Untersuchungen zum hereditären Angioödem im deutschsprachigen Raum

Abstract

A multicentre, retrospective study of hereditary deficiency of C1-esterase inhibitor (C1-INH) function, a deficiency which clinically manifests as hereditary angioedema (HAE), was performed in six centres in Germany, Austria and Switzerland. 242 individuals were registered with proven functional or quantitative deficiency of C1-INH who belonged to kindered with disease manifestation in 2 to 6 generations. Considering the total population in the three countries and the number of registered individuals, a frequency of the deficiency of 0.02 x 10(-4) was calculated. As this epidemiological study involved only 6 centres, a 10 to 100 times higher frequency of C1-INH deficiency is estimated to be a more realistic value. Out of the 242 registered individuals 110 were evaluated for type and location of clinical manifestation of the deficiency, the laboratory data and the therapy outcome. 86 (78.2%) of the patients belonged to the "common type" and 24 (21.8%) to the "variant type" of HAE. In 53.9% of the cases first manifestation of the disease was before the age of 20 years. In only 3.9% of the patient population did the disease begin after 40 years of age. A mean time lag of 5,3 years was observed, between the first manifestation and correct diagnosis. Initial diagnosis was correct in only 31.8% of the cases of which dermatologists provided 51.7%. False diagnoses include urticaria (41.3%), allergy (20%), acute abdomen (18.7%), angina (8%), rheumatoid disease (5.3%) and intracranial haemorrhage, CNS tumour, epilepsy, migraine (5.3%). The distribution pattern of HAE resembled that of intolerance reactions and pseudoallergies. Urticarial lesions were not associated with C1-INH deficiency. 24% of the patients had at least one episode of laryngeal edema. 40% of patients were unable to identify a trigger of edema formation. The others indicated as triggers trauma, hormonal changes, mental stress, insect stings and in a few cases food and drugs. Menstruation and oral contraceptives aggravated or made disease manifestations more frequent. In contrast, during pregnancy in many cases clinical manifestations improved and delivery posed no problems. The possibility of HAO is very much suggested by the tailure of edema to respond to classical anti-allergic therapy. Therapy of choice of acute attacks is C1-INH concentrate. No side reactions, antibody formation or virus transmission have been observed. For long term prophylaxis danazol, an attenuated androgen, or tranexamic acid, a protease inhibitor, was chosen. The daily dose of danazol should be kept as low as possible because of its anabolic, anti-estrogenic, anti-gestagenic, and anti-gonadotropic effects. Indeed, adverse reactions were observed in 41.7% of patients receiving danazol. Frequencies of adverse reactions were twice as common in women as in men. Adverse reactions were dose dependent and reversible except for one woman with irreversible deepening of her voice. Measuring C1r is a effective way to assess C1-INH function and monitor therapy.

WAO Guideline for the Management of Hereditary Angioedema

“…Results of search 8: Munch and Weeke, [3] Lewis, [4] Gluszko et al, [5] Cicardi et al, [6] Waytes et al, [7] Cicardi et al, [8] Goring et al, [9] Kunschak et al, [10] Farkas et al, [11] Bork and Barnstedt, [12] Gompels et al, [13] Weiler et al, [14] Szeplaki et al, [15] van Doorn et al, [16] Bas et al, [17] Bork et al, [18] Ott et al, [19] Schneider et al, [20] Varga et al, [21] Visy et al, [22] Birjmohun et al, [23] Cedzynski et al, [24] Szegedi et al, [25] Craig et al, [26] Kreuz et al, [27] Bas et al, [28] Bernstein et al, [29] Cicardi et al, [30] Cicardi et al, [31] Craig et al, [32] Levy et al, [33] Zuraw et al, [34] Zuraw et al [35]. …”

Evidence and evidence gaps of medical treatment of non-tumorous diseases of the head and neck

“…Even if such an edema was already known from earlier case descriptions, it was Quincke who accurately described this disease and differentiated it from urticaria [66]. Today, so-called Quincke’s edema is a synonym of angioedema and is used as generic term for description of defined edema without urticaria and/or pruritus.…”

Long-Term Prophylaxis of Hereditary Angioedema with a Pasteurized C1 Inhibitor Concentrate

“…Treatment of acute attacks is associated with rapid symptom relief, typically within 30–150 min, although some patients experience relief as early as 10 min after treatment [11], with complete resolution seen from approximately 1 h, but typically within 4 h, particularly with early treatment [11,13]. Adrenaline, antihistamines and corticosteroids are not effective for acute HAE attacks [17]. Because of the potential for viral contamination, the tolerability of C1-INH has been extensively investigated, with no viral transmission reported [18].…”