Omalizumab in complex conditions: when urticaria is associated with other diseases and safety may be a challenge

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Hereditary Angioedema due to C1 Inhibitor Deficiency: C1-INH Replacement Therapy

Hereditary angioedema (HAE) is a rare condition affecting about 1 in 50.000 individuals and caused by a mutation in the gene encoding the C1-esterase inhibitor (C1-INH), which is involved in the control of complement, clotting, fibrinolytic and kinin pathways. HAE is characterized by plasma outflow from blood vessels, leading to fluid collecting (edema) in the deep tissue layers of the face, larynx, abdomen, and extremities. Three different types of HAE have been identified: in type I the mutation leads to the lack of production of C1-INH, in type II the mutation leads to the production of dysfunctional C1-INH, while type III is extremely rare and still not fully understood. Therapeutic approaches for HAE include on-demand treatments to stop angioedema attacks and prophylactic treatment to prevent attacks both by pre-procedural (short-term) and routine (long-term) prophylaxis. Aim of the present review is to present an overview of C1-INH replacement therapy with the plasma-derived concentrate of C1-INH Berinert® (CSL Behring GmbH) in the treatment of type I and II HAE

Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series

Background: Hereditary angioedema (HAE) is characterized by potentially severe and life-threatening attacks of localized swelling. Prophylactic therapies are available, including attenuated androgens. Efficacy of attenuated androgens has not been assessed in large, randomized, placebo-controlled trials and can be associated with frequent, and sometimes severe, side effects. As better tolerated targeted therapies become available, attenuated androgen withdrawal is increasingly considered by physicians and their patients with HAE. Attenuated androgens withdrawal has not been systematically studied in HAE, although examination of other disorders indicates that attenuated androgen withdrawal may result in mood disturbances and flu-like symptoms. Standardized protocols for attenuated androgen discontinuation that continue to provide control of attacks while limiting potential attenuated androgen withdrawal symptoms are not established as the outcomes of different withdrawal strategies have not been compared. We aim to describe the challenges of attenuated androgen discontinuation in patients with HAE and how these may continue into the post-androgen period. Case presentation: We present a retrospective case series of 10 patients with confirmed type I HAE who have discontinued prophylactic treatment with attenuated androgens. The most common reason for attenuated androgen discontinuation was side effects. Attenuated androgens were either immediately withdrawn, tapered and/or overlapped with another treatment. The major challenge of discontinuation was the management of an increased frequency and severity of HAE attacks in some patients. Conclusions: Healthcare teams need to undertake careful planning and monitoring after attenuated androgens discontinuation, and modify treatment strategies if HAE control is destabilized with an increased number of attacks. Discontinuation of attenuated androgens is definitively an option in an evolving HAE treatment landscape, and outcomes can be favourable with additional patient support and education

life expectancy in italian patients with hereditary angioedema due to c1 inhibitor deficiency

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Therapeutic Value and Innovation of a Drug and Criteria for Evaluation: A Multidisciplinary Experience in the Veneto Region

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The impact of puberty on the onset, frequency, location, and severity of attacks in hereditary angioedema due to C1-inhibitor deficiency: A survey from the Italian Network for Hereditary and Acquired Angioedema (ITACA)

IntroductionHereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks.MethodsRetrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA).ResultsThe proportion of symptomatic patients increased significantly after puberty (98.2% vs 83.9%, p=0.002 in males; 96.3% vs 68,4%, p<0.001 in females); the monthly mean of acute attacks was significantly higher after puberty, and this occurred both in females (median (IQR) = 0.41(2) in the three years before puberty vs 2(2.17) in the three years after, p<0.001) and in males (1(1.92) vs 1.25(1.56) respectively, p<0.001). The increase was greater in females. No significant differences were detected in attack location before and after puberty.DiscussionOverall, our study confirms previous reports on a more severe phenotype in the female gender. Puberty predisposes to increased numbers of angioedema attacks, in particular in female patients

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients