Learning that we are neither freaks nor hypochondriacs is a great relief for us. A new era has begun in my life. I am simply overwhelmed by the opportunity to move around almost without any restrictions and there is no need to apologize. Our current safety had to be fought dearly.”

(Excerpts from patient diaries)

information on HAE for patients

FAQ on HAE

Why is this disease called ‘hereditary’?
This is a genetic disorder. If any of the parents has HAE, the offspring (regardless of gender) stands a 50-per-cent chance to inherit the disease.

What causes HAE?
The most common underlying cause is deficiency of the C1-inhibitor (C1-INH) protein, which is involved in the regulation of a primeval system of host defenses, i.e. the complement system. Additionally, it controls the functioning of several other (blood coagulation, plasma kinin, fibrinolytic) systems present in the blood. Under certain circumstances (e.g. trauma, infection, stress, etc.), the autosomal dominant trait of C1-inhibitor deficiency leads to the formation of bradykinin, which increases the permeability of blood vessels and thereby causes edema formation (‘soft tissue swelling’). Less frequently, HAE is not related to the deficiency of the C1-INH protein, but to other etiological factors, which have not yet been clarified accurately. In contrast to Type II HAE, this form of HAE – often referred to as Type III HAE – afflicts female members of families, primarily. It is linked to the fluctuations of female sex hormone levels (e.g. during sexual maturation, pregnancy, oral contraceptive use, etc).

What can precipitate a HAE attack?
Attacks can ensue without any apparent cause. In the majority of cases, however, there are specific triggering factors, such as mental stress, minor injury, dental treatment, and various infections. Patients recall edematous episodes occurring after typing, hammering, or shaving. Menstruation and pregnancy can also influence the evolution of attacks. A proportion of women of reproductive age experience an increase in the frequency of attacks during menses. During pregnancy, the incidence of HAE attacks can either increase or decrease. According to experience, the use of hormonal contraceptives increases attack frequency.

At what age do HAE symptoms occur for the first time?
Although the onset of the disease usually occurs during childhood, some patients have experienced an edematous attack as late as at the age of fifty. In general, subjective symptoms occur more frequently during adolescence and the initial period of adulthood.

How long do the attacks last?
The edema, which ensues during the attack, can persist for 2 to 3 days, or even for a week.

How often do the attacks recur?
Attack frequency is variable; some patients are afflicted by frequent recurrences (e.g. every week), whereas others experience only a couple of episodes per year.

What are the dangers of these attacks?
HAE attacks are especially dangerous when edema formation involves the airways. Laryngeal edema of sudden onset can prove life-threatening and cause suffocation, if untreated.
Edema of the gut can mimic life threatening abdominal emergencies (e.g. appendicitis, ileus). These misleading symptoms and signs can lead to unjustified surgical intervention.

What treatments are available for HAE?
Two treatment modalities are available currently:

  1. Prevention  in the form of either long- or short-term prophylaxis
  2. Emergency management of attacks

What does long-term prophylaxis mean?
Uninterrupted medication intended to prevent the occurrence of attacks.
This modality is not necessary for all HAE patients. Long-term prophylaxis is warranted if the attacks commonly involve the airways (danger of life threatening complications!), occur several times per month, or interfere with attending to the tasks of everyday life.

What drugs are used for long-term prophylaxis?
Danazol (marketed as Danoval® in Hungary) is effective for this purpose. This agent is an attenuated androgen (male sex hormone), which stimulates the production of C1-inhibitor by the liver. An alternative drug is tranexamic acid, which acts on the coagulation system (Exacyl® tablets). Similar to all medicines, both Danoval® and Exacyl® can cause adverse effects. These can be avoided by administering the lowest effective dose and implementing regular healthcare monitoring.

What constitutes short-term prophylaxis?
Short-term prophylaxis may prove necessary before elective surgery, dental treatment, or gastrointestinal endoscopy, for example. Before these events, the patient ingests a larger dose of the drugs prescribed for and regularly used in HAE, or receives C1-inhibitor concentrate.

Can HAE attacks be managed successfully?
Yes, by administering the missing or deficient protein – C1-inhibitor –by intravenous injection. This drug prevents progression of disease manifestations, which is followed by the rapid resolution of life-threatening laryngeal edema and thereby the reduction of attack duration. Several types of C1-INH-containing medicinal products are available currently. Berinert P® (CSL Behring GmbH, www.cslbehring.com) and Cetor® (Sanquin, www.sanquin.nl.) are marketed in Europe, whereas Cinryze® (ViroPharma Inc., www.viropharma.com) is available in the USA (for the time being) as a preventive remedy. All three preparations are manufactured from human blood through pasteurization. In Europe, Ruconest® – an innovative C1-INH product manufactured by recombinant technology (Pharming Group NV, www.pharming.com and SOBI AB, www.sobi.com) – has become available recently; the actions of this product are similar to those of blood-derived preparations. In Europe, additional options for the drug therapy of HAE attacks also include Firazyr® (Shire, www.shire.com). The structure of this synthetic peptide is very similar to that of bradykinin and therefore, it can bind to and then, block bradykinin receptors. Firazyr® is available as a subcutaneous injection for adult HAE patients. Kalbitor® is a medicinal product developed by Dyax Co. (www.kalbitor.com) and as yet, it is available only in the USA. This preparation is also injected subcutaneously; it acts by preventing the accumulation of bradykinin.

