Exploring the management of recurrent angioedema caused by different mechanisms.

Purpose Of Review: We aim to explore the most recent insights into the pathogenesis of recurrent angioedema caused by different mechanisms and then focus on the management and treatment approaches available.

Recent Findings: The recently developed DANCE consensus classification identifies five types of angioedema: mast cell-mediated (AE-MC), bradykinin-mediated, because of intrinsic vascular endothelium dysfunction (AE-VE), drug-induced (AE-DI), and due to unknown mechanisms (AE-UNK). These subtypes require different management with treatment choices targeting the main pathogenetic pathways involved in each form.

Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients.

Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges.

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations.

Interplay between C1-inhibitor and group IIA secreted phospholipase A impairs their respective function.

High levels of human group IIA secreted phospholipase A (hGIIA) have been associated with various inflammatory disease conditions. We have recently shown that hGIIA activity and concentration are increased in the plasma of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) and negatively correlate with C1-INH plasma activity. In this study, we analyzed whether the presence of both hGIIA and C1-INH impairs their respective function on immune cells.

Roles of Immune Cells in Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare genetic disease, characterized by recurrent and unexpected potentially life-threatening mucosal swelling. HAE may be further classified into HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nlC1-INH-HAE), mostly due to mutations leading to increased vascular permeability. Recent evidence implicates also the innate and adaptive immune responses in several aspects of angioedema pathophysiology.

Episodic Angioedema with Hypereosinophilia (Gleich's Syndrome): A Case Report and Extensive Review of the Literature.

Episodic angioedema with eosinophilia (EAE) (Gleich's syndrome) is a rare disease characterized by hypereosinophilia (up to 95 × 10 cells/L), recurrent episodes of angioedema, urticaria, weight gain, and fever, that occur at periodical intervals (usually every 3-4 weeks). The exact etiology of EAE is still unclear, but both eosinophils and abnormalities of cytokines homeostasis seem to play a pivotal role in the pathogenesis of the disease. In particular, the cyclic elevation of serum interleukin-5 before the increase in eosinophil count has been reported.

Analysis of Heart-Rate Variability during Angioedema Attacks in Patients with Hereditary C1-Inhibitor Deficiency.

C1-inhibitor hereditary angioedema (C1-INH-HAE) is a rare disease characterized by self-limiting edema associated with localized vasodilation due to increased levels of circulating bradykinin. C1-INH-HAE directly influences patients' everyday lives, as attacks are unpredictable in frequency, severity, and the involved anatomical site. The autonomic nervous system could be involved in remission.

Psychological processes in the experience of hereditary angioedema in adult patients: an observational study.

Background: Hereditary angioedema associated to C1 inhibitor deficiency (C1-INH-HAE) is a pathological condition characterized by episodes of subcutaneous swelling and it is frequently associated with discomfort and social impairment of the patients, due to the anxiety experienced for an unpreventable manifestation of an attack during daily life. In children increased level of stress and alexithymia have been associated to C1-INH-HAE, and the latter correlated also with the severity of the disease. We hypothesized that the involvement of psychological issues may impact on the severity of C1-INH-HAE in adult patients as well, interfering with their ability to engage with the management of the disease.

Psychology and hereditary angioedema: A systematic review.

Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor (C1-INH) gene Serpin Family G Member 1(), which results in either the decreased synthesis of normal C1-INH (C1-INH-HAE type I) or expression of unfunctional C1-INH (C1-INH-HAE type II). In recent studies, emotional stress was reported by patients as the most common trigger factor for C1-INH-HAE attacks. Moreover, patients reported considerable distress over the significant variability and uncertainty with which the disease manifests, in addition to the impact of physical symptoms on their overall quality of life.

The experience of living with a chronic disease in pediatrics from the mothers' narratives: The Clinical Interview on Parental Sense of Grip on the Disease.

