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Clinics (Sao Paulo, Brazil) May 2018
Topics: Angioedemas, Hereditary; Brazil; Humans; Practice Guidelines as Topic
PubMed: 29791522
DOI: 10.6061/clinics/2018/e354 -
Allergy and Asthma Proceedings Nov 2021Patients with hereditary angioedema (HAE) have been postulated to be at increased risk for coronavirus disease 2019 (COVID-19) infection due to inherent dysregulation...
Patients with hereditary angioedema (HAE) have been postulated to be at increased risk for coronavirus disease 2019 (COVID-19) infection due to inherent dysregulation of the plasma kallikrein-kinin system. Only limited data have been available to explore this hypothesis. To assess the interrelationship(s) between COVID-19 and HAE. Self-reported COVID-19 infection, complications, morbidity, and mortality were surveyed by using an online questionnaire. The participants included subjects with HAE with C1 inhibitor (C1INH) deficiency (HAE-C1INH) and subjects with HAE with normal C1-inhibitor (HAE-nl-C1INH), and household controls (normal controls). The impact of HAE medications was examined. A total of 1162 participants who completed the survey were analyzed, including: 695 subjects with HAE-C1INH, 175 subjects with HAE-nl-C1INH, and 292 normal controls. The incidence of reported COVID-19 was not significantly different between the normal controls (9%) and the subjects with HAE-C1INH (11%) but was greater in the subjects with HAE-nl-C1INH (19%; p = 0.006). Obesity was positively correlated with COVID-19 across the overall population (p = 0.012), with a similar but nonsignificant trend in the subjects with HAE-C1INH. Comorbid autoimmune disease was a risk factor for COVID-19 in the subjects with HAE-C1INH (p = 0.047). COVID-19 severity and complications were similar in all the groups. Reported COVID-19 was reduced in the subjects with HAE-C1INH who received prophylactic subcutaneous C1INH (5.6%; p = 0.0371) or on-demand icatibant (7.8%; p = 0.0016). The subjects with HAE-C1INH and not on any HAE medications had an increased risk of COVID-19 compared with the normal controls (24.5%; p = 0.006). The subjects with HAE-C1INH who were not taking HAE medications had a significantly higher rate of reported COVID-19 infection. Subcutaneous C1INH and icatibant use were associated with a significantly reduced rate of reported COVID-19. The results implicated potential roles for the complement cascade and tissue kallikrein-kinin pathways in the pathogenesis of COVID-19 in patients with HAE-C1INH.
Topics: Angioedema; Angioedemas, Hereditary; Angiotensin-Converting Enzyme 2; Bradykinin; COVID-19; Case-Control Studies; Complement C1 Inactivator Proteins; Complement C1 Inhibitor Protein; Hereditary Angioedema Types I and II; Humans; Incidence; Kallikreins; SARS-CoV-2
PubMed: 34871158
DOI: 10.2500/aap.2021.42.210083 -
Cleveland Clinic Journal of Medicine May 2013Hereditary angioedema is a rare but life-threatening disease characterized by recurring attacks of swelling of any part of the body, without hives. Prompt recognition is... (Review)
Review
Hereditary angioedema is a rare but life-threatening disease characterized by recurring attacks of swelling of any part of the body, without hives. Prompt recognition is critical so that treatment can be started to minimize morbidity and the risk of death. Drugs have recently become available to prevent and treat acute attacks.
Topics: Angioedemas, Hereditary; Diagnosis, Differential; Disease Management; Genetic Predisposition to Disease; Humans
PubMed: 23636922
DOI: 10.3949/ccjm.80a.12073 -
Clinics (Sao Paulo, Brazil) 2022The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs "HAAAAE (H4AE)" to...
OBJECTIVES
The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs "HAAAAE (H4AE)" to enable early identification of this disease.
METHODS
The authors analyzed the C1INH-HAE cohort to analyze the clinical aspects of the present study's patients and corroborate the six clinical warning signs of the Hereditary Angioedema Brazilian Guidelines. Data regarding demographics, the onset of disease, time to diagnosis, frequency of attacks per year, organs involved, triggers, crisis duration and their outcomes, and disease treatment were collected. Then the authors developed an acronym, H4AE, to help healthcare professionals remember the warning signs.
