevated, but it is dysfunctional. C1, C3 and C1q are normal, but C4 is almost always low.	Same as HAE-1
Acquired Type I (AAE-I) AAE-I & II are considered very rare; there are few reported cases.	Immune complexes that are usually linked to an underlying lymphoproliferative disorder destroy the function of C1 inhibitor. Angioedema can be an indicator that a lymphoproliferative disease is developing, so early detection needs to be emphasized.	Similar to HAE. The symptoms typically appear in the fourth decade of life or later. Because acquired angioedema is not related to a genetic defect there is an absence of a family history of symptoms.	Low level of C1 inhibitor and C4. C1q is usually reduced, but not always.	Diagnosis and treatment of underlying lymphoproliferative disease often eliminates the root cause. Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid for possible prevention of episodes. Androgen therapy may help.
Acquired Type II (AAE-II) AAE-I & II are considered very rare; there are few reported cases.	Autoantibodies are present and destroy C1 inhibitor function. There is no apparent underlying disorder.	Same as AAE-I.	Same as AAE-I. A lab test for autoantibodies may be appropriate.	Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid for possible prevention. It is possible that immunosuppressive therapy might be successful.
Idiopathic	Swelling and/or hives persist beyond 6 weeks. Thyroid dysfunction should be considered.	Swelling may occur just about anywhere and may be accompanied by urticaria (hives).	Normal	Primarily antihistamines. DHEA. 1-thyroxine for thyroid dysfunction. Prednisone therapy.
Nonhistaminergic (INAE) May occur in about 1 out of 20 cases of angioedema	Angioedema without urticaria (usually not responsive to H1 antihistamine blockers). Parasites, infections and autoimmune diseases are not present.	Swelling may occur anywhere: face, arms, legs, genitalia, throat, abdomen (but abdomen is less frequent than those with HAE). Symptoms do not change due to menstrual period or pregnancy.	Normal	Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid.
Allergic This is the most common form of angioedema.	Swelling and/or hives are a reaction to an outside influence such as food, bee sting, cold, heat, latex or drug. The outside influence provokes a histamine reaction, which leads to swelling and/or the hives.	Swelling occurs most often in the face and throat area. Urticaria (hives) may be present. If condition persists beyond 6 weeks it is considered chronic idiopathic and not an allergic reaction.	Normal	Avoid the substance or behavior that causes the allergic reaction. Antihistamines. Adrenaline (epinephrine) possibly as self-injecting Epi pens for emergencies.
ACE-Inhibitor (Angiotensin-Converting Enzyme Inhibition) Possible cause for 4 to 8% of people with angioedema.	Caused by ACE-Inhibitors for high blood pressure (captopril, enalapril, genzapril, quinapril, ramipril). Swelling may commence anywhere from a few hours to years after first starting medication.	Swelling may occur just about anywhere: throat, face, lips, tongue, hands, feet, genitals, intestines. If urticaria is present it reduces the probability of a link to ACE-Inhibitors.	Normal	Suspension or change of medication.

Revised 01/04/02

*Patients with the slightest hint of throat swelling should seek immediate treatment to ensure that their airway is not compromised. The medical literature and practitioner experience confirms that corticosteriods (Prednisone), antihistamines, and epinephrine are not effective in treating angioedema created by C1-inhibitor deficiency. However, a recent study noted success using inhaled epinephrine to prevent complete airway closure.

NOTES:

The presence of urticaria associated with angioedema usually suggests a diagnosis other than HAE or AAE.
C1 inhibitor concentrate is undergoing clinical trials in the United States that may lead to FDA approval. It is currently available in other countries. In the US, C1INH concentrate can be purchased under the FDA’s Personal Importation guidelines. The HAE Association provides patients with technical assistance on personal importation of C1INH concentrate.

A Brief Description of the Complement System: The Complement is part of our immune system. It involves a series of complex proteins (C1 thru C9 in addition to C1 inhibitor) that act in "concert" to clear foreign organisms from our bodies. C1 inhibitor essentially monitors the complement system and prevents it from having a "runaway" reaction. When C1 inhibitor is not present at an adequate level, or is dysfunctional, the system "overreacts" resulting in abnormal swelling.

Angioedema Basics was compiled based upon current research and medical knowledge. The emphasis has been on presenting the information in language that is not technical and is primarily for those that are trying to understand the different types of angioedema.

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