Acquired Deficiency of the Inhibitor of the First Complement Component: Presentation, Diagnosis, Course, and Conventional Management

Zingale, Lorenza C.; Castelli, Roberto; Zanichelli, Andrea; Cicardi, Marco

doi:10.1016/j.iac.2006.08.002

Cited by 110 publications

(108 citation statements)

References 78 publications

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“…It is clinically identical to the hereditary form, except that onset occurs after the fourth decade of life [30]. We recently reviewed a case series of 77 patients diagnosed since 1975 (Zanichelli et al, manuscript in preparation).…”

Section: Acquired Angioedemamentioning

confidence: 99%

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: Acquired Angioedemamentioning

confidence: 99%

Novelties in the Diagnosis and Treatment of Angioedema

Cicardi¹,

Suffritti²,

Perego³

et al. 2016

J Investig Allergol Clin Immunol

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“…In most cases of C1-INH-AAE, an underlying disorder, such as a lymphoproliferative disease (B-NHL) or autoimmune disease, can be found (64,65). However, as in other autoimmune disorders, AAE might also be a herald of future autoimmune disease or lymphoma, respectively.…”

Section: C1-inhibitor Regulates Bk Generationmentioning

confidence: 99%

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

Zeerleder

Levi

2016

Annals of Medicine

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Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitordependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation. ä KEY MESSAGESInadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema. Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis. Submucosal edema formation in hereditary and acquired C1-inhibitor-dependent angioedema is potentially life threatening and can occur at any age. To date effective therapies for acute and prophylactic treatment are available. ARTICLE HISTORY

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“…AAE is extremely rare with roughly 100 reported cases in literature [3]. HAE prevalence has been estimated between 1:10,000 and 1:50,000 [4].…”

Section: Discussionmentioning

confidence: 99%

“…Standard treatment for an AAE episode is replacement therapy with plasma-derived C1-INH concentrate (pd C1-INH), however some patients become progressively less responsive to pd C1-INH over time. Case studies have shown efficacy in AAE treatment with Icatibant (a selective bradykinin B 2 receptor antagonist), Ecallantide (a kallikrein inhibitor), and Rituximab (CD20 monoclonal ab) [3][4][5].…”

Section: Discussionmentioning

confidence: 99%

A unique case of delayed diagnosis of early onset acquired angioedema

Parikh¹,

Yusin²,

Klaustermeyer³

2013

Hypersensitivity

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Acquired angioedema (AAE) is a very rare condition caused by an acquired deficiency in C1 esterase inhibitor (C1 INH). Pathogenesis of AAE can entail abnormal B cell lymphoproliferation ranging from benign monoclonal gammopathy of undetermined significance (MGUS) to malignant forms of lymphoma. Symptoms related to MGUS or malignancy are often salient and age is often used as a diagnostic tool in considering in making this diagnosis. These bradykinin-mediated angioedema episodes commonly involve face, gastrointestinal system, and pharynx with associated potential for fatality and lack associated urticaria. Hence early diagnosis is vital. This case is unique, in that it describes a very early age of presentation of AAE related to MGUS. Given young age and lack of symptoms associated with MGUS, diagnosis was delayed and significant patient morbidity and healthcare expenses occurred which could have been avoided. A 41 year-old male presented to the allergy/immunology clinic with facial, lip, and tongue swelling following tooth extraction. His history began 5 years prior, after suffering complications from a motor vehicle accident including anterograde amnesia, multiple broken ribs, and a splenic hemorrhage requiring splenectomy. Six months after the accident he developed acute onset bilateral facial swelling, lip swelling, and difficulty breathing. He had no family history of angioedema, was not taking any medications, and his serum tryptase level checked during the episode was normal. He was diagnosed with presumed food-induced allergic angioedema. The patient suffered four additional episodes of varying degree over the next five years and developed clinical depression. Immunological evaluation showed low C1-INH, low C1-INH functional percentage, C4, C2, and C1q, consistent with AAE. Further workup to determine the etiology of AAE included serum protein electrophoresis demonstrating an M-spike in the gamma region with immunofixation showing a monoclonal protein band and a serum IgM level of 1.3 g/dl. The patient was diagnosed with AAE related to MGUS.

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Acquired Deficiency of the Inhibitor of the First Complement Component: Presentation, Diagnosis, Course, and Conventional Management

Cited by 110 publications

References 78 publications

Novelties in the Diagnosis and Treatment of Angioedema

Novelties in the Diagnosis and Treatment of Angioedema

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

A unique case of delayed diagnosis of early onset acquired angioedema

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