RESULTS
The authors included 98 patients in the study, with a mean age of 38.1 years, 67.3% being female, and 75.3% with a family history of HAE. HAE diagnosis was delayed, on average, 13.7 years after its initial manifestation. Exploratory laparotomy was reported by 26.9%, and orotracheal intubation by 21.3% of the present study's patients; 61.3% and 30.3% of them were admitted at least once in the hospital and in the intensive care unit, respectively. The authors constructed an acronym "H4AE" with the six warning signs of HAE: Hereditary, recurrent Angioedema, Abdominal pain, Absence of urticaria, Absence of response to antihistamines, Estrogen association.
CONCLUSION
C1INH-HAE is still underdiagnosed and associated with high morbidity. The study showed clinical features of this disease, corroborating the warning signs, which may be useful in raising awareness and improving the diagnosis of C1INH-HAE. The authors suggest the acronym "H4AE" to remind the warning signs.
Topics: Adult; Angioedemas, Hereditary; Brazil; Estrogens; Female; Humans; Male
PubMed: 35318167
DOI: 10.1016/j.clinsp.2022.100023 -
Allergology International : Official... Jul 2023Hereditary angioedema (HAE) is a rare disorder characterized by cutaneous and submucosal swelling caused mostly by excessive local bradykinin production. Bradykinin is a... (Review)
Review
Hereditary angioedema (HAE) is a rare disorder characterized by cutaneous and submucosal swelling caused mostly by excessive local bradykinin production. Bradykinin is a vasoactive peptide generated by the limited proteolysis of high molecular weight kininogen (HMWK) by plasma kallikrein via the contact activation system. The contact activation system occurs not only in solution but also on the cell surface. Factor XII (FXII), prekallikrein, and HMWK are assembled on the endothelial cell surface via several proteins, including a trimer of a receptor for globular C1q domain in a Zn-dependent manner, and the reciprocal activation on the cell surface is believed to be physiologically important in vivo. Thus, the contact activation system leads to the activation of coagulation, complement, inflammation, and fibrinolysis. C1-inhibitor (C1-INH) is a plasma protease inhibitor that is a member of the serpin family. It mainly inhibits activated FXII (FXIIa), plasma kallikrein, and C1s. C1-INH hereditary deficiency induces HAE (HAE-C1-INH) due to excessive bradykinin production via the incomplete inhibition of plasma kallikrein and FXIIa through the low C1-INH level. HAE is also observed in patients with normal C1-INH (HAEnCI) who carry pathogenic variants in genes of factor XII, plasminogen, angiopoietin 1, kininogen, myoferlin, and heparan sulfate 3-O-sulfotransferase 6, which are associated with bradykinin production and/or vascular permeability. HAE-causing pathways triggered by pathogenic variants in patients with HAE-C1-INH and HAEnCI are reviewed and discussed.
Topics: Humans; Angioedemas, Hereditary; Factor XII; Bradykinin; Plasma Kallikrein; Kininogen, High-Molecular-Weight; Complement C1 Inhibitor Protein; Molecular Biology
PubMed: 37169642
DOI: 10.1016/j.alit.2023.04.004 -
British Journal of Haematology Jun 2016Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can... (Review)
Review
Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can result in significant morbidity and even mortality. Several novel therapies introduced since 2008 have dramatically transformed the approach to management. In this review we will discuss the current understanding of the pathophysiology of HAE, diagnostic evaluation of recurrent angioedema without urticaria, and the therapeutic approach to HAE. We advocate taking an integrative approach to care in order to normalize the lives of affected patients.
Topics: Adolescent; Adult; Angioedemas, Hereditary; Child; Disease Management; Female; Humans; Male; Recurrence; Young Adult
PubMed: 27071490
DOI: 10.1111/bjh.14059 -
Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges.International Journal of Molecular... Jul 2023Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series... (Review)
Review
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. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease.
