The Hungarian HAE experience

doi:10.1016/j.transci.2003.08.003

Transfusion and Apheresis Science

Volume 29, Issue 3, December 2003, Pages 229-233

https://doi.org/10.1016/j.transci.2003.08.003 Get rights and content

Abstract

The Hungarian HAE Center was established in 1994, in Budapest. Assignments of the Center include diagnostic work-up of patients with angioedema; developing national guidelines for the recognition, treatment of patients with HAE; maintaining the registry, patient education, supply patients with info-card and C1-INH concentrate, follow-up of patients, telephone ‘hot-line’ service, under- and postgraduate education as well as pursues scientific activities. Established in 1996, the Hungarian HAE Patients’ Association a foundation to support HAE patients; and a Hungarian HAE website. Hungarian HAE Working Group is the main organizer of the European C1-INH Deficiency Workshops to be held at two-year intervals from 1999.

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Acknowledgements

The assistance from the members of the Hungarian HAE Working Group is highly appreciated (George Füst, István Nagy, George Harmat, Attila Tordai, Lajos Kalmár, Béla Fekete, László Jakab, Beáta Visy, Tı́mea Kollár, Éva Németh, Gábor Széplaki, Judit Bali, Nagyné Vers Mária, Dóczi Andrásné).

References (13)

H. Farkas et al.
Acquired angioedema associated with chronic hepatitis C
J Allergy Clin Immun
(1999)
H. Farkas et al.
Association of celiac disease and hereditary angioneurotic edema
Am. J. Gastroenterol.
(2002)
H. Farkas et al.
Esophageal leiomyoma incidentally recognized during acut oedematosus attack of HAE
J Allergy Clin Immunol
(2001)
H. Farkas et al.
Danazol therapy for hereditary angio-oedema in children
Lancet
(1999)
H. Farkas et al.
Eradication of Helicobacter pylori and improvement of hereditary angioneurotic oedema
Lancet
(2001)
H. Farkas et al.
Angioedema due to acquired C1-esterase inhibitor deficiency in a patient with Helicobacter pylori infection
Z. Gastroenterol.
(1999)

There are more references available in the full text version of this article.

Cited by (16)

