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Urticaria and Angioedema
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Jenny M Stitt, Stephen C Dreskin
Hereditary angioedema types I and II are caused by deficient or defective C1 inhibitor, a regulatory protein which is involved in controlling the complement and kinin-generating pathways (Dreskin 2012, Hiragun et al. 2013, Longhurst and Cicardi 2012, Sardana and Craig 2011). C1 inhibitor inhibits proteins that promote bradykinin generation and activation of the classic complement cascade. Excess bradykinin, a vasoactive peptide, leads to plasma leakage and resultant angioedema.
Primary immunodeficiency diseases
Published in Gabriel Virella, Medical Immunology, 2019
John W. Sleasman, Gabriel Virella
Hereditary angioedema (HAE) is due to a deficiency of C1 inhibitor that modulates the C1 binding in the classical pathway. Inability to produce protein (type 1) or production of a nonfunctional protein (type 2) results in the inability to downmodulate activation of the classical pathway leading to the production of complement split (C4a) productions and consumption of C4. C4a activates the Kallikrein pathway consisting of a group of serine proteases that activate bradykinins. This activation leads to uncontrolled nonpruritic angioedema of the lips, tongue, GI tract, and soft tissues and can result in life-threatening airway compromise. Activation is sporadic but is generally induced by mild trauma to the face or airways as can occur during routine dental and anesthesia procedures or simply by stress. Diagnosis is suspected on the basis of low C4 levels during attacks and confirmed based on measurements of serum levels and function of C1 inhibitor. Treatment options include treating attacks or giving regular prophylaxis by infusing purified C1 inhibitor isolated from human plasma administration of recombinant proteins that block the Kallikrein pathway.
Edema
Published in Giuseppe Micali, Pompeo Donofrio, Maria Rita Nasca, Stefano Veraldi, Vulval Dermatologic Diagnosis, 2015
Stefano Veraldi, Maria Rita Nasca, Giuseppe Micali
Therapy: The treatment of idiopathic angioedema is the same as that of urticaria and includes the use of systemic antihistamines and corticosteroids. Hereditary angioedema requires proper prophylactic strategies and pharmacological management of the acute attacks.
A safety review of prophylaxis drugs for adolescent patients with hereditary angioedema
Published in Expert Opinion on Drug Safety, 2023
Henriette Farkas, Zsuzsanna Balla
Hereditary angioedema puts a significant burden on patients since the development of HAE attacks cannot be foreseen, and it can cause a life-threatening state. The unpredictability of the attacks may cause anxiety and depression, and has an impact on everyday life, learning and career building. With preventive treatments, the risk of AE can be minimized in exposure situations where the risk of an attack is increased, and by long-term prophylaxis, the adequate control of the disease can be done, and therefore the lifestyle of patients can be normalized. HAE attacks may occur more frequently and in a more severe form in adolescents, therefore the prevention of the edematous attacks in this population is especially emphasized. During the last decade, significant progress has been made regarding the expansion of possibilities in the prophylactic treatment of C1-INH-HAE. Based on the clinical trials and clinical practice, the use of targeted therapies as intravenous and subcutaneous plasma derived C1-INH concentrate, orally given KK inhibitor and the long-acting monoclonal antibody against KK as first line treatment are safe and effective treatment options in adolescents. Not targeted therapies (AAs, AFs) are second-line treatments in cases where targeted therapies are not available. With the broadening therapeutic spectrum and shared-making decision, a personalized treatment strategy can be developed in case of adolescent patients as well.
Emerging drugs for the treatment of hereditary angioedema due to C1-inhibitor deficiency
Published in Expert Opinion on Emerging Drugs, 2022
Andrea Zanichelli, Vincenzo Montinaro, Massimo Triggiani, Francesco Arcoleo, Debora Visigalli, Mauro Cancian
In conclusion, understanding the pathogenetic mechanism of hereditary angioedema allowed multiple number of drugs to be available and under development, a fact otherwise unexplainable considering the rarity of the disease. However, several drawbacks in existing treatments prompted pharmaceutical companies to study new drugs, possibly characterized by more convenient administration routes, less side effects, and a lower number of administrations. Regarding the mechanism of action of investigational drugs, KVD-824, KVD-900, and ATN-249 target kallikrein. PHA-121 seems more potent than icatibant in inhibiting the bradykinin 2 receptor. Garadacimab blocks a hitherto untargeted molecule, i.e. factor XIIa. Donidalorsen inhibits prekallikrein. Finally, gene therapy might cure a chronic, life-threatening disease. Preliminary data about effectiveness, safety, and conveniency of new products are promising. After marketing, costs considerations will need to be made.
Lanadelumab for the prevention of attacks in hereditary angioedema
Published in Expert Review of Clinical Immunology, 2019
Anna Valerieva, Riccardo Senter, Maddalena Alessandra Wu, Andrea Zanichelli, Marco Cicardi
Hereditary angioedema with C1 esterase inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare autosomal dominant disorder affecting approximately 1 per 50,000 people. Deficiency (type I) or dysfunction (type II) of C1-INH lead to dysregulated plasma kallikrein activity, bradykinin generation, increased vasopermeability, and unpredictable recurrent angioedema attacks lasting for 2–5 days. When edema affects the larynx, attacks are potentially lethal [1,2]. Patients with hereditary angioedema are often limited in their ability to perform daily activities at work or school and may experience symptoms of anxiety and depression resulting in poor quality of life [3–5].