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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
Acquired angioedema involves a secondary immune process causing dysfunction or inactivation of C1 inhibitor. C1 inhibitor is unable to regulate the complement and kinin pathways due to inhibition by an autoantibody or immune complexes (Hiragun et al. 2013).
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.
Angioedema and anaphylaxis: Angioedema
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder resulting from an inherited deficiency or dysfunction of the C1 inhibitor (a plasma protease inhibitor that regulates several proinflammatory pathways) (Figure 55.1).
Acquired C1-inhibitor deficiency due to splenic marginal zone lymhoma: Case Report
Published in Acta Clinica Belgica, 2021
Jolien Verschueren, Rik Schrijvers, Karolien E. Goffin, Natalie Put, Thomas Tousseyn, Daan Dierickx, Olivier Gheysens
Acute attacks can be effectively treated by prompt infusion of plasma-derived C1-INH concentrate in both AAE and HAE. However, due to accelerated C1-INH catabolism in AAE, often higher doses are considered to be necessary to overcome the presence of anti-C1-INH autoantibodies [1,4]. Alternatively, a potent, specific and selective bradykinin B2 receptor antagonist (icatibant) and/or a kallikrein inhibitor (ecallantide), can be effective for treating acute AAE attacks because they are not influenced by anti-C1-INH autoantibodies [1]. Besides symptomatic therapy, optimal treatment of the underlying disease by cytotoxic chemotherapy or immunosuppressive medication can partially or completely resolve clinical symptoms and biochemical complement impairment. Patients with acquired C1-INH deficiency caused by low grade B-cell lymphoma may benefit from treatment with rituximab (anti-CD20 immunotherapy) alone or in combination with chemotherapy. Indeed, two small case series including three patients each suffering from C1-INH-AAE who were treated with rituximab have been published. In both studies, the angioedema attacks were markedly reduced with the use of rituximab. In addition, most of the patients showed a normalization of C1-inhibitor levels demonstrating a good match between the clinical and biologic response [5,14].
Sepsis target validation for repurposing and combining complement and immune checkpoint inhibition therapeutics
Published in Expert Opinion on Drug Discovery, 2021
Patrícia R.S. Rodrigues, Noemi Picco, B Paul Morgan, Peter Ghazal
Fluid-phase complement regulators target both host and non-host surfaces and act at multiple levels of the complement cascade [56]. For instance, C1 inhibitor (C1INH) inhibits the CP and LP of the complement system by neutralization of C1r and C1s or MASP activities and is the main inhibitor of the contact phase system by inhibition of factor FXIIa, kallikrein, and FXIa [57].Due to the anti-inflammatory properties of C1INH, it has been considered as a potential therapy to treat inflammatory diseases such as sepsis [58]. Properdin is the only known positive regulator of complement activation. A serum protein, it increases the production of complement activation products in the alternative pathway by binding and stabilizing the convertase complex, C3bBb [59]. In sepsis patients, properdin concentrations at ICU admission were decreased in non-survivors of sepsis, suggesting that Properdin may be used as a predictive marker of outcome in the initial stage of sepsis. Factor H is a fluid phase negative regulator of amplification through the alternative pathway [56].
Can the neutrophil–lymphocyte ratio predict type 1 hereditary angioedema attacks?
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2020
Guzin Ozden, Didar Yanardag Acik
Hereditary angioedema (HAE) caused by C1-inhibitor deficiency (C1-INH-AAE), having a course with recurrent episodes of angioedema, is a rare autosomal dominant disorder. The cause of HAE is the low antigenic level and inadequate functional activity of C1-inhibitor (C1-INH) because of a mutation of the gene encoding C1-INH (SERPING1). In C1-INH deficiency, the kallikrein-kinin system undergoes activation, causing cleavage of bradykinin from high-molecular-weight kininogen. The prevalence of the disease is estimated to be one in 50,000–100,000 births, equally distributed in both genders [1,2]. Angioedema is most commonly seen in extremities, genitalia, and larynx. Intestinal mucosal edema may lead to transient intestinal obstruction and severe abdominal pain, which might be confused with the acute abdomen [3].