Aygören-Pürsün et al. Allergy, Asthma & Clinical Immunology 2010, 6:21 http://www.aacijournal.com/content/6/1/21 antagonist Icatibant is an entirely different approach. Additionally, inhibition of kallikrein, the activator of high molecular weight kininogen (HMWK) and there- fore promotor of bradykinin formation, is a further potential therapeutic alternative. In Germany, current treatment options approved for therapy of acute angioedema in HAE-Type I and II patients comprise intravenous replacement therapy with a pasteurized pd C1-INH concentrate and subcutaneous injection of the bradykinin B2-receptor antagonist Icati- bant. Clinical efficacy has been demonstrated in retro- spective studies for pasteurized pd C1-INH concentrate [3-5] and in prospective studies for both substances [6,7]. The clinical safety of pasteurized pd C1-NH concen- trate has been proven over the last 25 years in more than 500,000 administrations (data on file, CSL Behr- ing), which were well tolerated. In this period of time, only 8 allergic or anaphylactic reactions, including four episodes in one HAE-Type I patient from Frankfurt, have been observed. This corresponds to 1:50,000 administrations and thus to classification of allergic reactions as a “very rare” (< 1:10,000) adverse event according to the CIOMS III standard categories for clas- sification of adverse drug reaction frequency [8]. No proven cases of viral transmission from pasteurized pd C1-INH concentrate have been shown in the last 25 years (data on file, CSL Behring) [9]. Pasteurized pd C1- INH concentrate can be used in pediatric and adult patients. It is well tolerated also in pregnant and breast- feeding women [10]. Clinical experience with Icatibant is limited up to now, as it has been only recently (2008) approved for HAE in Germany. The safety of Icatibant has been shown in clinical studies [11]. The most frequent side effect, encountered in almost all treated subjects, is a transient, itchy, and sometimes painful erythema at the subcutaneous injection site. Common adverse reactions of Icatibant are nausea, abdominal pain, asthenia, increased blood creatinine phosphokinase, abnormal liver function test, dizziness, headache, nasal congestion and rash. Icatibant may be used up to 3 times within 24 hours. In the elderly patient (> 65 years) experience with Icatibant is limited, as less than 5% of the study population belongs to this age group [11]. Moreover, clearance of Icatibant may decline with age, which may lead to a higher exposure in elderly patients (> 75 yrs.). Presently, no experience with administration of Icatibant in pregnant or breastfeeding women or in children exists. Caution should be observed in the administration of Icatibant to patients with acute ischemic heart disease or unstable angina pectoris and to patients in the weeks following a stroke. According to the product’s prescrib- ing information, no dose adjustment with hepatic or renal impairment is required. Page 2 of 4 Differential therapy of C1-INH deficiency at the Frankfurt HAE Center Our HAE center at Frankfurt University Hospital cur- rently treats 450 adults with hereditary or acquired (AAE) C1-INH deficiency (430 HAE and 20 AAE patients), and 107 pediatric HAE patients with highly individualized therapeutic approaches. The majority (73.7%) of adult patients at the center are candidates for sole on-demand therapy with pasteur- ized pd C1-INH concentrate of acute HAE attacks. However, 9.8% of adult patients qualify for long-term prophylaxis with attenuated androgens (e.g., danazol), although the latter, while being widely-used worldwide, is not licensed for use in HAE [2]. Potential break- through attacks in attenuated androgen-treated patients are treated using pasteurized pd C1-INH concentrate on demand. In addition, we provide the option of individual repla- cement therapy (IRT) with pd C1-INH concentrate for high-risk patients [2]. HAE patients affected by a high frequency of severe attacks (> 1 per week), and unre- sponsive to long-term prophylaxis with attenuated androgens were advised to administer pasteurized pd C1-INH concentrate on early signs of an acute attack. Patients usually administer a dose of 500 to 1000 U of pasteurized pd C1-INH at each early sign of attack (i.e. up to twice a week). This therapy protocol is being sup- ported by the favorable pharmacokinetic properties of a long half-life of pasteurized pd C1-INH concentrate in different HAE patient subgroups (see Table 1) [12]. With IRT, a significant reduction of annual attack rates compared to previous danazol prophylaxis was seen. Particularly, laryngeal attacks were entirely abolished. Moreover, a significant efficacy of IRT on all items of quality of life (QoL) investigated was verified [2]. Ongoing long-term studies will furthermore evaluate the efficacy and safety of IRT. Home therapy with pd C1-INH concentrate in HAE patients was developed in line with hemophilia therapy, where the missing protein is administered by the patient at home on an as-needed basis. Home treatment with plasma derived and recombinant factor VIII and factor IX concentrates is an established therapy in North America since 1975 [13] and is included in the German Guidelines on hemophilia therapy. In Frankfurt, home therapy with pd C1-INH concentrate for use in on demand treatment or within the IRT protocol has been implemented for a period of 28 years. At present, a total of 274 patients (49% of all patients with C1-INH defi- ciency treated by the center) are practicing home treat- ment. Out of these, 248 are adult patients (55% of adult patients) and 26 children (24% of pediatric patients). The age of the relevant patient groups ranges between 18-81 years and 6-17 years, respectively. In young