Hereditary angioedema due to C1 - inhibitor deficiency in Switzerland: clinical characteristics and therapeutic modalities within a cohort study

BACKGROUND Registration of trigger factors, prodromal symptoms, swelling localization, therapeutic behavior and gender-specific differences of the largest cohort of patients with hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) in Switzerland. METHODS Questionnaire survey within a cohort study: Consenting eligible patients with diagnosed HAE according to clinical history, physical examination and laboratory results, including plasma values for C1-INH and C4 were selected. To each participant we sent a questionnaire assessing patients' birthday, sex, date of first symptoms and diagnosis, trigger factors, prodromal symptoms, frequency and localization of angioedema, medication use and co-morbidities. Clinical information was collected in each center and then transmitted to the cohort database. Frequencies and distributions were summarized. Associations between gender and trigger factors or prodromal symptoms or localization of angioedema were assessed in multivariate analyses correcting for patients' age. RESULTS Of 135 patients, data from 104 patients (77%) were available for analysis. Fifty- four percent were female, mean age at diagnosis was 19.5 years (SD 14.1), Mean age when completing the questionnaire was 44.0 (SD 19.8). More women than men were symptomatic (44/57 vs. 36/47; p = 0.005). This association remained when correcting for age at diagnosis (16.10. 95%CI (5.17 to 26.70); p = 0.004). Swelling episodes ranged between 1 and 136 episodes/year. Swelling was more common among female than among male (-13.15 (95% CI; -23.10 to -3.22), p = 0.010). Age at diagnosis was inversely associated with the total number of attacks 0.50 (-0.88 to -.011); p = 0.012). One third of patients were on danazol prophylaxis. CONCLUSION We found large differences of HAE in male and female both in terms of symptom number and swelling episodes. Women are more affected by intensity and frequency of angioedema episodes than men. Danazol treatment remains widely used as effective prophylaxis despite its side effects. New therapies which selectively influence the hormonal estrogen balance could open new therapeutic options mainly for women and maybe also for men

Food as a trigger for abdominal angioedema attacks in patients with hereditary angioedema

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited disease. In most HAE-affected subjects, defined trigger factors precede angioedema attacks. Mechanisms of how trigger factors stimulate the contact activation pathway with bradykinin generation are not well elucidated. In recent studies, hypersensitivity reactions and food were stated as relevant triggers. We investigated HAE affected people for possible hypersensitivity reactions or intolerances and their relation in triggering angioedema attacks. METHODS: A questionnaire was filled in, recording date of birth, gender, and self-reported angioedema attacks associated with the ingestion of foodstuffs, administration of drugs, hymenoptera stings and hypersensitivity reactions against inhalation allergens. All participants performed a skin prick test against inhalation allergens and food. In patients who stated an association of possible hypersensitivity with angioedema, a serological ImmunoCAP test was also performed. RESULTS: From the 27 women and 15 men analyzed, 79% stated trigger factors. From those food was mentioned in 36%. The suspected food included tomato, green salad, fish, citrus fruits, apple, onion, garlic, cheese, chili, kiwi, milk, tree nuts, strawberry, pineapple, shrimps, bread, banana, leek, chicken and alcohol, and were associated with abdominal angioedema. Neither the skin prick test nor the ImmunoCAP-test turned out positive for the tested food allergens. CONCLUSION:Food seems to be a relevant trigger factor, causing angioedema in HAE affected patients. The reason, however, is not IgE-mediated hypersensitivity, but most probably an intolerance reaction to food products