A novel prophylaxis with C1-inhibitor concentrate in hereditary angioedema during erythema marginatum
2017, Immunology Letters
Citation Excerpt :
Our aim was to introduce a safe and effective, novel prophylactic treatment during EM in patients whose HAE attacks are preceded by EM in a considerable proportion of the cases. We conducted our prospective study at the Hungarian Angioedema Centre (Budapest, Hungary), in 173 C1-INH-HAE patients (77 males and 96 females) diagnosed and followed up at the Centre in compliance with the international criteria [11]. The laboratory findings and the patients’ clinical parameters – including the number of prodromal symptoms and HAE attacks – are recorded in the Hungarian HAE Registry.
Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. The characteristic episodes of subcutaneous/submucosal edema formation may be preceded by erythema marginatum (EM) – the occurrence of a ‘map-like’ pattern on the skin. EM can occur as an isolated finding or accompanying a hereditary angiooedema (HAE) attack as well. Nevertheless, it is unknown whether a HAE attack can be prevented by the proper prophylactic treatment during EM.
Our aim was to assess the prevalence of EM in the Hungarian C1-INH-HAE population and to introduce a safe and effective novel prophylactic treatment during EM in patients who’s HAE attacks are preceded by EM in a considerable proportion of the cases.
Based on the data of the Hungarian HAE Registry, 49 among 173 C1-INH-HAE patients (28.3%) from 32 families had EM in their life. According to the clinical data and the patient’s HAE diaries, two patients (Patient #1, Patient #2) were selected who frequently had EM as a prodromal symptom. Both patients were instructed to administer plasma-derived C1-inhibitor concentrate (pdC1-INH) as soon as possible after the onset of EM, in order to prevent the development of HAE attack. Interestingly, HAE attacks never developed if pdC1-INH was administered within 6 h from the occurrence of EM in both patients. In contrast, without pdC1-INH treatment, in Patient 1 and Patient 2, 97.0% and 44.3% of the EM were followed by a HAE attack, respectively (p < 0.0001, Fisher’s exact test).
As a novel prophylaxis in C1-INH-HAE, intravenous administration of pdC1-INH concentrate during EM might be an effective, individual therapeutic strategy in those patients who’s HAE attacks are often preceded by EM. Besides it can improve the quality of life of these selected patients, pdC1-INH administration during EM provides the lowest effective dose for the prophylaxis of their HAE attacks.
Lack of increased prevalence of immunoregulatory disorders in hereditary angioedema due to C1-inhibitor deficiency
2011, Clinical Immunology
Citation Excerpt :
The impact of such conditions on the natural course of HAE-C1-INH was studied and the rationale for using immunoserology tests to screen HAE-C1-INH patients for such immunoregulatory disorders was evaluated in addition. The study was implemented in the Hungarian Angioedema Center responsible for the diagnosis, management, and long-term follow-up (at 6-month to one-year intervals) of the 130 patients enrolled into this study (Table 1) [20]. Clinical and laboratory data of this population are recorded in the National HAE Registry.
Hereditary angioedema due to deficiency of C1-INH (HAE-C1-INH) is associated with enhanced consumption of the early complement components, which may predispose for autoimmune disease.
We assessed the prevalence of such disorders among HAE- C1-INH patients and their impact on the natural course of HAE-C1-INH.
Clinical data and immunoserological parameters of 130 HAE-C1-INH and 174 non-C1-INH-deficient patients with angioedema were analyzed.
In our study, the incidence of immunoregulatory disorders was 11.5% in the population of HAE-C1-INH patients and 5.2% among non-C1-INH-deficient controls with angioedema. Immunoserology screening revealed a greater prevalence of anticardiolipin IgM (p = 0.0118) among HAE-C1-INH patients, than in those with non-C1-INH-deficient angioedema.
We did not find higher prevalence of immunoregulatory disorders among our HAE-C1-INH patients. However, in patients with confirmed immunoregulatory disorders, the latter influenced both the severity of HAE-C1-INH and the effectiveness of its long-term management. Appropriate management of the immunoregulatory disease thus identified improves the symptoms of HAE-C1-INH.
Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients?
2010, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
Levels of C4 are low in patients with HAE secondary to defective control of the classical pathway of the complement cascade. In a Hungarian population,8 borderline normal C4 levels were detected in only 4% of newly diagnosed patients with HAE. Another study7 showed that C4 levels are normal between attacks in 2% of patients.
Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor (C1 INH) protein or function. Guidelines do not exist regarding diagnostic criteria or routine testing of family members of patients with HAE. Laboratory data for diagnosis include complement factor 4 level; C1 INH antigenic protein level, which is reduced in approximately 85% of patients with HAE; and C1 INH functional assay, which is considered an unreliable test in the United States secondary to inconsistent standardization of assays.
To assess the shortcomings of diagnosing HAE and to determine whether family members of patients with HAE are being adequately screened.
The top physician prescribers of danazol in the United States were screened via an Internet questionnaire focusing on the diagnosis and current management of HAE. To assess the patient perspective on HAE, affected individuals in the United States, the United Kingdom, France, Germany, and the Netherlands participated in the Web-based International Survey of Patient Experience of Hereditary Angioedema.
All 80 physicians who completed the survey were allergist or immunologists with a mean of 7 patients with C1 INH deficiency in their practices. Almost 84% of physician respondents used C1 INH level and function for diagnosis, and 63.8% used complement factor 4 levels. A total of 313 patients with HAE completed the survey. Respondents noted that only 48% of immediate family members and 26% of extended family members had been tested.
Guidelines could potentially alleviate delays in diagnosis and incorrect diagnoses and could lead to adequate screening of family members.
Hereditary angiodema: A current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema
2008, Annals of Allergy, Asthma and Immunology
We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004.
To ensure that this consensus remains current.
In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted.
This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings.
There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.
Hereditary angioedema: A decade of human C1-inhibitor concentrate therapy
2007, Journal of Allergy and Clinical Immunology
Citation Excerpt :
Relevant data of 112 patients treated at the center18 since 1996 were analyzed (Table I).
C1-inhibitor (C1-INH) is a serine protease inhibitor regulating the complement, kinin-kallikrein, coagulation, and fibrinolytic systems. Hereditary angioedema (HAE) is caused by an inherited deficiency of C1-INH characterized by sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. The optional therapy for the acute management of HAE is administration of human C1-INH (hC1-INH) concentrate. However, hC1-INH is not available in many countries, in which case fresh frozen plasma is an alternative.
To summarize our experience with hC1-INH concentrate in patients with HAE.
Clinical and laboratory information on the effectiveness and safety of hC1-INH administered to relieve 468 acute edematous attacks in 61 patients with HAE was analyzed.
Severe abdominal or subcutaneous attacks and laryngeal edema were consistently relieved by the administration of 500 U hC1-INH concentrate. Symptoms improved within 15 to 60 minutes of administration. Progression of the attacks was never observed, and there were no recurrent attacks within 72 hours. hC1-INH concentrate requirements did not change after repeated use. hC1-INH concentrate proved effective in the management of 94 attacks in 22 children and 6 attacks in 4 pregnant women. Adverse reactions, viral infections, and antibody formation against the purified protein did not occur.
The administration of hC1-INH concentrate in HAE is highly effective and safe for the treatment of acute attacks and short-term prophylaxis and in pediatric patients and pregnant women.
Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis.
Adverse effects of danazol prophylaxis on the lipid profiles of patients with hereditary angioedema
2005, Journal of Allergy and Clinical Immunology
Citation Excerpt :
All 64 adult patients with HAE (37 women and 27 men; age, 18-71 years) registered at and managed by the Hungarian HAE Center until November 2003 were included in this study.21
Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH). Patients experience recurrent bouts of edema, which can occur in almost any region of the body. As regards the treatment of the disease, danazol (an attenuated androgen) is used, among other agents, for long-term prophylaxis.
The aim of this study was to investigate the possible adverse effects of danazol on serum lipid profile, as well as to ascertain whether danazol treatment is associated with an increased risk of atherosclerosis.
Serum concentrations of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, apolipoprotein A-I, apolipoprotein B-100, and lipoprotein(a) were compared between danazol-treated patients with HAE and 2 control groups (ie, patients who did not receive long-term danazol prophylaxis and untreated healthy subjects).
Serum concentrations of HDL (P = .0002 and P < .0001) and apolipoprotein A-I (P = .0015 and P < .0001) were significantly lower, whereas LDL (P = .0129 and P = .0127) and apolipoprotein B-100 (P = .0456 and P = .0013) were higher in the danazol-treated patients compared with the 2 control groups, respectively. No significant difference was found in total cholesterol, triglyceride, or lipoprotein(a) levels. Patients who received danazol had an 11.6 (95% CI, 2.7-49.7) times higher risk for abnormally low HDL levels and a 4.4 (95% CI, 1.2-16.0) times lower risk for high LDL concentrations.
Our findings indicate that the long-term use of danazol is associated with an increased risk for early atherosclerosis in patients with HAE. Consequently, monitoring of HDL and LDL levels at regular intervals is recommended during follow-up.

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Transfusion and Apheresis Science

Abstract

Section snippets

Acknowledgements

References (13)

Acquired angioedema associated with chronic hepatitis C

J Allergy Clin Immun

Association of celiac disease and hereditary angioneurotic edema

Am. J. Gastroenterol.

Esophageal leiomyoma incidentally recognized during acut oedematosus attack of HAE

J Allergy Clin Immunol

Danazol therapy for hereditary angio-oedema in children

Lancet

Eradication of Helicobacter pylori and improvement of hereditary angioneurotic oedema

Lancet

Angioedema due to acquired C1-esterase inhibitor deficiency in a patient with Helicobacter pylori infection

Z. Gastroenterol.

Cited by (16)

A novel prophylaxis with C1-inhibitor concentrate in hereditary angioedema during erythema marginatum

Lack of increased prevalence of immunoregulatory disorders in hereditary angioedema due to C1-inhibitor deficiency

Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients?

Hereditary angiodema: A current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema

Hereditary angioedema: A decade of human C1-inhibitor concentrate therapy

Adverse effects of danazol prophylaxis on the lipid profiles of patients with hereditary angioedema