Hereditary Angioedema : New Therapies for Rare but Potentially Fatal Disease

Health Professional, Medical Reviewer

"Doc, I've had swelling off and on for more than 15 years. The medications my doctor has been giving me don't seem to work as well. It seems like when I get upset or stressed, my feet or hands start to swell. Sometimes my face swells. I have taken many courses of steroids and Benadryl but it seems to be getting worse".

The above comments were made by a 32-year-old female patient that came to my office for an initial evaluation in January of last year. She has a rare disease that is associated with recurrent swelling of the hands, feet, arms, legs, face, genitalia and throat. The disease is hereditary (other family members usually have it), and frequently the cause of unexplained bouts of abdominal pain that may be extremely severe.

Weeks ago (Feb 2011) she had a sudden severe episode of throat swelling which required intubation (a breathing tube placed into the throat and lung) and a seven day hospital intensive care unit visit.

Hereditary Angioedema (HAE) was elegantly reviewed by Dr. Busse about four years ago. In 2007 when Dr. Busse posted the article, treatment for HAE was very limited. In the last three years the FDA (Food and Drug Administration) has approved three medications for the treatment of this rare, but potentially life-threatening disorder.

More about Hereditary AngioedemaHAE occurs in about one in 50,000 people worldwide, and has no racial or gender preference. It has been highly researched for several decades. The majority of patients with HAE have a low amounts or low functioning levels of a protein in the blood called** C-1 esterase**. This protein has many roles in biochemical processes that keep the human body healthy, such as blood clotting/healing, immune defense and blood flow. Low levels of C-1 esterase (or poor function of this protein) may cause another substance naturally found in our body,** bradykinin**, to reach dangerously high levels. It is believed that high levels of the bradykinin causes the swelling associated with HAE.

Attacks of swelling are typically delayed until puberty but sometimes occur for the first time, much later in life. Many people with HAE have between two to five episodes per month.   The attacks are often highly variable in severity and may be preceded by warning signs, such as tingling, nausea, headache or fatigue. The attacks generally peak at 24 hours and may last two to five days.

Severe episodes of unexplained abdominal pain have resulted in unnecessary exploratory surgery, thinking that the patient had appendicitis or some other surgical emergency.

Common trigger factors include trauma, emotional or physical stress, surgical or dental procedures, certain drugs (birth control pills, estrogen and certain type of blood pressure meds). But attacks are often unpredictable (with no apparent trigger).

As Dr. Busse noted previously, the scariest aspect of HAE is the potential for throat swelling which may close the throat completely. Almost 50% of people with HAE will experience throat swelling at some point in their life. Fatalities have occurred because of severe throat swelling and asphyxiation (severe deficiency of oxygen supply).

How is Hereditary Angioedema Diagnosed?

HAE is not difficult to diagnose once the suspicion surfaces. Blood tests are available to confirm the diagnosis and identify the subtype of HAE (there are three subtypes). If you think you may have HAE talk to your doctor.  You may need to generate the suspicion first.

Once the diagnosis is confirmed a decision on how to proceed with treatment is made.

Treatment is categorized into:

-Management of an acute attack

-Short term Prevention  (prep for surgical or dental procedure)

-Long term Prevention

The new therapeutic agents are:** Cinryze** (C-1 esterase inhibitor - replacement derived from human plasma donors) Indicated for prevention of attacks in teenagers and adults with HAE.

Berinert (C-1 esterase inhibitor- also human derived) Indicated for on-demand treatment of acute abdominal or facial attacks of HAE in adolescents and adults.

Ellecantide (Kalbitor- a non-blood product, blocks the activity of a protein that increases bradykinin levels) Indicated for use in those age 16 or older who are having an attack of HAE.

In my next posting I will discuss treatment therapies and some associated pitfalls. I will also provide you with a few other diagnostic "pearls" and some other resources for information on HAE.

So stay tuned

By the way, my patient is doing very well and taking further steps to prevent future attacks of HAE.