angioedema (HAE) is a rare, potentially fatal genetic disorder characterized
clinically by swelling of the extremities, face, trunk, abdominal
viscera, and upper airway (1).
Abdominal attacks can cause severe pain, and mortality from oedema
induced airway closure has been reported to be as high as 30% in
affected patients. Certain procedures, such as dental work are known
to trigger attacks and while patients in other stressful situations
may suffer more attacks there are no definite triggers and attacks
can come on at any time.
urticaria (itching) and angioedema are fairly common problems that
affect nearly 20% of the population, HAE is a rare disease that
accounts for about 2% of clinical angioedema cases (2). The vast majority of patients who experience episodic swelling
will be diagnosed with histamine mediated allergic angioedema. Epidemiological
studies estimate the incidence of HAE at 1/10,000 to 1/50,000 individuals.
This means that there may be up to 1850 patients in the UK . In contrast
to allergic angioedema, HAE-related swelling is caused by an autosomal
dominant genetic defect that results in reduced
levels of or malfunctioning plasma protein C1
. Because defective C1-inhibitor does not adequately perform
its normal regulatory function, an imbalance can occur and produce
Bradykinin, a small protein that causes the capillaries to release
fluids into surrounding tissues, thereby causing oedema. A child
has a 50 percent chance of inheriting this disease if a parent possesses
the genetic defect, however, the absence of family history does
not rule out the HAE diagnosis. Scientists report that as many as
one quarter of newly diagnosed HAE cases result from new
mutations of the C1-inhibitor gene at conception(4) .
HAE is rare and the symptoms are varied, it is sometimes difficult
for doctors to make the right diagnosis. Some patients have undergone
multiple operations because their symptoms appear to be intestinal
obstruction. Patients often suffer multiple attacks before being
correctly referred to a Clinical Immunologist who will understand
your condition and will be able to provide the
Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema:
the clinical syndrome and its management. Ann Intern Med. 1976 May;84(5):580-93
et. al. Hereditary and acquired angioedema: problems and progress:
proceedings of the third C1 esterase inhibitor deficiency workshop
and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S55
E et. al. Frequent de novo mutations and exon deletions in the C1inhibitor
gene of patients with angioedema. J Allergy Clin Immunol. 2000 Dec;106(6):1147-54.
is no ‘cure’ for HAE, however, there are drugs that are effective
treatments for acute attacks and we will describe them below. If
you are having more frequent attacks, your doctor may suggest that
you take a medicine regularly to try and reduce the number of attacks
you are having.
are two drugs licensed for use in the UK for treating acute attacks
of HAE. Berinert ® a C1 inhibitor concentrate and Firazyr ® ,a new
drug called Icatibant.
is a plasma-derived intravenous therapy which has been used in the
treatment and prevention of acute HAE. Berinert® (CSL Behring) is
a freeze-dried C1- inhibitor concentrate and is obtained by separating
the protein from lots of blood donations, which is then purified
(Firazyr®- Jerini/Shire) is a first in class Bradykinin B2 receptor
blocker. It is a synthetic protein which is given by a subcutaneous
injection. It works by preventing Bradykinin from causing the dilation
of blood vessels and therefore stops the leakage of fluid which
leads to oedema. Firazyr is licensed in all countries in Europe.
types of drugs are used to reduce the number of attacks that a patient
may suffer; you may still get an acute attack while taking these
so you should always be prepared to seek treatment for an acute
Androgens (e.g. Danazol, Stanozolol)
can the PiA do for me?
Primary Immunodeficiency Association (PiA) aims to improve the quality
of life of all people with primary immunodeficiencies. For the HAE
sufferer we can provide a wide variety of services and resources.
These would include :
Publications such as the 'booklet' Understanding
Hereditary Angioedema and Acquired C1-Inhibitor Deficiency'.
PiA information packs for the lay person and the
Regional Days at different locations around the
U.K. where members can meet up with others in similar situations.
Assistance with benefits. To download our Guide
to Claiming DLA for persons with HAE , click....HERE
Condition Specific Contact : speak in confidence
to another H.A.E. sufferer for advice and sharing of experiences
For more information on any of the above topics please contact the
PiA through the home
What is the Consensus Document?
The Consensus Document
represents the outcome of discussion and research on the best practice
for the diagnosis, treatment and management of C1-inhibitor deficiency.
It’s adoption will mean that there is a standard set out for
patients that will ensure uniformity of treatment (hopefully) throughout