Patients with Hymenoptera venom allergy and high levels (>250 kU/l) of total IgE, predominantly develop grade I and grade II reactions and appear to be protected from grade III reactions. However, this hypothesis should be confirmed by extended studies with sting challenges.

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Cerebral cavernous malformations (CCM) are prevalent vascular malformations occurring in familial autosomal dominantly inherited or isolated forms. Once CCM are diagnosed by magnetic resonance imaging, the indication for genetic testing requires either a positive family history of cavernous lesions or clinical symptoms such as chronic headaches, epilepsy, neurological deficits, and hemorrhagic stroke or the occurrence of multiple lesions in an isolated case. Following these inclusion criteria, the mutation detection rates in a consecutive series of 105 probands were 87% for familial and 57% for isolated cases. Thirty-one novel mutations were identified with a slight shift towards proportionally more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%, CCM3: 22%). In-frame deletions and exonic missense variants requiring functional analyses to establish their pathogenicity were rare: An in-frame deletion within the C-terminal FERM domain of CCM1 resulted in decreased protein expression and impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. Since fulminant disease courses during the first years of life were observed in CCM1 and CCM3 mutation carriers, predictive testing of minor siblings became an issue.

Background: The detection of specific serum immunoglobulin E (sIgE) to Hymenoptera venoms is an established diagnostic tool to diagnose insect venom hypersensitivity. However, the specificity of sIgE detection is a debated issue. Methods: In 145 subjects, total IgE (tIgE) and sIgE to Hymenoptera venoms as well as sIgE to rapeseed as a marker of cross-reactive carbohydrate determinants were measured. In addition, an atopy score was determined for each patient. We looked for a possible association between tIgE and the presence of sIgE in subjects with a negative history of large local or systemic reactions to insect stings. Results: Fifteen of 65 subjects (23.1%) with low levels of tIgE (<50 kU/l) had sIgE for bee or wasp venom, and 23 of 47 subjects (48.9%) with a tIgE from 50 to 250 kU/l showed sIgE. The highest rate of asymptomatic sensitization (22 of 33; 66.7%) was found in patients with tIgE levels higher than 250 kU/l. Median sIgE was approximately 4.8 times higher in subjects with tIgE levels above 250 kU/l than in those with tIgE levels <50 kU/l. Interestingly, a significant difference in median tIgE was recorded between individuals with and without sIgE to rapeseed [776.5 kU/l (25, 75% percentiles: 252.5, 2,000.0) vs. 50.5 kU/l (20.1, 172.0), respectively; p < 0001]. Conclusion: Specific antibodies are frequently seen in individuals with high tIgE, but appear to be largely irrelevant in clinical terms. This might lead to misdiagnosis in persons with an inconclusive sting history.

SummaryHereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach -in some cases, however, short-or long-term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German-speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1-inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long-term prophylaxis. According to the most recent international consensus papers and our own experience, self-administered C1-inhibitors are now the first option for long-term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE.