Angioedema Table

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.

Four 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 16 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.

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

Common Symptoms ¹
Same as HAE-I.

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
Same as HAE-1

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.

Complement System
Normal.

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

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. 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.

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
Same as AAE-I.

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.

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.

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.

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.

(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.