Categories: NewsAngioedema is the medical term for swelling of the skin and soft tissue. This can happen for different reasons such as from an insect sting, medication, or food allergy. One rare cause of angioedema is an inherited condition called Hereditary Angioedema (HAE).
Hereditary Angioedema (HAE) is a very rare and potentially life-threatening genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE symptoms include episodes of edema (swelling) in various body parts including the hands, feet, face and airway. This swelling can also occur in the wall of the intestine leading to bouts of excruciating abdominal pain, nausea and vomiting. Airway swelling is particularly dangerous and can lead to death. HAE patients have a defect in the gene that controls a blood protein called C1 Inhibitor. The genetic defect results in production of either inadequate or non-functioning C1-Inhibitor protein. Normal C1-Inhibitor helps to regulate the complex biochemical interactions of blood-based systems involved in disease fighting, inflammatory response and coagulation. Because defective C1-Inhibitor does not adequately perform its regulatory function, a biochemical imbalance can occur and produce unwanted peptides that induce the capillaries to release fluids into surrounding tissue, thereby causing edema. HAE is called hereditary because the genetic defect is passed on in families. A child has a 50 percent chance of inheriting this disease if one of his or her parents has it. The absence of family history does not rule out the HAE diagnosis, however. Scientists report that as many as 20 percent of HAE cases result from patients who had a spontaneous mutation of the C1-Inhibitor gene at conception. These patients can pass the defective gene to their offspring. Because the disease is very rare, it is not uncommon for patients to remain undiagnosed for many years. In some patients with frequent and severe abdominal pain, it has been inappropriately diagnosed as psychosomatic or unnecessary exploratory surgery has been performed on patients because abdominal HAE attacks mimic a surgical abdomen.
How HAE Is Diagnosed
Most cases of angioedema turn out to not be HAE, because most swelling attacks are typically allergic reactions, or swellings caused by something other than C1-inhibitor deficiency. Laboratory analysis of blood samples or genetic testing is required to establish the HAE diagnosis. Routine blood tests of the complement system are often performed first. If these are abnormal, there are two specific blood tests that confirm HAE: a) C1-inhibitor quantitative and b) C1-inhibitor functional assay.
The most common form of the disease–Type I–is characterized by low quantitative levels of C1-inhibitor and affects about 85% of patients. Type II HAE affects the other 15% of patients who have normal or elevated levels of C1-inhibitor, but the protein does not function properly. Several investigators have noted a familial (and therefore inherited) angioedema in patients with normal levels of C1-inhibitor. Often found under the designation of “HAE Type III”, this form of angioedema is yet to be fully understood. In women, swellings have been correlated with pregnancy or the use of oral contraceptives; however, affected male family members have also been identified. Some scientists believe that a mutation in the gene for human coagulation Factor XII may be a potential cause of swelling in these patients with familial estrogen-exacerbated angioedema.
Treatments for HAE: FDA-approved medication for treating the symptoms of HAE became available in the US for the first time in late 2008. This has been a major breakthrough for patients in their quality of life and controlling the disease.
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.
Four new treatments are now FDA approved for treating HAE, including two 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 home infusion.
- Berinert® brand of C1-inhibitor. The Berinert® brand of C1-inhibitor concentrate has been FDA-approved for treating acute facial and abdominal HAE attacks. Berinert® is delivered intravenously.
- 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.
The providers at OIAA are experts at treating Hereditary Angioedema and currently see numerous patients with this rare condition. We offer a full range of treatment options to help control this serious disease and allow patients to live as symptom free as possible. If you or someone you know has this condition, call the clinic to make an appointment for an evaluation.