Additionally, fresh frozen plasma may be administered when these state-of-the-art preparations are not available.

Conventional remedies for angioedema (such as epinephrine, antihistamines, and corticosteroids) are useless (ineffective) in acute attacks of HAE.

What to do if the symptoms of incipient laryngeal edema occur?
Early symptoms of laryngeal edema include globus sensation in the throat, difficulty in swallowing, alteration of the patient’s voice (pitch and/or tone), and hoarseness. When these symptoms occur, medical help should be sought immediately, because dyspnea and suffocation can ensue rapidly. The administration of special medicinal products is necessary to reverse this condition (see the section “Can HAE attacks be managed successfully?”).

How can HAE be diagnosed?
Among others, HAE should be considered if the characteristic signs and symptoms such as painless subcutaneous swelling, edema (of the extremities, face, torso, genitals), paroxysms of abdominal pain, laryngeal edema recur or afflict several members of the family.
The diagnosis is verified by special blood tests.
Link
 // accessibility of the Complement Laboratory

Patients’ organization
HAE patients have established their self-help groups several years earlier. Acting as an organization facilitates claiming due rights (e.g. to the continuous availability of necessary medication free of charge or with reimbursement). The international organization, HAEI (international patient organization for C1-inhibitor deficiencies, http://www.haei.org) unites the members of national organizations since 2004.

The Hungarian Association of HAE Patients was established in the spring of 2005. [link—information on the association]

HAE patients’ club

Since 1996, the annual meeting of the HAE patients’ club has been organized in the autumn. This event offers an opportunity for patients to meet each other, as well as with professionals involved in their management (e.g. physicians, laboratory specialists, clinical assistants, etc.). The annual conference is a useful source of information for all patients, new and experienced alike. Doctors and researchers lecture on the latest accomplishments of scientific research, as well as on the objectives of ongoing studies. Furthermore, these events create a forum for engaging in an amicable chat, as well as for exchanging experiences with other patients.
// photos of club events

 

What to do, if...

...you experience an edematous attack in Hungary?
In Hungary, every registered HAE patient is entitled to 2 vials of life-saving injection (Berinert P®, C1-inhibitor) to be kept ready at home for the alleviation of suddenly occurring edematous attacks. This preparation must be administered by intravenous injection, which is performed by the general practitioner or other physician on duty. Non-stop (round-the-clock) emergency care is provided by the following institutions: adult HAE patients should visit the 3rd Department of Internal Medicine of the Semmelweis University (Budapest) [link – address], whereas pediatric patients (under 18 years of age) should seek help from the ‘Madarász street’ Pediatric Hospital of the Budapest Municipal Health Authority [link – address]. The life-saving injection is constantly available in these two hospitals. In the country, the Clinical Pharmacy of the Debrecen University keeps two vials on stock for emergencies.

...you experience an edematous attack abroad?

Every HAE patient, registered with the Hungarian HAE Center is supplied with a multilingual ’Patient Passport’ [PICTURE], which provides a concise description of the essentials of the disorder as well as of emergency treatment. This is supplemented by a Patient Diary, intended for recording symptoms, as well as the treatments received.

 
HAE Patient Passport

  HAE Patient Diary

 
HAE Patient Diary inside

If you travel abroad, you are free to carry your vial of C1-inhibitor with yourself. However, a permission to import drugs may be required in certain countries – this should be ascertained in advance. It is expedient to seek advice from the embassy of the target country. If necessary, foreign medical professionals specializing in the care of HAE patients can be contacted. [link]

Self-help options for HAE patients

Be on the alert for changes in your condition and avoid factors known to trigger edematous attacks. This is made easier by keeping your HAE Patient Diary up to date and taking it along with you to control visits.

Abide by the instructions of your doctor. If you need to take concomitant medications (e.g. antihypertensives, an oral contraceptive, etc.), consult your doctor first.

Do not skip attending the annual control visit at the HAE Center.

Always keep ready at least 2 vials of C1-inhibitor concentrate (Berinert P injection) for the sake of your own safety.

If you are planning to have a child, it is advisable to consult your doctor in advance. Although pregnancy is not a disease, it may require making changes to the current therapeutic regimen for HAE.

Neonates born to parents with HAE should be checked for inherited HAE between the age of 6 months and one year. This can be arranged with the HAE Center.

Useful links

http://www.hano.sokoldal.hu
http://www.angioedemaereditario.org/angioedema%20Europe%20GB.htm http://www.haei.org/inforequest.php?language=en&section=7