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Background 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. Objectives 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. Results 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). Conclusions 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. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema-formation, which may occur in response to stress. The individual's response to stress stimuli is partly genetically determined. Activation of the hypothalamic-pituitary-adrenal axis results in the release of cortisol. In turn, the secreted gluco- and mineralocorticoids affect the metabolism, as well as the cardiovascular and immune systems. We hypothesized that changes in serum cortisol level and polymorphisms of the glucocorticoid receptor (GR) modify the individual sensitivity to stressor stimuli of C1-INH-HAE patients.Results: We compared the response to stress with Rahe's Brief Stress and Coping Inventory of 43 C1-INH-HAE patients, 18 angioedema patients and 13 healthy controls. 139 C1-INH-HAE patients and 160 healthy controls were genotyped for glucocorticoid receptor polymorphisms BclI, N363S and A3669G. Serum cortisol levels were determined during attacks and during symptom-free periods in 36 C1-INH-HAE patients. The relationships between clinical, laboratory data and GR SNPs (Single Nucleotide Polymorphisms) were assessed using ANOVA. C1-INH-HAE patients have decreased coping capabilities compared to healthy controls. Cortisol levels were significantly higher during attacks than in symptom-free periods (p = 0.004). The magnitude of the elevation of cortisol levels did not show a significant correlation with any clinical or laboratory data. Among the C1-INH-HAE patients, the carriers of the A3669G allele had significantly lower cortisol levels, and increased body mass index compared with non-carriers.Conclusions: The higher cortisol level observed during attacks may reflect the effect of a stressful situation (such as of the attack itself), on the patients' neuroendocrine system. In A3669G carriers, the lower cortisol levels might reflect altered feedback to the hypothalamic-pituitary-adrenal axis, due to decreased sensitivity to glucocorticoids. [ABSTRACT FROM AUTHOR]

Background: The 17-alpha-alkylated derivatives of testosterone are often used for the prevention of oedematous episodes in hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE). However, these agents can have many adverse effects, including erythrocytosis and polyglobulia. Our aim was to investigate occurrence of erythrocytosis and polyglobulia after long-term danazol prophylaxis in C1-INH-HAE.Methods: During the initial stage of our retrospective study, we explored whether C1-INH-HAE is associated with susceptibility to erythrocytosis and/or polyglobulia. In the second stage, we analyzed the haematological parameters of 39 C1-INH-HAE patients before, as well as after treatment with danazol for 1, 3, or 5 years. In the third stage, we studied the incidence of erythrocytosis and of polyglobulia after dosing with danazol for more than 5 years.Results: We did not find any significant difference between C1-INH-HAE patients not receiving danazol and healthy controls as regards the occurrence of erythrocytosis or polyglobulia. The haematological parameters did not change after treatment with danazol for 1, 3, or 5 years. Platelet count was an exception-it decreased significantly (p = 0.0115) versus baseline, but within the reference range. Treatment-related polyglobulia did not occur. We observed erythrocytosis in a single female patient after 1-year-and in three female patients after more than 5-year long-treatment with danazol. Erythrocytosis did not require intervention or the discontinuation of danazol therapy.Conclusions: We conclude that neither erythrocytosis, nor polyglobulia occurs more often in C1-INH-HAE patients than in healthy individuals; it can be observed only sporadically even after treatment with danazol. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Whether NGs undergo activation during attack has not yet been investigated. However, as neutrophil elastase (NE) can cleave and inactivate C1-INH which may contribute to the dysregulation of the kallikrein-kinin system and hence, to edema formation. Our aim was to investigate the possible activation of NGs during attacks.Methods: We studied blood samples obtained from 26 patients with C1-INH-HAE during symptom-free periods and during attacks, along with samples from 26 healthy volunteers. NG count (NGC), NE, myeloperoxidase (MPO), pentraxin 3 (PTX3), CRP, C5a, factor H, IL-8, and TNF-α levels were measured.Results: NGC was higher during attacks than during symptom-free periods (p = 0.0132), and the same was observed for NE (p = 0.0026), MPO (p = 0.0008), and PTX3 levels (p = 0.0409). There was a strong positive correlation between NE and MPO levels during attacks (p < 0.0001, R = 0.709). Furthermore, IL-8 (p = 0.0061) and TNF-α (p = 0.0186) levels were also elevated during attacks, compared with symptom-free periods. By contrast, C5a and factor H levels were similar in samples obtained during attacks or in symptom-free periods.Conclusion: Increased NGC was associated with elevated NE and MPO levels - this suggests neutrophil activation during attacks. The strong positive correlation between NE and MPO levels, together with the elevated PTX3 concentration, may indicate the expression of neutrophil extracellular traps. All these processes may contribute to the activation of kallikrein-kinin system, which leads to the onset of an edematous episode. [ABSTRACT FROM AUTHOR]