Angioedema (Quincke's edema) and hereditary angioedema

“I’ve got Quincke's edema again today, so my lips are swollen.”

You may encounter blog entries like this mentioning Quincke's edema, but what sort of condition is Quincke's edema?  Even if you want to understand it, you may in fact not understand it.

Quincke's edema is another name for angioedema (edema of sudden onset in parts of the body).  If an individual’s eyelids, lips, or skin suddenly swell up, that person may be diagnosed with Quincke's edema. Having been told that there is nothing that can be done since the cause of that edema is unknown, an affected person may leave things at that.  However, this angioedema is known to have various symptoms and manifestations.  Here, those symptoms are described and compared to those of other forms of angioedema (Quincke's edema) in order to better explain hereditary angioedema (HAE).

Types of angioedema (Quincke's edema) shown in the chart below.
Idiopathic angioedema is said to account for about half of the cases of angioedema and it is said to occur frequently.  In fact, this type of angioedema includes several forms with causes that cannot be identified, no matter how detailed the patient’s medical records or how many blood tests are performed.
Known forms of idiopathic angioedema, as indicated by their cause, include allergic angioedema caused by an allergic reaction to food or medication; angioedema triggered by a physical stimulus such as heat, cold, vibrations, trauma, emotional stress, or sunlight; and angioedema developing in 0.1-0.5% of patients taking ACE inhibitors (which are drugs used to treat hypertension).
HAE is a type of angioedema caused by a deficiency of C1 inhibitor protein or dysfunction of the C1 inhibitor gene (a rare genetic defect in coagulation factor XII).
Thus, angioedema can be largely divided into 2 types, angioedema that is due to causes other than genetic mutations and HAE that is due to genetic mutations.

Characteristics of angioedema (Quincke's edema) are shown in the chart.  Angioedema differs from edema associated with heart disease, liver disease, or kidney disease.  Edema develops fully within several hours and disappears in about 3 days.  Symptoms are localized and asymmetrical and do not include itching.  Pushing on the skin with a finger does not leave an indentation (a “pit”).

The major differences between angioedema due to causes other than genetic mutations and HAE due to genetic mutations are (in addition to the characteristics in the chart) recurring edema and the likely presence of HAE if the same symptoms are noted in family members.  However, there are instances where angioedema is not noted in family members even though they have HAE.

 

Laboratory testing at a hospital is a useful way to determine whether angioedema is HAE or some other form.  With angioedema associated with urticaria, total IgE levels in serum and allergen-specific IgE levels are measured and an attempt is made to identify the allergen.  With HAE, complement tests are performed in addition to routine blood tests, facilitating a diagnosis of HAE.  If complement C4 and C1 inhibitor activity is measured, as shown in the chart, then differentiation is possible.  Testing should be undergone when edema has developed.
A characteristic of HAE is that genetic diagnosis is required to make a definitive diagnosis.  That said, type III HAE is rare, and this type has yet to be reported in Japan.

Angioedema with a known cause is treatable.  Edema triggered by an allergic reaction or physical stimulus can also be prevented by identifying the cause and avoiding it.  The same is true for edema triggered by ACE inhibitors.  HAE is due to a deficiency or dysfunction of C1 inhibitor in the blood, so acute episodes can be treated effectively with a C1 inhibitor.
A C1 inhibitor is a pharmaceutical prepared by purifying C1 inhibitor from blood and concentrating it.  If injected intravenously, a C1 inhibitor immediately compensates for insufficient C1 inhibitor, so this pharmaceutical can alleviate episodes of acute edema.

HAE is a Complement Deficiency as falls under Primary Immunodeficiency Syndromes that have been nationally designated as diseases with an unknown cause, no established treatment, and a considerable risk of sequelae (“Specified Diseases”).  Thus, affected individuals can use the system of subsidized medical expenses for specified diseases.  Specific procedures to apply for coverage differ depending on the prefecture or city, so potential applicants should ask their physician or inquire at the public health center in the area where they live.