Topics: Humans; Angioedemas, Hereditary; Bradykinin; Tissue Plasminogen Activator; Angioedema; Angiotensin-Converting Enzyme Inhibitors
PubMed: 37569559
DOI: 10.3390/ijms241512184 -
The American Journal of Managed Care Aug 2018Hereditary angioedema (HAE) is a rare disorder, characterized by intermittent attacks of swelling in any part of the body, without the presence of hives. This lifelong... (Review)
Review
Hereditary angioedema (HAE) is a rare disorder, characterized by intermittent attacks of swelling in any part of the body, without the presence of hives. This lifelong disease typically presents in the first 2 decades of life, and is commonly associated with a deficiency in functional C1 esterase inhibitor (C1-INH) activity. C1-INH levels may be decreased or normal, with an accompanied decrease in functionality, depending on the type of HAE present. The frequency and severity of attacks are highly variable among patients with HAE, but can have a significant impact on a patient's quality of life, and may be fatal if not properly managed. Early diagnosis of the disease can lead to the development of an individualized treatment plan to assist with prevention and management of angiodema attacks. Delays in diagnosis remain, as healthcare professionals often fail to include HAE in the differential diagnosis when patients present with attacks, and patients therefore often go undiagnosed or are misdiagnosed for several years before a diagnosis of HAE is made. It is important for providers to recognize the most common clinical features of HAE and how to evaluate patients to effectively diagnose, prevent, and treat future attacks.
Topics: Angioedemas, Hereditary; Cost of Illness; Diagnosis, Differential; Humans; Prevalence
PubMed: 30132643
DOI: No ID Found -
Frontiers in Immunology 2019Plasminogen activation is essential for fibrinolysis-the breakdown of fibrin polymers in blood clots. Besides this important function, plasminogen activation... (Review)
Review
Plasminogen activation is essential for fibrinolysis-the breakdown of fibrin polymers in blood clots. Besides this important function, plasminogen activation participates in a wide variety of inflammatory conditions. One of these conditions is hereditary angioedema (HAE), a rare disease with characteristic attacks of aggressive tissue swelling due to unregulated production and activity of the inflammatory mediator bradykinin. Plasmin was already implicated in this disease decades ago, but a series of recent discoveries have made it clear that plasmin actively contributes to this pathology. Collective evidence points toward an axis in which the plasminogen activation system and the contact system (which produces bradykinin) are mechanistically coupled. This is amongst others supported by findings in subtypes of HAE that are caused by gain-of-function mutations in the genes that respectively encode factor XII or plasminogen, as well as clinical experience with the antifibrinolytic agents in HAE. The concept of a link between plasminogen activation and the contact system helps us to explain the inflammatory side effects of fibrinolytic therapy, presenting as angioedema or tissue edema. Furthermore, these observations motivate the development and characterization of therapeutic agents that disconnect plasminogen activation from bradykinin production.
Topics: Angioedemas, Hereditary; Animals; Blood Coagulation; Bradykinin; Brain; Complement C1 Inhibitor Protein; Factor XII; Humans; Molecular Targeted Therapy; Plasminogen; Tissue Plasminogen Activator
PubMed: 31507620
DOI: 10.3389/fimmu.2019.02046 -
A Comprehensive Management Approach in Pediatric and Adolescent Patients With Hereditary Angioedema.Clinical Pediatrics Oct 2023Hereditary angioedema (HAE) is a rare autosomal-dominant disorder; most cases are characterized by low plasma levels of C1 esterase inhibitor (C1-INH). Clinical... (Review)
Review
Hereditary angioedema (HAE) is a rare autosomal-dominant disorder; most cases are characterized by low plasma levels of C1 esterase inhibitor (C1-INH). Clinical manifestations of HAE due to C1-INH deficiency include unpredictable, acute, recurrent episodes of nonpruritic swelling that can affect the face, trunk, limbs, and the respiratory, gastrointestinal, and genitourinary tracts. Attacks can be disfiguring, disabling, painful, and even life-threatening if laryngeal swelling occurs. Symptoms of HAE generally manifest in childhood. Effective medications are available and approved to treat HAE in children. However, evidence informing use of these medications in pediatric clinical practice is limited. Hereditary angioedema management plans are critical to optimize outcomes and should address on-demand treatment for acute attacks and plans to prevent potentially fatal laryngeal attacks. The plan should also comprise a holistic approach to address nonclinical aspects of HAE, including quality of life (QoL) and psychological issues. This article provides an overview of HAE management principles that health care providers can apply to treat pediatric patients to improve their QoL.
Topics: Humans; Child; Adolescent; Angioedemas, Hereditary; Quality of Life
PubMed: 36908071
DOI: 10.1177/00099228231155703