Types of Angioedema

This page contains a comprehensive list of the different types of angioedema.

The information was compiled based upon current research and medical knowledge. 
The goal is to present the material in language that is not technical, but primarily for those trying 
to understand the different types of angioedema.  It is not to be construed or used in any way as
medical or diagnostic information.

*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.

Hereditary Type I (HAE-I)

Description

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.  Does not respond to antihistamines and corticosteroids.

Common Symptoms 1

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.

Complement System

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.

Possible Treatment

Anabolic steroids (also known as androgens) such as danazol, oxandrolone and stanozolol have, historically, been the most commonly prescribed preventative HAE therapies. While anabolic steroids have been shown to be useful, they are not well-tolerated by many women, directly linked to liver toxicity and can cause an increase in cholesterol levels. In addition, these drugs should not be used to treat children, some of whom, tragically, are severely affected and suffer frequent attacks. Research indicates that patients treated with anabolic steroids can experience breakthrough laryngeal or abdominal attacks that require hospitalization.

Five new treatments are now FDA approved for treating HAE, including 2 C1 inhibitor products, a kalikrein inhibitor and a bradykinin receptor antagonists. Patients and their physicians now have options for developing a non-steroidal HAE treatment plan tailored to meet each patient’s unique needs.

  • Cinryze ™ brand of C1-inhibitor
    The Cinryze ™ brand of C1-inhibitor concentrate has been FDA-approved for preventing HAE attacks.
Cinryze ™ is delivered intravenously and is approved for self-administration.
  • Berinert® brand of C1-inhibitor
    The Berinert® brand of C1-inhibitor concentrate has been FDA-approved for treating acute facial, abdominal and laryngeal HAE attacks. Berinert® is delivered intravenously and is approved for self-administration.
  • Kalbitor® brand of plasma kalikrein inhibitor
    Kalbitor® brand of plasma kalikrein inhibitor has been FDA-approved to treat acute HAE attacks in patients 12 years of age and older. Kalbitor® is delivered through subcutaneous injections.
  • Firazyr® brand of bradykinin receptor
    Firazyr® brand of bradykinin receptor antagonist has been FDA-approved for treating acute HAE attacks in patients 18 years of age and older.  Firazyr®  is delivered by subcutaneous injection and is approved for self-administration.
  • Ruconest® brand of C1-inhibitor [recombinant]
    Ruconest® has been FDA-approved for treating acute HAE attacks in adults and adolescents. RUCONEST is delivered intravenously and is approved for self-administration.

Hereditary Type II (HAE-II)

Description

Represents approximately 15 to 20% of HAE cases. Similar description to Type I, but C1 inhibitor does not function properly.

Common Symptoms 1

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.

Complement System

C1 inhibitor level may be normal or elevated, but it is dysfunctional. C1, C3 and C1q are normal, but C4 is almost always low.

Possible Treatments

Anabolic steroids (also known as androgens) such as danazol, oxandrolone and stanozolol have, historically, been the most commonly prescribed preventative HAE therapies. While anabolic steroids have been shown to be useful, they are not well-tolerated by many women, directly linked to liver toxicity and can cause an increase in cholesterol levels. In addition, these drugs should not be used to treat children, some of whom, tragically, are severely affected and suffer frequent attacks. Research indicates that patients treated with anabolic steroids can experience breakthrough laryngeal or abdominal attacks that require hospitalization.

Five new treatments are now FDA approved for treating HAE, including 2 C1 inhibitor products, a kalikrein inhibitor and a bradykinin receptor antagonists. Patients and their physicians now have options for developing a non-steroidal HAE treatment plan tailored to meet each patient’s unique needs.

  • Cinryze ™ brand of C1-inhibitor
    The Cinryze ™ brand of C1-inhibitor concentrate has been FDA-approved for preventing HAE attacks.
Cinryze ™ is delivered intravenously and is approved for self-administration.
  • Berinert® brand of C1-inhibitor
    The Berinert® brand of C1-inhibitor concentrate has been FDA-approved for treating acute facial, abdominal and laryngeal HAE attacks. Berinert® is delivered intravenously and is approved for self-administration.
  • Kalbitor® brand of plasma kalikrein inhibitor
    Kalbitor® brand of plasma kalikrein inhibitor has been FDA-approved to treat acute HAE attacks in patients 12 years of age and older. Kalbitor® is delivered through subcutaneous injections.
  • Firazyr® brand of bradykinin receptor
    Firazyr® brand of bradykinin receptor antagonist has been FDA-approved for treating acute HAE attacks in patients 18 years of age and older.  Firazyr®  is delivered by subcutaneous injection and is approved for self-administration.
  • Ruconest® brand of C1-inhibitor [recombinant]
    Ruconest® has been FDA-approved for treating acute HAE attacks in adults and adolescents. RUCONEST is delivered intravenously and is approved for self-administration.

Hereditary with Normal C1 Inhibitor (formerly known as ‘HAE Type III’)

Description

Number of cases unknown.  Family history must be present.  C1 inhibitor levels and function are normal.    A minority of cases associated with mutations in the coagulation factor XII gene, however, this mutation has not been shown to be the cause of the condition.  Predominantly reported in women, but affected male family members have also been identified.  Swelling sometimes associated with pregnancy and the use of estrogen-containing oral contraceptives. Does not respond to antihistamines and corticosteroids.

Common Symptoms 1

Similar to HAE caused by C1 Inhibitor deficiency: 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.

Complement System

Normal.

Possible Treatments

Research continues.   Published cases document response to FDA-approved HAE therapies.

Acquired Type I (AAE-I)

AAE-I & II are considered very rare; there are few reported cases.

Description

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.

Common Symptoms 1

Similar to HAE: 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.

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.

Complement System

Low level of C1 inhibitor and C4. C1q is usually reduced, but not always.

Treatments

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.

Description

Autoantibodies are present and destroy C1 inhibitor function. There is no apparent underlying disorder.

Common Symptoms 1

Similar to HAE: 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.

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.

Complement System

Same as AAE-I.  A lab test for autoantibodies may be appropriate.

Possible Treatments

Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid for possible prevention. It is possible that immunosuppressive therapy might be successful.

Idiopathic

Description

Swelling and/or hives persist beyond 6 weeks. Thyroid dysfunction should be considered.

Common Symptoms 1

Swelling may occur just about anywhere and may be accompanied by urticaria (hives).

Complement System

Normal

Possible Treatment

Primarily antihistamines. DHEA.  1-thyroxine for thyroid dysfunction.  Prednisone therapy.

Nonhistaminergic (INAE)

May occur in about 1 out of 20 cases of angioedema

Description

Angioedema without urticaria (usually not responsive to H1 antihistamine blockers). Parasites, infections and autoimmune diseases are not present.

Common Symptoms 1

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.

Complement System

Normal

Possible Treatment

Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid.

Allergic

This is the most common form of angioedema.

Description

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.

Common Symptoms 1

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.

Complement System

Normal

Possible Treatment

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.

Description

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.

Common Symptoms 1

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

Complement System

Normal

Possible Treatment

Suspension or change of medication.

NOTES: 1. The presence of urticaria associated with angioedema usually suggests a diagnosis other than HAE or AAE.

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 Types 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.

DISCLAIMER: The information, including opinions and recommendations, contained in this document is for educational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. No one should act upon any information provided in this document without first seeking medical advice from a qualified, licensed medical doctor. Information derived from the internet, no matter how accurate or relevant is no substitute for competent medical care.

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