The Clinical Interview on the Sense of Grip on Chronic Disease has been administered to 68 mothers of children affected by Hereditary Angioedema (C1-Inh HAE), Type 1 Diabetes (T1D), Juvenile Rheumatoid Arthritis (JRA). The objectives are to detect general features of the experience of parenting children with chronic illness as well as the specificities of this experience related to the different conditions. Four Profiles of Sense of Grip were identified: Adempitive, Controlling, Reactive, Dynamic.

Deciphering the Genetics of Primary Angioedema with Normal Levels of C1 Inhibitor.

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with alterations as well as those with histaminergic acquired angioedema were excluded.

Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.

Excessive BK (bradykinin) stimulation is responsible for the exaggerated permeabilization of the endothelium in angioedema. However, the molecular mechanisms underlying these responses have not been investigated. BK receptors are Gq-protein-coupled receptors phosphorylated by GRK2 (G protein-coupled receptor kinase 2) with a hitherto unknown biological and pathophysiological significance.

Gastrointestinal manifestations of angioedema: a potential area of misdiagnosis.

Abdominal pain is one of the most common conditions leading people to the emergency department. An uncommon but well described cause of abdominal pain is angioedema of the gastrointestinal tract due to recurrent angioedema without wheals. Abdominal involvement is very common in hereditary angioedema (HAE), but it is also described in acquired angioedema and allergic forms.

The central role of endothelium in hereditary angioedema due to C1 inhibitor deficiency.

An impairment of the endothelial barrier function underlies a wide spectrum of pathological conditions. Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) can be considered the "pathophysiological and clinical paradigm" of Paroxysmal Permeability Diseases (PPDs), conditions characterized by recurrent transient primitively functional alteration of the endothelial sieving properties, not due to inflammatory-ischemic-degenerative injury and completely reversible after the acute flare. It is a rare yet probably still underdiagnosed disease which presents with localized, non-pitting swelling of the skin and submucosal tissues of the upper respiratory and gastrointestinal tracts, without significant wheals or pruritus.

Impaired control of the contact system in hereditary angioedema with normal C1-inhibitor.

Background: Hereditary angioedema (HAE) comprises HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nl-C1-INH-HAE), due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 genes (KNG1-HAE), or angioedema of unknown origin (U-HAE). The Italian network for C1-INH-HAE (ITACA) created a registry including different forms of angioedema without wheals.

Objective: We analyzed clinical and laboratory features of a cohort of Italian subjects with nl-C1-INH-HAE followed by ITACA to identify specific biomarkers.

Hereditary angioedema attack: what happens to vasoactive mediators?

Hereditary angioedema is a disabling, life-threatening condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) leading to bradykinin accumulation and recurrent episodes of edema attack. Vascular leakage is a complex process sustained by the coordinated production of several permeabilizing factors including vascular endothelial growth factors (VEGFs), angiopoietins (ANGPTs) and phospholipase A enzymes (PLA). We previously reported that patients with C1-INH-HAE in remission have increased plasma levels of VEGFs, ANGPTs and secreted PLA.

Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy.

Despite the efficacy of the on-demand treatment for the control of acute attacks of Hereditary Angioedema due to C1-Inhibitor Deficiency (C1-INH-HAE), the number and severity of attacks and the impairment in the quality of life of the affected patients have led to the development of a new monoclonal antibody, lanadelumab, directly addressed to the blockage of bradykinin, the principal mediator of vasodilation during angioedema attacks. It is indicated for the prophylactic treatment, it is easy to administer, highly effective and with known limited side effects. The current review summarizes the development of the drug, its clinical background and its perspectives.

Prophylaxis of Acute Attacks with a Novel Short-term Protocol in Hereditary Angioedema Patients Requiring Periodontal Treatment.

Purpose: C1-inhibitor (C1-INH) related hereditary angioedema (C1-INH-HAE) is a rare pathological condition caused by a deficiency or a functional alteration of serum protein C1-INH. Clinical manifestations are represented by recurrent, potentially life-threatening episodes of cutaneous or mucosal oedema. The present study analysed the effectiveness of a specific short-term prophylaxis protocol for the management of C1-INH-HAE patients requiring chronic periodontitis treatment.