Pathophysiology of Hereditary Angioedema

Caccia, Sonia; Suffritti, Chiara; Cicardi, Marco

doi:10.1089/ped.2014.0425

Cited by 65 publications

(48 citation statements)

References 60 publications

(59 reference statements)

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“…The leakage depends on accumulation of endogenous inflammatory compounds that increase endothelial cell permeability without a fullblown inflammatory process. Hence, of the Celsus tetrad of inflammation (tumor, rubor, dolor, and calor) only tumor (edema) is characteristic of angioedema, thus confirming local accumulation of fluid and absence of inflammatory infiltrate [1]. This "limited inflammation" manifests clinically as the edema described above, which remits in no longer than 5 days with no residual damage.…”

Section: Introductionmentioning

confidence: 60%

Novelties in the Diagnosis and Treatment of Angioedema

Cicardi¹,

Suffritti²,

Perego³

et al. 2016

J Investig Allergol Clin Immunol

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Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis. Key words: Angioedema. Bradykinin. Histamine. C1 inhibitor. Coagulation factor XII. Angiotensin-converting enzyme inhibitors. Urticaria. ResumenAngioedema se define como un edema local, autolimitado, no-inflamatorio. Se trata de un edema circunscrito debido a la trasvasación de plasma de los capilares localizados en los sustratos profundos de la piel y de las mucosas. En la mayoría de los casos están implicados dos mediadores, la histamina y la serotonina. Puede manifestarse en forma de habones como en la urticaria de origen alérgico. El angioedema de origen no alérgico es el motivo de esta revisión. Se puede presentar bajo 3 formas adquiridas y 4 formas hereditarias. La histamina es el mediador implicado en el angioedema adquirido de etiología desconocida (angioedema adquirido idiopático histaminérgico). En las otras formas se sospecha que es la serotonina el mediador principal. La etiología del angioedema puede ser identificado en 4 tipos: una deficiencia de C1-inhibidor (C1-INH-angioedema hereditario y C1-INH-angioedema adquirido), mutaciones en el factor XII de coagulación (FXII-angioedema hereditario), tratamiento con inhibidores del enzima convertidor de la angiotensina (ACEi-angioedema adquirido). En uno de los adquiridos (angioedema adquirido idiopático no histaminérgico) y en el hereditario de origen desconocido, no se ha identificado todavía su etiología. Varios tratamientos están aprobados para revertir los síntomas clínicos y se aplican en la deficiencia de angioedema hereditario por déficit de C1-INH: Derivados de plasma y C1-IN...

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Section: Introductionmentioning

confidence: 60%

Novelties in the Diagnosis and Treatment of Angioedema

Cicardi¹,

Suffritti²,

Perego³

et al. 2016

J Investig Allergol Clin Immunol

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“…The lack of functional C1-INH results in uncontrolled activation of the contact system, leading to an excessive release of bradykinin causing increased vascular permeability (Figure 1) [3]. The fluid leak from the intravascular compartment into the subcutaneous or submucosal space becomes manifest as an acute episode of angioedema, which is the hallmark of an C1-INH-HAE attack.…”

Section: Background Haementioning

confidence: 99%

Recombinant Replacement Therapy for Hereditary Angioedema Due to C1 Inhibitor Deficiency

2015

Self Cite

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Hereditary angioedema is a rare genetic condition transmitted as an autosomal dominant trait and characterized most commonly by the production of either inadequate or nonfunctioning C1 esterase inhibitor (C1-INH), a blood protein that regulates proteases in the complement, fibrinolytic and contact systems. Patients with hereditary angioedema suffer from episodic, unpredictable manifestations of edema affecting multiple anatomical locations, including the GI tract, facial tissue, the upper airway, oropharynx, urogenital region and/or the arms and legs. A rational approach to treatment is replacement of C1-INH protein, to normalize the levels of C1-INH activity and halt the progression of the biochemical activation processes underlying the edema formation. Ruconest is a highly purified recombinant human C1-INH. This article will focus on the results of ten clinical studies demonstrating the efficacy and safety of Ruconest(®) (Pharming Group NV, Leiden, the Netherlands), which is now approved for use in Europe, Israel and the USA.

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“…The disease is characterized by severe episodes of edema in the skin and mucosa that can be extremely debilitating, particularly if the airways are affected. The symptoms are caused by the leakage of fluids from the capillaries as a result of uncontrolled activation of the plasma cascade systems and generation of vasoactive peptides, especially bradykinin [18]. Given its chronic presentation, the disease carries a substantial socio-economic burden, with costs per patient reaching as high as US$230,000 annually [19].…”

Section: Targeting the Initiatorsmentioning

confidence: 99%

Applying complement therapeutics to rare diseases

Reis

Mastellos

Yancopoulou³

et al. 2015

Clinical Immunology

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Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis.

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Pathophysiology of Hereditary Angioedema

Cited by 65 publications

References 60 publications

Novelties in the Diagnosis and Treatment of Angioedema

Novelties in the Diagnosis and Treatment of Angioedema

Recombinant Replacement Therapy for Hereditary Angioedema Due to C1 Inhibitor Deficiency

Applying complement therapeutics to rare diseases

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