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Background Plasma-derived C1-inhibitor (pdC1-INH) is a first-line therapy for hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) in pediatric patients. Objective We intended to study the clinical characteristics and safety of treatment with pdC1-INH in this population. Methods In the prospective, long-term survey, real-world data on pdC1-INH (Berinert, CSL Behring) use in pediatric patients, diagnosed and followed up at our Angioedema Reference Center, were analyzed for the period from 1986 to 2018. Results A total of 70 pediatric patients (31 boys and 39 girls) experienced a total of 3009 HAE attacks. The most common location of HAE attacks was subcutaneous. HAE attacks of any location were more frequent in girls versus boys, except for genital edema. Among the 70 patients, 37 received pdC1-INH for 456 HAE attacks, or as prophylaxis (69 vials). On average, 14.2 vials were administered per patient. The distribution of pdC1-INH use in the different age groups was as follows: no use (0-1 years), 0.11 vials/year (1-3 years), 0.7 vials/year (3-6 years), 1.26 vials/year (6-12 years), and 1.28 vials/year (12-18 years). No systemic allergic reactions, viral transmission, development of anti-C1-INH antibodies, or thromboembolic events occurred in relation to treatment with this drug. Conclusion We confirmed that the clinical manifestations and the use of pdC1-INH are different in the various age groups of pediatric patients with C1-INH-HAE. Our long-term survey shows that the use of pdC1-INH is safe in this patient population.

Abstract: Introduction: In recent years, many papers analyzed the relationship between serum vitamin D3 level and the frequency and activity of various diseases at least partially attributed to immune mechanisms. Aim: We looked for correlations among the number and location of edematous episodes occurring in patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) and the quantity of the C1-inhibitor used for supplementation as well as the vitamin D3 levels of patients. Method: We measured vitamin D3 levels in 118 of the 175 C1-INH-HAE patients of the National Angioedema Reference Center during the winter–spring (n = 111) and the summer–autumn periods (n = 105) in 2013–2014. Complement levels and clinical data were extracted from the National Angioedema Registry and from patient diaries. Results: The proportion of vitamin D3 deficient patients (serum level 3 serum levels measured in the winter–spring or in the summer–autumn months (p3 level did not correlate with the number of attacks experienced by the patients during the given period or of the vials of C1-inhibitor concentrate administered. Conclusions: We could not demonstrate a relationship between vitamin D3 level and the frequency or location of edematous episodes in HAE patients. The need for treatment (as reflected by the number of the vials administered) was higher in the winter–spring period. As vitamin D3 deficiency was more severe than expected in our patients, supplementation is clearly necessary. Orv Hetil. 2019; 160(25): 987–993.

Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients.Characteristic parameters of liver function (including bilirubin, GOT, GPT, gammaGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively.From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study.Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

Hereditary angioedema (HAE), a condition caused by deficiency of C1 inhibitor that results in acute and painful swelling in locations that can include the face, neck, abdomen, extremities and genitals, is a potentially life-threatening disorder. Many factors may contribute to phenotype development. A case report prompted us to investigate the potential influence of early weaning on HAE gastrointestinal symptoms. Retrospective analysis was performed based on clinical data from 89 patients registered with our HAE center, including duration of breast-feeding, timing of cow's milk introduction, age at symptom onset and localization of the attacks. We did not find any relationship between these factors. Although breastfeeding is known to confer protection against numerous diseases, it showed no efficacy against the manifestations of HAE in our patient population.

Henriette Farkas1, George Harmat2, Andrea Fay3, Bela Fekete4, Istvan Karadi4, Beata Visy1 and Lilian Varga5 1Allergology & Angioedema Outpatient Clinic and 3Dermatology Outpatient Clinic, Semmelweis University, Kutvolgyi Clinical Centre, Kutvolgyi ut 4., H-1125 Budapest, Hungary. 2First Department of Paediatrics, Madarasz Children’s Hospital, Budapest, Hungary. 4Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary. 5Complement Laboratory, National Institute of Haematology and Immunology, Budapest, Hungary. E-mail: farkash@kut.sote.hu